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Yr3 Med Conditions > ENDO > Flashcards

ENDO Flashcards

1
Q

Define Acromegaly

A

Constellation of signs and symptoms caused by hyper secretion of GH in adults
- Excess GH before puberty results in GIGANTISM

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2
Q

Define Acromegaly

A

Constellation of signs and symptoms caused by hyper secretion of GH in adults
- Excess GH before puberty results in GIGANTISM

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3
Q

Aetiology/ Risk Factors of Acromegaly

A

• Most cases are caused by a GHJsecreting pituitary adenoma
• RARELY caused by excess GHRH causing somatotroph hyperplasia from hypothalamic
ganglioneuroma, bronchial carcinoid or pancreatic tumours

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4
Q

Epidemiology of Acromegaly

A
  • RARE
  • 5/1,000,000
  • Age affected: 40M50 yrs
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5
Q

Presenting Symptoms of Acromegaly

A 
•  Very gradual progression of symptoms over many years   
•  Rings and shoes becoming tight  
•  Increased sweating  
•  Headaches  
•  Carpal tunnel syndrome   
•  Hypopituitary symptoms:  
o  Hypogonadism 
o  Hypothyroidism 
o  Hypoadrenalism 
•  Visual disturbances (due to compression of optic chiasm by tumour)  
•  Hyperprolactinaemia leading to: 
o  Irregular periods   
o  Decreased libido  
o  Impotence
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6
Q

Signs of Acromegaly on physical examination

A 
•  Hands 
o  Large spade-like hands  
o  Thick greasy skin  
o  Carpel tunnel syndrome signs  
 o  Premature osteoarthritis  
•  Face 
o  Prominent eyebrow ridge  
o  Prominent cheeks  
o  Broad nose bridge  
o  Prominent nasolabial folds   
o  Thick lips  
o  Increased gap between teeth
o  Large tongue  
o  Prognathism 
o  Husky resonant voice (due to thickening of vocal cords)  
•  Visual Field Loss 
o  Bitemporal superior quadrantopia progressing to bitemporal hemianopia 
•  Neck 
o  Multinodular goitre 
•  Feet 
o  Enlarged
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7
Q

Investigations for acromegaly

A 
•  Serum IGF-1 -useful screening test   
o  GH stimulates IGF-1 secretion   
•  Oral Glucose Tolerance Test (OGTT) 
o  Positive result: failure of suppression of GH after 75 g oral glucose load   
•  Pituitary Function Tests 
o  9am cortisol 
o  Free T4 and TSH  
o  LH and FSH 
o  Testosterone 
o  Prolactin  
•  MRI of Brain - visualise the pituitary adenoma
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8
Q

Management plan for Acromegaly

A

• Surgical - trans-sphenoidal hypophysectomy

• Radiotherapy - adjunctive to surgery
• Medical - if surgery is contraindicated or refused
o Subcutaneous Somatostatin Analogues
• Examples: octreotide, lanreotide
• Side-effects: abdominal pain, steatorrhoea, glucose intolerance, gallstones
o Oral Dopamine Agonists
• Examples: bromocriptine, cabergoline
• Side-effects: nausea, vomiting, constipation, postural hypotension,
psychosis (RARE)
o GH Antagonist (pegvisomant)
o Monitor
• GH and IGF1 levels can be used to monitor disease control

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9
Q

Identify complications of acromegaly

A 
•  CVS 
o  Cardiomegaly  
o  Hypertension  
•  Respiratory 
o  Obstructive sleep apnoea  
•  GI 
o  Colonic polyps  
•  Reproductive 
o  Hyperprolactinaemia (in 30% of cases)  
•  Metabolic 
o  Hypercalcaemia 
o  Hyperphosphataemia 
 o  Renal stones  
o  Diabetes mellitus  
o  Hypertriglyceridaemia 
•  Psychological 
o  Depression 
o  Psychosis (from dopamine agonists)  
•  Complications of Surgery 
o  Nasoseptal perforation  
o  Hypopituitarism 
o  Adenoma recurrence   
o  CSF leak 
o  Infection
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10
Q

Prognosis for patients with acromegaly

A
  • GOOD with early diagnosis and treatment

* Physical changes are irreversible

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11
Q

Define Adrenal Insufficiency

A

Deficiency of adrenal cortical hormones (e.g. mineralocorticoids, glucocorticoids and androgens)

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12
Q

Aetiology/ Risk Factors of adrenal insufficiency

A 
•  Primary Adrenal Insufficiency 
o  Addison's disease (usually autoimmune)  
•  Secondary Adrenal Insufficiency 
o  Pituitary or hypothalamic disease   
•  Infections 
o  Tuberculosis  
o  Meningococcal septicaemia (Waterhouse-Friderichsen Syndrome)  
o  CMV  
o  Histoplasmosis 
•  Infiltration 
o  Metastasis (mainly from lung, breast, melanoma)  
o  Lymphomas 
o  Amyloidosis   
•  Infarction 
o  Secondary to thrombophilia  
•  Inherited 
o  Adrenoleukodystrophy 
o  ACTH receptor mutation   
•  Surgical  
o  After bilateral adrenalectomy  
•  Iatrogenic 
o  Sudden cessation of long-term steroid therapy
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13
Q

Epidemiology of adrenal insufficiency

A
  • Most common cause is IATROGENIC

* Primary causes are rare

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14
Q

Presenting symptoms of adrenal insufficiency (chronic and acute)

A 
•  Chronic Presentation - the symptoms tend to be VAGUE and NON-SPECIFIC 
o  Dizziness 
o  Anorexia 
o  Weight loss  
o  Diarrhoea and Vomiting   
o  Abdominal pain 
o  Lethargy 
o  Weakness  
o  Depression  
•  Acute Presentation (Addisonian Crisis) 
o  Acute adrenal insufficiency 
o  Major haemodynamic collapse  
o  Precipitated by stress (e.g. infection, surgery)
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15
Q

Signs of adrenal insufficiency on physical examination

A 
•  Postural hypotension  
•  Increased pigmentation  
o  More noticeable on buccal mucosa, scars, skin creases, nails and pressure points   
•  Loss of body hair in women (due to androgen deficiency) 
•  Associated autoimmune condition (e.g. vitiligo) 
•  Addisonian Crisis Signs:
o  Hypotensive shock  
o  Tachycardia 
o  Pale  
o  Cold  
o  Clammy  
o  Oliguria
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16
Q

Investigations for adrenal insufficiency

A

• To confirm the diagnosis
o 9 am Serum Cortisol (< 100 nmol/L is diagnostic of adrenal insufficiency)
• > 550 nmol/L makes adrenal insufficiency unlikely
o Short Synacthen Test
• IM 250 μg tetrocosactrin (synthetic ACTH)
• Serum cortisol < 550 nmol/L at 30 mins indicates adrenal failure
• Identify the level of the defect in the hypothalamo-pituitary-adrenal axis
o HIGH in primary disease
o LOW in secondary

o  Long Synacthen Test 
•  1 mg synthetic ACTH administered  
•  Measure serum cortisol at 0, 30, 60, 90 and 120 minutes  
•  Then measure again at 4, 6, 8, 12 and 24 hours  
•  Patients with primary adrenal insufficiency show no increased after 6 hours  
•  Identify the cause 
o  Autoantibodies (against 21-hydroxylase)   
o  Abdominal CT or MRI 
o  Other tests (adrenal biopsy, culture, PCR) 
•  Check TFTs 
•  Investigations in Addisonian crisis 
o  FBC (neutrophilia MM> infection)   
o  U&amp;Es 
•  High urea 
•  Low sodium 
•  High potassium 
o  CRP/ESR 
o  Calcium (may be raised)  
o  Glucose - low  
o  Blood cultures  
o  Urinalysis 
o  Culture and sensitivity
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17
Q

Management plan for adrenal insufficiency

A

• Addisonian Crisis
o Rapid IV fluid rehydration
o 50 mL of 50% dextrose to correct hypoglycaemia
o IV 200 mg hydrocortisone bolus
o Followed by 100 mg 6 hourly hydrocortisone until BP is stable o Treat precipitating cause (e.g. antibiotics for infection)
o Monitor
• Chronic Adrenal Insufficiency
o Replacement of:
• Glucocorticoids with hydrocortisone (3/day)
• Mineralocorticoids with fludrocortisone
o Hydrocortisone dosage needs to be increased during times of acute illness or stress
o NOTE: if the patient also has hypothyroidism, give hydrocortisone BEFORE thyroxine (to prevent precipitating an Addisonian crisis)
• Advice
o Have a steroid warning card
o Wear a medic-alert bracelet
o Emergency hydrocortisone on hand

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18
Q

Identify possible complications of adrenal insufficiency

A
  • HYPERKALAEMIA

* Death during Addisonian crisis

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19
Q

Prognosis for patients with adrenal insufficiency

A 
•  Adrenal function rarely recovers  
•  Normal life expectancy if treated  
•  Autoimmune Polyendocrine Syndrome  
o  Type 1 - autosomal recessive disorder caused by mutations in the AIRE gene.  Consists of the following diseases: 
•  Addison's disease  
•  Chronic mucocutaneous candidiasis   
•  Hypoparathyroidism 
o  Type 2 M also known as Schmidt's Syndrome  
•  Addison's disease  
•  Type 1 Diabetes  
•  Hypothyroidism 
•  Hypogonadism
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20
Q

Define Carcinoid Syndrome

A

Constellation of symptoms caused by systemic release of humeral factors from carcinoid tumours

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21
Q

Aetiology/ Risk Factors of Carcinoid syndrome

A

• Carcinoid tumours are slowMgrowing neuroendocrine tumours
• They are mostly derived from serotonin-producing enterochromaffin cells
• They produce secretory products like serotonin, histamine, tachykinins, kallikrein and prostaglandins
• 75-80% of patients with carcinoid syndrome have small bowel carcinoids
• NOTE: hormones released into the portal circulation will be metabolised by the liver so
symptoms don’t tend to appear until there are hepatic metastases or release into the
systemic circulation from bronchial or extensive retroperitoneal tumours

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22
Q

Epidemiology of Carcinoid Syndrome

A
  • RARE
  • UK incidence : 1/1,000,000
  • Asymptomatic carcinoid tumours are more common
  • 10% of patients with MEN-1 have carcinoid tumours
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23
Q

Presenting symptoms of carcinoid syndrome

A
  • Paroxysmal FLUSHING
  • Diarrhoea
  • Crampy abdominal pain
  • Wheeze
  • Sweating
  • Palpitations
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24
Q

Signs of carcinoid syndrome on physical examination

A 
•  Facial flushing  
•  Telangiectasia 
•  Wheeze  
•  Right-sided murmurs (tricuspid stenosis/regurgitation or pulmonary stenosis)  
•  Nodular hepatomegaly in cases of metastatic disease  
•  Carcinoid Crisis Signs: 
o  Profound flushing  
o  Bronchospasm 
o  Tachycardia 
o  Fluctuating blood pressure
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25
Q

Investigations for carcinoid syndrome

A 
•  24 hours urine collection :
o  Check 5-HIAA levels (metabolite of serotonin) 
•  Blood: 
o  Plasma chromogranin A and B   
o  Fasting gut hormones  
•  CT or MRI Scan :
o  To localise the tumour  
•  Radioisotope Scan :
o  Radiolabelled somatostatin analogue helps localise the tumour  
•  Investigations for MEN-1
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26
Q

Define Cushing’s Syndrome

A

Syndrome associated with chronic inappropriate elevation of free circulating cortisol

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27
Q

Aetiology/ Risk Factors for Cushing’s syndrome

A

It can be divided into ACTH Dependent (80%) and ACTH Independent (20%)
• ACTH Dependent
o Excess ACTH from a pituitary adenoma (Cushing’s disease)
o Ectopic ACTH (e.g. lung cancer, pulmonary carcinoid tumours)
• ACTH Independent
o Benign adrenal adenoma
o Adrenal carcinoma

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28
Q

Epidemiology of Cushing’s syndrome

A
  • Incidence: 2-4/1,000,000 per year

* Peak incidence 20-40 yrs

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29
Q

Presenting symptoms of Cushing’s syndrome

A
  • Increasing weight
  • Fatigue
  • Muscle weakness
  • Myalgia
  • Thin skin
  • Easy bruising
  • Poor wound healing
  • Fractures
  • Hirsuitism
  • Acne
  • Frontal balding
  • Oligomenorrhoea/amenorrhoea
  • Depression or psychosis
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30
Q

Signs of cushion’s syndrome on physical examination

A
  • moon face
  • facial plethora
  • inter scapular fat pad
  • proximal muscle weakness
  • thin skin
  • bruises
  • central obesity
  • pink/purple striae on abdomen/breast/thighs
  • kyphosis (due to vertebral fracture)
  • Poorly healing wounds
  • Hirsuitism, acne, frontal balding
  • Hypertension
  • Ankle oedema (due to salt and water retention from the mineralocorticoid effect of excess cortisol)
  • Pigmentation in ACTH dependent cases
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31
Q

Investigations for Cushing’s syndrome

A

• Must be performed on patients with a high pre-test probability
• Bloods
o U&Es - hypokalaemia due to mineralocorticoid effect
o BM - high glucose
• Initial High-Sensitivity Tests
o Urinary free cortisol
o Late-night salivary cortisol
o Overnight dexamethasone suppression test
o Low dose dexamethasone suppression test (LDDST)
• Give 0.5 mg dexamethasone orally ever 6 hrs for 48 hrs
• In Cushing’s syndrome, serum cortisol measured 48 hrs after the first dose
of dexamethasone fails to suppress below 50 nmol/L
• Tests to determine the underlying cause
o ACTH-independent (adrenal adenoma/carcinoma)
• Low plasma ACTH
• CT or MRI of adrenals
o ACTH-dependent (pituitary adenoma)
• High plasma ACTH
• Pituitary MRI
• High-dose dexamethasone suppression test
• Inferior petrosal sinus sampling (SUPERIOR to high-dose dexamethasone
suppression test)
! Central: peripheral ratio of venous ACTH > 2:1 (or > 3:1 after CRH administration) in Cushing’s disease
o ACTH-dependent (ectopic)
• If lung cancer suspected: CXR, sputum cytology, bronchoscopy, CT san
• Radiolabelled octreotide scans can detect carcinoid tumours because they express somatostatin receptors

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32
Q

Generate a management plan for Cushing’s syndrome

A

• If iatrogenic - discontinue steroids, use lower dose or use a steroid-sparing agent
• Medical
o Used pre-operatively or if unfit for surgery
o Inhibit cortisol synthesis with metyrapone or ketoconazole
o Treat osteoporosis
o Physiotherapy for muscle weakness
• Surgical
o Pituitary Adenomas - trans-sphenoidal adenoma resection o Adrenal adenoma/carcinoma - surgical removal of tumour
o Ectopic ACTH - treatment directed at the tumour
• Radiotherapy
o Performed in those who are not cured and have persistent high cortisol after trans-sphenoidal resection of the tumour
• Bilateral adrenalectomy may be performed in refractory Cushing’s disease

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33
Q

Complications of Cushing’s syndrome

A 
•  Diabetes  
•  Osteoporosis 
•  Hypertension 
•  Pre-disposition to infections  
•  Complications of surgery: 
o  CSF leakage  
o  Meningitis  
o  Sphenoid sinusitis   
o  Hypopituitarism 
•  Complications of radiotherapy: 
 o  Hypopituitarism 
o  Radionecrosis 
o  Increased risk of second intracranial tumours and stroke 
•  Bilateral adrenalectomy may be complicated by the development of Nelson's 
syndrome (locally aggressive pituitary tumour causing skin pigmentation due to ACTH 
secretion)
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34
Q

Prognosis for patients with Cushing’s syndrome

A

Untreated - 5 yr survival = 50%

• Depression persists for many years following treatment

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35
Q

Define Type 2 diabetes mellitus

A

Characterised by increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output

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36
Q

Aetiology/ Risk Factors

A

• Genetic and environmental
• There are a few monogenic causes of diabetes (e.g. MODY, mitochondrial diabetes)
• Obesity increases the risk of T2DM (due to the action of adipocytokines)
• Diabetes can happen secondary to:
o Pancreatic disease (e.g. chronic pancreatitis)
o Endocrine disease (e.g. Cushing’s syndrome, acromegaly, phaeochromocytoma,
glucagonoma)
o Drugs (e.g. corticosteroids, atypical antipsychotics, protease inhibitors)

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37
Q

Summarise the epidemiology of type 2 diabetes mellitus

A
  • UK Prevalence: 5-10%
  • Asian, African and Hispanic people are at greater risk
  • Incidence has increased over the past 20 yrs
  • This is linked to an increasing prevalence of obesity
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38
Q

Presenting symptoms of type 2 diabetes mellitus

A
  • May be an incidental finding • Polyuria
  • Polydipsia
  • Tiredness
  • Patients may present with hyperosmolar hyperglycaemic state (HHS)
  • Infections (e.g. infected foot ulcers, candidiasis, balanitis)
  • Assess cardiovascular risk factors: hypertension, hyperlipidaemia and smoking
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39
Q

Recognise the signs of T2DM on physical examination

A

• Calculate BMI
• Waist circumference
• Blood pressure
• Diabetic foot (ischaemic and neuropathic signs)
o Dry skin
o Reduced subcutaneous tissue
o Ulceration
o Gangrene
o Charcot’s arthropathy
o Weak foot pulses
• Skin changes (RARE):
o Necrobiosis lipoidica diabeticorum (well-demarcated plaques on shins or arms
with shiny atrophic surface and red-brown edges)
o Granuloma annulare (flesh-coloured papules coalescing in rings on the back of hands and fingers)
o Diabetic dermopathy (depressed pigmented scars on shins)

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40
Q

Investigations for type 2 diabetes mellitus

A

• T2DM is diagnosed if one or more of the following are present:
o Symptoms of diabetes and a random plasma glucose > 11.1 mmol/L
o Fasting plasma glucose > 7 mmol/L
o Two-hour plasma glucose > 11.1 mmol/L after 75 g oral glucose tolerance test
• Monitor:
o HbA1c
o U&Es
o Lipid profile
o eGFR
o Urine albumin: creatinine ration (look out for microalbuminuria)

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41
Q

Management plan for T2DM

A

• Glycaemic control - there is a step-
wise approach to the management of T2DM:
o At diagnosis: lifestyle + metformin
o If HbA1c > 7% after 3 months: lifestyle + metformin + sulphonylurea
o If HbA1c > 7% after 3 months: lifestyle + metformin + basal insulin
o If HbA1c > 7% after 3 months and fasting blood glucose > 7 mmol/L: add premeal rapid-acting insulin
o NOTE: sulphonylurea may be given as a monotherapy if patients cannot tolerate metformin
o NOTE: pioglitazone (thiazolidinedione) may also be given alongside metformin and a sulphonylurea
• Screening for complications
o Retinopathy
o Nephropathy
o Vascular disease
o Diabetic foot
o Cardiovascular risk factors (e.g. blood pressure, cholesterol)
• Pregnancy - requires strict glycaemic control and planning of conception
• Hyperosmolar Hyperglycaemic State - management is similar DKA
o Except use 0.45% saline if serum Na+ > 170 mmol/L

