Endocrine Flashcards
1
Q
Learning objectives
A
Answer
2
Q
Define acromegaly
A
• Constellation of signs and symptoms caused by hypersecretion of GH in adults
o Excess GH before puberty results in GIGANTISM
3
Q
Explain the aetiology/risk factors of acromegaly
A
- Most cases are caused by a GH-secreting pituitary adenoma
- RARELY caused by excess GHRH causing somatotroph hyperplasia from hypothalamic ganglioneuroma, bronchial carcinoid or pancreatic tumours
4
Q
Summarise the epidemiology of acromegaly
A
- RARE
- 5/1,000,000
- Age affected: 40-50 yrs
5
Q
Recognise the 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
6
Q
Recognise the 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
7
Q
Identify appropriate 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
8
Q
Generate a 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
9
Q
Identify possible 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
10
Q
Summarise the prognosis for patients with acromegaly
A
- GOOD with early diagnosis and treatment
* Physical changes are irreversible
11
Q
Define adrenal insufficiency
A
Deficiency of adrenal cortical hormones (e.g. mineralocorticoids, glucocorticoids and androgens)
12
Q
Explain the 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
13
Q
Summarise the epidemiology of adrenal insufficiency
A
- Most common cause is IATROGENIC
* Primary causes are rare
14
Q
Recognise the presenting symptoms of adrenal insufficiency
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)
15
Q
Recognise the 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
16
Q
Identify appropriate investigations for adrenal insufficiency and interpret the results
A
To confirm the diagnosis
9 am Serum Cortisol (< 100 nmol/L is diagnostic of adrenal insufficiency)
• > 550 nmol/L makes adrenal insufficiency unlikely
Short Synacthen Test
• IM 250 g 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
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 –> infection)
o U&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
17
Q
Generate a 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
18
Q
Identify the possible complications of adrenal insufficiency and its management
A
HYPERKALAEMIA
Death during Addisonian crisis
19
Q
Summarise the prognosis for patients with adrenal insufficiency
A
• Adrenal function rarely recovers • Normal life expectancy if treated Autoimmune Polyendocrine Syndrome Type 1 - autosomal recessive disorder caused by mutations in the AIRE gene. Consists of the following diseases: • Addison's disease • Chronic mucocutaneous candidiasis • Hypoparathyroidism Type 2 - also known as Schmidt's Syndrome • Addison's disease • Type 1 Diabetes • Hypothyroidism • Hypogonadism
20
Q
Define carcinoid syndrome
A
• Constellation of symptoms caused by systemic release of humoral factors from carcinoid tumours
21
Q
Explain the aetiology/risk factors of carcinoid syndrome
A
- Carcinoid tumours are slow-growing 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
22
Q
Summarise the 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
23
Q
Recognise the presenting symptoms of carcinoid syndrome
A
- Paroxysmal FLUSHING
- Diarrhoea
- Crampy abdominal pain
- Wheeze
- Sweating
- Palpitations
24
Q
Recognise the 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
25
Identify appropriate investigations for carcinoid syndrome
```
• 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
```
26
Define Cushing's syndrome
• Syndrome associated with chronic inappropriate elevation of free circulating cortisol
27
Explain the aetiology/risk factors for Cushing's syndrome
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
28
Summarise the epidemiology of Cushing's syndrome
* Incidence: 2-4/1,000,000 per year
| * Peak incidence 20-40 yrs
29
Recognise the presenting symptoms of Cushing's syndrome
* Increasing weight
* Fatigue
* Muscle weakness
* Myalgia
* Thin skin
* Easy bruising
* Poor wound healing
* Fractures
* Hirsuitism
* Acne
* Frontal balding
* Oligomenorrhoea/amenorrhoea
* Depression or psychosis
30
Recognise the signs of Cushing's syndrome on physical examination
* Moon face
* Facial plethora
* Interscapular 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
31
Identify appropriate investigations for Cushing's syndrome
• 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
32
Generate a management plan for Cushing's syndrome
• 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
33
Identify possible complications of Cushing's syndrome
```
• 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)
```
34
Summarise the prognosis for patients with Cushing's syndrome
* Untreated - 5 yr survival = 50%
| * Depression persists for many years following treatment
35
Define diabetes insipidus
• A disorder of inadequate secretion or of insensitivity to vasopressin (ADH) leading to hypotonic polyuria
36
Explain the aetiology/risk factors of diabetes insipidus
• 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)
37
Summarise the epidemiology of diabetes insipidus
* Median onset is 24 yrs
| * Depends on cause
38
Recognise the presenting symptoms of diabetes insipidus
```
• Polyuria
• Nocturia
• Polydipsia
• In children:
o Enuresis (bed-wetting)
o Sleep disturbance
• Other symptoms depend on aetiology
```
39
Recognise the signs of diabetes insipidus on physical examination
