Endocrine Flashcards
Learning objectives
Answer
Define acromegaly
• Constellation of signs and symptoms caused by hypersecretion of GH in adults
o Excess GH before puberty results in GIGANTISM
Explain the aetiology/risk factors of acromegaly
- 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
Summarise the epidemiology of acromegaly
- RARE
- 5/1,000,000
- Age affected: 40-50 yrs
Recognise the presenting symptoms of acromegaly
• 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
Recognise the signs of acromegaly on physical examination
• 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
Identify appropriate investigations for acromegaly
• 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
Generate a management plan for acromegaly
• 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
Identify possible complications of acromegaly
• 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
Summarise the prognosis for patients with acromegaly
- GOOD with early diagnosis and treatment
* Physical changes are irreversible
Define adrenal insufficiency
Deficiency of adrenal cortical hormones (e.g. mineralocorticoids, glucocorticoids and androgens)
Explain the aetiology / risk factors of adrenal insufficiency
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
Summarise the epidemiology of adrenal insufficiency
- Most common cause is IATROGENIC
* Primary causes are rare
Recognise the presenting symptoms of adrenal insufficiency
• 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)
Recognise the signs of adrenal insufficiency on physical examination
• 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
Identify appropriate investigations for adrenal insufficiency and interpret the results
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
Generate a management plan for adrenal insufficiency
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
Identify the possible complications of adrenal insufficiency and its management
HYPERKALAEMIA
Death during Addisonian crisis
Summarise the prognosis for patients with adrenal insufficiency
• 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
Define carcinoid syndrome
• Constellation of symptoms caused by systemic release of humoral factors from carcinoid tumours
Explain the aetiology/risk factors of carcinoid syndrome
- 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
Summarise the epidemiology of carcinoid syndrome
- RARE
- UK incidence : 1/1,000,000
- Asymptomatic carcinoid tumours are more common
- 10% of patients with MEN-1 have carcinoid tumours
Recognise the presenting symptoms of carcinoid syndrome
- Paroxysmal FLUSHING
- Diarrhoea
- Crampy abdominal pain
- Wheeze
- Sweating
- Palpitations
Recognise the signs of carcinoid syndrome on physical examination
• 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
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
Define Cushing’s syndrome
• Syndrome associated with chronic inappropriate elevation of free circulating cortisol
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
Summarise the epidemiology of Cushing’s syndrome
- Incidence: 2-4/1,000,000 per year
* Peak incidence 20-40 yrs
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
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
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
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
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)
Summarise the prognosis for patients with Cushing’s syndrome
- Untreated - 5 yr survival = 50%
* Depression persists for many years following treatment
Define diabetes insipidus
• A disorder of inadequate secretion or of insensitivity to vasopressin (ADH) leading to hypotonic polyuria
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)
Summarise the epidemiology of diabetes insipidus
- Median onset is 24 yrs
* Depends on cause
Recognise the presenting symptoms of diabetes insipidus
• Polyuria • Nocturia • Polydipsia • In children: o Enuresis (bed-wetting) o Sleep disturbance • Other symptoms depend on aetiology
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)
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
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
Identify possible complications of diabetes insipidus
- Hypernatraemic dehydration
* Excess desmopressin –> hyponatraemia
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)
Define type 1 diabetes mellitus
• Metabolic hyperglycaemic condition caused by absolute insufficiency of pancreatic insulin production
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
Summarise the epidemiology of type 1 diabetes mellitus
• 0.25% prevalence in the UK
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
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
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
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
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
Define type 2 diabetes mellitus
• Characterised by increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output
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)
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
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
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)
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)
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
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
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
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.
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.
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
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
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
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.
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)
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)
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.
Define dyslipidaema (hypercholesterolaemia & hypertriglyceridaemia)
Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood.
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
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.
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.
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
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
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.
Summarise the prognosis for patients with dyslipidaema (hypercholesterolaemia & hypertriglyceridaemia)
Significantly reduced risk of CHD if managed well.
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.
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
Summarise the epidemiology of Graves disease
- Hyperthyroidism is COMMON
- Graves’ is the most common cause of hyperthyroidism (75%)
- Rarely occurs in children
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
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
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
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
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