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42
Q

Complications of T2DM

A 
- Hyperosmolar hyperglycaemic state :
o  Due to insulin deficiency  
 o  Marked dehydration  
o  High Na+ 
o  High glucose  
o  High osmolality  
o  No acidosis  
- Neuropathy
o  Distal symmetrical sensory neuropathy   
o  Painful neuropathy 
o  Carpel tunnel syndrome  
o  Diabetic amyotrophy 
o  Mononeuritis  
o  Autonomic neuropathy 
o  Gastroparesis (abdominal pain, nausea, vomiting)  
o  Impotence  
o  Urinary retention  
- Nephropathy: 
o  Microalbuminuria  
o  Proteinuria 
o  Renal failure  
o  Prone to UTI 
o  Renal papillary necrosis  
- Retinopathy:
o  Background 
o  Pre-proliferative 
o  Proliferative  
o  Maculopathy 
o  Prone to glaucoma, cataracts and transient visual loss  
- Microvascular complications :
o  Ischaemic heart disease  
o  Stroke  
o  Peripheral vascular disease
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43
Q

Summarise the prognosis for patients with T2DM

A

• Good prognosis with good control
• Pre-diabetes can be diagnosed based on fasting blood glucose and oral glucose
tolerance test:
o Impaired Fasting Glucose (IFG) = fasting blood glucose 5.6-6.9 mmol/L
o Impaired Glucose Tolerance (IGT) = plasma glucose level of 7.8-11.0 mmol/L measured 2 hrs after a 75 g oral glucose tolerance test
• People with IFG or IGT are at high risk of developing type 2 diabetes

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44
Q

Define Diabetes Insipidus

A

A disorder of inadequate secretion or of insensitivity to vasopressin (ADH) leading to hypotonic polyuria

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45
Q

Aetiology/ Risk Factors

A

• Central DI: failure of ADH secretion by the posterior pituitary
• Nephrogenic DI: insensitivity of the collecting duct to ADH
o Water channels fail to activate and the luminal membrane of the collecting duct remains impermeable to water
• DI results in large volumes of hypotonic urine and polydipsia • Causes
o Central
• Idiopathic
• Tumours (e.g. pituitary tumour)
• Infiltrative (e.g. sarcoidosis)
• Infection (e.g. meningitis)
• Vascular (e.g. aneurysms, Sheehan syndrome)
• Trauma (e.g. head injury, neurosurgery)
o Nephrogenic
• Idiopathic
• Drugs (e.g. lithium)
• Post-obstructive uropathy
• Pyelonephritis
• Pregnancy
• Osmotic diuresis (e.g. diabetes mellitus)

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46
Q

Epidemiology of diabetes insipidus

A
  • Median onset is 24 yrs

* Depends on cause

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47
Q

Presenting symptoms of diabetes insipidus

A 
•  Polyuria 
•  Nocturia 
•  Polydipsia 
•  In children: 
o  Enuresis (bed-wetting) 
 o  Sleep disturbance 
•  Other symptoms depend on aetiology
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48
Q

Signs of diabetes insipidus on physical examination

A

• Central DI has few signs if the patient drinks sufficiently to maintain adequate fluid
levels
• Urine output > 3 L/day
• If fluid intake < fluid output, signs of dehydration will be present (e.g. tachycardia,
reduced tissue turgor, postural hypotension, dry mucous membranes)
• Signs related to the cause (e.g. visual defect due to pituitary tumour)

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49
Q

Investigations for diabetes insipidus

A

• Bloods
o U&Es and Ca2+
o Increased plasma osmolality
o Decreased urine osmolality • Water Deprivation Test
o Water is restricted for 8 hrs
o Plasma and urine osmolality are measured every hour for 8 hrs
o Weight the patient hourly to monitor level of dehydration
o STOP the test if the fall in body weight is > 3%
o Desmopressin is given after 8 hrs and urine osmolality is measured
o Results
• Normal - water restriction causes:
! Increased plasma osmolality
! Increased ADH secretion
! Increased water reabsorption
! Increase in urine osmolality (urine > 600 mosmol/kg)
• Diabetes Insipidus
! Lack of ADH activity means that urine CANNOT be concentrated
! Urine osmolality is LOW (< 400 mosmol/kg)
! Cranial M urine osmolality rises > 50% following administration of
desmopressin
! Nephrogenic - urine osmolality rises by < 45% following
administration of desmopressin

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50
Q

Management plan for diabetes insipidus

A

• Treat the CAUSE
• Cranial DI
o Give desmopressin (vasopressin analogue)
o If mild - chlorpropamide or carbamazepine can be used to potentiate the residual
effects of any residual vasopressin
• Nephrogenic DI
o Sodium and/or protein restriction helps with polyuria
o Thiazide diuretics

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51
Q

Complications of diabetes insipidus

A
  • Hypernatraemic dehydration

* Excess desmopressin –> hyponatraemia

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52
Q

Prognosis for patients with diabetes insipidus

A
  • Depends on CAUSE
  • Cranial DI may be transient following head trauma
  • It may be cured by removing the cause (e.g. drug discontinuation, tumour resection)
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53
Q

Define Type 1 Diabetes Mellitus

A

Metabolic hyperglycaemic condition caused by absolute insufficiency of pancreatic insulin production

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54
Q

Aetiology/ Risk Factors of T1DM

A 
•  Caused by destruction of pancreatic insulin-producing beta cells  
•  Autoimmune process  
•  Occurs in genetically susceptible individuals with an environmental trigger   
•  Autoantigens associated with T1DM: 
o  Glutamic acid decarboxylase (GAD)  
o  Insulin 
o  Insulinoma-associated protein 2  
o  Cation efflux zinc transporter
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55
Q

Summarise the epidemiology of T1DM

A

• 0.25% prevalence in the UK

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56
Q

Symptoms and signs of T1DM

A 
•  Juvenile onset (< 30 yrs)  
•  Polyuria/nocturia 
•  Polydipsia 
•  Tiredness 
•  Weight loss  
•  DKA Symptoms: 
o  Nausea and vomiting  
o  Abdominal pain  
o  Polyuria, polydipsia 
 o  Drowsiness 
o  Confusion 
o  Coma 
o  Kussmaul breathing  
 o  Ketotic breath  
o  Signs of dehydration  
•  Signs of complications: 
o  Fundoscopy - check for diabetic retinopathy 
o  Examine feet for evidence of neuropathy (monofilament test, pulses)   
o  Monitor BP  
•  Signs of associated autoimmune conditions  
o  Vitiligo 
o  Addison's disease  
o  Autoimmune thyroid disease
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57
Q

Investigations for T1DM

A

• Blood Glucose - fasting blood glucose > 7 mmol/L or random blood glucose > 11.1
mmol/L
• HbA1c
• FBC - MCV, reticulocytes
• U&Es - monitor for nephropathy and hyperkalaemia
• Lipid profile
• Urine albumin creatinine ratio - used to detect microalbuminuria
• Urine - glycosuria, ketonuria, MSU
• Investigations for DKA
o FBC (raised WCC without infection in DKA)
o U&Es (raised urea and creatinine due to dehydration) o LFT
o CRP
o Glucose
o Amylase
o Blood cultures
o ABG (metabolic acidosis with high anion gap)
o Blood/urinary ketones

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58
Q

Management plan for T1DM

A

• Glycaemic Control
o Advice and patient education
• Short-acting insulin (three times daily before meals):
! Lispro
! Aspart
! Glulisine
• Long-acting insulin (once daily):
! Isophane
! Glargine
! Detemir
o Insulin pumps
o DAFNE courses (dose adjustment for normal eating)
o Monitor
• Regular capillary blood glucose tests
• HbA1c every 3-6 months
o Screening and management of complications
o Treatment of hypoglycaemia
• If reduced consciousness: 50 ml of 50% glucose IV OR 1 mg glucagon IM
• If consciousness and cooperative: 50 g oral glucose + starchy snack o Screening and management of cardiovascular risk factors
• DKA Management
o 50 U soluble insulin in 50 mL of normal saline
o Use an insulin sliding scale
o Continue until:
• Capillary ketones < 0.3
• Venous pH > 7.30
• Venous bicarbonate > 18 mmol/L
o From this point onwards change to SC insulin
o Don’t stop the insulin infusion until 1-2 hrs after the SC insulin has restarted
o 500 mL normal saline over 15M30 mins until SBP > 100
o Potassium replacement (because insulin drives potassium into cells)
o Monitor blood glucose, capillary ketones and urine output hourly
o Monitor U&Es and venous blood gas
o Broad spectrum antibiotics if infection is suspected
o Thromboprophylaxis
o NBM for at least 6 hrs
o NG tube if GCS is reduced

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59
Q

Possible complications of T1DM

A 
•  Diabetic ketoacidosis  
o  Can be precipitated by infection, errors in management of diabetes, newly 
diagnosed diabetes, idiopathic  •  Microvascular complications: 
o  Retinopathy  
o  Nephropathy  
o  Neuropathy  
•  Macrovascular complications: 
o  Peripheral vascular disease   o  Ischaemic heart disease  
o  Stroke/TIA 
•  Increased risk of infection   
•  Complications of treatment:
o  Weight gain  
o  Fat hypertrophy at insulin injection sites   
o  Hypoglycaemia  
•  Personality changes  
 •  Fits  
•  Confusion 
•  Coma  
•  Pallor  
•  Sweating  
•  Tremor  
•  Tachycardia 
•  Palpitations  
•  Dizziness  
•  Hunger  
•  Focal neurological symptoms
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60
Q

Prognosis for patients with T1DM

A
  • Depends on early diagnosis, good glycaemic control and compliance with treatment and screening
  • Vascular disease and renal failure are the main causes of increased morbidity and mortality
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61
Q

Define Graves disease

A

The most common cause of hyperthyroidism. Caused by the presence of TSH-receptor stimulating antibodies that lead to hyperthyroidism due to loss of negative feedback.

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62
Q

Aetiology/ risk factors of Graves disease

A

• Caused by the presence of TSH-receptor stimulating antibodies
• These antibodies are also responsible for the special features of Graves disease
(exophthalmos, pretibial myxoedema)
• Risk Factors for Hyperthyroidism :
o Family history
o High iodine intake
o Smoking
o Trauma to the thyroid gland o Toxic multinodular goitre
o HAART
o Childbirth

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63
Q

Summarise the epidemiology of Graves disease

A
  • Hyperthyroidism is COMMON

* Graves’ is the most common cause of hyperthyroidism (75%) • Rarely occurs in children

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64
Q

Presenting symptoms of Graves disease

A
  • Weight loss despite increased appetite
  • Irritability
  • Weakness
  • Diarrhoea
  • Sweating
  • Tremor
  • Anxiety
  • Heat intolerance
  • Loss of libido
  • Oligomenorrhoea/ amenorrhoea
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65
Q

Signs of Graves disease on physical examination

A
  • Palmar erythema
  • Sweaty and warm palms
  • Fine tremor
  • Tachycardia (may be AF)
  • Hair thinning
  • Urticaria/pruritus
  • Brisk reflexes
  • Goitre
  • Proximal myopathy
  • Lid lag
  • Gynaecomastia
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66
Q

Investigations for Graves disease

A

• TFTs - low TSH + high T3/T4
• Autoantibodies
o Anti-TPO antibodies (thyroid peroxidase) - found in 75% of Graves
o Anti-thyroglobulin antibodies
o TSH-receptor antibodies - very sensitive and specific for Graves
• Imaging
o Thyroid ultrasound
o Thyroid uptake scan
• Inflammatory Markers -CRP/ESR will be raised in subacute thyroiditis

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67
Q

Define Hyperparathyroidism (Primary, Secondary, Tertiary)

A

• Primary Hyperparathyroidism - increased secretion of PTH unrelated to the plasma
calcium concentration
• Secondary Hyperparathyroidism - increased secretion of PTH secondary to
hypocalcaemia
• Tertiary Hyperparathyroidism - autonomous PTH secretion following chronic
secondary hyperparathyroidism

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68
Q

Aetiology/ Risk Factors of hyperparathyroidism

A 
•  Primary  
o  Parathyroid adenoma 
o  Parathyroid hyperplasia   
o  Parathyroid carcinoma   
o  MEN syndrome  
•  Secondary  
o  Chronic renal failure   
o  Vitamin D deficiency
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69
Q

Summarise the epidemiology of hyperparathyroidism

A
  • Primary - incidence of 5/100,000
  • Twice as common in FEMALES
  • Peak incidence: 40-60 yrs
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70
Q

Recognise the presenting symptoms and signs of hyperparathyroidism

A

• Primary - many patients have mild hypercalcaemia and may be asymptomatic
• Symptoms/Signs of hyperclacaemia:
o Polyuria
o Polydipsia
o Renal calculi
o Bone pain
o Abdominal pain
o Nausea
o Constipation
o Psychological depression o Lethargy
• Secondary - may present with signs/symptoms of HYPOcalcaemia or of the underlying cause (e.g. renal failure, vitamin D deficiency)

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71
Q

Investigations for hyperparathyroidism

A

• U&Es
• Serum calcium (high in primary and tertiary, low/normal in secondary)
• Serum phosphate (low in primary and tertiary, high in secondary)
• Albumin
• ALP
• Vitamin D
• PTH
• Primary Hyperparathyroidism:
o Hyperchloraemic acidosis
o Normal anion gap
o Due to PTH inhibition of renal reabsorption of bicarbonate
o Urine - high PTH in the presence of high calcium can also be caused by familial
hypocalciuric hypercalcaemia (FHH)
• Calcium: creatinine clearance ratio can help differentiate between primary
hyperparathyroidism and FHH
• Renal ultrasound - can visualise renal calculi

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72
Q

Management plan for hyperparathyroidism

A

• Acute Hypercalcaemia
o IV fluids
o Avoid factors that exacerbate hypercalcaemia (e.g. thiazide diuretics)
o Maintain adequate hydration
o Moderate calcium and vitamin D intake
• Surgical Management
o Subtotal parathyroidectomy o Total parathyroidectomy
• Secondary Hyperparathyroidism Management
o Treat underlying cause (e.g. renal failure)
o Calcium and vitamin D supplements may be needed

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73
Q

Complications of hyperparathyroidism

A

• Primary
o Increased bone resorption
o Increased tubular calcium reabsorption
o Increased 1alpha-hydroxylation of vitamin D
o All of these lead to hypercalcaemia
• Secondary
o Increased stimulation of osteoclasts and increased bone turnover
o This leads to osteitis fibrosa cystica
• Complications of surgery
o Hypocalcaemia
o Recurrent laryngeal nerve palsy

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74
Q

Summarise the prognosis for patients with hyperparathyrodisim

A
  • Primary - surgery is curative for benign disease in most cases
  • Secondary or Tertiary - same prognosis as chronic renal failure
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75
Q

Define Hypogonadism (female)

A

Characterised by impairment of ovarian function

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76
Q

Aetiology/ Risk Factors of hypogonadism (female)

A

• Primary Hypogonadism
o Gonadal dysgenesis (due to chromosomal abnormalities e.g. Turner’s syndrome)
o Gonadal damage (e.g. autoimmune, chemotherapy, radiotherapy)
• Secondary Hypogonadism
o Functional (e.g. stress, weight loss, excessive exercise, eating disorders)
o Pituitary/Hypothalamic Tumours and Infiltrative Lesions (e.g. pituitary
adenomas, haemochromatosis)
o Hyperprolactinaemia (e.g. due to prolactinoma)
o Congenital GnRH deficiency: Kallmann’s syndrome, idiopathic

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77
Q

Epidemiology of hypogonadism (female)

A
  • Secondary hypogonadism is a more common cause of anovulation/amenorrhoea
  • Turner’s syndrome occurs in around 1.5% of conceptions
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78
Q

Recognise the presenting symptoms of hypogonadism (female)

A 
•  Symptoms of oestrogen deficiency: 
o  Night sweats  
o  Hot flushing  
o  Vaginal dryness   
o  Dyspareunia 
o  Decreased libido 
o  Infertility  
•  Symptoms of the underlying cause
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79
Q

Signs of hypogonadism on physical examination (female)

A

• PRE-Pubertal Hypogonadism
o Delayed puberty (primary amenorrhoea, absent breast development, no
secondary sexual characteristics)
o Eunuchoid (long legs, arm span greater than height)
• POST-Pubertal Hypogonadism
o Regression of secondary sexual characteristics (e.g. loss of secondary sexual hair,
breast atrophy)
o Perioral and periorbital fine facial wrinkles
o Signs of underlying cause
• Hypothalamic/Pituitary disease - visual field defects
• Kallmann’s syndrome M-anosmia
• Turner’s syndrome
o Short statue
o Low posterior hair line
o High arched palate
o Widely spaced nipples
o Wide carrying angle
o Short fourth and fifth metacarpals
o Congenital lymphoedema
• Autoimmune primary ovarian
failure - there may be signs of other autoimmune diseases (e.g. vitiligo)

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80
Q

Investigations for hypogonadism (female)

A

• Low serum oestradiol
• Serum FSH/LH
o Primary hypogonadism = HIGH
o Secondary hypogonadism = LOW
• Primary Hypogonadism Investigations
o Karyotype (look for chromosomal abnormalities)
o Pelvic imaging (US or MRI)- performed in primary amenorrhoea to check for
structural defects (e.g. androgen insensitivity)
• Screen for FMR1 gene in patients with unexplained preMmature ovarian failure
• Secondary Hypogonadism Investigations
o Pituitary function tests (e.g. 9 am cortisol, TFTs, prolactin)
o Visual field testing
o Hypothalamic-pituitary MRI
o Smell tests for anosmia
o Serum transferrin saturation (check for haemochromatosis)
• Investigating associated conditions
o Turner’s Syndrome - periodic echocardiography, renal US
o Autoimmune Oophoritis - check autoimmune adrenal insufficiency

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81
Q

Define Hypogonadism (male)

A

A syndrome of decreased testosterone production, sperm production or both

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82
Q

Aetiology/ Risk Factors of hypogonadism

A

• Primary Hypogonadism
o Gonadal dysgenesis (e.g. Klinefelter’s syndrome, undescended testicles)
o Gonadal damage (e.g. infection, torsion, trauma, autoimmune, iatrogenic)
o Rare causes (e.g. defects in enzymes involved in testosterone synthesis)
• Secondary Hypogonadism
o Pituitary/Hypothalamic lesions
o GnRH deficiency (Kallmann’s syndrome)
o Hyperprolactinaemia
o Systemic/chronic diseases
o o
o
Rare causes: genetic mutations Prader-Willi syndrome (short, small hands, almond-shaped eyes, learning difficulty, postnatal hypotonia) Laurence-Moon-Biedl syndrome (obesity, polydactyly, retinitis pigmentosa, learning difficulty)

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83
Q

Epidemiology of hypogonadism

A

Primary hypogonadism accounts for 30-40% of male infertility
- Most common cause: Klinefelter’s Syndrome (XXY)

Secondary hypogonadism accounts for 1-2%

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84
Q

Presenting symptoms of hypogonadism

A 
•  Delayed puberty 
•  Decreased libido 
•  Impotence  
•  Infertility  
•  Symptoms of underlying cause (e.g. Klinefelters --> intellectual dysfunction, 
behavioural abnormalities)
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85
Q

Signs of hypogonadism on physical examination

A

• Measure testicular volume using Prader’s orchidometer (normal adult volume = 15-25
mL)
• Prepubertal Hypogonadism
o Signs of delayed puberty
• High pitched voice
• Decreased pubic/axillary/facial hair
• Small or undescended testicles
• Small penis
o Gynaecomastia
o Eunuchoid proportions (arm span > height)
o Features of underlying cause (e.g. undescended testicle, anosmia in Kallmann’s
syndrome)
• Postpubertal Hypogonadism
o Decreased pubic/axillary/facial hair
o Soft and small eyes
o Gynaecomastia
o Fine perioral wrinkles
o Features of underlying cause (e.g. visual defects if pituitary cause)

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86
Q

Investigations for hypogonadism

A 
•  Serum total testosterone 
•  Sex hormone binding globulin (SHBG)  
•  Albumin 
•  LH and FSH  
•  Primary Hypogonadism: 
o  Low testosterone  
o  High LH and FSH  
•  Secondary Hypogonadism: 
o  Low testosterone  
o  Inappropriately normal/low LH and FSH 
•  Primary M can be investigated using karyotyping (check for Klinefelter's syndrome)  
•  Secondary 
o  Pituitary function tests  
o  MRI of the hypothalamic/pituitary area 
o  Visual field testing  
o  Smell testing (for anosmia) 
o  Iron testing (for hereditary haemochromatosis) 
•  Assess bone age (risk of fracture)
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87
Q

Define Hypopituitarism

A

Deficiency is one or more of the hormones secreted by the anterior pituitary. Panhypopituitarism is deficiency of ALL pituitary hormones.