* 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)
40
Identify appropriate investigations for diabetes insipidus
• 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 - urine osmolality rises > 50% following administration of desmopressin
Nephrogenic - urine osmolality rises by < 45% following administration of desmopressin
41
Generate a management plan for diabetes insipidus
• 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
42
Identify possible complications of diabetes insipidus
* Hypernatraemic dehydration
| * Excess desmopressin --> hyponatraemia
43
Summarise the prognosis for patients with diabetes insipidus
* 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)
44
Define type 1 diabetes mellitus
• Metabolic hyperglycaemic condition caused by absolute insufficiency of pancreatic insulin production
45
Explain the aetiology/risk factors of type 1 diabetes mellitus
```
• 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
```
46
Summarise the epidemiology of type 1 diabetes mellitus
• 0.25% prevalence in the UK
47
Recognise the symptoms and signs of type 1 diabetes mellitus
```
• 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
```
48
Identify appropriate investigations for type 1 diabetes mellitus
• 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
49
Generate a management plan for type 1 diabetes mellitus
• 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 15-30 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
50
Identify possible complications of type 1 diabetes mellitus
```
• 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
```
51
Summarise the prognosis for patients with type 1 diabetes mellitus
* 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
52
Define type 2 diabetes mellitus
• Characterised by increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output
53
Explain the aetiology/risk factors of type 2 diabetes mellitus
• 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)
54
Summarise the epidemiology of type 2 diabetes mellitus
* 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
55
Recognise the presenting symptoms of type 2 diabetes mellitus
* 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
56
Recognise the signs of type 2 diabetes mellitus on physical examination
```
• 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)
57
Identify appropriate investigations for type 2 diabetes mellitus
• 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)
58
Generate a management plan for type 2 diabetes mellitus
• 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
59
Identify possible complications of type 2 diabetes mellitus
```
• 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 Microabuminuria
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
• Macrovascular complications:
o Ischaemic heart disease
o Stroke
o Peripheral vascular disease
```
60
Summarise the prognosis for patients with type 2 diabetes mellitus
• 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
61
Define diabetic ketoacidosis
Diabetic ketoacidosis is a serious complication of diabetes that occurs when your body produces high levels of blood acids called ketones.
The condition develops when your body can't produce enough insulin. Insulin normally plays a key role in helping sugar (glucose) — a major source of energy for your muscles and other tissues — enter your cells. Without enough insulin, your body begins to break down fat as fuel. This process produces a buildup of acids in the bloodstream called ketones, eventually leading to diabetic ketoacidosis if untreated.
62
Explain the aetiology / risk factors of diabetic ketoacidosis
The risk of diabetic ketoacidosis is highest if you:
Have type 1 diabetes
Frequently miss insulin doses
Stress of intercurrent illness
Common cause is omission of insulin because the patient feels unable to eat owing to nausea/vomiting
Uncommonly, diabetic ketoacidosis can occur if you have type 2 diabetes. In some cases, diabetic ketoacidosis may be the first sign that a person has diabetes.
63
Summarise the epidemiology of diabetic ketoacidosis
0-128 per 1000 people. Prevalence decreased with increasing age. High prevalence in women, non-whites and patients treated with insulin injections
64
Recognise the presenting symptoms of diabetic ketoacidosis
```
Excessive thirst
Frequent urination
Nausea and vomiting
Abdominal pain
Weakness or fatigue
Shortness of breath
Fruity-scented breath
Confusion
More-specific signs of diabetic ketoacidosis — which can be detected through home blood and urine testing kits — include:
```
High blood sugar level (hyperglycemia)
High ketone levels in your urine
65
Recognise the signs of diabetic ketoacidosis on physical examination
```
Ill appearance
Dry skin
Labored respiration
Dry mucous membranes
Decreased skin turgor
Decreased reflexes
Characteristic acetone (ketotic) breath odor
```
```
Effects on vital signs that are related to DKA may include the following:
Tachycardia
Hypotension
Tachypnea
Hypothermia
Fever, if infection is present
```
Specific signs of DKA may include the following:
Confusion
Coma
Abdominal tenderness
66
Identify appropriate investigations for diabetic ketoacidosis and interpret the results
Capillary blood glucose (remember to send a plasma glucose also).
