Master CPS - Endocrinology/Metabolic
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Core Concepts
Endocrinology involves the intricate system of glands and hormones regulating vital bodily functions, including metabolism, growth, reproduction, and stress response. Key glands like the pituitary, thyroid, adrenals, and pancreas produce hormones essential for homeostasis. Metabolic disorders primarily focus on imbalances in glucose, lipid, and electrolyte metabolism. Dysregulation in these systems can lead to both underproduction (hypo-) or overproduction (hyper-) states, often presenting with systemic symptoms.
Clinical Presentation
- Diabetes Mellitus (DM)
- Type 1: Polyuria, polydipsia, weight loss, fatigue. Can present acutely with Diabetic Ketoacidosis (DKA) – abdominal pain, Kussmaul breathing, altered mental status.
- Type 2: Often asymptomatic, fatigue, recurrent infections, slow wound healing. Can present with Hyperosmolar Hyperglycaemic State (HHS) – extreme dehydration, confusion, hyperosmolarity.
- Thyroid Disorders
- Hypothyroidism: Fatigue, weight gain, cold intolerance, constipation, bradycardia, dry skin, hair loss.
- Hyperthyroidism (Thyrotoxicosis): Weight loss, heat intolerance, palpitations, tremor, anxiety, diarrhoea, exophthalmos (Graves' disease), goitre.
- Adrenal Disorders
- Addison's Disease (Primary Adrenal Insufficiency): Fatigue, weakness, weight loss, postural hypotension, hyperpigmentation. Adrenal Crisis: severe hypotension, hypoglycaemia.
- Cushing's Syndrome (Hypercortisolism): Central obesity, moon face, buffalo hump, purple striae, hypertension, hyperglycaemia, muscle weakness.
- Phaeochromocytoma: Paroxysmal hypertension (classic triad: headache, palpitations, sweating), anxiety.
- Calcium Disorders
- Hypercalcaemia: "Stones, bones, groans, psychiatric moans" (renal stones, bone pain, abdominal pain, lethargy/confusion), polyuria, polydipsia.
- Hypocalcaemia: Perioral numbness/tingling, muscle cramps/spasms, Chvostek's sign, Trousseau's sign, tetany, seizures.
- Pituitary Disorders
- Acromegaly: Gradual enlargement of hands/feet/jaw, coarse facial features, joint pain, sweating, headaches, visual field defects (bitemporal hemianopia).
- Prolactinoma: Galactorrhoea, amenorrhoea (females), impotence (males), headaches, visual field defects.
- SIADH (Syndrome of Inappropriate ADH Secretion): Euvolvaemic hyponatremia, confusion, weakness, seizures.
- Diabetes Insipidus (DI): Polyuria, polydipsia, hypernatremia (if unable to drink).
Diagnosis (Gold Standard)
DM: Fasting plasma glucose ≥7.0 mmol/L, random plasma glucose ≥11.1 mmol/L (with symptoms), HbA1c ≥48 mmol/mol (6.5%). Type 1: GAD antibodies, low C-peptide.
Hypothyroidism: High TSH, low free T4.
Hyperthyroidism: Low TSH, high free T4/T3. Graves' disease: TSH receptor antibodies (TRABs).
Addison's: Short synacthen test (low cortisol response), high ACTH.
Cushing's: Overnight dexamethasone suppression test (failure to suppress cortisol), 24-hr urinary free cortisol.
Phaeochromocytoma: 24-hr urinary or plasma free metanephrines/normetanephrines.
Hypercalcaemia: Corrected calcium >2.6 mmol/L, intact PTH levels.
Hypocalcaemia: Corrected calcium <2.1 mmol/L, PTH levels.
Acromegaly: IGF-1 (elevated), Oral Glucose Tolerance Test (failure to suppress GH).
Prolactinoma: High serum prolactin, MRI pituitary.
SIADH: Euvolvaemic hyponatremia, high urine osmolality, low serum osmolality.