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88
Q

Aetiology/ Risk Factors for hypopituitarism

A

• Pituitary Masses
o Most commonly adenomas
o Others include craniopharyngioma, meningioma, glioma, metastases
o Cysts
• Pituitary Trauma - radiation, surgery, base of skull fractures
• Hypothalamic Dysfunction - due to anorexia, starvation, overMexercise
• Infiltrative Diseases - sarcoidosis, haemochromatosis, Langerhans’ cell histiocytosis
• Vascular - pituitary apoplexy, Sheehan’s syndrome
• Infection - meningitis, encephalitis
• Genetic Mutations - Pit-1 and Prop-1 genes

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89
Q

Epidemiology of hypopituitarism

A

• Pituitary adenoma annual incidence: 1/100,000

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90
Q

Signs and symptoms of hypopituitarism

A

• Depends on CAUSE
• Symptoms and signs are dependent on the hormone that is deficient:
o GH
• CHILDREN: short stature
• ADULTS: low mood, fatigue, reduced exercise capacity and muscle strength,
increased abdominal fat mass o LH or FSH
• Delayed puberty
• FEMALES: loss of secondary sexual hair, breast atrophy, menstrual
irregularities, dyspareunia, decreased libido, infertility
• MALES: loss of secondary sexual hair, gynaecomastia, small and soft testes,
decreased libido, impotence
o ACTH - signs/symptoms of adrenal insufficiency
o TSH - signs/symptoms of hypothyroidism
o Prolactin - absence of lactation (not usually noticed clinically)
• Pituitary Apoplexy has some other symptoms:
o Headache
o Visual loss
o Cranial nerve palsies

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91
Q

Investigations for hypopituitarism

A 
•  Pituitary Function Tests 
o  Basal Tests 
 •  9 am cortisol 
 •  LH and FSH levels  
 •  Testosterone levels  
 •  Oestrogen levels  
 •  IGF-1 levels  
 •  Prolactin levels  
 •  Free T4 and TSH levels  
o  Dynamic Tests (rarely performed) 
 •  Insulin-induced hypoglycaemic (should cause a rise in GH and cortisol)  
o  Short synacthen test (for adrenal insufficiency)  
o  MRI/CT of brain  
o  Visual field testing
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92
Q

Management plan for hypopituitarism

A 
•  Hormone Replacement  
o  Hydrocortisone  
o  Levothyroxine  
o  Sex hormones  
•  Testosterone in males  
•  Oestrogen with/without progesterone in females  
•  Growth hormone  
•  Desmopressin (if central diabetes insipidus as a result of 
panhypopituitarism)
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93
Q

Possible complications of hypopituitarism

A 
•  Addisonian crisis  
•  Hypoglycaemia  
•  Myxoedema coma  
•  Infertility 
•  Osteroporosis  
•  Dwarfism (children)  
•  Complications of pituitary mass: 
o  Optic chiasm compression (leading to bitemporal hemianopia)   
o  Hydrocephalus  
o  Temporal lobe epilepsy
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94
Q

Prognosis for patients with hypopituitarism

A

Good prognosis with lifelong treatment

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95
Q

Define hypothyroidism

A

The clinical syndrome resulting from insufficiency secretion of thyroid hormones

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96
Q

Aetiology/ Risk Factors of hypothyroidism

A

• PRIMARY HYPOTHYROIDISM (decreased thyroid hormone production)
o Acquired
• Hashimoto’s thyroiditis (autoimmune)
• Iatrogenic (post-surgery, radioiodine, hyperthyroid medication)
• Severe iodine deficiency
• Iodine excess (Wolff-Chaikoff effect)
• Thyroiditis
o Congenital
• Thyroid dysgenesis
• Inherited defects in thyroid hormone biosynthesis
• SECONDARY HYPOTHYROIDISM (5% of cases)
o Pituitary and Hypothalamic Disease - resulting in reduced TSH and TRH and,
hence, reduced stimulation of thyroid hormone production

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97
Q

Summarise the epidemiology of hypothyroidism

A
  • 0.1-2% of adults
  • 6 x more common in FEMALES
  • Most common age of onset > 40 yrs
  • Iodine deficiency is seen in mountainous areas (e.g. Himalayas)
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98
Q

Presenting symptoms of hypothyroidism

A 
•  INSIDIOUS onset  
•  Cold intolerance  
•  Lethargy  
•  Weight gain  
•  Reduced appetite  
•  Constipation  
•  Dry skin  
•  Hair loss  
•  Hoarse voice  
•  Mental slowness 
•  Depression  
•  Cramps  
•  Ataxia  
•  Paraesthesia 
•  Menstrual disturbance (irregular cycles, menorrhagia) 
•  History of surgery or radioiodine therapy for hyperthyroidism 
•  Personal/family history of other autoimmune conditions (e.g. Addison's, type 1 
diabetes mellitus)  
•  Myxoedema coma (severe hypothyroidism usually seen in the elderly): 
o  Hypothermia 
o  Hypoventilation 
 o  Hyponatraemia  
o  Heart failure  
o  Confusion  
o  Coma
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99
Q

Signs of hypothyroidism on physical examination

A 
•  Hands 
o  Bradycardia 
o  Cold hands   
•  Head/Neck/Skin 
o  Pale puffy face   
o  Goitre  
o  Oedema  
o  Hair loss  
o  Dry skin   
o  Vitiligo 
•  Chest 
o  Pericardial effusion  
o  Pleural effusion  
•  Abdomen 
o  Ascites  
•  Neurological 
o  Slow relaxation of reflexes  
o  Signs of carpal tunnel syndrome
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100
Q

Investigations for hypothyroidism

A 
•  Bloods 
o  TFTs 
o  FBC - may show normocytic anaemia   
o  U&amp;Es - may show low sodium  
o  Cholesterol - may be high
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101
Q

Management plan for hypothyroidism

A

• CHRONIC
o Levothyroxine (25-200 mcg/day)
• IMPORTANT: rule out underlying adrenal insufficiency before starting thyroid hormone replacement
• Thyroid hormone replacement in the context of adrenal insufficiency can precipitate an Addisonian crisis
• Adjust dose based on clinical picture and TFTs
• MYXOEDEMA COMA
o Oxygen
o Rewarming
o Rehydration
o IV T4/T3
o IV hydrocortisone
o Treat underlying cause (e.g. infection)

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102
Q

Complications of hypothyroidism

A
  • Myxoedema coma

* Myxoedema madness (psychosis with delusions and hallucinations or dementia)

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103
Q

Prognosis for patients with hypothyroidism

A
  • Lifelong levothyroxine is required

* Myxoedema coma mortality = 80%

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104
Q

Define Multiple Endocrine Neoplasia (MEN)

A

An autosomal dominant condition characterised by a predilection to develop tumours of endocrine glands

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105
Q

Aetiology/ Risk Factors of MEN

A 
•  Autosomal dominant inheritance   
•  Patterns of features: 
o  MEN 1  (Wermer's Syndrome)
•  Pituitary adenomas 
•  Parathyroid tumours  
•  Pancreatic islet-cell tumours (and other endocrine tumours of the 
gastroenterohepatic tract e.g. gastrinomas) 
•  Fascial angiofibromas and collagenomas 
o  MEN 2a (Sipple Syndrome) 
•  Parathyroid tumours 
•  Medullary thyroid cancer   
•  Phaeochromocytomas 
o  MEN 2b (Marfanoid Phenotype) 
•  Same as MEN 2a 
•  Marfanoid appearance  
•  Neuromas of the GI tract
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106
Q

Summarise the epidemiology of MEN

A

Very Rare

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107
Q

Presenting symptoms and signs of MEN (1 & 2)

A

• MEN 1
o Age of onset of tumours is usually teenage years
o However, symptoms of the tumours may not become apparent for years
o Diagnosis is commonly made in the 4th decade of life
o Symptoms and signs are dependent on the organs affects:
• Hyperparathyroidism –> symptoms of hypercalcaemia + nephrolithiasis
• Hypergastrinaemia –> Zollinger-Ellison syndrome
• Hyperinsulinaemia –> hypoglycaemia
• Hyperprolactinaemia –> amenorrhoea
• Hypersomatotrophinaemia –> acromegaly
o Pituitary tumours may cause visual defects
• MEN 2
o Symptoms of medullary thyroid cancer, hyperparathyroidism or
phaeochromocytoma
o Medullary thyroid cancer symptoms:
• Hypertension
• Episodic sweating
• Diarrhoea
• Pruritic skin lesions
• Lump in the neck
o Hypercalcaemia symptoms:
• Constipation
• Polyuria/polydipsia
• Depression
• Kidney stones
• Fatigue

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108
Q

Investigations for MEN

A

• MEN 1
o Screening first or second degree relatives
o Hormone hypersecretion blood tests
o DNA testing
• MEN 2
o Phaeochromocytoma test - 24hr urine metanephrines
• Can be followed by abdominal MRI
o Medullary thyroid cancer test - elevated calcitonin concentration
• Can also be investigated with ultrasound and FNA
o Parathyroid tumours- simultaneously elevated Ca2+ and PTH

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109
Q

Define Obesity

A 
A BMI >30kg/m^2
- Can also be defined using wait circumference:
•  Men 
!  Low Risk = < 94 cm 
!  Very High Risk = > 102 cm   •  Women 
!  Low Risk = < 80 cm  
!  Very High Risk = > 88 cm
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110
Q

Aetiology/ Risk Factors

A

• There are genetic factors that affect the risk of become obese
• There are a few monogenic forms of obesity (e.g. leptin deficiency, Prader-Willi
syndrome)
• Common obesity is caused by energy intake > energy usage

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111
Q

Epidemiology of obesity

A

• 24% of men and 25% of women are obese

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112
Q

Presenting symptoms and signs of obesity

A

• Noticing that you’re fat
• Routine health check
• Symptoms of complications (e.g. T2DM, coronary heart disease, obstructive sleep
apnoea)
• High body weight, BMI and waist circumference

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113
Q

Investigations for obesity

A
  • Measure serum lipids
  • Measure HbA1c
  • Hormone profile (check for hormonal cause of obesity)
  • TFTs - hypothyroidism can cause obesity
  • Other investigations depending on comorbidities
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114
Q

Define Osteoporosis

A

Reduced bone density (defined as >2.5 standard deviations below peak bone mass achieved by healthy adults (i.e. T-score >2.5) resulting bone fragility and increased fracture risk

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115
Q

Aetiology/ Risk Factors of osteoporosis

A 
•  Primary: 
o  Idiopathic (if < 50 yrs)  
o  Post-menopausal  
•  Secondary: 
o  Malignancy - myeloma, metastatic carcinoma   
o  Endocrine: 
•  Cushing's disease  
•  Thyrotoxicosis 
•  Primary hyperparathyroidism  •  Hypogonadism 
o  Drugs - corticosteroids, heparin 
o  Rheumatological - rheumatoid arthritis, ankylosing spondylitis  
o  Gastrointestinal: 
•  Malabsorption (e.g. coeliac disease, partial gastrectomy)  
•  Liver disease (e.g. primary biliary cirrhosis)  
•  Anorexia 
•  RISK FACTORS:  
o  Age  
o  Family history 
o  Low BMI  
o  Low calcium intake  
o  Smoking  
o  Lack of physical exercise   
o  Low exposure to sunlight   
o  Alcohol abuse  
o  Late menarche  
o  Early menopause   
o  Hypogonadism
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116
Q

Epidemiology of osteoporosis

A 
•  COMMON  
•  In > 50 yrs 
o  Females: 1/3 
o  Males: 1/12  
•  More common in CAUCASIANS than Afro-Caribbeans
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117
Q

Presenting symptoms of osteoporosis

A

• Often ASYMPTOMATIC until fractures occur
• Characteristic fractures:
o Neck of femur (after minimal trauma)
o Vertebral fractures (leading to loss of height, stooped posture and acute back pain on lifting)
o Colles’ fracture (of the distal radius after falling on an outstretched hand)

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118
Q

Signs of osteoporosis on physical examination

A

• Often NO SIGNS until complications develop:
o Tenderness on percussion (over vertebral fractures)
o Thoracic kyphosis (due to multiple vertebral fractures)
o Severe pain when hip flexed and externally rotated (suggests neck of femur fracture)

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119
Q

Investigations for osteoporosis

A

• Bloods
o Calcium
o Phosphate
o ALP
o IMPORTANT: these are NORMAL in PRIMARY osteoporosis
• X-Ray
o Used to diagnose fractures
o Often normal because it takes > 30% loss of bone density before showing any
changes in radiolucency or cortical thinning
o May show biconcave vertebrae and crush fractures
• Isotope Bone Scans
o Highlights areas of stress and microfractures
• DEXA (Dual-Energy X-Ray Absorptiometry) Scan
o T-score: the number of standards deviations the bone mineral density
measurement is above or below the young normal mean bone mineral density
o Z-score: the number of standard deviations the measurement is above or below the ageJmatched mean bone mineral density. Z-score may be helpful in identifying patients who may need a work-up for secondary causes of osteoporosis

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120
Q

Define Paget’s disease of the bone

A

Characterised by excessive bone remodelling at one (monostotic) or more (polyostotic) sites resulting in bone that is structurally disorganised

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121
Q

Aetiology/ Risk factors of Paget’s disease

A

• UNKNOWN
• Genetic factors and viral infection may play a role
• Excessive bone resorption by abnormally large osteoclasts is followed by increased
bone formation by osteoblasts in a disorganised fashion
• This results in an abnormal pattern of lamellar bone
• Marrow spaces are filled by an excess of fibrous tissue with a marked increase in blood
vessels

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122
Q

Summarise epidemiology of Paget’s disease

A
  • Common in ELDERLY
  • 3% of > 50 yrs
  • 10% of > 80 yrs
  • Males = Females
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123
Q

Presenting symptoms of Paget’s disease

A 
•  May be ASYMPTOMATIC  
•  May present with insidious onset pain, which is aggravated by weight bearing and 
movement  
•  Headaches  
•  Deafness  
•  Increasing skull size
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124
Q

Signs of Paget’s disease on physical examination

A
  • Bitemporal skull enlargement with frontal bossing (prominent, protruding forehead)
  • Spinal kyphosis
  • Anterolateral bowing of femur, tibia or forearm
  • Skin over the affected bone may be warm (due to increased vascularity)
  • Sensorineural deafness (due to compression of vestibulocochlear nerve)
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125
Q

Investigations for Paget’s disease

A 
•  Bloods 
o  High ALP 
o  Ca2+ and phosphate = NORMAL   
•  Bone Radiographs 
o  Enlarged, deformed bones  
o  Lytic and sclerotic appearance  
o  Lack of distinction between cortex and medulla   
o  Skull changes: 
•  Osteoporosis circumscripta  
•  Enlargement of frontal and occipital areas  
 •  Cotton wool appearance  
•  Bone Scan 
o  Assesses extent of skeletal involvement  
o  Pagetic bone lesions appear as areas with markedly increased uptake  
•  Resorption Markers 
o  Monitors disease activity  
o  Check urinary hydroxyproline
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126
Q

Define Phaeochromocytoma

A

Catecholamine-producing tumours that usually arise from chromaffin cells of the adrenal medulla but are extra-adrenal in about 10% of cases

  • 10% are bilateral
  • 10% are malignant
  • Extra-adrenal phaeochromocytomas are referred to as paragangliomas
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127
Q

Aetiology/ Risk Factors of phaeochromocytoma

A

• Sporadic cases are of unknown aetiology
• Familial in up to 30%
• Familial cases are seen in patients with:
o MEN2a
o von Hippel-Lindau syndrome
o Neurofibromatosis type 1

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128
Q

Epidemiology of phaeochromocytoma

A
  • RARE

* < 0.2% of hypertensive patients

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129
Q

Presenting symptoms of patients with phaeochromocytoma

A 
•  PAROXYSMAL episodes  
•  Headache (due to malignant hypertension) 
•  Sweating  
•  Cardiorespiratory Symptoms  o  Palpitations  
o  Chest pain  
o  Dyspnoea   
•  GI Symptoms 
o  Epigastric pain   
o  Nausea  
o  Constipation 
•  Neuropsychiatric Symptoms  o  Weakness  
o  Tremor  
o  Anxiety
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130
Q

Signs of pheochromocytoma on physical examination

A
  • Hypertension
  • Postural hypotension
  • Pallor
  • Tachycardia
  • Fever
  • Weight loss
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131
Q

Investigations for pheochromocytoma

A

• 24 hr urine collection - check for catecholamine levels (and check for fractionated metanephrine levels)
o NOTE: metanephrines are metabolites of adrenaline
• Plasma free metanephrines
• Tumour localisation (MRI or CT)
• I-MIBG scintigraphy (another way of visualising the tumour)
• Screen for associated conditions
• Genetic testing

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132
Q

Define non-functioning pituitary tumours

A

Benign tumours of the pituitary gland formed from pituitary cells that do not produce any active pituitary hormones

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133
Q

Aetiology/risk factors of non-functioning pituitary tumours

A
  • No specific cause

- Can occur as a part of MEN 1 syndrome

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134
Q

Epidemiology of non-functioning pituitary tumours

A
  • Most common type of macroadenoma (> 1 cm)

* Most common type of pituitary tumour in patients > 60 yrs

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135
Q

Presenting symptoms and signs of non-functioning pituitary tumours

A

• Symptoms develop very SLOWLY because there are no
hormonal derangements
• Headaches
• Pressure on surrounding structures:
o Optic chiasm - bitemporal hemianopia
o Normal pituitary gland - panhypopituitarism
• Symptoms develop depending on which hormone is affected

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136
Q

Investigations for non-functioning pituitary tumours

A
  • MRI
  • CT
  • Bloods - check hormone levels
  • Visual fields testing
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137
Q

Define polycystic ovarian syndrome

A

• Characterised by oligomenorrhoea/amenorrhoea and hyperandrogenism (clinical or
biochemical). Frequently associated with:
o Obesity
o Insulin resistance
o Type 2 diabetes mellitus
o Dyslipidaemia