Urine dipstick testing shows marked glycosuria and ketonuria (also send urine for microscopy and culture).
Assay of blood ketones is more sensitive and specific in detecting ketonaemia but is not always available.
Blood tests:
Plasma glucose will be elevated.
FBC - raised WCC is often seen but this does not necessarily indicate sepsis, as it may occur in DKA.
Electrolytes - Na+ may be high due to dehydration, low due to interference of glucose/ketones with assay, or normal; K+ may be high due to the effect of acidosis, normal or occasionally low but overall there is cell depletion of K+.
Urea and creatinine - elevated due to prerenal acute kidney injury or where renal impairment is the primary cause.
Arterial blood gases - metabolic acidosis with low pH and low HCO3; pCO2 should be normal but can be depressed by respiratory compensation; low pO2 may indicate a primary respiratory problem as a precipitant.
Cardiac enzymes - if myocardial ischaemia/infarction is suspected - eg, troponin.
Creatine kinase - rhabdomyolysis may also exist (also increased in myocardial infarction).
Amylase - if pancreatitis is suspected.
Blood cultures.
12-lead ECG.
CXR.
Abdominal X-ray - if indicated by history and examination.
CT/MRI scan of the head - if there is impairment of consciousness or focal neurology.
Lumbar puncture - may be indicated if meningitis is a possible precipitant.
67
Generate a management plan for diabetic ketoacidosis
• Replace fluid losses with normal saline
• Replace electrolyte losses:
o Potassium levels need to be monitored with great care
o Patients have a total body potassium deficit although initial plasma levels may not be low
o Insulin therapy leads to uptake of potassium by the cells with a consequent fall in plasma levels
o Potassium is, therefore, given as soon as insulin therapy is started
• Restore the acid-base balance:
o A patient with healthy kidneys will rapidly compensate for the metabolic acidosis once the circulating volume is restored
o Only consider bicarbonate if the pH is < 7
• Administer insulin:
o Soluble insulin is given as an IV infusion where facilities for adequate supervision exist, otherwise as hourly IM injections
o Do not give subcutaneously as the peripheral blood flow is reduced in a shocked patient
• Monitor blood glucose closely
• Replace the energy losses
• Seek the underlying cause (especially infection)
68
Identify the possible complications of diabetic ketoacidosis and its management
Problems of management:
• Hypotension:
o This may lead to renal failure. Give plasma expanders or whole blood if systolic BP < 80mmHg
• Coma:
o It is essential to pass a NG tube to prevent a drowsy patient aspirating when vomiting
• Cerebral oedema:
o Rare and believed to be due to excessive rehydration.
High mortality
• Hypothermia:
o Monitor patient’s temperature rectally to avoid this
• Late complications (e.g. stasis pneumonia and DVT)
69
Summarise the prognosis for patients with diabetic ketoacidosis
Mortality rates have fallen significantly in a period of 20 years - from 7.96% to 0.67%. The mortality rate is still high in developing countries and among non-hospitalised patients.
Prognosis worsens with age and the nature and severity of the underlying precipitating pathology (particularly myocardial infarction, sepsis and pneumonia).
The presence of coma at presentation, hypothermia or persistent oliguria are poor prognostic indicators.
Cerebral oedema remains the most common cause of mortality, particularly in young children and adolescents.
The main causes of mortality in the adult population include severe hypokalaemia, adult respiratory distress syndrome and comorbid states such as pneumonia, acute myocardial infarction and sepsis.
70
Define dyslipidaema (hypercholesterolaemia & hypertriglyceridaemia)
Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood.
71
Explain the aetiology / risk factors of dyslipidaema (hypercholesterolaemia & hypertriglyceridaemia)
Primary dyslipidemia
Blood sample being tested by lab technician.
Dyslipidemia can be diagnosed with a blood test.
Genetic factors cause primary dyslipidemia, and it is inherited. Common causes of primary dyslipidemia include:
Familial combined hyperlipidemia, which develops in teenagers and young adults and can lead to high cholesterol.
Familial hyperapobetalipoproteinemia, a mutation in a group of LDL lipoproteins called apolipoproteins.
Familial hypertriglyceridemia, which leads to high triglyceride levels.
Homozygous familial or polygenic hypercholesterolemia, a mutation in LDL receptors.
Secondary dyslipidemia
Secondary dyslipidemia is caused by lifestyle factors or medical conditions that interfere with blood lipid levels over time.