DI: Water deprivation test.
Management (First Line)
DM: Type 1: Insulin replacement. Type 2: Lifestyle, Metformin, SGLT2 inhibitors/GLP-1 analogues, insulin. DKA/HHS: IV fluids, insulin infusion, electrolyte correction.
Hypothyroidism: Levothyroxine.
Hyperthyroidism: Beta-blockers (symptomatic), Carbimazole/Propylthiouracil, radioiodine, surgery. Thyroid storm: Propylthiouracil, iodine, beta-blocker, hydrocortisone.
Addison's: Hydrocortisone, Fludrocortisone. Adrenal Crisis: IV hydrocortisone, IV fluids.
Cushing's: Surgical resection (transsphenoidal for pituitary adenoma), medical therapy (e.g., Ketoconazole).
Phaeochromocytoma: Alpha-blockade then beta-blockade, prior to surgical resection.
Hypercalcaemia: IV fluids (saline), Bisphosphonates.
Hypocalcaemia: IV calcium gluconate (acute), oral calcium/Vit D (chronic).
Acromegaly/Prolactinoma: Surgical resection, medical therapy (e.g., Dopamine agonists for prolactinoma, Somatostatin analogues for acromegaly).
SIADH: Fluid restriction, treat underlying cause, Tolvaptan.
DI: Desmopressin (central DI), Thiazide diuretics (nephrogenic DI).
Exam Red Flags
- Acute Adrenal Crisis: Hypotension, hypovolaemic shock, hypoglycaemia, severe abdominal pain. Requires immediate IV hydrocortisone and fluids.
- DKA/HHS: Metabolic emergencies requiring prompt IV fluids, insulin, and electrolyte correction.
- Thyroid Storm/Myxoedema Coma: Life-threatening exacerbations of hyper/hypothyroidism. Look for marked alteration in consciousness, fever, tachycardia (storm) or hypothermia, bradycardia (coma).
- Severe Hypercalcaemia: Risk of cardiac arrhythmias, coma. Aggressive hydration is crucial.
- Phaeochromocytoma Crisis: Sudden, severe hypertension with headache, palpitations, sweating. Rule out before surgery or starting beta-blockers alone.
- Hyponatremia with neurological symptoms: Consider SIADH vs. adrenal insufficiency. Rapid correction can cause osmotic demyelination syndrome.
- Visual field defects (bitemporal hemianopia): Always raises suspicion for pituitary mass affecting the optic chiasm.
Sample Practice Questions
A 68-year-old male is found to have an elevated serum calcium level of 2.9 mmol/L (normal range 2.1-2.6 mmol/L) during routine blood work. He reports mild fatigue and increased thirst. Subsequent investigations reveal a parathyroid hormone (PTH) level of 9.5 pmol/L (normal range 1.6-6.9 pmol/L) and a serum phosphate of 0.8 mmol/L (normal range 0.8-1.4 mmol/L). What is the most likely diagnosis?
A 58-year-old man is admitted to the Intensive Care Unit following a subarachnoid haemorrhage. Three days post-admission, he becomes increasingly confused. His urine output is consistently low, and routine blood tests show a serum sodium of 118 mmol/L. His serum osmolality is 245 mOsm/kg, and urine osmolality is 450 mOsm/kg. His volume status appears euvolaemic, and his blood pressure is stable.
A 22-year-old male with Type 1 Diabetes Mellitus presents to the emergency department with a 12-hour history of severe polyuria, polydipsia, abdominal pain, nausea, and vomiting. He appears dehydrated, his breath smells of ketones, and he is hyperventilating (Kussmaul breathing). Capillary blood glucose is 28 mmol/L. Urine dipstick is strongly positive for ketones. Arterial blood gas shows pH 7.15, PaCO2 2.5 kPa, Bicarbonate 8 mmol/L. What is the most immediate and critical management step?
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