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138
Q

Aetiology/ Risk factors of polycystic ovarian syndrome

A

• Environmental factors
• Genetic variants
• Hyperinsulinaemia results in increased ovarian androgen synthesis and reduced
hepatic sex hormone binding globulin (SHBG) synthesis
• This leads to an increase in free androgens (which gives rise to the symptoms)

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139
Q

Epidemiology of polycystic ovarian syndrome

A
  • PCOS is the MOST COMMON cause of infertility in women

* Affects 6-8% of women

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140
Q

Presenting symptoms of polycystic ovarian syndrome

A 
•  Menstrual irregularities  
•  Dysfunctional uterine bleeding  
•  Infertility  
•  Symptoms of hyperandrogenism:  
o  Hirsuitism 
o  Male-pattern hair loss  
o  Acne
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141
Q

Signs of polycystic ovarian syndrome on physical examination

A

• Hirsuitism
• Male-pattern hair loss
• Acne
• Acanthosis nigricans (sign of severe insulin
resistance) - velvety thickening and hyperpigmentation of the skin of the axillar or neck

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142
Q

Investigations for polycystic ovarian syndrome

A

• Bloods
o High LH
o High LH: FSH ratio
o High testosterone, androstenedione and DHEA-S
o Low sex hormone binding globulin
• Other things to test for:
o Hyperprolactinaemia
o Hypo/hyperthyroidism
o Congenital adrenal hyperplasia (check 17OH-progesterone levels)
o Cushing’s syndrome
• Look for impaired glucose tolerance/T2DM:
o Fasting blood glucose
o HbA1c
• Fasting lipid profile
• Transvaginal USS: look for ovarian follicles and an increase in ovarian volume

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143
Q

Define primary hyperaldosternoism

A

Characterised by autonomous aldosterone overproduction from the adrenal gland with subsequent suppression of plasma renin activity

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144
Q

Aetiology / Risk Factors of primary hyperaldosteronism

A

• Adrenal adenoma (Conn’s syndrome) - responsible for 70% of cases
• Adrenal cortex hyperplasia (30% of cases)
• RARE:
o Glucocorticoid-suppressible hyperaldosteronism
o Aldosterone producing adrenal carcinoma
• Pathophysiology:
o Excess aldosterone leads to increased Na+ and water retention
o This leads to hypertension
o It also causes increased renal K+ loss leading to hypokalaemia
o Renin is suppressed due to NaCl retention

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145
Q

Epidemiology of primary hyperaldosteronism

A
  • 1-2% of hypertensive patients
  • Conn’s syndrome is more common in WOMEN and YOUNG patients
  • Bilateral adrenal hyperplasia is more common in MEN and presents at an older age
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146
Q

Presenting symptoms of primary hyperaldosteronism

A

• Usually ASYMPTOMATIC
• Tends to be an incidental finding on routine blood tests • Symptoms of Hypokalaemia
o Muscle weakness
o Polyuria and polydipsia (due to nephrogenic DI)
o Paraesthesia
o Tetany

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147
Q

Signs of primary hyperaldosteronism on physical examination

A
  • Hypertension

* Complications of hypertension (e.g. hypertensive retinopathy)

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148
Q

Investigations for primary hyperaldosteronism

A

• Screening Tests
o Low Serum K+
• NOTE: Serum Na+ is usually normal because the Na+ reabsorption is matched by water reabsorption
o High Urine K+
o High Plasma Aldosterone Concentration
o High aldosterone: renin activity ratio
• Confirmatory Tests
o Salt Loading
• Failure of aldosterone suppression following salt load confirms primary
hyperaldosteronism
o Postural Test
• Measure plasma aldosterone, renin activity and cortisol when the patient is lying down at 8 am
• Measure again after 4 hrs of the patient being upright
• Aldosterone-producing adenoma - aldosterone secretion decreases
between 8 am and noon
• Bilateral adrenal hyperplasia - adrenals respond to standing posture and
increase renin production leading to increased aldosterone secretion
o CT/MRI
o Bilateral adrenal vein catheterisation
• Measures adrenal vein aldosterone levels and allows you to distinguish
between Conn’s syndrome and bilateral adrenal hyperplasia
o Radio-labelled cholesterol scanning
• Unilateral uptake in adrenal adenomas
• Bilateral uptake in bilateral adrenal hyperplasia

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149
Q

Management plan for primary hyperaldosteronism

A

• Bilateral Adrenal Hyperplasia
o Spironolactone
o Eplerenone can be used if the spironolactone side-effects are intolerable
o Amiloride (potassium-sparing diuretic)
o Monitor serum K+, creatinine and BP
o ACE inhibitors and CCBs may also be added
• Aldosterone Producing Adenomas
o Adrenalectomy
• Adrenal Carcinoma
o Surgery
o Post-operative mitotane (antineoplastic)

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150
Q

Complications of primary hyperaldosteronism

A

Complications of hypertension

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151
Q

Prognosis for patients with primary hyperaldosteronism

A
  • Surgery may cure hypertension

- Or it may make the hypertension easier to treat with anti-hypertensive medication

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152
Q

Define Prolactinoma

A

A pituitary adenoma that overproduces prolactin

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153
Q

Aetiology/ Risk Factors of prolactinoma

A

• There are different types of prolactinoma
o Microadenomas: < 1 cm
o Macroadenomas: > 1 cm
o Giant Pituitary Adenomas: > 4 cm
o Malignant Prolactinoma (RARE)
• Cause if UNKNOWN
• Some may occur as a consequence of MEN 1 syndrome
• Risk Factors
o Risk of tumour enlargement in pregnancy

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154
Q

Epidemiology of prolactinoma

A
  • Relatively common

* Higher incidence in premenopausal women

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155
Q

Presenting symptoms and signs of prolactinoma on physical examination (in men and women)

A

• NOTE: microprolactinomas rarely expand to become macroprolactinomas
• Women
o Amenorrhoea/oligomenorrhoea o Galactorrhoea
o Infertility
o Hirsuitism
o Reduced libido
• Men
o Symptoms are subtle and develop slowly
o Reduced libido
o Reduced beard growth
o Erectile dysfunction
• Symptoms caused by tumour size o Headache
o Visual disturbance (bitemporal hemianopia)
o Cranial nerve palsies
o Signs and symptoms of hypopituitarism

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156
Q

Investigations for prolactinoma

A

• Exclude pregnancy
• TFTs - hypothyroidism –> high TRH –> stimulates prolactin release
• Serum prolactin level (extremely high levels (> 5000 mU/L) suggests true
prolactinoma)
• MRI
• Assessment of pituitary function

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157
Q

Management plan for prolactinoma

A

• Goals
o Treat cause
o Relieve symptoms
o Prevent complications
o Restore fertility
• Dopamine Agonists (e.g. cabergoline and bromocriptine)
o Effective in most patients
o Usually need to be continued on a long-term basis
• If dopamine agonists are ineffective:
o Surgery
o Radiotherapy

158
Q

Complications of prolactinoma

A

• Complications of hypogonadism
o Osteoporosis
o Reduced fertility
o Erectile dysfunction
• Complications of tumour size o Visual loss
o Headache
o Pituitary apoplexy o CSF rhinorrhoea

159
Q

Prognosis for patients with prolactinoma

A

• Microprolactinomas will spontaneously resolve in about 1/3 cases
• Dopamine agonist withdrawal is usually attempted after about 2-3 years if prolactin
levels have normalised and tumour volume is reduced
• High rates of recurrence

160
Q

Define SIADH

A

Characterised by continued secretion of ADH, despite the absence of normal stimuli for secretion (i.e. increased serum osmolality or decreased blood volume)

161
Q

Aetiology/ Risk factors of SIADH

A 
•  Brain 
o  Haemorrhage/thrombosis  
o  Meningitis   
o  Abscess  
o  Trauma 
o  Tumour 
o  Guillain-Barre syndrome   
•  Lung 
o  Pneumonia 
o  TB 
o  Other: abscess, aspergillosis, small cell carcinoma 
•  Tumours 
o  Small cell lung caner  
o  Lymphoma  
o  Leukaemia  
o  Others: pancreatic cancer, prostate cancer, mesothelioma, sarcoma, thymoma 
•  Drugs 
o  Vincristine  
o  Opiates  
o  Carbamazepine   
o  Chlorpropamide 
•  Metabolic 
o  Porphyria 
o  Alcohol withdrawal
162
Q

Epidemiology of SIADH

A
  • Hyponatraemia is the MOST COMMON electrolyte imbalance seen in hospital
  • < 50% of severe hyponatraemia is caused by SIADH
163
Q

Presenting symptoms of SIADH

A
  • Mild hyponatraemia may be ASYMPTOMATIC
  • Headache
  • Nausea/vomiting
  • Muscle cramp/weakness
  • Irritability
  • Confusion
  • Drowsiness
  • Convulsions
  • Coma
  • Symptoms of underlying cause
164
Q

Signs of SIADH on physical examination

A

• MILD hyponatraemia - no signs
• SEVERE hyponatraemia:
o Reduced reflexes
o Extensor plantar reflexes
• Signs of underlying cause
• NOTE: the hyponatraemia in SIADH is due to dilution from excessive water
reabsorption and not due to a decrease in total body Na+

165
Q

Identify appropriate investigations for SIADH

A

• Things to check:
o Low serum sodium
o Creatinine (check renal function)
o Glucose, serum protein and lipids - to rule out pseudohyponatraemia
• Pseudohyponatraemia = when the sodium concentration is actually normal but is erroneously reported as being low because of the presence of either hyperlipidaemia or hyperproteinaemia
o Free T4 and TSH - hypothyroidism can cause hyponatraemia
o Short synacthen test - adrenal insufficiency can cause hyponatraemia
• SIADH Diagnosis
o Low plasma osmolality
o Low serum Na+ concentration
o High urine osmolality
o High urine Na+
o The presence of the above results and the absence of hypovolaemia, oedema,
renal failure, adrenal insufficiency and hypothyroidism are required for the
diagnosis of SIADH
• Investigations for identifying the cause (e.g. CXR, CT, MRI)

166
Q

Management plan for SIADH

A
  • Treat underlying cause
  • Fluid restriction
  • Vasopressin receptor antagonists (e.g. tolvaptan)
  • In SEVERE cases - slow IV hypertonic saline and furosemide with close monitoring
167
Q

Complications of SIADH

A 
•  Convulsions  
•  Coma  
•  Death  
•  Central pontine myelinolysis - occurs with rapid correction of hyponatraemia 
o  Characterised by: 
•  Quadriparesis  
•  Respiratory arrest  
•  Fits
168
Q

Prognosis for patients with SIADH

A
  • Depends on the CAUSE
  • Na+ < 110 mmol/L is associated with a HIGH MORBIDITY and MORTALITY
  • 50% mortality with central pontine myelinolysis
169
Q

Define thyroid cancer

A

A malignancy arising in the thyroid gland. Types include:

  • Papillary
  • Follicular
  • Medullary
  • Anaplastic
170
Q

Aetiology/ Risk Factors of thyroid cancer

A

• UNKNOWN
• Risk Factors
o Childhood exposure to radiation
o Medullary thyroid cancers may be familial and are associated with MEN IIa or IIb
o Lymphoma is associated with Hashimoto’s thyroiditis

171
Q

Epidemiology of thyroid cancer

A
  • RARE
  • More common in FEMALES
  • Papillary: 20-40 yrs
  • Follicular: 40-50 yrs
  • Anaplastic: more common in the ELDERLY
172
Q

Presenting symptoms of thyroid cancer

A
  • Slow-growing neck lump
  • Discomfort swallowing
  • Hoarse voice
173
Q

Signs of thyroid cancer on physical examination

A
  • Palpable nodules or diffuse enlargement of thyroid gland
  • Cervical lymphadenopathy –> suspect malignancy
  • NOTE: the patient is usually euthyroid
174
Q

Investigations for thyroid cancer

A

• Bloods
o TFTs
o Bone profile
o Tumour Markers
• Thyroglobulin - papillary and follicular
• Calcitonin - medullary
• Fine-Needle Aspiration Cytology (FNA)
o Allows histological diagnosis • Excision Lymph Node Biopsy
o If there is cervical lymphadenopathy
• Isotope Scan
o If the cause of the thyroid lump is unclear
• CT/MRI - for staging

175
Q

Define Thyroid Nodules

A

Abnormal growth of thyroid cells that forms a lump in the thyroid gland

176
Q

Aetiology/ Risk factors of thyroid nodules

A
  • The vast majority of thyroid nodules are BENIGN, but a small proportion turn into thyroid cancer
  • Most thyroid nodules are adenomatous and most are multiple
  • The nodules are usually non-functioning
177
Q

Epidemiology of thyroid nodules

A
  • 40% of the general population have a single nodule or multiple nodules
  • More common in WOMEN
  • Very small proportion of thyroid nodules will be malignant
178
Q

Presenting symptoms of thyroid nodules

A

• Most are ASYMPTOMATIC
• Usually found on self-examination or clinical examination
• A single isolated nodule is more likely to be malignant
• They can sometimes cause pain and will rarely compress the trachea or cause
dysphagia

179
Q

Signs of thyroid nodules on physical examination

A
  • Ask the patient to drink some water and see if the nodule moves when swallowing
  • Check for regional lymphadenopathy (consider malignancy)
180
Q

Investigations for thyroid nodules

A
  • TFTs - most patients will be euthyroid
  • Ultrasound - useful for determining the character of the thyroid nodules
  • FNA - allows cytological analysis
  • Radionuclide Isotope Scanning - checks iodine uptake
  • CT/MRI - detect spread of thyroid cancer
181
Q

Define thyroiditis

A

Inflammation of the thyroid gland

182
Q

Aetiology/ Risk factors of thyroiditis

A

• Hashimoto’s thyroiditis - an autoimmune condition. The most common cause of
hypothyroidism in the UK.
• Other types of thyroiditis:
o de Quervain’s thyroiditis
o Postpartum thyroiditis
o Drug-induced thyroiditis
o Acute or infectious thyroiditis o Riedel’s thyroiditis
• Pathogenesis of Hashimoto’s thyroiditis
o Aggressive destruction of thyroid cells by the immune system
o Environmental triggers have been hypothesised (e.g. smoking, infection)

183
Q

Epidemiology of thyroiditis

A
  • True incidence is UNKNOWN
  • 15-20 x more common in WOMEN
  • Usually occurs in 30-50 yrs
184
Q

Presenting symptoms and signs of thyroiditis

A 
•  Symptoms of hypothyroidism  o  Fatigue  
o  Constipation  
o  Dry skin  
o  Weight gain  
o  Cold intolerance  
o  Menstrual irregularities   
o  Depression  
o  Hair loss  
•  Symptoms caused by rapid enlargement of the thyroid gland 
o  Dyspnoea   
o  Dysphagia   
o  Tenderness
185
Q

Investigations for thyroiditis

A 
•  Based on clinical observations  
•  Histology: diffuse lymphocytic and plasma cell infiltration with formation of lymphoid 
follicles  
•  TSH - raised  
•  Antibodies: 
o  Anti-TPO antibodies  
o  Anti-thyroglobulin antibodies  
•  Thyroid ultrasound  
•  Radionuclide isotope scanning
186
Q

Management plan for thyroiditis

A

• Pharmacological
o Thyroid hormone replacement - oral levothyroxine sodium
o Titrate dose based on patient’s needs
• Surgical
o Considered if there is a large goitre that is causing symptoms due to compression of surrounding structures or if there is a malignant nodule

187
Q

Complications of thyroiditis

A
  • Thyroid hormone overMreplacement –> bone loss + tachycardia
  • Hyperlipidaemia
  • Hashimoto’s encephalopathy
  • Myxoedema coma
188
Q

Prognosis for patients with thyroiditis

A

• GOOD PROGNOSIS with early diagnosis and levothyroxine replacement

189
Q

Define Vitamin D deficiency and osteomalacia

A

Osteomalacia is a disorder of mineralisation of bone matrix (osteoid). Rickets is a disorder of defective mineralisation of cartilage in the epiphyseal growth plates of children

190
Q

Aetiology/ risk factors for vitamin D deficiency and osteomalacia

A

• Risk Factors for Vitamin D Deficiency
o Lack of exposure to sunlight
o Dietary deficiency
o Malabsorption
o Decreased 25-hydroxylation of vitamin D (due to liver disease, anticonvulsants)
o Decrease 1alpha-hydroxylation of vitamin D (due to chronic kidney disease,
hypoparathyroidism)
o Vitamin D resistance
• Renal Phosphate Wasting
o Fanconi’s syndrome - characterised by:
• Phosphaturia
• Glycosuria
• Amino aciduria
o Renal tubular acidosis (type 2)
o Hereditary hypophosphataemic rickets (X-linked or autosomal dominant)
o Tumour induced osteomalacia

191
Q

Epidemiology of vitamin D deficiency and osteomalacia

A
  • COMMON in industrialised countries

* More common in FEMALES

192
Q

Presenting symptoms of vitamin D deficiency and osteomalacia

A 
•  Osteomalacia 
o  Bone pain (mainly in the axial skeleton)  
o  Weakness 
o  Malaise   
•  Rickets 
o  Hypotonia 
o  Growth retardation   
o  Skeletal deformities
193
Q

Signs of vitamin D deficiency and osteomalacia on physical examination

A

• Osteomalacia
o Bone tenderness
o Proximal muscle weakness o Waddling gait
o Signs of hypocalcaemia:
• Trousseau’s sign - inflation of a blood pressure cuff to above the systolic pressure for > 3 mins causes tetanic spasm of the wrist and fingers

• Chvostek’s sign - tapping over the facial nerve causes twitching of the
ipsilateral facial muscles

• Rickets
o Bossing of frontal and parietal bones
o Swelling of costochondral junctions (rickety rosary)
o Bow legs in early childhood
o ‘Knock knees’ in later childhood
o Short stature

194
Q

Investigations for vitamin D deficiency and osteomalacia

A

• Bloods
o Low or normal Ca2+
o Low phosphate
o High ALP
o Low 25-hydroxy vitamin D
o High PTH (secondary hyperparathyroidism)
o Check U&Es
o Check ABGs (for renal tubular acidosis)
o Increased phosphate excreting (in renal phosphate wasting)
• Radiographs
o May appear normal
o May show osteopaenia
o Looser’s zones = wide, transverse lucencies
traversing part way through a bone, usually at right angles to the involved cortex and are associated most frequently with osteomalacia and rickets (AKA pseudofractures)

• Bone biopsy after double tetracycline labelling
o Tetracycline is deposited at the mineralisation front as a band
o After two course of tetracycline (separated by a few days), the distance between
the bands of deposited tetracycline is reduced in osteomalacia o Not usually necessary for the diagnosis of osteomalacia

195
Q

Management plan for vitamin D deficiency and osteomalacia

A 
•  Vitamin D and calcium replacement   
•  Monitor 24 hr urinary calcium 
•  Also monitor: 
o  Serum calcium  
 o  Phosphate  
o  ALP 
o  PTH  
o  Vitamin D  
•  Treat the underlying CAUSE
196
Q

Complications of vitamin D deficiency and osteomalacia

A 
•  Bone deformities  
•  Hypocalcaemia can cause epileptic seizures   
•  Cardiac arrhythmias  
•  Hypocalcaemic tetany  
•  Depression  
•  Hypocalcaemia symptoms = CATs go NUMB 
o  Convulsions 
o  Arrhythmias 
o  Tetany 
o  NUMBness/paraesthesia
197
Q