Common causes of secondary dyslipidemia include:
obesity, especially excess weight around the waist
diabetes
hypothyroidism
alcohol use disorder, also known as alcoholism
polycystic ovary syndrome
metabolic syndrome
excessive consumption of fats, especially saturated and trans fats
Cushing's syndrome
inflammatory bowel disease, commonly known as IBS
severe infections, such as HIV
an abdominal aortic aneurysm
Several factors are known to increase the chances of developing dyslipidemia and related conditions. These risk factors include:
```
obesity
a sedentary lifestyle
a lack of regular physical exercise
alcohol use
tobacco use
use of illegal or illicit drugs
sexually transmitted infections
type 2 diabetes
hypothyroidism
chronic kidney or liver conditions
digestive conditions
older age
a diet rich in saturated and trans fats
a parent or grandparent with dyslipidemia
female sex, as women tend to experience higher LDL levels after menopause
```
72
Summarise the epidemiology of dyslipidaema (hypercholesterolaemia & hypertriglyceridaemia)
In high-income countries, over 50% of adults had raised total cholesterol; more than double the level of the low-income countries.
73
Recognise the presenting symptoms & signs of dyslipidaema (hypercholesterolaemia & hypertriglyceridaemia)
Unless it is severe, most people with dyslipidemia are unaware that they have it. A doctor will usually diagnose dyslipidemia during a routine blood test or a test for another condition.
Severe or untreated dyslipidemia can lead to other conditions, including coronary artery disease (CAD) and peripheral artery disease (PAD).
Both CAD and PAD can cause serious health complications, including heart attacks and strokes. Common symptoms of these conditions include:
leg pain, especially when walking or standing
chest pain
tightness or pressure in the chest and shortness of breath
pain, tightness, and pressure in the neck, jaw, shoulders, and back
indigestion and heartburn
sleep problems and daytime exhaustion
dizziness
heart palpitations
cold sweats
vomiting and nausea
swelling in the legs, ankles, feet, stomach, and veins of the neck
fainting
These symptoms may get worse with activity or stress and get better when a person rests.
Anyone who experiences severe chest pain, dizziness, and fainting, or problems breathing should seek emergency care.
74
Identify appropriate investigations for dyslipidaema (hypercholesterolaemia & hypertriglyceridaemia) and interpret the results
The most common goals are:
Total cholesterol: Below 200 mg/dL
HDL cholesterol: Men - above 40 mg/dL; Women - above 50 mg/dL
LDL cholesterol: Below 100 mg/dL; Below 70 mg/dL for people with diabetes or heart disease.
Triglycerides: Below 150 mg/dL
75
Generate a management plan for dyslipidaema (hypercholesterolaemia & hypertriglyceridaemia)
A doctor will usually focus on lowering a person's levels of triglycerides and LDL. However, treatment can vary, depending on the underlying cause of dyslipidemia and how severe it is.
Doctors may prescribe one or more lipid-modifying medications for people with very high total cholesterol levels of at least 200 milligrams per deciliter of blood.
High cholesterol is usually treated with statins, which interfere with the production of cholesterol in the liver.
If statins fail to lower LDL and triglyceride levels, a doctor may recommend additional medications, including:
```
ezetimibe
niacin
fibrates
bile acid sequestrants
evolocumab and alirocumab
lomitapide and mipomersen
Some lifestyle changes and supplements can help to encourage healthy blood lipid levels.
```
Natural treatments include:
reducing the consumption of unhealthy fats, such as those found in red meats, full-fat dairy products, refined carbohydrates, chocolate, chips, and fried foods
exercising regularly
maintaining a healthy body weight, by losing weight if necessary
reducing or avoiding alcohol consumption
quitting smoking and other use of tobacco products
avoiding sitting for long periods of time
increasing consumption of healthy polyunsaturated fats, such as those found in nuts, seeds, legumes, fish, whole grains, and olive oil
taking omega-3 oil, either as a liquid or in capsules
eating plenty of dietary fiber from whole fruits, vegetables, and whole grains
getting at least 6– 8 hours of sleep a night
drinking plenty of water
76
Identify the possible complications of dyslipidaema (hypercholesterolaemia & hypertriglyceridaemia) and its management
People with minor dyslipidemia usually have no symptoms. They can often manage or resolve the condition by making lifestyle adjustments.
People with dyslipidemia should contact a doctor if they experience symptoms relating to the heart or circulation, including:
```
chest pains or tightness
dizziness
heart palpitations
exhaustion
swelling of the ankles and feet
trouble breathing
cold sweats
nausea and heartburn
People who have severe dyslipidemia, especially those with other medical conditions, may need to manage their blood lipid levels with medication, in addition to making lifestyle changes.
