Master Endocrinology
for MRCP Part 1

Core Concepts

Endocrinology involves the study of glands, hormones, and their effects on the body, primarily through negative feedback loops regulating homeostasis. Key axes include the Hypothalamic-Pituitary-Adrenal (HPA), Hypothalamic-Pituitary-Thyroid (HPT), and Hypothalamic-Pituitary-Gonadal (HPG) axes. Endocrine disorders arise from hormone deficiency (e.g., hypothyroidism), excess (e.g., Cushing's), or receptor insensitivity (e.g., Type 2 Diabetes). Hormones act on target cells, regulating metabolism, growth, reproduction, and stress responses. Understanding the interplay and feedback mechanisms is crucial for diagnosis and management.

Clinical Presentation

• Diabetes Mellitus (Type 1 & 2): Polydipsia, polyuria, polyphagia, weight changes (loss in T1, gain in T2), blurred vision, recurrent infections. DKA: Kussmaul breathing, abdominal pain, fruity breath. HONK: Severe dehydration, altered mental status.
• Hypothyroidism: Fatigue, weight gain, cold intolerance, constipation, bradycardia, dry skin, hair loss, menorrhagia, puffy face (myxoedema).
• Hyperthyroidism (e.g., Graves'): Weight loss, heat intolerance, palpitations, tremor, anxiety, diarrhoea, brisk reflexes, goitre. Graves' specific: exophthalmos, pretibial myxoedema.
• Addison's Disease (Primary Adrenal Insufficiency): Chronic fatigue, weight loss, anorexia, postural hypotension, hyperpigmentation (skin/mucosa), GI symptoms (nausea, vomiting), hyponatraemia, hyperkalaemia. Crisis: Acute shock, severe abdominal pain.
• Cushing's Syndrome: Central obesity, moon facies, buffalo hump, purple striae, hypertension, hyperglycaemia, hypokalaemia, proximal myopathy, easy bruising, hirsutism.
• Phaeochromocytoma: Paroxysmal or sustained hypertension, headache, palpitations, sweating (the classic triad). Anxiety, tremor.
• Primary Hyperaldosteronism (Conn's Syndrome): Hypertension (often resistant), hypokalaemia (weakness, polyuria, nocturia), metabolic alkalosis.
• Hyperparathyroidism (Primary): "Stones, bones, abdominal groans, psychiatric overtones." Recurrent renal stones, bone pain/osteoporosis, abdominal pain, fatigue, depression.
• Hypoparathyroidism: Hypocalcaemia symptoms: Tetany, perioral numbness, paraesthesia, muscle cramps, positive Chvostek's/Trousseau's signs.
• Acromegaly: Gradual onset. Enlargement of hands/feet, coarsening facial features, prognathism, excessive sweating, headaches, hypertension, diabetes, arthralgia.
• Prolactinoma: Females: Galactorrhoea, amenorrhoea/oligomenorrhoea, infertility. Males: Erectile dysfunction, decreased libido, galactorrhoea (less common). Macroadenoma: Headaches, visual field defects (bitemporal hemianopia).
• Diabetes Insipidus (DI): Polyuria (dilute urine), polydipsia, nocturia.
• SIADH: Symptoms of hyponatraemia (nausea, vomiting, headache, confusion, seizures, coma), but euvolaemic.

Diagnosis (Gold Standard)

Diabetes: Fasting plasma glucose ≥7.0 mmol/L, OGTT 2-hour value ≥11.1 mmol/L, or HbA1c ≥48 mmol/mol (6.5%). Thyroid disorders: TSH, Free T4/T3. Autoantibodies (TPOAb for Hashimoto's, TRAb for Graves'). Addison's: Short Synacthen Test (ACTH stimulation test) showing inadequate cortisol response. Cushing's: Initial screening with 24-hour urinary free cortisol (x2), overnight 1mg dexamethasone suppression test, or late-night salivary cortisol. Low-dose DST for confirmation; high-dose DST and ACTH levels for differentiation. Phaeochromocytoma: 24-hour urinary fractionated metanephrines and normetanephrines or plasma free metanephrines. Conn's: Aldosterone-Renin Ratio (ARR) followed by confirmatory tests (e.g., saline suppression test). Adrenal CT for localisation. Hyperparathyroidism: Elevated PTH with hypercalcaemia. Hypoparathyroidism: Low PTH with hypocalcaemia. Acromegaly: Elevated IGF-1, confirmed by failure of GH suppression during an oral glucose tolerance test (OGTT). Prolactinoma: Persistently elevated serum prolactin; pituitary MRI for tumour visualisation. DI: Water deprivation test, measuring urine osmolality response to fluid restriction and desmopressin. SIADH: Hyponatraemia (plasma Na <135 mmol/L), low plasma osmolality (<275 mOsm/kg), high urine osmolality (>100 mOsm/kg), euvolaemia, and normal adrenal/thyroid function.

Management (First Line)

Diabetes T1: Lifelong insulin replacement (basal-bolus regimen). Diabetes T2: Lifestyle modifications + Metformin. SGLT2 inhibitors or GLP-1 receptor agonists often added for cardiovascular/renal benefits. Hypothyroidism: Levothyroxine replacement. Hyperthyroidism: Antithyroid drugs (Carbimazole/Propylthiouracil), beta-blockers for symptomatic control. Radioiodine therapy or surgery (thyroidectomy) are definitive options. Addison's: Glucocorticoid (Hydrocortisone) and mineralocorticoid (Fludrocortisone) replacement. Acute crisis: IV hydrocortisone and aggressive fluid resuscitation. Cushing's: Surgical resection of the underlying tumour (transsphenoidal for pituitary adenoma). Medications (e.g., Metyrapone, Ketoconazole) for pre-operative control or in inoperable cases. Phaeochromocytoma: Pre-operative alpha-blockade (e.g., Phenoxybenzamine) followed by beta-blockade, then surgical resection. Conn's: Unilateral adrenalectomy for adenoma; mineralocorticoid receptor antagonists (Spironolactone/Eplerenone) for bilateral adrenal hyperplasia. Hyperparathyroidism (Primary): Parathyroidectomy for symptomatic patients or those meeting specific criteria. Hypoparathyroidism: Calcium and active Vitamin D (Alfacalcidol). Acromegaly: Transsphenoidal surgery. Somatostatin analogues (Octreotide, Lanreotide) or GH receptor antagonists (Pegvisomant) if surgery fails or contraindicated. Prolactinoma: Dopamine agonists (Cabergoline, Bromocriptine) are first-line for most tumours. Surgery if medical therapy fails or for macroadenomas causing compression that doesn't resolve. Central DI: Desmopressin (synthetic ADH). Nephrogenic DI: Thiazide diuretics, NSAIDs (e.g., Indomethacin), low sodium diet. SIADH: Fluid restriction. Demeclocycline (for chronic/severe cases). Vaptans (e.g., Tolvaptan) in selected cases.