Prognosis for patients with vitamin D deficiency and osteomalacia

A
  • Symptoms and radiological appearances improve with vitamin D treatment
  • Bone deformities in children tend to be permanent 9
198
Q

Aetiology/ Risk Factors of Acromegaly

A

• Most cases are caused by a GHJsecreting pituitary adenoma
• RARELY caused by excess GHRH causing somatotroph hyperplasia from hypothalamic
ganglioneuroma, bronchial carcinoid or pancreatic tumours

199
Q

Epidemiology of Acromegaly

A
  • RARE
  • 5/1,000,000
  • Age affected: 40M50 yrs
200
Q

Presenting Symptoms of Acromegaly

A 
•  Very gradual progression of symptoms over many years   
•  Rings and shoes becoming tight  
•  Increased sweating  
•  Headaches  
•  Carpal tunnel syndrome   
•  Hypopituitary symptoms:  
o  Hypogonadism 
o  Hypothyroidism 
o  Hypoadrenalism 
•  Visual disturbances (due to compression of optic chiasm by tumour)  
•  Hyperprolactinaemia leading to: 
o  Irregular periods   
o  Decreased libido  
o  Impotence
201
Q

Signs of Acromegaly on physical examination

A 
•  Hands 
o  Large spade-like hands  
o  Thick greasy skin  
o  Carpel tunnel syndrome signs  
 o  Premature osteoarthritis  
•  Face 
o  Prominent eyebrow ridge  
o  Prominent cheeks  
o  Broad nose bridge  
o  Prominent nasolabial folds   
o  Thick lips  
o  Increased gap between teeth
o  Large tongue  
o  Prognathism 
o  Husky resonant voice (due to thickening of vocal cords)  
•  Visual Field Loss 
o  Bitemporal superior quadrantopia progressing to bitemporal hemianopia 
•  Neck 
o  Multinodular goitre 
•  Feet 
o  Enlarged
202
Q

Investigations for acromegaly

A 
•  Serum IGF-1 -useful screening test   
o  GH stimulates IGF-1 secretion   
•  Oral Glucose Tolerance Test (OGTT) 
o  Positive result: failure of suppression of GH after 75 g oral glucose load   
•  Pituitary Function Tests 
o  9am cortisol 
o  Free T4 and TSH  
o  LH and FSH 
o  Testosterone 
o  Prolactin  
•  MRI of Brain - visualise the pituitary adenoma
203
Q

Management plan for Acromegaly

A

• Surgical - trans-sphenoidal hypophysectomy

• Radiotherapy - adjunctive to surgery
• Medical - if surgery is contraindicated or refused
o Subcutaneous Somatostatin Analogues
• Examples: octreotide, lanreotide
• Side-effects: abdominal pain, steatorrhoea, glucose intolerance, gallstones
o Oral Dopamine Agonists
• Examples: bromocriptine, cabergoline
• Side-effects: nausea, vomiting, constipation, postural hypotension,
psychosis (RARE)
o GH Antagonist (pegvisomant)
o Monitor
• GH and IGF1 levels can be used to monitor disease control

204
Q

Identify complications of acromegaly

A 
•  CVS 
o  Cardiomegaly  
o  Hypertension  
•  Respiratory 
o  Obstructive sleep apnoea  
•  GI 
o  Colonic polyps  
•  Reproductive 
o  Hyperprolactinaemia (in 30% of cases)  
•  Metabolic 
o  Hypercalcaemia 
o  Hyperphosphataemia 
 o  Renal stones  
o  Diabetes mellitus  
o  Hypertriglyceridaemia 
•  Psychological 
o  Depression 
o  Psychosis (from dopamine agonists)  
•  Complications of Surgery 
o  Nasoseptal perforation  
o  Hypopituitarism 
o  Adenoma recurrence   
o  CSF leak 
o  Infection
205
Q

Prognosis for patients with acromegaly

A
  • GOOD with early diagnosis and treatment

* Physical changes are irreversible

206
Q

Define Adrenal Insufficiency

A

Deficiency of adrenal cortical hormones (e.g. mineralocorticoids, glucocorticoids and androgens)

207
Q

Aetiology/ Risk Factors of adrenal insufficiency

A 
•  Primary Adrenal Insufficiency 
o  Addison's disease (usually autoimmune)  
•  Secondary Adrenal Insufficiency 
o  Pituitary or hypothalamic disease   
•  Infections 
o  Tuberculosis  
o  Meningococcal septicaemia (Waterhouse-Friderichsen Syndrome)  
o  CMV  
o  Histoplasmosis 
•  Infiltration 
o  Metastasis (mainly from lung, breast, melanoma)  
o  Lymphomas 
o  Amyloidosis   
•  Infarction 
o  Secondary to thrombophilia  
•  Inherited 
o  Adrenoleukodystrophy 
o  ACTH receptor mutation   
•  Surgical  
o  After bilateral adrenalectomy  
•  Iatrogenic 
o  Sudden cessation of long-term steroid therapy
208
Q

Epidemiology of adrenal insufficiency

A
  • Most common cause is IATROGENIC

* Primary causes are rare

209
Q

Presenting symptoms of adrenal insufficiency (chronic and acute)

A 
•  Chronic Presentation - the symptoms tend to be VAGUE and NON-SPECIFIC 
o  Dizziness 
o  Anorexia 
o  Weight loss  
o  Diarrhoea and Vomiting   
o  Abdominal pain 
o  Lethargy 
o  Weakness  
o  Depression  
•  Acute Presentation (Addisonian Crisis) 
o  Acute adrenal insufficiency 
o  Major haemodynamic collapse  
o  Precipitated by stress (e.g. infection, surgery)
210
Q

Signs of adrenal insufficiency on physical examination

A 
•  Postural hypotension  
•  Increased pigmentation  
o  More noticeable on buccal mucosa, scars, skin creases, nails and pressure points   
•  Loss of body hair in women (due to androgen deficiency) 
•  Associated autoimmune condition (e.g. vitiligo) 
•  Addisonian Crisis Signs:
o  Hypotensive shock  
o  Tachycardia 
o  Pale  
o  Cold  
o  Clammy  
o  Oliguria
211
Q

Investigations for adrenal insufficiency

A

• To confirm the diagnosis
o 9 am Serum Cortisol (< 100 nmol/L is diagnostic of adrenal insufficiency)
• > 550 nmol/L makes adrenal insufficiency unlikely
o Short Synacthen Test
• IM 250 μg tetrocosactrin (synthetic ACTH)
• Serum cortisol < 550 nmol/L at 30 mins indicates adrenal failure
• Identify the level of the defect in the hypothalamo-pituitary-adrenal axis
o HIGH in primary disease
o LOW in secondary

o  Long Synacthen Test 
•  1 mg synthetic ACTH administered  
•  Measure serum cortisol at 0, 30, 60, 90 and 120 minutes  
•  Then measure again at 4, 6, 8, 12 and 24 hours  
•  Patients with primary adrenal insufficiency show no increased after 6 hours  
•  Identify the cause 
o  Autoantibodies (against 21-hydroxylase)   
o  Abdominal CT or MRI 
o  Other tests (adrenal biopsy, culture, PCR) 
•  Check TFTs 
•  Investigations in Addisonian crisis 
o  FBC (neutrophilia MM> infection)   
o  U&amp;Es 
•  High urea 
•  Low sodium 
•  High potassium 
o  CRP/ESR 
o  Calcium (may be raised)  
o  Glucose - low  
o  Blood cultures  
o  Urinalysis 
o  Culture and sensitivity
212
Q

Management plan for adrenal insufficiency

A

• Addisonian Crisis
o Rapid IV fluid rehydration
o 50 mL of 50% dextrose to correct hypoglycaemia
o IV 200 mg hydrocortisone bolus
o Followed by 100 mg 6 hourly hydrocortisone until BP is stable o Treat precipitating cause (e.g. antibiotics for infection)
o Monitor
• Chronic Adrenal Insufficiency
o Replacement of:
• Glucocorticoids with hydrocortisone (3/day)
• Mineralocorticoids with fludrocortisone
o Hydrocortisone dosage needs to be increased during times of acute illness or stress
o NOTE: if the patient also has hypothyroidism, give hydrocortisone BEFORE thyroxine (to prevent precipitating an Addisonian crisis)
• Advice
o Have a steroid warning card
o Wear a medic-alert bracelet
o Emergency hydrocortisone on hand

213
Q

Identify possible complications of adrenal insufficiency

A
  • HYPERKALAEMIA

* Death during Addisonian crisis

214
Q

Prognosis for patients with adrenal insufficiency

A 
•  Adrenal function rarely recovers  
•  Normal life expectancy if treated  
•  Autoimmune Polyendocrine Syndrome  
o  Type 1 - autosomal recessive disorder caused by mutations in the AIRE gene.  Consists of the following diseases: 
•  Addison's disease  
•  Chronic mucocutaneous candidiasis   
•  Hypoparathyroidism 
o  Type 2 M also known as Schmidt's Syndrome  
•  Addison's disease  
•  Type 1 Diabetes  
•  Hypothyroidism 
•  Hypogonadism
215
Q

Define Carcinoid Syndrome

A

Constellation of symptoms caused by systemic release of humeral factors from carcinoid tumours

216
Q

Aetiology/ Risk Factors of Carcinoid syndrome

A

• Carcinoid tumours are slowMgrowing neuroendocrine tumours
• They are mostly derived from serotonin-producing enterochromaffin cells
• They produce secretory products like serotonin, histamine, tachykinins, kallikrein and prostaglandins
• 75-80% of patients with carcinoid syndrome have small bowel carcinoids
• NOTE: hormones released into the portal circulation will be metabolised by the liver so
symptoms don’t tend to appear until there are hepatic metastases or release into the
systemic circulation from bronchial or extensive retroperitoneal tumours

217
Q

Epidemiology of Carcinoid Syndrome

A
  • RARE
  • UK incidence : 1/1,000,000
  • Asymptomatic carcinoid tumours are more common
  • 10% of patients with MEN-1 have carcinoid tumours
218
Q

Presenting symptoms of carcinoid syndrome

A
  • Paroxysmal FLUSHING
  • Diarrhoea
  • Crampy abdominal pain
  • Wheeze
  • Sweating
  • Palpitations
219
Q

Signs of carcinoid syndrome on physical examination

A 
•  Facial flushing  
•  Telangiectasia 
•  Wheeze  
•  Right-sided murmurs (tricuspid stenosis/regurgitation or pulmonary stenosis)  
•  Nodular hepatomegaly in cases of metastatic disease  
•  Carcinoid Crisis Signs: 
o  Profound flushing  
o  Bronchospasm 
o  Tachycardia 
o  Fluctuating blood pressure
220
Q

Investigations for carcinoid syndrome

A 
•  24 hours urine collection :
o  Check 5-HIAA levels (metabolite of serotonin) 
•  Blood: 
o  Plasma chromogranin A and B   
o  Fasting gut hormones  
•  CT or MRI Scan :
o  To localise the tumour  
•  Radioisotope Scan :
o  Radiolabelled somatostatin analogue helps localise the tumour  
•  Investigations for MEN-1
221
Q

Define Cushing’s Syndrome

A

Syndrome associated with chronic inappropriate elevation of free circulating cortisol

222
Q

Aetiology/ Risk Factors for Cushing’s syndrome

A

It can be divided into ACTH Dependent (80%) and ACTH Independent (20%)
• ACTH Dependent
o Excess ACTH from a pituitary adenoma (Cushing’s disease)
o Ectopic ACTH (e.g. lung cancer, pulmonary carcinoid tumours)
• ACTH Independent
o Benign adrenal adenoma
o Adrenal carcinoma

223
Q

Epidemiology of Cushing’s syndrome

A
  • Incidence: 2-4/1,000,000 per year

* Peak incidence 20-40 yrs

224
Q

Presenting symptoms of Cushing’s syndrome

A
  • Increasing weight
  • Fatigue
  • Muscle weakness
  • Myalgia
  • Thin skin
  • Easy bruising
  • Poor wound healing
  • Fractures
  • Hirsuitism
  • Acne
  • Frontal balding
  • Oligomenorrhoea/amenorrhoea
  • Depression or psychosis
225
Q

Signs of cushion’s syndrome on physical examination

A
  • moon face
  • facial plethora
  • inter scapular fat pad
  • proximal muscle weakness
  • thin skin
  • bruises
  • central obesity
  • pink/purple striae on abdomen/breast/thighs
  • kyphosis (due to vertebral fracture)
  • Poorly healing wounds
  • Hirsuitism, acne, frontal balding
  • Hypertension
  • Ankle oedema (due to salt and water retention from the mineralocorticoid effect of excess cortisol)
  • Pigmentation in ACTH dependent cases
226
Q

Investigations for Cushing’s syndrome

A

• Must be performed on patients with a high pre-test probability
• Bloods
o U&Es - hypokalaemia due to mineralocorticoid effect
o BM - high glucose
• Initial High-Sensitivity Tests
o Urinary free cortisol
o Late-night salivary cortisol
o Overnight dexamethasone suppression test
o Low dose dexamethasone suppression test (LDDST)
• Give 0.5 mg dexamethasone orally ever 6 hrs for 48 hrs
• In Cushing’s syndrome, serum cortisol measured 48 hrs after the first dose
of dexamethasone fails to suppress below 50 nmol/L
• Tests to determine the underlying cause
o ACTH-independent (adrenal adenoma/carcinoma)
• Low plasma ACTH
• CT or MRI of adrenals
o ACTH-dependent (pituitary adenoma)
• High plasma ACTH
• Pituitary MRI
• High-dose dexamethasone suppression test
• Inferior petrosal sinus sampling (SUPERIOR to high-dose dexamethasone
suppression test)
! Central: peripheral ratio of venous ACTH > 2:1 (or > 3:1 after CRH administration) in Cushing’s disease
o ACTH-dependent (ectopic)
• If lung cancer suspected: CXR, sputum cytology, bronchoscopy, CT san
• Radiolabelled octreotide scans can detect carcinoid tumours because they express somatostatin receptors

227
Q

Generate a management plan for Cushing’s syndrome

A

• If iatrogenic - discontinue steroids, use lower dose or use a steroid-sparing agent
• Medical
o Used pre-operatively or if unfit for surgery
o Inhibit cortisol synthesis with metyrapone or ketoconazole
o Treat osteoporosis
o Physiotherapy for muscle weakness
• Surgical
o Pituitary Adenomas - trans-sphenoidal adenoma resection o Adrenal adenoma/carcinoma - surgical removal of tumour
o Ectopic ACTH - treatment directed at the tumour
• Radiotherapy
o Performed in those who are not cured and have persistent high cortisol after trans-sphenoidal resection of the tumour
• Bilateral adrenalectomy may be performed in refractory Cushing’s disease

228
Q

Complications of Cushing’s syndrome

A 
•  Diabetes  
•  Osteoporosis 
•  Hypertension 
•  Pre-disposition to infections  
•  Complications of surgery: 
o  CSF leakage  
o  Meningitis  
o  Sphenoid sinusitis   
o  Hypopituitarism 
•  Complications of radiotherapy: 
 o  Hypopituitarism 
o  Radionecrosis 
o  Increased risk of second intracranial tumours and stroke 
•  Bilateral adrenalectomy may be complicated by the development of Nelson's 
syndrome (locally aggressive pituitary tumour causing skin pigmentation due to ACTH 
secretion)
229
Q

Prognosis for patients with Cushing’s syndrome

A

Untreated - 5 yr survival = 50%

• Depression persists for many years following treatment

230
Q

Define Type 2 diabetes mellitus

A

Characterised by increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output

231
Q

Aetiology/ Risk Factors

A

• Genetic and environmental
• There are a few monogenic causes of diabetes (e.g. MODY, mitochondrial diabetes)
• Obesity increases the risk of T2DM (due to the action of adipocytokines)
• Diabetes can happen secondary to:
o Pancreatic disease (e.g. chronic pancreatitis)
o Endocrine disease (e.g. Cushing’s syndrome, acromegaly, phaeochromocytoma,
glucagonoma)
o Drugs (e.g. corticosteroids, atypical antipsychotics, protease inhibitors)

232
Q

Summarise the epidemiology of type 2 diabetes mellitus

A
  • UK Prevalence: 5-10%
  • Asian, African and Hispanic people are at greater risk
  • Incidence has increased over the past 20 yrs
  • This is linked to an increasing prevalence of obesity
233
Q

Presenting symptoms of type 2 diabetes mellitus

A
  • May be an incidental finding • Polyuria
  • Polydipsia
  • Tiredness
  • Patients may present with hyperosmolar hyperglycaemic state (HHS)
  • Infections (e.g. infected foot ulcers, candidiasis, balanitis)
  • Assess cardiovascular risk factors: hypertension, hyperlipidaemia and smoking
234
Q

Recognise the signs of T2DM on physical examination

A

• Calculate BMI
• Waist circumference
• Blood pressure
• Diabetic foot (ischaemic and neuropathic signs)
o Dry skin
o Reduced subcutaneous tissue
o Ulceration
o Gangrene
o Charcot’s arthropathy
o Weak foot pulses
• Skin changes (RARE):
o Necrobiosis lipoidica diabeticorum (well-demarcated plaques on shins or arms
with shiny atrophic surface and red-brown edges)
o Granuloma annulare (flesh-coloured papules coalescing in rings on the back of hands and fingers)
o Diabetic dermopathy (depressed pigmented scars on shins)

235
Q

Investigations for type 2 diabetes mellitus

A

• T2DM is diagnosed if one or more of the following are present:
o Symptoms of diabetes and a random plasma glucose > 11.1 mmol/L
o Fasting plasma glucose > 7 mmol/L
o Two-hour plasma glucose > 11.1 mmol/L after 75 g oral glucose tolerance test
• Monitor:
o HbA1c
o U&Es
o Lipid profile
o eGFR
o Urine albumin: creatinine ration (look out for microalbuminuria)

236
Q

Management plan for T2DM

A

• Glycaemic control - there is a step-
wise approach to the management of T2DM:
o At diagnosis: lifestyle + metformin
o If HbA1c > 7% after 3 months: lifestyle + metformin + sulphonylurea
o If HbA1c > 7% after 3 months: lifestyle + metformin + basal insulin
o If HbA1c > 7% after 3 months and fasting blood glucose > 7 mmol/L: add premeal rapid-acting insulin
o NOTE: sulphonylurea may be given as a monotherapy if patients cannot tolerate metformin
o NOTE: pioglitazone (thiazolidinedione) may also be given alongside metformin and a sulphonylurea
• Screening for complications
o Retinopathy
o Nephropathy
o Vascular disease
o Diabetic foot
o Cardiovascular risk factors (e.g. blood pressure, cholesterol)
• Pregnancy - requires strict glycaemic control and planning of conception
• Hyperosmolar Hyperglycaemic State - management is similar DKA
o Except use 0.45% saline if serum Na+ > 170 mmol/L