```
77
Summarise the prognosis for patients with dyslipidaema (hypercholesterolaemia & hypertriglyceridaemia)
Significantly reduced risk of CHD if managed well.
78
Define Graves disease
• 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.
79
Explain the aetiology/risk factors of Graves disease
```
• 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
```
80
Summarise the epidemiology of Graves disease
* Hyperthyroidism is COMMON
* Graves' is the most common cause of hyperthyroidism (75%)
* Rarely occurs in children
81
Recognise the presenting symptoms of Graves disease
* Weight loss despite increased appetite
* Irritability
* Weakness
* Diarrhoea
* Sweating
* Tremor
* Anxiety
* Heat intolerance
* Loss of libido
* Oligomenorrhoea/amenorrhoea
82
Recognise the signs of Graves disease on physical examination
* Palmar erythema
* Sweaty and warm palms
* Fine tremor
* Tachycardia (may be AF)
* Hair thinning
* Urticaria/pruritus
* Brisk reflexes
* Goitre
* Proximal myopathy
* Lid lag
* Gynaecomastia
83
Identify appropriate investigations for Graves disease
• 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
84
Define hyperparathyroidism
* 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
85
Explain the aetiology/risk factors of hyperparathyroidism
```
• Primary
o Parathyroid adenoma
o Parathyroid hyperplasia
o Parathyroid carcinoma
o MEN syndrome
• Secondary
o Chronic renal failure
o Vitamin D deficiency
```
86
Summarise the epidemiology of hyperparathyroidism
* Primary - incidence of 5/100,000
* Twice as common in FEMALES
* Peak incidence: 40-60 yrs
87
Recognise the presenting symptoms and signs of hyperparathyroidism
```
• 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)
```
88
Identify appropriate investigations for hyperparathyroidism
• 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
89
Generate a management plan for hyperparathyroidism
• 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
90
Identify possible complications of hyperparathyroidism
```
• Primary
o Increased bone resorption
o Increased tubular calcium reabsorption
o Increased 1-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
```
91
Summarise the prognosis for patients with hyperparathyroidism
* Primary - surgery is curative for benign disease in most cases
* Secondary or Tertiary - same prognosis as chronic renal failure
92
Define hypogonadism
• Characterised by impairment of ovarian function
93
Explain the aetiology/risk factors of hypogonadism
• 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
94
Summarise the epidemiology of hypogonadism
* Secondary hypogonadism is a more common cause of anovulation/amenorrhoea
* Turner's syndrome occurs in around 1.5% of conceptions
95
Recognise the presenting symptoms of hypogonadism
```
• 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
```
96
Recognise the signs of hypogonadism on physical examination
• 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 - 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)
```
97
Identify appropriate investigations for hypogonadism
• 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 pre-mature 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
98
Define hypogonadism
• A syndrome of decreased testosterone production, sperm production or both
99
Explain the aetiology/risk factors of hypogonadism
• 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 Rare causes: genetic mutations
o Prader-Willi syndrome (short, small hands, almond-shaped eyes, learning difficulty, postnatal hypotonia)
o Laurence-Moon-Biedl syndrome (obesity, polydactyly, retinitis pigmentosa, learning difficulty)
100
Summarise the epidemiology of hypogonadism
• Primary hypogonadism accounts for 30-40% of male infertility
o Most common cause: Klinefelter's Syndrome (XXY)
• Secondary hypogonadism accounts for 1-2%
101
Recognise the presenting symptoms of hypogonadism
* Delayed puberty
* Decreased libido
* Impotence
* Infertility
* Symptoms of underlying cause (e.g. Klinefelters --> intellectual dysfunction, behavioural abnormalities)
102
Recognise the signs of hypogonadism on physical examination
```
• 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)
```
103
Identify appropriate investigations for hypogonadism
```
• 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 - 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)
```
104
Define hypopituitarism
• Deficiency in one or more of the hormones secreted by the anterior pituitary. Panhypopituitarism is deficiency of ALL pituitary hormones.
