Master Endocrinology & Diabetes
for PLAB 1

Core Concepts

Endocrinology involves the study of glands that secrete hormones directly into the bloodstream to regulate various bodily functions. Key concepts include feedback loops (negative and positive), hormone synthesis, transport, and action. Disorders arise from hormone excess, deficiency, or receptor dysfunction. Diabetes Mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both. Type 1 DM (T1DM) is an autoimmune destruction of pancreatic beta cells, while Type 2 DM (T2DM) involves insulin resistance and progressive beta cell dysfunction.

Clinical Presentation

• Diabetes Mellitus:
  • Polydipsia, polyuria, polyphagia, unexplained weight loss (T1DM often acute).
  • Fatigue, blurred vision, recurrent infections (e.g., thrush, UTIs), slow wound healing.
  • Diabetic Ketoacidosis (DKA): Abdominal pain, nausea/vomiting, Kussmaul breathing, fruity breath, confusion.
  • Hyperosmolar Hyperglycemic State (HHS): Severe dehydration, altered mental status, high glucose.
• Thyroid Disorders:
  • Hypothyroidism: Weight gain, fatigue, cold intolerance, constipation, bradycardia, dry skin, hair loss, myxoedema.
  • Hyperthyroidism (Thyrotoxicosis): Weight loss, palpitations, heat intolerance, tremor, anxiety, diarrhea, fine hair, exophthalmos (Graves' ophthalmopathy), pretibial myxoedema.
• Adrenal Disorders:
  • Addison's Disease (Adrenal Insufficiency): Fatigue, weight loss, postural hypotension, hyperpigmentation (especially creases/mucosa), hyponatremia, hyperkalemia. Crisis: acute collapse, severe hypotension.
  • Cushing's Syndrome (Cortisol Excess): Central obesity, 'moon face', 'buffalo hump', purple striae, muscle weakness, easy bruising, hypertension, hyperglycemia.
  • Phaeochromocytoma (Catecholamine Excess): Paroxysmal hypertension, palpitations, headache, sweating ('PCC triad').
• Pituitary Disorders:
  • Hypopituitarism: Symptoms depend on deficient hormone (e.g., fatigue, secondary hypothyroidism/adrenal insufficiency).
  • Prolactinoma: Galactorrhea, amenorrhea/oligomenorrhea (women), impotence/loss of libido (men), visual field defects (bitemporal hemianopsia if large).
  • Acromegaly (GH Excess): Coarsening facial features, enlarged hands/feet, joint pain, headache, sweating, visual field defects.
• Calcium Disorders:
  • Hypercalcemia: 'Bones, stones, groans, psychiatric overtones' (bone pain, renal stones, abdominal pain, confusion/depression).
  • Hypocalcemia: Tetany, perioral numbness, muscle cramps, Chvostek's (facial twitch with tap), Trousseau's (carpopedal spasm with BP cuff).

Diagnosis (Gold Standard)

• Diabetes:
  • Fasting Plasma Glucose ≥ 7.0 mmol/L, or Random Plasma Glucose ≥ 11.1 mmol/L with symptoms.
  • Oral Glucose Tolerance Test (OGTT) 2-hour ≥ 11.1 mmol/L.
  • HbA1c ≥ 48 mmol/mol (6.5%) (not for T1DM diagnosis or gestational diabetes).
  • T1DM: C-peptide (low/absent), autoantibodies (GAD, ICA, IA-2, ZnT8).
• Thyroid:
  • TSH, Free T4 (fT4), Free T3 (fT3).
  • Autoantibodies: TPO (Hashimoto's), TRAb (Graves').
• Adrenal:
  • Addison's: Short Synacthen test (low cortisol response to synthetic ACTH).
  • Cushing's: Overnight Dexamethasone Suppression Test (lack of cortisol suppression), 24-hour urinary free cortisol (elevated).
  • Phaeochromocytoma: 24-hour urinary metanephrines and normetanephrines, or plasma free metanephrines.
• Pituitary:
  • Hormone levels (Prolactin, IGF-1 for Acromegaly), dynamic tests (e.g., insulin tolerance test for GH/cortisol reserve), MRI pituitary.
• Calcium: Serum Calcium (corrected), PTH, Vitamin D.

Management (First Line)

• Diabetes:
  • T1DM: Basal-bolus insulin regimen.
  • T2DM: Lifestyle modification, Metformin. If uncontrolled, add SGLT2i, GLP-1 RA, SU, DPP-4i, or insulin.
  • DKA/HHS: IV fluids, IV insulin infusion, careful electrolyte (K+) monitoring and replacement.
• Thyroid:
  • Hypothyroidism: Levothyroxine replacement.
  • Hyperthyroidism (Graves'): Beta-blockers (symptomatic control), Carbimazole or Propylthiouracil (PTU), radioiodine therapy, or surgery.
• Adrenal:
  • Addison's: Hydrocortisone (glucocorticoid) and Fludrocortisone (mineralocorticoid) replacement. Adrenal crisis: IV hydrocortisone, IV fluids.
  • Cushing's: Transsphenoidal surgery (pituitary adenoma), adrenalectomy. Medical: Ketoconazole, Metyrapone.
  • Phaeochromocytoma: Alpha-blockade (e.g., Phenoxybenzamine) followed by beta-blockade, then surgical resection.
• Pituitary:
  • Prolactinoma: Dopamine agonists (Cabergoline, Bromocriptine).
  • Acromegaly: Transsphenoidal surgery. Somatostatin analogues (Octreotide).
• Calcium:
  • Hypercalcemia: IV fluids, Bisphosphonates. Address underlying cause (e.g., parathyroidectomy for primary hyperparathyroidism).
  • Hypocalcemia: IV calcium gluconate (acute), oral calcium and Vitamin D.