237
Q

Complications of T2DM

A 
- Hyperosmolar hyperglycaemic state :
o  Due to insulin deficiency  
 o  Marked dehydration  
o  High Na+ 
o  High glucose  
o  High osmolality  
o  No acidosis  
- Neuropathy
o  Distal symmetrical sensory neuropathy   
o  Painful neuropathy 
o  Carpel tunnel syndrome  
o  Diabetic amyotrophy 
o  Mononeuritis  
o  Autonomic neuropathy 
o  Gastroparesis (abdominal pain, nausea, vomiting)  
o  Impotence  
o  Urinary retention  
- Nephropathy: 
o  Microalbuminuria  
o  Proteinuria 
o  Renal failure  
o  Prone to UTI 
o  Renal papillary necrosis  
- Retinopathy:
o  Background 
o  Pre-proliferative 
o  Proliferative  
o  Maculopathy 
o  Prone to glaucoma, cataracts and transient visual loss  
- Microvascular complications :
o  Ischaemic heart disease  
o  Stroke  
o  Peripheral vascular disease
238
Q

Summarise the prognosis for patients with T2DM

A

• Good prognosis with good control
• Pre-diabetes can be diagnosed based on fasting blood glucose and oral glucose
tolerance test:
o Impaired Fasting Glucose (IFG) = fasting blood glucose 5.6-6.9 mmol/L
o Impaired Glucose Tolerance (IGT) = plasma glucose level of 7.8-11.0 mmol/L measured 2 hrs after a 75 g oral glucose tolerance test
• People with IFG or IGT are at high risk of developing type 2 diabetes

239
Q

Define Diabetes Insipidus

A

A disorder of inadequate secretion or of insensitivity to vasopressin (ADH) leading to hypotonic polyuria

240
Q

Aetiology/ Risk Factors

A

• Central DI: failure of ADH secretion by the posterior pituitary
• Nephrogenic DI: insensitivity of the collecting duct to ADH
o Water channels fail to activate and the luminal membrane of the collecting duct remains impermeable to water
• DI results in large volumes of hypotonic urine and polydipsia • Causes
o Central
• Idiopathic
• Tumours (e.g. pituitary tumour)
• Infiltrative (e.g. sarcoidosis)
• Infection (e.g. meningitis)
• Vascular (e.g. aneurysms, Sheehan syndrome)
• Trauma (e.g. head injury, neurosurgery)
o Nephrogenic
• Idiopathic
• Drugs (e.g. lithium)
• Post-obstructive uropathy
• Pyelonephritis
• Pregnancy
• Osmotic diuresis (e.g. diabetes mellitus)

241
Q

Epidemiology of diabetes insipidus

A
  • Median onset is 24 yrs

* Depends on cause

242
Q

Presenting symptoms of diabetes insipidus

A 
•  Polyuria 
•  Nocturia 
•  Polydipsia 
•  In children: 
o  Enuresis (bed-wetting) 
 o  Sleep disturbance 
•  Other symptoms depend on aetiology
243
Q

Signs of diabetes insipidus on physical examination

A

• Central DI has few signs if the patient drinks sufficiently to maintain adequate fluid
levels
• Urine output > 3 L/day
• If fluid intake < fluid output, signs of dehydration will be present (e.g. tachycardia,
reduced tissue turgor, postural hypotension, dry mucous membranes)
• Signs related to the cause (e.g. visual defect due to pituitary tumour)

244
Q

Investigations for diabetes insipidus

A

• Bloods
o U&Es and Ca2+
o Increased plasma osmolality
o Decreased urine osmolality • Water Deprivation Test
o Water is restricted for 8 hrs
o Plasma and urine osmolality are measured every hour for 8 hrs
o Weight the patient hourly to monitor level of dehydration
o STOP the test if the fall in body weight is > 3%
o Desmopressin is given after 8 hrs and urine osmolality is measured
o Results
• Normal - water restriction causes:
! Increased plasma osmolality
! Increased ADH secretion
! Increased water reabsorption
! Increase in urine osmolality (urine > 600 mosmol/kg)
• Diabetes Insipidus
! Lack of ADH activity means that urine CANNOT be concentrated
! Urine osmolality is LOW (< 400 mosmol/kg)
! Cranial M urine osmolality rises > 50% following administration of
desmopressin
! Nephrogenic - urine osmolality rises by < 45% following
administration of desmopressin

245
Q

Management plan for diabetes insipidus

A

• Treat the CAUSE
• Cranial DI
o Give desmopressin (vasopressin analogue)
o If mild - chlorpropamide or carbamazepine can be used to potentiate the residual
effects of any residual vasopressin
• Nephrogenic DI
o Sodium and/or protein restriction helps with polyuria
o Thiazide diuretics

246
Q

Complications of diabetes insipidus

A
  • Hypernatraemic dehydration

* Excess desmopressin –> hyponatraemia

247
Q

Prognosis for patients with diabetes insipidus

A
  • Depends on CAUSE
  • Cranial DI may be transient following head trauma
  • It may be cured by removing the cause (e.g. drug discontinuation, tumour resection)
248
Q

Define Type 1 Diabetes Mellitus

A

Metabolic hyperglycaemic condition caused by absolute insufficiency of pancreatic insulin production

249
Q

Aetiology/ Risk Factors of T1DM

A 
•  Caused by destruction of pancreatic insulin-producing beta cells  
•  Autoimmune process  
•  Occurs in genetically susceptible individuals with an environmental trigger   
•  Autoantigens associated with T1DM: 
o  Glutamic acid decarboxylase (GAD)  
o  Insulin 
o  Insulinoma-associated protein 2  
o  Cation efflux zinc transporter
250
Q

Summarise the epidemiology of T1DM

A

• 0.25% prevalence in the UK

251
Q

Symptoms and signs of T1DM

A 
•  Juvenile onset (< 30 yrs)  
•  Polyuria/nocturia 
•  Polydipsia 
•  Tiredness 
•  Weight loss  
•  DKA Symptoms: 
o  Nausea and vomiting  
o  Abdominal pain  
o  Polyuria, polydipsia 
 o  Drowsiness 
o  Confusion 
o  Coma 
o  Kussmaul breathing  
 o  Ketotic breath  
o  Signs of dehydration  
•  Signs of complications: 
o  Fundoscopy - check for diabetic retinopathy 
o  Examine feet for evidence of neuropathy (monofilament test, pulses)   
o  Monitor BP  
•  Signs of associated autoimmune conditions  
o  Vitiligo 
o  Addison's disease  
o  Autoimmune thyroid disease
252
Q

Investigations for T1DM

A

• Blood Glucose - fasting blood glucose > 7 mmol/L or random blood glucose > 11.1
mmol/L
• HbA1c
• FBC - MCV, reticulocytes
• U&Es - monitor for nephropathy and hyperkalaemia
• Lipid profile
• Urine albumin creatinine ratio - used to detect microalbuminuria
• Urine - glycosuria, ketonuria, MSU
• Investigations for DKA
o FBC (raised WCC without infection in DKA)
o U&Es (raised urea and creatinine due to dehydration) o LFT
o CRP
o Glucose
o Amylase
o Blood cultures
o ABG (metabolic acidosis with high anion gap)
o Blood/urinary ketones

253
Q

Management plan for T1DM

A

• Glycaemic Control
o Advice and patient education
• Short-acting insulin (three times daily before meals):
! Lispro
! Aspart
! Glulisine
• Long-acting insulin (once daily):
! Isophane
! Glargine
! Detemir
o Insulin pumps
o DAFNE courses (dose adjustment for normal eating)
o Monitor
• Regular capillary blood glucose tests
• HbA1c every 3-6 months
o Screening and management of complications
o Treatment of hypoglycaemia
• If reduced consciousness: 50 ml of 50% glucose IV OR 1 mg glucagon IM
• If consciousness and cooperative: 50 g oral glucose + starchy snack o Screening and management of cardiovascular risk factors
• DKA Management
o 50 U soluble insulin in 50 mL of normal saline
o Use an insulin sliding scale
o Continue until:
• Capillary ketones < 0.3
• Venous pH > 7.30
• Venous bicarbonate > 18 mmol/L
o From this point onwards change to SC insulin
o Don’t stop the insulin infusion until 1-2 hrs after the SC insulin has restarted
o 500 mL normal saline over 15M30 mins until SBP > 100
o Potassium replacement (because insulin drives potassium into cells)
o Monitor blood glucose, capillary ketones and urine output hourly
o Monitor U&Es and venous blood gas
o Broad spectrum antibiotics if infection is suspected
o Thromboprophylaxis
o NBM for at least 6 hrs
o NG tube if GCS is reduced

254
Q

Possible complications of T1DM

A 
•  Diabetic ketoacidosis  
o  Can be precipitated by infection, errors in management of diabetes, newly 
diagnosed diabetes, idiopathic  •  Microvascular complications: 
o  Retinopathy  
o  Nephropathy  
o  Neuropathy  
•  Macrovascular complications: 
o  Peripheral vascular disease   o  Ischaemic heart disease  
o  Stroke/TIA 
•  Increased risk of infection   
•  Complications of treatment:
o  Weight gain  
o  Fat hypertrophy at insulin injection sites   
o  Hypoglycaemia  
•  Personality changes  
 •  Fits  
•  Confusion 
•  Coma  
•  Pallor  
•  Sweating  
•  Tremor  
•  Tachycardia 
•  Palpitations  
•  Dizziness  
•  Hunger  
•  Focal neurological symptoms
255
Q

Prognosis for patients with T1DM

A
  • Depends on early diagnosis, good glycaemic control and compliance with treatment and screening
  • Vascular disease and renal failure are the main causes of increased morbidity and mortality
256
Q

Define Graves disease

A

The most common cause of hyperthyroidism. Caused by the presence of TSH-receptor stimulating antibodies that lead to hyperthyroidism due to loss of negative feedback.

257
Q

Aetiology/ risk factors of Graves disease

A

• Caused by the presence of TSH-receptor stimulating antibodies
• These antibodies are also responsible for the special features of Graves disease
(exophthalmos, pretibial myxoedema)
• Risk Factors for Hyperthyroidism :
o Family history
o High iodine intake
o Smoking
o Trauma to the thyroid gland o Toxic multinodular goitre
o HAART
o Childbirth

258
Q

Summarise the epidemiology of Graves disease

A
  • Hyperthyroidism is COMMON

* Graves’ is the most common cause of hyperthyroidism (75%) • Rarely occurs in children

259
Q

Presenting symptoms of Graves disease

A
  • Weight loss despite increased appetite
  • Irritability
  • Weakness
  • Diarrhoea
  • Sweating
  • Tremor
  • Anxiety
  • Heat intolerance
  • Loss of libido
  • Oligomenorrhoea/ amenorrhoea
260
Q

Signs of Graves disease on physical examination

A
  • Palmar erythema
  • Sweaty and warm palms
  • Fine tremor
  • Tachycardia (may be AF)
  • Hair thinning
  • Urticaria/pruritus
  • Brisk reflexes
  • Goitre
  • Proximal myopathy
  • Lid lag
  • Gynaecomastia
261
Q

Investigations for Graves disease

A

• TFTs - low TSH + high T3/T4
• Autoantibodies
o Anti-TPO antibodies (thyroid peroxidase) - found in 75% of Graves
o Anti-thyroglobulin antibodies
o TSH-receptor antibodies - very sensitive and specific for Graves
• Imaging
o Thyroid ultrasound
o Thyroid uptake scan
• Inflammatory Markers -CRP/ESR will be raised in subacute thyroiditis

262
Q

Define Hyperparathyroidism (Primary, Secondary, Tertiary)

A

• Primary Hyperparathyroidism - increased secretion of PTH unrelated to the plasma
calcium concentration
• Secondary Hyperparathyroidism - increased secretion of PTH secondary to
hypocalcaemia
• Tertiary Hyperparathyroidism - autonomous PTH secretion following chronic
secondary hyperparathyroidism

263
Q

Aetiology/ Risk Factors of hyperparathyroidism

A 
•  Primary  
o  Parathyroid adenoma 
o  Parathyroid hyperplasia   
o  Parathyroid carcinoma   
o  MEN syndrome  
•  Secondary  
o  Chronic renal failure   
o  Vitamin D deficiency
264
Q

Summarise the epidemiology of hyperparathyroidism

A
  • Primary - incidence of 5/100,000
  • Twice as common in FEMALES
  • Peak incidence: 40-60 yrs
265
Q

Recognise the presenting symptoms and signs of hyperparathyroidism

A

• Primary - many patients have mild hypercalcaemia and may be asymptomatic
• Symptoms/Signs of hyperclacaemia:
o Polyuria
o Polydipsia
o Renal calculi
o Bone pain
o Abdominal pain
o Nausea
o Constipation
o Psychological depression o Lethargy
• Secondary - may present with signs/symptoms of HYPOcalcaemia or of the underlying cause (e.g. renal failure, vitamin D deficiency)

266
Q

Investigations for hyperparathyroidism

A

• U&Es
• Serum calcium (high in primary and tertiary, low/normal in secondary)
• Serum phosphate (low in primary and tertiary, high in secondary)
• Albumin
• ALP
• Vitamin D
• PTH
• Primary Hyperparathyroidism:
o Hyperchloraemic acidosis
o Normal anion gap
o Due to PTH inhibition of renal reabsorption of bicarbonate
o Urine - high PTH in the presence of high calcium can also be caused by familial
hypocalciuric hypercalcaemia (FHH)
• Calcium: creatinine clearance ratio can help differentiate between primary
hyperparathyroidism and FHH
• Renal ultrasound - can visualise renal calculi

267
Q

Management plan for hyperparathyroidism

A

• Acute Hypercalcaemia
o IV fluids
o Avoid factors that exacerbate hypercalcaemia (e.g. thiazide diuretics)
o Maintain adequate hydration
o Moderate calcium and vitamin D intake
• Surgical Management
o Subtotal parathyroidectomy o Total parathyroidectomy
• Secondary Hyperparathyroidism Management
o Treat underlying cause (e.g. renal failure)
o Calcium and vitamin D supplements may be needed

268
Q

Complications of hyperparathyroidism

A

• Primary
o Increased bone resorption
o Increased tubular calcium reabsorption
o Increased 1alpha-hydroxylation of vitamin D
o All of these lead to hypercalcaemia
• Secondary
o Increased stimulation of osteoclasts and increased bone turnover
o This leads to osteitis fibrosa cystica
• Complications of surgery
o Hypocalcaemia
o Recurrent laryngeal nerve palsy

269
Q

Summarise the prognosis for patients with hyperparathyrodisim

A
  • Primary - surgery is curative for benign disease in most cases
  • Secondary or Tertiary - same prognosis as chronic renal failure
270
Q

Define Hypogonadism (female)

A

Characterised by impairment of ovarian function

271
Q

Aetiology/ Risk Factors of hypogonadism (female)

A

• Primary Hypogonadism
o Gonadal dysgenesis (due to chromosomal abnormalities e.g. Turner’s syndrome)
o Gonadal damage (e.g. autoimmune, chemotherapy, radiotherapy)
• Secondary Hypogonadism
o Functional (e.g. stress, weight loss, excessive exercise, eating disorders)
o Pituitary/Hypothalamic Tumours and Infiltrative Lesions (e.g. pituitary
adenomas, haemochromatosis)
o Hyperprolactinaemia (e.g. due to prolactinoma)
o Congenital GnRH deficiency: Kallmann’s syndrome, idiopathic

272
Q

Epidemiology of hypogonadism (female)

A
  • Secondary hypogonadism is a more common cause of anovulation/amenorrhoea
  • Turner’s syndrome occurs in around 1.5% of conceptions
273
Q

Recognise the presenting symptoms of hypogonadism (female)

A 
•  Symptoms of oestrogen deficiency: 
o  Night sweats  
o  Hot flushing  
o  Vaginal dryness   
o  Dyspareunia 
o  Decreased libido 
o  Infertility  
•  Symptoms of the underlying cause
274
Q

Signs of hypogonadism on physical examination (female)

A

• PRE-Pubertal Hypogonadism
o Delayed puberty (primary amenorrhoea, absent breast development, no
secondary sexual characteristics)
o Eunuchoid (long legs, arm span greater than height)
• POST-Pubertal Hypogonadism
o Regression of secondary sexual characteristics (e.g. loss of secondary sexual hair,
breast atrophy)
o Perioral and periorbital fine facial wrinkles
o Signs of underlying cause
• Hypothalamic/Pituitary disease - visual field defects
• Kallmann’s syndrome M-anosmia
• Turner’s syndrome
o Short statue
o Low posterior hair line
o High arched palate
o Widely spaced nipples
o Wide carrying angle
o Short fourth and fifth metacarpals
o Congenital lymphoedema
• Autoimmune primary ovarian
failure - there may be signs of other autoimmune diseases (e.g. vitiligo)

275
Q

Investigations for hypogonadism (female)

A

• Low serum oestradiol
• Serum FSH/LH
o Primary hypogonadism = HIGH
o Secondary hypogonadism = LOW
• Primary Hypogonadism Investigations
o Karyotype (look for chromosomal abnormalities)
o Pelvic imaging (US or MRI)- performed in primary amenorrhoea to check for
structural defects (e.g. androgen insensitivity)
• Screen for FMR1 gene in patients with unexplained preMmature ovarian failure
• Secondary Hypogonadism Investigations
o Pituitary function tests (e.g. 9 am cortisol, TFTs, prolactin)
o Visual field testing
o Hypothalamic-pituitary MRI
o Smell tests for anosmia
o Serum transferrin saturation (check for haemochromatosis)
• Investigating associated conditions
o Turner’s Syndrome - periodic echocardiography, renal US
o Autoimmune Oophoritis - check autoimmune adrenal insufficiency

276
Q

Define Hypogonadism (male)

A

A syndrome of decreased testosterone production, sperm production or both

277
Q

Aetiology/ Risk Factors of hypogonadism

A

• Primary Hypogonadism
o Gonadal dysgenesis (e.g. Klinefelter’s syndrome, undescended testicles)
o Gonadal damage (e.g. infection, torsion, trauma, autoimmune, iatrogenic)
o Rare causes (e.g. defects in enzymes involved in testosterone synthesis)
• Secondary Hypogonadism
o Pituitary/Hypothalamic lesions
o GnRH deficiency (Kallmann’s syndrome)
o Hyperprolactinaemia
o Systemic/chronic diseases
o o
o
Rare causes: genetic mutations Prader-Willi syndrome (short, small hands, almond-shaped eyes, learning difficulty, postnatal hypotonia) Laurence-Moon-Biedl syndrome (obesity, polydactyly, retinitis pigmentosa, learning difficulty)

278
Q

Epidemiology of hypogonadism

A

Primary hypogonadism accounts for 30-40% of male infertility
- Most common cause: Klinefelter’s Syndrome (XXY)

Secondary hypogonadism accounts for 1-2%

279
Q

Presenting symptoms of hypogonadism

A 
•  Delayed puberty 
•  Decreased libido 
•  Impotence  
•  Infertility  
•  Symptoms of underlying cause (e.g. Klinefelters --> intellectual dysfunction, 
behavioural abnormalities)
280
Q

Signs of hypogonadism on physical examination

A

• Measure testicular volume using Prader’s orchidometer (normal adult volume = 15-25
mL)
• Prepubertal Hypogonadism
o Signs of delayed puberty
• High pitched voice
• Decreased pubic/axillary/facial hair
• Small or undescended testicles
• Small penis
o Gynaecomastia
o Eunuchoid proportions (arm span > height)
o Features of underlying cause (e.g. undescended testicle, anosmia in Kallmann’s
syndrome)
• Postpubertal Hypogonadism
o Decreased pubic/axillary/facial hair
o Soft and small eyes
o Gynaecomastia
o Fine perioral wrinkles
o Features of underlying cause (e.g. visual defects if pituitary cause)

281
Q

Investigations for hypogonadism

A 
•  Serum total testosterone 
•  Sex hormone binding globulin (SHBG)  
•  Albumin 
•  LH and FSH  
•  Primary Hypogonadism: 
o  Low testosterone  
o  High LH and FSH  
•  Secondary Hypogonadism: 
o  Low testosterone  
o  Inappropriately normal/low LH and FSH 
•  Primary M can be investigated using karyotyping (check for Klinefelter's syndrome)  
•  Secondary 
o  Pituitary function tests  
o  MRI of the hypothalamic/pituitary area 
o  Visual field testing  
o  Smell testing (for anosmia) 
o  Iron testing (for hereditary haemochromatosis) 
•  Assess bone age (risk of fracture)
282
Q

Define Hypopituitarism

A

Deficiency is one or more of the hormones secreted by the anterior pituitary. Panhypopituitarism is deficiency of ALL pituitary hormones.