105
Explain the aetiology/risk factors for hypopituitarism
• 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, over-exercise
• Infiltrative Diseases - sarcoidosis, haemochromatosis, Langerhans' cell histiocytosis
• Vascular - pituitary apoplexy, Sheehan's syndrome
• Infection - meningitis, encephalitis
• Genetic Mutations - Pit-1 and Prop-1 genes
106
Summarise the epidemiology of hypopituitarism
• Pituitary adenoma annual incidence: 1/100,000
107
Recognise the signs and symptoms of hypopituitarism
• 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
108
Identify appropriate investigations for hypopituitarism
```
• 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
```
109
Generate a management plan for hypopituitarism
```
• 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)
```
110
Identify possible complications of hypopituitarism
```
• 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
```
111
Summarise the prognosis for patients with hypopituitarism
• GOOD prognosis with lifelong treatment
112
Define hypothyroidism
• The clinical syndrome resulting from insufficiency secretion of thyroid hormones
113
Explain the aetiology/risk factors of hypothyroidism
• 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
114
Summarise the epidemiology of hypothyroidism
* 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)
115
Recognise the presenting symptoms of hypothyroidism
```
• 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
```
116
Recognise the signs of hypothyroidism on physical examination
```
• 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
```
117
Identify appropriate investigations for hypothyroidism
```
• Bloods
o TFTs
o FBC - may show normocytic anaemia
o U&Es - may show low sodium
o Cholesterol - may be high
```
118
Generate a management plan for hypothyroidism
• 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)
119
Identify possible complications of hypothyroidism
* Myxoedema coma
| * Myxoedema madness (psychosis with delusions and hallucinations or dementia)
120
Summarise the prognosis for patients with hypothyroidism
* Lifelong levothyroxine is required
| * Myxoedema coma mortality = 80%
121
Define multiple endocrine neoplasia
• An autosomal dominant condition characterised by a predilection to develop tumours of endocrine glands.
122
Explain the aetiology/risk factors of MEN
```
• Autosomal dominant inheritance
• Patterns of features:
o MEN 1
• 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
• Parathyroid tumours
• Medullary thyroid cancer
• Phaeochromocytomas
o MEN 2b
• Same as MEN 2a
• Marfanoid appearance
• Neuromas of the GI tract
```
123
Summarise the epidemiology of MEN
• VERY RARE
124
Recognise the presenting symptoms and signs of MEN
• 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
125
Identify appropriate investigations for MEN
• MEN 1
o Screening first or second degree relatives
o Hormone hypersecretion blood tests
o DNA testing
• MEN 2
o Phaeochromocytoma test - 24 hr 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
126
Define obesity
```
• A BMI > 30 kg/m2
o Can also be defined using waist circumference:
• Men
Low Risk = < 94 cm
Very High Risk = > 102 cm
• Women
Low Risk = < 80 cm
Very High Risk = > 88 cm
```
127
Explain the aetiology/risk factors of obesity
* 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
128
Summarise the epidemiology of obesity
• 24% of men and 25% of women are obese
129
Recognise the presenting symptoms and signs of obesity
* Noticing a high body habitus
* Routine health check
* Symptoms of complications (e.g. T2DM, coronary heart disease, obstructive sleep apnoea)
* High body weight, BMI and waist circumference
130
Identify appropriate investigations for obesity
* Measure serum lipids
* Measure HbA1c
* Hormone profile (check for hormonal cause of obesity)
* TFTs - hypothyroidism can cause obesity
* Other investigations depending on comorbidities
131
Define vitamin D deficiency and osteomalacia
• Osteomalacia is a disorder of mineralisation of bone matrix (osteoid)
o Rickets is a disorder of defective mineralisation of cartilage in the epiphyseal growth plates of children
132
Explain the aetiology/risk factors of vitamin D deficiency and osteomalacia
```
• 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 1-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
```
133
Summarise the epidemiology of vitamin D deficiency and osteomalacia
* COMMON in industrialised countries
| * More common in FEMALES
134
Recognise the presenting symptoms of vitamin D deficiency and osteomalacia
```
• Osteomalacia
o Bone pain (mainly in the axial skeleton)
o Weakness
o Malaise
• Rickets
o Hypotonia
o Growth retardation
o Skeletal deformities
```
135
Recognise the signs of vitamin D deficiency and osteomalacia on physical examination
```
• 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
```
136
Identify appropriate investigations for vitamin D deficiency and osteomalacia
• 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
137
Generate a management plan for vitamin D deficiency and osteomalacia
```
• 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
```
138
Identify possible complications of vitamin D deficiency and osteomalacia
```
• 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
```
139
Summarise the prognosis for patients with vitamin D deficiency and osteomalacia