283
Q

Aetiology/ Risk Factors for hypopituitarism

A

• Pituitary Masses
o Most commonly adenomas
o Others include craniopharyngioma, meningioma, glioma, metastases
o Cysts
• Pituitary Trauma - radiation, surgery, base of skull fractures
• Hypothalamic Dysfunction - due to anorexia, starvation, overMexercise
• Infiltrative Diseases - sarcoidosis, haemochromatosis, Langerhans’ cell histiocytosis
• Vascular - pituitary apoplexy, Sheehan’s syndrome
• Infection - meningitis, encephalitis
• Genetic Mutations - Pit-1 and Prop-1 genes

284
Q

Epidemiology of hypopituitarism

A

• Pituitary adenoma annual incidence: 1/100,000

285
Q

Signs and symptoms of hypopituitarism

A

• Depends on CAUSE
• Symptoms and signs are dependent on the hormone that is deficient:
o GH
• CHILDREN: short stature
• ADULTS: low mood, fatigue, reduced exercise capacity and muscle strength,
increased abdominal fat mass o LH or FSH
• Delayed puberty
• FEMALES: loss of secondary sexual hair, breast atrophy, menstrual
irregularities, dyspareunia, decreased libido, infertility
• MALES: loss of secondary sexual hair, gynaecomastia, small and soft testes,
decreased libido, impotence
o ACTH - signs/symptoms of adrenal insufficiency
o TSH - signs/symptoms of hypothyroidism
o Prolactin - absence of lactation (not usually noticed clinically)
• Pituitary Apoplexy has some other symptoms:
o Headache
o Visual loss
o Cranial nerve palsies

286
Q

Investigations for hypopituitarism

A 
•  Pituitary Function Tests 
o  Basal Tests 
 •  9 am cortisol 
 •  LH and FSH levels  
 •  Testosterone levels  
 •  Oestrogen levels  
 •  IGF-1 levels  
 •  Prolactin levels  
 •  Free T4 and TSH levels  
o  Dynamic Tests (rarely performed) 
 •  Insulin-induced hypoglycaemic (should cause a rise in GH and cortisol)  
o  Short synacthen test (for adrenal insufficiency)  
o  MRI/CT of brain  
o  Visual field testing
287
Q

Management plan for hypopituitarism

A 
•  Hormone Replacement  
o  Hydrocortisone  
o  Levothyroxine  
o  Sex hormones  
•  Testosterone in males  
•  Oestrogen with/without progesterone in females  
•  Growth hormone  
•  Desmopressin (if central diabetes insipidus as a result of 
panhypopituitarism)
288
Q

Possible complications of hypopituitarism

A 
•  Addisonian crisis  
•  Hypoglycaemia  
•  Myxoedema coma  
•  Infertility 
•  Osteroporosis  
•  Dwarfism (children)  
•  Complications of pituitary mass: 
o  Optic chiasm compression (leading to bitemporal hemianopia)   
o  Hydrocephalus  
o  Temporal lobe epilepsy
289
Q

Prognosis for patients with hypopituitarism

A

Good prognosis with lifelong treatment

290
Q

Define hypothyroidism

A

The clinical syndrome resulting from insufficiency secretion of thyroid hormones

291
Q

Aetiology/ Risk Factors of hypothyroidism

A

• PRIMARY HYPOTHYROIDISM (decreased thyroid hormone production)
o Acquired
• Hashimoto’s thyroiditis (autoimmune)
• Iatrogenic (post-surgery, radioiodine, hyperthyroid medication)
• Severe iodine deficiency
• Iodine excess (Wolff-Chaikoff effect)
• Thyroiditis
o Congenital
• Thyroid dysgenesis
• Inherited defects in thyroid hormone biosynthesis
• SECONDARY HYPOTHYROIDISM (5% of cases)
o Pituitary and Hypothalamic Disease - resulting in reduced TSH and TRH and,
hence, reduced stimulation of thyroid hormone production

292
Q

Summarise the epidemiology of hypothyroidism

A
  • 0.1-2% of adults
  • 6 x more common in FEMALES
  • Most common age of onset > 40 yrs
  • Iodine deficiency is seen in mountainous areas (e.g. Himalayas)
293
Q

Presenting symptoms of hypothyroidism

A 
•  INSIDIOUS onset  
•  Cold intolerance  
•  Lethargy  
•  Weight gain  
•  Reduced appetite  
•  Constipation  
•  Dry skin  
•  Hair loss  
•  Hoarse voice  
•  Mental slowness 
•  Depression  
•  Cramps  
•  Ataxia  
•  Paraesthesia 
•  Menstrual disturbance (irregular cycles, menorrhagia) 
•  History of surgery or radioiodine therapy for hyperthyroidism 
•  Personal/family history of other autoimmune conditions (e.g. Addison's, type 1 
diabetes mellitus)  
•  Myxoedema coma (severe hypothyroidism usually seen in the elderly): 
o  Hypothermia 
o  Hypoventilation 
 o  Hyponatraemia  
o  Heart failure  
o  Confusion  
o  Coma
294
Q

Signs of hypothyroidism on physical examination

A 
•  Hands 
o  Bradycardia 
o  Cold hands   
•  Head/Neck/Skin 
o  Pale puffy face   
o  Goitre  
o  Oedema  
o  Hair loss  
o  Dry skin   
o  Vitiligo 
•  Chest 
o  Pericardial effusion  
o  Pleural effusion  
•  Abdomen 
o  Ascites  
•  Neurological 
o  Slow relaxation of reflexes  
o  Signs of carpal tunnel syndrome
295
Q

Investigations for hypothyroidism

A 
•  Bloods 
o  TFTs 
o  FBC - may show normocytic anaemia   
o  U&amp;Es - may show low sodium  
o  Cholesterol - may be high
296
Q

Management plan for hypothyroidism

A

• CHRONIC
o Levothyroxine (25-200 mcg/day)
• IMPORTANT: rule out underlying adrenal insufficiency before starting thyroid hormone replacement
• Thyroid hormone replacement in the context of adrenal insufficiency can precipitate an Addisonian crisis
• Adjust dose based on clinical picture and TFTs
• MYXOEDEMA COMA
o Oxygen
o Rewarming
o Rehydration
o IV T4/T3
o IV hydrocortisone
o Treat underlying cause (e.g. infection)

297
Q

Complications of hypothyroidism

A
  • Myxoedema coma

* Myxoedema madness (psychosis with delusions and hallucinations or dementia)

298
Q

Prognosis for patients with hypothyroidism

A
  • Lifelong levothyroxine is required

* Myxoedema coma mortality = 80%

299
Q

Define Multiple Endocrine Neoplasia (MEN)

A

An autosomal dominant condition characterised by a predilection to develop tumours of endocrine glands

300
Q

Aetiology/ Risk Factors of MEN

A 
•  Autosomal dominant inheritance   
•  Patterns of features: 
o  MEN 1  (Wermer's Syndrome)
•  Pituitary adenomas 
•  Parathyroid tumours  
•  Pancreatic islet-cell tumours (and other endocrine tumours of the 
gastroenterohepatic tract e.g. gastrinomas) 
•  Fascial angiofibromas and collagenomas 
o  MEN 2a (Sipple Syndrome) 
•  Parathyroid tumours 
•  Medullary thyroid cancer   
•  Phaeochromocytomas 
o  MEN 2b (Marfanoid Phenotype) 
•  Same as MEN 2a 
•  Marfanoid appearance  
•  Neuromas of the GI tract
301
Q

Summarise the epidemiology of MEN

A

Very Rare

302
Q

Presenting symptoms and signs of MEN (1 & 2)

A

• MEN 1
o Age of onset of tumours is usually teenage years
o However, symptoms of the tumours may not become apparent for years
o Diagnosis is commonly made in the 4th decade of life
o Symptoms and signs are dependent on the organs affects:
• Hyperparathyroidism –> symptoms of hypercalcaemia + nephrolithiasis
• Hypergastrinaemia –> Zollinger-Ellison syndrome
• Hyperinsulinaemia –> hypoglycaemia
• Hyperprolactinaemia –> amenorrhoea
• Hypersomatotrophinaemia –> acromegaly
o Pituitary tumours may cause visual defects
• MEN 2
o Symptoms of medullary thyroid cancer, hyperparathyroidism or
phaeochromocytoma
o Medullary thyroid cancer symptoms:
• Hypertension
• Episodic sweating
• Diarrhoea
• Pruritic skin lesions
• Lump in the neck
o Hypercalcaemia symptoms:
• Constipation
• Polyuria/polydipsia
• Depression
• Kidney stones
• Fatigue

303
Q

Investigations for MEN

A

• MEN 1
o Screening first or second degree relatives
o Hormone hypersecretion blood tests
o DNA testing
• MEN 2
o Phaeochromocytoma test - 24hr urine metanephrines
• Can be followed by abdominal MRI
o Medullary thyroid cancer test - elevated calcitonin concentration
• Can also be investigated with ultrasound and FNA
o Parathyroid tumours- simultaneously elevated Ca2+ and PTH

304
Q

Define Obesity

A 
A BMI >30kg/m^2
- Can also be defined using wait circumference:
•  Men 
!  Low Risk = < 94 cm 
!  Very High Risk = > 102 cm   •  Women 
!  Low Risk = < 80 cm  
!  Very High Risk = > 88 cm
305
Q

Aetiology/ Risk Factors

A

• There are genetic factors that affect the risk of become obese
• There are a few monogenic forms of obesity (e.g. leptin deficiency, Prader-Willi
syndrome)
• Common obesity is caused by energy intake > energy usage

306
Q

Epidemiology of obesity

A

• 24% of men and 25% of women are obese

307
Q

Presenting symptoms and signs of obesity

A

• Noticing that you’re fat
• Routine health check
• Symptoms of complications (e.g. T2DM, coronary heart disease, obstructive sleep
apnoea)
• High body weight, BMI and waist circumference

308
Q

Investigations for obesity

A
  • Measure serum lipids
  • Measure HbA1c
  • Hormone profile (check for hormonal cause of obesity)
  • TFTs - hypothyroidism can cause obesity
  • Other investigations depending on comorbidities
309
Q

Define Osteoporosis

A

Reduced bone density (defined as >2.5 standard deviations below peak bone mass achieved by healthy adults (i.e. T-score >2.5) resulting bone fragility and increased fracture risk

310
Q

Aetiology/ Risk Factors of osteoporosis

A 
•  Primary: 
o  Idiopathic (if < 50 yrs)  
o  Post-menopausal  
•  Secondary: 
o  Malignancy - myeloma, metastatic carcinoma   
o  Endocrine: 
•  Cushing's disease  
•  Thyrotoxicosis 
•  Primary hyperparathyroidism  •  Hypogonadism 
o  Drugs - corticosteroids, heparin 
o  Rheumatological - rheumatoid arthritis, ankylosing spondylitis  
o  Gastrointestinal: 
•  Malabsorption (e.g. coeliac disease, partial gastrectomy)  
•  Liver disease (e.g. primary biliary cirrhosis)  
•  Anorexia 
•  RISK FACTORS:  
o  Age  
o  Family history 
o  Low BMI  
o  Low calcium intake  
o  Smoking  
o  Lack of physical exercise   
o  Low exposure to sunlight   
o  Alcohol abuse  
o  Late menarche  
o  Early menopause   
o  Hypogonadism
311
Q

Epidemiology of osteoporosis

A 
•  COMMON  
•  In > 50 yrs 
o  Females: 1/3 
o  Males: 1/12  
•  More common in CAUCASIANS than Afro-Caribbeans
312
Q

Presenting symptoms of osteoporosis

A

• Often ASYMPTOMATIC until fractures occur
• Characteristic fractures:
o Neck of femur (after minimal trauma)
o Vertebral fractures (leading to loss of height, stooped posture and acute back pain on lifting)
o Colles’ fracture (of the distal radius after falling on an outstretched hand)

313
Q

Signs of osteoporosis on physical examination

A

• Often NO SIGNS until complications develop:
o Tenderness on percussion (over vertebral fractures)
o Thoracic kyphosis (due to multiple vertebral fractures)
o Severe pain when hip flexed and externally rotated (suggests neck of femur fracture)

314
Q

Investigations for osteoporosis

A

• Bloods
o Calcium
o Phosphate
o ALP
o IMPORTANT: these are NORMAL in PRIMARY osteoporosis
• X-Ray
o Used to diagnose fractures
o Often normal because it takes > 30% loss of bone density before showing any
changes in radiolucency or cortical thinning
o May show biconcave vertebrae and crush fractures
• Isotope Bone Scans
o Highlights areas of stress and microfractures
• DEXA (Dual-Energy X-Ray Absorptiometry) Scan
o T-score: the number of standards deviations the bone mineral density
measurement is above or below the young normal mean bone mineral density
o Z-score: the number of standard deviations the measurement is above or below the ageJmatched mean bone mineral density. Z-score may be helpful in identifying patients who may need a work-up for secondary causes of osteoporosis

315
Q

Define Paget’s disease of the bone

A

Characterised by excessive bone remodelling at one (monostotic) or more (polyostotic) sites resulting in bone that is structurally disorganised

316
Q

Aetiology/ Risk factors of Paget’s disease

A

• UNKNOWN
• Genetic factors and viral infection may play a role
• Excessive bone resorption by abnormally large osteoclasts is followed by increased
bone formation by osteoblasts in a disorganised fashion
• This results in an abnormal pattern of lamellar bone
• Marrow spaces are filled by an excess of fibrous tissue with a marked increase in blood
vessels

317
Q

Summarise epidemiology of Paget’s disease

A
  • Common in ELDERLY
  • 3% of > 50 yrs
  • 10% of > 80 yrs
  • Males = Females
318
Q

Presenting symptoms of Paget’s disease

A 
•  May be ASYMPTOMATIC  
•  May present with insidious onset pain, which is aggravated by weight bearing and 
movement  
•  Headaches  
•  Deafness  
•  Increasing skull size
319
Q

Signs of Paget’s disease on physical examination

A
  • Bitemporal skull enlargement with frontal bossing (prominent, protruding forehead)
  • Spinal kyphosis
  • Anterolateral bowing of femur, tibia or forearm
  • Skin over the affected bone may be warm (due to increased vascularity)
  • Sensorineural deafness (due to compression of vestibulocochlear nerve)
320
Q

Investigations for Paget’s disease

A 
•  Bloods 
o  High ALP 
o  Ca2+ and phosphate = NORMAL   
•  Bone Radiographs 
o  Enlarged, deformed bones  
o  Lytic and sclerotic appearance  
o  Lack of distinction between cortex and medulla   
o  Skull changes: 
•  Osteoporosis circumscripta  
•  Enlargement of frontal and occipital areas  
 •  Cotton wool appearance  
•  Bone Scan 
o  Assesses extent of skeletal involvement  
o  Pagetic bone lesions appear as areas with markedly increased uptake  
•  Resorption Markers 
o  Monitors disease activity  
o  Check urinary hydroxyproline
321
Q

Define Phaeochromocytoma

A

Catecholamine-producing tumours that usually arise from chromaffin cells of the adrenal medulla but are extra-adrenal in about 10% of cases

  • 10% are bilateral
  • 10% are malignant
  • Extra-adrenal phaeochromocytomas are referred to as paragangliomas
322
Q

Aetiology/ Risk Factors of phaeochromocytoma

A

• Sporadic cases are of unknown aetiology
• Familial in up to 30%
• Familial cases are seen in patients with:
o MEN2a
o von Hippel-Lindau syndrome
o Neurofibromatosis type 1

323
Q

Epidemiology of phaeochromocytoma

A
  • RARE

* < 0.2% of hypertensive patients

324
Q

Presenting symptoms of patients with phaeochromocytoma

A 
•  PAROXYSMAL episodes  
•  Headache (due to malignant hypertension) 
•  Sweating  
•  Cardiorespiratory Symptoms  o  Palpitations  
o  Chest pain  
o  Dyspnoea   
•  GI Symptoms 
o  Epigastric pain   
o  Nausea  
o  Constipation 
•  Neuropsychiatric Symptoms  o  Weakness  
o  Tremor  
o  Anxiety
325
Q

Signs of pheochromocytoma on physical examination

A
  • Hypertension
  • Postural hypotension
  • Pallor
  • Tachycardia
  • Fever
  • Weight loss
326
Q

Investigations for pheochromocytoma

A

• 24 hr urine collection - check for catecholamine levels (and check for fractionated metanephrine levels)
o NOTE: metanephrines are metabolites of adrenaline
• Plasma free metanephrines
• Tumour localisation (MRI or CT)
• I-MIBG scintigraphy (another way of visualising the tumour)
• Screen for associated conditions
• Genetic testing

327
Q

Define non-functioning pituitary tumours

A

Benign tumours of the pituitary gland formed from pituitary cells that do not produce any active pituitary hormones

328
Q

Aetiology/risk factors of non-functioning pituitary tumours

A
  • No specific cause

- Can occur as a part of MEN 1 syndrome

329
Q

Epidemiology of non-functioning pituitary tumours

A
  • Most common type of macroadenoma (> 1 cm)

* Most common type of pituitary tumour in patients > 60 yrs

330
Q

Presenting symptoms and signs of non-functioning pituitary tumours

A

• Symptoms develop very SLOWLY because there are no
hormonal derangements
• Headaches
• Pressure on surrounding structures:
o Optic chiasm - bitemporal hemianopia
o Normal pituitary gland - panhypopituitarism
• Symptoms develop depending on which hormone is affected

331
Q

Investigations for non-functioning pituitary tumours

A
  • MRI
  • CT
  • Bloods - check hormone levels
  • Visual fields testing
332
Q

Define polycystic ovarian syndrome

A

• Characterised by oligomenorrhoea/amenorrhoea and hyperandrogenism (clinical or
biochemical). Frequently associated with:
o Obesity
o Insulin resistance
o Type 2 diabetes mellitus
o Dyslipidaemia

333
Q

Aetiology/ Risk factors of polycystic ovarian syndrome

A

• Environmental factors
• Genetic variants
• Hyperinsulinaemia results in increased ovarian androgen synthesis and reduced
hepatic sex hormone binding globulin (SHBG) synthesis
• This leads to an increase in free androgens (which gives rise to the symptoms)