* Symptoms and radiological appearances improve with vitamin D treatment
* Bone deformities in children tend to be permanent
140
Define osteoporosis
• 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
141
Explain the aetiology/risk factors of osteoporosis
```
• 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
```
142
Summarise the epidemiology of osteoporosis
```
• COMMON
• In > 50 yrs
o Females: 1/3
o Males: 1/12
• More common in CAUCASIANS than Afro-Caribbeans
```
143
Recognise the presenting symptoms of osteoporosis
• 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)
144
Recognise the signs of osteoporosis on physical examination
• 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 NOF fracture)
145
Identify appropriate investigations for osteoporosis
• 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 age-matched mean bone mineral density. Z-score may be helpful in identifying patients who may need a work-up for secondary causes of osteoporosis
146
Define Paget's disease of bone
• Characterised by excessive bone remodelling at one (monostotic) or more (polyostotic) sites resulting in bone that is structurally disorganised
147
Explain the aetiology/risk factors of Paget's disease
* 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
148
Summarise the epidemiology of Paget's disease
* Common in ELDERLY
* 3% of > 50 yrs
* 10% of > 80 yrs
* Males = Females
149
Recognise the presenting symptoms of Paget's disease
* May be ASYMPTOMATIC
* May present with insidious onset pain, which is aggravated by weight bearing and movement
* Headaches
* Deafness
* Increasing skull size
150
Recognise the signs of Paget's disease on physical examination
* 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)
151
Identify appropriate investigations for Paget's disease
```
• 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
```
152
Define phaeochromocytoma
• Catecholamine-producing tumours that usually arise from chromaffin cells of the adrenal medulla but are extra-adrenal in about 10% of cases.
o 10% are bilateral
o 10% are malignant
o Extra-adrenal phaeochromocytomas are referred to as paragangliomas
153
Explain the aetiology/risk factors of phaeochromocytoma
• 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
154
Summarise the epidemiology of phaeochromocytoma
* RARE
| * < 0.2% of hypertensive patients
155
Recognise the presenting symptoms of patients with phaeochromocytoma
```
• 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
```
156
Recognise the signs of phaeochromocytoma on physical examination
* Hypertension
* Postural hypotension
* Pallor
* Tachycardia
* Fever
* Weight loss
157
Identify appropriate investigations for phaeochromocytoma
• 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
158
Define non-functioning pituitary tumours
• Benign tumours of the pituitary gland formed from pituitary cells that do not produce any active pituitary hormones.
159
Explain the aetiology/risk factors of non-functioning pituitary tumours
* No specific cause
| * Can occur as a part of MEN 1 syndrome
160
Summarise the epidemiology of non-functioning pituitary tumours
* Most common type of macroadenoma (> 1 cm)
| * Most common type of pituitary tumour in patients > 60 yrs
161
Recognise the presenting symptoms and signs of non-functioning pituitary tumours
• 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
162
Identify appropriate investigations for non-functioning pituitary tumours
* MRI
* CT
* Bloods - check hormone levels
* Visual fields testing
163
Define polycystic ovarian syndrome
```
• Characterised by oligomenorrhoea/amenorrhoea and hyperandrogenism (clinical or biochemical). Frequently associated with:
o Obesity
o Insulin resistance
o Type 2 diabetes mellitus
o Dyslipidaemia
```
164
Explain the aetiology/risk factors of polycystic ovarian syndrome
* 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)
165
Summarise the epidemiology of polycystic ovarian syndrome
* PCOS is the MOST COMMON cause of infertility in women
| * Affects 6-8% of women
166
Recognise the presenting symptoms of polycystic ovarian syndrome
```
• Menstrual irregularities
• Dysfunctional uterine bleeding
• Infertility
• Symptoms of hyperandrogenism:
o Hirsuitism
o Male-pattern hair loss
o Acne
```
167
Recognise the signs of polycystic ovarian syndrome on physical examination
* 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
168
Identify appropriate investigations for polycystic ovarian syndrome
• 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
169
Define primary hyperaldosteronism
• Characterised by autonomous aldosterone overproduction from the adrenal gland with subsequent suppression of plasma renin activity
170
Explain the aetiology/risk factors of primary hyperaldosteronism
• 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
171
Summarise the epidemiology of primary hyperaldosteronism
* 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
172
Recognise the presenting symptoms of primary hyperaldosteronism
• 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
173
Recognise the signs of primary hyperaldosteronism on physical examination
* Hypertension
| * Complications of hypertension (e.g. hypertensive retinopathy)
174
Identify appropriate investigations for primary hyperaldosteronism
• 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
175
Generate a management plan for primary hyperaldosteronism