334
Q

Epidemiology of polycystic ovarian syndrome

A
  • PCOS is the MOST COMMON cause of infertility in women

* Affects 6-8% of women

335
Q

Presenting symptoms of polycystic ovarian syndrome

A 
•  Menstrual irregularities  
•  Dysfunctional uterine bleeding  
•  Infertility  
•  Symptoms of hyperandrogenism:  
o  Hirsuitism 
o  Male-pattern hair loss  
o  Acne
336
Q

Signs of polycystic ovarian syndrome on physical examination

A

• Hirsuitism
• Male-pattern hair loss
• Acne
• Acanthosis nigricans (sign of severe insulin
resistance) - velvety thickening and hyperpigmentation of the skin of the axillar or neck

337
Q

Investigations for polycystic ovarian syndrome

A

• Bloods
o High LH
o High LH: FSH ratio
o High testosterone, androstenedione and DHEA-S
o Low sex hormone binding globulin
• Other things to test for:
o Hyperprolactinaemia
o Hypo/hyperthyroidism
o Congenital adrenal hyperplasia (check 17OH-progesterone levels)
o Cushing’s syndrome
• Look for impaired glucose tolerance/T2DM:
o Fasting blood glucose
o HbA1c
• Fasting lipid profile
• Transvaginal USS: look for ovarian follicles and an increase in ovarian volume

338
Q

Define primary hyperaldosternoism

A

Characterised by autonomous aldosterone overproduction from the adrenal gland with subsequent suppression of plasma renin activity

339
Q

Aetiology / Risk Factors of primary hyperaldosteronism

A

• Adrenal adenoma (Conn’s syndrome) - responsible for 70% of cases
• Adrenal cortex hyperplasia (30% of cases)
• RARE:
o Glucocorticoid-suppressible hyperaldosteronism
o Aldosterone producing adrenal carcinoma
• Pathophysiology:
o Excess aldosterone leads to increased Na+ and water retention
o This leads to hypertension
o It also causes increased renal K+ loss leading to hypokalaemia
o Renin is suppressed due to NaCl retention

340
Q

Epidemiology of primary hyperaldosteronism

A
  • 1-2% of hypertensive patients
  • Conn’s syndrome is more common in WOMEN and YOUNG patients
  • Bilateral adrenal hyperplasia is more common in MEN and presents at an older age
341
Q

Presenting symptoms of primary hyperaldosteronism

A

• Usually ASYMPTOMATIC
• Tends to be an incidental finding on routine blood tests • Symptoms of Hypokalaemia
o Muscle weakness
o Polyuria and polydipsia (due to nephrogenic DI)
o Paraesthesia
o Tetany

342
Q

Signs of primary hyperaldosteronism on physical examination

A
  • Hypertension

* Complications of hypertension (e.g. hypertensive retinopathy)

343
Q

Investigations for primary hyperaldosteronism

A

• Screening Tests
o Low Serum K+
• NOTE: Serum Na+ is usually normal because the Na+ reabsorption is matched by water reabsorption
o High Urine K+
o High Plasma Aldosterone Concentration
o High aldosterone: renin activity ratio
• Confirmatory Tests
o Salt Loading
• Failure of aldosterone suppression following salt load confirms primary
hyperaldosteronism
o Postural Test
• Measure plasma aldosterone, renin activity and cortisol when the patient is lying down at 8 am
• Measure again after 4 hrs of the patient being upright
• Aldosterone-producing adenoma - aldosterone secretion decreases
between 8 am and noon
• Bilateral adrenal hyperplasia - adrenals respond to standing posture and
increase renin production leading to increased aldosterone secretion
o CT/MRI
o Bilateral adrenal vein catheterisation
• Measures adrenal vein aldosterone levels and allows you to distinguish
between Conn’s syndrome and bilateral adrenal hyperplasia
o Radio-labelled cholesterol scanning
• Unilateral uptake in adrenal adenomas
• Bilateral uptake in bilateral adrenal hyperplasia

344
Q

Management plan for primary hyperaldosteronism

A

• Bilateral Adrenal Hyperplasia
o Spironolactone
o Eplerenone can be used if the spironolactone side-effects are intolerable
o Amiloride (potassium-sparing diuretic)
o Monitor serum K+, creatinine and BP
o ACE inhibitors and CCBs may also be added
• Aldosterone Producing Adenomas
o Adrenalectomy
• Adrenal Carcinoma
o Surgery
o Post-operative mitotane (antineoplastic)

345
Q

Complications of primary hyperaldosteronism

A

Complications of hypertension

346
Q

Prognosis for patients with primary hyperaldosteronism

A
  • Surgery may cure hypertension

- Or it may make the hypertension easier to treat with anti-hypertensive medication

347
Q

Define Prolactinoma

A

A pituitary adenoma that overproduces prolactin

348
Q

Aetiology/ Risk Factors of prolactinoma

A

• There are different types of prolactinoma
o Microadenomas: < 1 cm
o Macroadenomas: > 1 cm
o Giant Pituitary Adenomas: > 4 cm
o Malignant Prolactinoma (RARE)
• Cause if UNKNOWN
• Some may occur as a consequence of MEN 1 syndrome
• Risk Factors
o Risk of tumour enlargement in pregnancy

349
Q

Epidemiology of prolactinoma

A
  • Relatively common

* Higher incidence in premenopausal women

350
Q

Presenting symptoms and signs of prolactinoma on physical examination (in men and women)

A

• NOTE: microprolactinomas rarely expand to become macroprolactinomas
• Women
o Amenorrhoea/oligomenorrhoea o Galactorrhoea
o Infertility
o Hirsuitism
o Reduced libido
• Men
o Symptoms are subtle and develop slowly
o Reduced libido
o Reduced beard growth
o Erectile dysfunction
• Symptoms caused by tumour size o Headache
o Visual disturbance (bitemporal hemianopia)
o Cranial nerve palsies
o Signs and symptoms of hypopituitarism

351
Q

Investigations for prolactinoma

A

• Exclude pregnancy
• TFTs - hypothyroidism –> high TRH –> stimulates prolactin release
• Serum prolactin level (extremely high levels (> 5000 mU/L) suggests true
prolactinoma)
• MRI
• Assessment of pituitary function

352
Q

Management plan for prolactinoma

A

• Goals
o Treat cause
o Relieve symptoms
o Prevent complications
o Restore fertility
• Dopamine Agonists (e.g. cabergoline and bromocriptine)
o Effective in most patients
o Usually need to be continued on a long-term basis
• If dopamine agonists are ineffective:
o Surgery
o Radiotherapy

353
Q

Complications of prolactinoma

A

• Complications of hypogonadism
o Osteoporosis
o Reduced fertility
o Erectile dysfunction
• Complications of tumour size o Visual loss
o Headache
o Pituitary apoplexy o CSF rhinorrhoea

354
Q

Prognosis for patients with prolactinoma

A

• Microprolactinomas will spontaneously resolve in about 1/3 cases
• Dopamine agonist withdrawal is usually attempted after about 2-3 years if prolactin
levels have normalised and tumour volume is reduced
• High rates of recurrence

355
Q

Define SIADH

A

Characterised by continued secretion of ADH, despite the absence of normal stimuli for secretion (i.e. increased serum osmolality or decreased blood volume)

356
Q

Aetiology/ Risk factors of SIADH

A 
•  Brain 
o  Haemorrhage/thrombosis  
o  Meningitis   
o  Abscess  
o  Trauma 
o  Tumour 
o  Guillain-Barre syndrome   
•  Lung 
o  Pneumonia 
o  TB 
o  Other: abscess, aspergillosis, small cell carcinoma 
•  Tumours 
o  Small cell lung caner  
o  Lymphoma  
o  Leukaemia  
o  Others: pancreatic cancer, prostate cancer, mesothelioma, sarcoma, thymoma 
•  Drugs 
o  Vincristine  
o  Opiates  
o  Carbamazepine   
o  Chlorpropamide 
•  Metabolic 
o  Porphyria 
o  Alcohol withdrawal
357
Q

Epidemiology of SIADH

A
  • Hyponatraemia is the MOST COMMON electrolyte imbalance seen in hospital
  • < 50% of severe hyponatraemia is caused by SIADH
358
Q

Presenting symptoms of SIADH

A
  • Mild hyponatraemia may be ASYMPTOMATIC
  • Headache
  • Nausea/vomiting
  • Muscle cramp/weakness
  • Irritability
  • Confusion
  • Drowsiness
  • Convulsions
  • Coma
  • Symptoms of underlying cause
359
Q

Signs of SIADH on physical examination

A

• MILD hyponatraemia - no signs
• SEVERE hyponatraemia:
o Reduced reflexes
o Extensor plantar reflexes
• Signs of underlying cause
• NOTE: the hyponatraemia in SIADH is due to dilution from excessive water
reabsorption and not due to a decrease in total body Na+

360
Q

Identify appropriate investigations for SIADH

A

• Things to check:
o Low serum sodium
o Creatinine (check renal function)
o Glucose, serum protein and lipids - to rule out pseudohyponatraemia
• Pseudohyponatraemia = when the sodium concentration is actually normal but is erroneously reported as being low because of the presence of either hyperlipidaemia or hyperproteinaemia
o Free T4 and TSH - hypothyroidism can cause hyponatraemia
o Short synacthen test - adrenal insufficiency can cause hyponatraemia
• SIADH Diagnosis
o Low plasma osmolality
o Low serum Na+ concentration
o High urine osmolality
o High urine Na+
o The presence of the above results and the absence of hypovolaemia, oedema,
renal failure, adrenal insufficiency and hypothyroidism are required for the
diagnosis of SIADH
• Investigations for identifying the cause (e.g. CXR, CT, MRI)

361
Q

Management plan for SIADH

A
  • Treat underlying cause
  • Fluid restriction
  • Vasopressin receptor antagonists (e.g. tolvaptan)
  • In SEVERE cases - slow IV hypertonic saline and furosemide with close monitoring
362
Q

Complications of SIADH

A 
•  Convulsions  
•  Coma  
•  Death  
•  Central pontine myelinolysis - occurs with rapid correction of hyponatraemia 
o  Characterised by: 
•  Quadriparesis  
•  Respiratory arrest  
•  Fits
363
Q

Prognosis for patients with SIADH

A
  • Depends on the CAUSE
  • Na+ < 110 mmol/L is associated with a HIGH MORBIDITY and MORTALITY
  • 50% mortality with central pontine myelinolysis
364
Q

Define thyroid cancer

A

A malignancy arising in the thyroid gland. Types include:

  • Papillary
  • Follicular
  • Medullary
  • Anaplastic
365
Q

Aetiology/ Risk Factors of thyroid cancer

A

• UNKNOWN
• Risk Factors
o Childhood exposure to radiation
o Medullary thyroid cancers may be familial and are associated with MEN IIa or IIb
o Lymphoma is associated with Hashimoto’s thyroiditis

366
Q

Epidemiology of thyroid cancer

A
  • RARE
  • More common in FEMALES
  • Papillary: 20-40 yrs
  • Follicular: 40-50 yrs
  • Anaplastic: more common in the ELDERLY
367
Q

Presenting symptoms of thyroid cancer

A
  • Slow-growing neck lump
  • Discomfort swallowing
  • Hoarse voice
368
Q

Signs of thyroid cancer on physical examination

A
  • Palpable nodules or diffuse enlargement of thyroid gland
  • Cervical lymphadenopathy –> suspect malignancy
  • NOTE: the patient is usually euthyroid
369
Q

Investigations for thyroid cancer

A

• Bloods
o TFTs
o Bone profile
o Tumour Markers
• Thyroglobulin - papillary and follicular
• Calcitonin - medullary
• Fine-Needle Aspiration Cytology (FNA)
o Allows histological diagnosis • Excision Lymph Node Biopsy
o If there is cervical lymphadenopathy
• Isotope Scan
o If the cause of the thyroid lump is unclear
• CT/MRI - for staging

370
Q

Define Thyroid Nodules

A

Abnormal growth of thyroid cells that forms a lump in the thyroid gland

371
Q

Aetiology/ Risk factors of thyroid nodules

A
  • The vast majority of thyroid nodules are BENIGN, but a small proportion turn into thyroid cancer
  • Most thyroid nodules are adenomatous and most are multiple
  • The nodules are usually non-functioning
372
Q

Epidemiology of thyroid nodules

A
  • 40% of the general population have a single nodule or multiple nodules
  • More common in WOMEN
  • Very small proportion of thyroid nodules will be malignant
373
Q

Presenting symptoms of thyroid nodules

A

• Most are ASYMPTOMATIC
• Usually found on self-examination or clinical examination
• A single isolated nodule is more likely to be malignant
• They can sometimes cause pain and will rarely compress the trachea or cause
dysphagia

374
Q

Signs of thyroid nodules on physical examination

A
  • Ask the patient to drink some water and see if the nodule moves when swallowing
  • Check for regional lymphadenopathy (consider malignancy)
375
Q

Investigations for thyroid nodules

A
  • TFTs - most patients will be euthyroid
  • Ultrasound - useful for determining the character of the thyroid nodules
  • FNA - allows cytological analysis
  • Radionuclide Isotope Scanning - checks iodine uptake
  • CT/MRI - detect spread of thyroid cancer
376
Q

Define thyroiditis

A

Inflammation of the thyroid gland

377
Q

Aetiology/ Risk factors of thyroiditis

A

• Hashimoto’s thyroiditis - an autoimmune condition. The most common cause of
hypothyroidism in the UK.
• Other types of thyroiditis:
o de Quervain’s thyroiditis
o Postpartum thyroiditis
o Drug-induced thyroiditis
o Acute or infectious thyroiditis o Riedel’s thyroiditis
• Pathogenesis of Hashimoto’s thyroiditis
o Aggressive destruction of thyroid cells by the immune system
o Environmental triggers have been hypothesised (e.g. smoking, infection)

378
Q

Epidemiology of thyroiditis

A
  • True incidence is UNKNOWN
  • 15-20 x more common in WOMEN
  • Usually occurs in 30-50 yrs
379
Q

Presenting symptoms and signs of thyroiditis

A 
•  Symptoms of hypothyroidism  o  Fatigue  
o  Constipation  
o  Dry skin  
o  Weight gain  
o  Cold intolerance  
o  Menstrual irregularities   
o  Depression  
o  Hair loss  
•  Symptoms caused by rapid enlargement of the thyroid gland 
o  Dyspnoea   
o  Dysphagia   
o  Tenderness
380
Q

Investigations for thyroiditis

A 
•  Based on clinical observations  
•  Histology: diffuse lymphocytic and plasma cell infiltration with formation of lymphoid 
follicles  
•  TSH - raised  
•  Antibodies: 
o  Anti-TPO antibodies  
o  Anti-thyroglobulin antibodies  
•  Thyroid ultrasound  
•  Radionuclide isotope scanning
381
Q

Management plan for thyroiditis

A

• Pharmacological
o Thyroid hormone replacement - oral levothyroxine sodium
o Titrate dose based on patient’s needs
• Surgical
o Considered if there is a large goitre that is causing symptoms due to compression of surrounding structures or if there is a malignant nodule

382
Q

Complications of thyroiditis

A
  • Thyroid hormone overMreplacement –> bone loss + tachycardia
  • Hyperlipidaemia
  • Hashimoto’s encephalopathy
  • Myxoedema coma
383
Q

Prognosis for patients with thyroiditis

A

• GOOD PROGNOSIS with early diagnosis and levothyroxine replacement

384
Q

Define Vitamin D deficiency and osteomalacia

A

Osteomalacia is a disorder of mineralisation of bone matrix (osteoid). Rickets is a disorder of defective mineralisation of cartilage in the epiphyseal growth plates of children

385
Q

Aetiology/ risk factors for vitamin D deficiency and osteomalacia

A

• Risk Factors for Vitamin D Deficiency
o Lack of exposure to sunlight
o Dietary deficiency
o Malabsorption
o Decreased 25-hydroxylation of vitamin D (due to liver disease, anticonvulsants)
o Decrease 1alpha-hydroxylation of vitamin D (due to chronic kidney disease,
hypoparathyroidism)
o Vitamin D resistance
• Renal Phosphate Wasting
o Fanconi’s syndrome - characterised by:
• Phosphaturia
• Glycosuria
• Amino aciduria
o Renal tubular acidosis (type 2)
o Hereditary hypophosphataemic rickets (X-linked or autosomal dominant)
o Tumour induced osteomalacia

386
Q

Epidemiology of vitamin D deficiency and osteomalacia

A
  • COMMON in industrialised countries

* More common in FEMALES

387
Q

Presenting symptoms of vitamin D deficiency and osteomalacia

A 
•  Osteomalacia 
o  Bone pain (mainly in the axial skeleton)  
o  Weakness 
o  Malaise   
•  Rickets 
o  Hypotonia 
o  Growth retardation   
o  Skeletal deformities
388
Q

Signs of vitamin D deficiency and osteomalacia on physical examination

A

• Osteomalacia
o Bone tenderness
o Proximal muscle weakness o Waddling gait
o Signs of hypocalcaemia:
• Trousseau’s sign - inflation of a blood pressure cuff to above the systolic pressure for > 3 mins causes tetanic spasm of the wrist and fingers

• Chvostek’s sign - tapping over the facial nerve causes twitching of the
ipsilateral facial muscles

• Rickets
o Bossing of frontal and parietal bones
o Swelling of costochondral junctions (rickety rosary)
o Bow legs in early childhood
o ‘Knock knees’ in later childhood
o Short stature

389
Q

Investigations for vitamin D deficiency and osteomalacia

A

• Bloods
o Low or normal Ca2+
o Low phosphate
o High ALP
o Low 25-hydroxy vitamin D
o High PTH (secondary hyperparathyroidism)
o Check U&Es
o Check ABGs (for renal tubular acidosis)
o Increased phosphate excreting (in renal phosphate wasting)
• Radiographs
o May appear normal
o May show osteopaenia
o Looser’s zones = wide, transverse lucencies
traversing part way through a bone, usually at right angles to the involved cortex and are associated most frequently with osteomalacia and rickets (AKA pseudofractures)

• Bone biopsy after double tetracycline labelling
o Tetracycline is deposited at the mineralisation front as a band
o After two course of tetracycline (separated by a few days), the distance between
the bands of deposited tetracycline is reduced in osteomalacia o Not usually necessary for the diagnosis of osteomalacia

390
Q

Management plan for vitamin D deficiency and osteomalacia

A 
•  Vitamin D and calcium replacement   
•  Monitor 24 hr urinary calcium 
•  Also monitor: 
o  Serum calcium  
 o  Phosphate  
o  ALP 
o  PTH  
o  Vitamin D  
•  Treat the underlying CAUSE
391
Q

Complications of vitamin D deficiency and osteomalacia

A 
•  Bone deformities  
•  Hypocalcaemia can cause epileptic seizures   
•  Cardiac arrhythmias  
•  Hypocalcaemic tetany  
•  Depression  
•  Hypocalcaemia symptoms = CATs go NUMB 
o  Convulsions 
o  Arrhythmias 
o  Tetany 
o  NUMBness/paraesthesia
392
Q

Prognosis for patients with vitamin D deficiency and osteomalacia

A
  • Symptoms and radiological appearances improve with vitamin D treatment
  • Bone deformities in children tend to be permanent 9

Yr3 Med Conditions (9 decks)

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