• 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)
176
Identify possible complications of primary hyperaldosteronism
• Complications of hypertension
177
Summarise the prognosis for patients with primary hyperaldosteronism
* Surgery may cure hypertension
| * Or it may make the hypertension easier to treat with anti-hypertensive medication
178
Define prolactinoma
• A pituitary adenoma that overproduces prolactin
179
Explain the aetiology/risk factors of prolactinoma
• 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
180
Summarise the epidemiology of prolactinoma
* Relatively common
| * Higher incidence in premenopausal women
181
Recognise the presenting symptoms and signs of prolactinoma on physical examination
```
• 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
```
182
Identify appropriate investigations for prolactinoma
* 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
183
Generate a management plan for prolactinoma
```
• 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
```
184
Identify possible complications of prolactinoma
```
• 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
```
185
Summarise the prognosis for patients with prolactinoma
* 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
186
Define SIADH
• Characterised by continued secretion of ADH, despite the absence of normal stimuli for secretion (i.e. increased serum osmolality or decreased blood volume)
187
Explain the aetiology/risk factors of SIADH
```
• 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
```
188
Summarise the epidemiology of SIADH
* Hyponatraemia is the MOST COMMON electrolyte imbalance seen in hospital
* < 50% of severe hyponatraemia is caused by SIADH
189
Recognise the presenting symptoms of SIADH
* Mild hyponatraemia may be ASYMPTOMATIC
* Headache
* Nausea/vomiting
* Muscle cramp/weakness
* Irritability
* Confusion
* Drowsiness
* Convulsions
* Coma
* Symptoms of underlying cause
190
Recognise the signs of SIADH on physical examination
```
• 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+
```
191
Identify appropriate investigations for SIADH
• 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)
192
Generate a management plan for SIADH
* Treat underlying cause
* Fluid restriction
* Vasopressin receptor antagonists (e.g. tolvaptan)
* In SEVERE cases - slow IV hypertonic saline and furosemide with close monitoring
193
Identify possible complications of SIADH
```
• Convulsions
• Coma
• Death
• Central pontine myelinolysis - occurs with rapid correction of hyponatraemia
o Characterised by:
• Quadriparesis
• Respiratory arrest
• Fits
```
194
Summarise the prognosis for patients with SIADH
Depends on the CAUSE
• Na+ < 110 mmol/L is associated with a HIGH MORBIDITY and MORTALITY
• 50% mortality with central pontine myelinolysis
195
Define thyroid cancer
```
• Malignancy arising in the thyroid gland. Types include:
o Papillary
o Follicular
o Medullary
o Anaplastic
```
196
Explain the aetiology/risk factors of thyroid cancer
• 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
197
Summarise the epidemiology of thyroid cancer
* RARE
* More common in FEMALES
* Papillary: 20-40 yrs
* Follicular: 40-50 yrs
* Anaplastic: more common in the ELDERLY
198
Recognise the presenting symptoms of thyroid cancer
* Slow-growing neck lump
* Discomfort swallowing
* Hoarse voice
199
Recognise the signs of thyroid cancer on physical examination
* Palpable nodules or diffuse enlargement of thyroid gland
* Cervical lymphadenopathy --> suspect malignancy
* NOTE: the patient is usually euthyroid
200
Identify appropriate investigations for thyroid cancer
```
• 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
```
201
Define thyroid nodules
• Abnormal growth of thyroid cells that forms a lump in the thyroid gland.
202
Explain the aetiology/risk factors of thyroid nodules
* 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
203
Summarise the epidemiology of thyroid nodules
* 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
204
Recognise the presenting symptoms of thyroid nodules
* 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
205
Recognise the signs of thyroid nodules on physical examination
* Ask the patient to drink some water and see if the nodule moves when swallowing
* Check for regional lymphadenopathy (consider malignancy)
206
Identify appropriate investigations for thyroid nodules
* 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
207
Define thyroiditis
• Inflammation of the thyroid gland.
208
Explain the aetiology/risk factors of thyroiditis
• 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)
209
Summarise the epidemiology of thyroiditis
* True incidence is UNKNOWN
* 15-20 x more common in WOMEN
* Usually occurs in 30-50 yrs
210
Recognise the presenting symptoms and signs of thyroiditis
```
• 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
```
211
Identify appropriate investigations for thyroiditis
```
• 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
```
212
Generate a management plan for thyroiditis
• 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
213
Identify possible complications of thyroiditis
* Thyroid hormone over-replacement --> bone loss + tachycardia
* Hyperlipidaemia
* Hashimoto's encephalopathy
* Myxoedema coma
214
Summarise the prognosis for patients with thyroiditis
• GOOD PROGNOSIS with early diagnosis and levothyroxine replacement
