Adrenal and Pituitary Disorders

The adrenal glands sit atop the kidneys and have two distinct regions. The adrenal cortex (under ACTH control) produces: glucocorticoids (cortisol — zona fasciculata), mineralocorticoids (aldosterone — zona glomerulosa), and sex steroids (zona reticularis). The adrenal medulla produces catecholamines (adrenaline, noradrenaline).

Cushing's syndrome is the clinical state of chronic glucocorticoid excess. It is ACTH-dependent (more common) or ACTH-independent. ACTH-dependent causes: (1) Cushing's disease — pituitary ACTH-secreting adenoma (most common endogenous cause); (2) ectopic ACTH secretion (small cell lung cancer, carcinoid). ACTH-independent causes: adrenal adenoma or carcinoma, exogenous glucocorticoid use (iatrogenic — most common overall cause). Clinical features: central obesity (buffalo hump, moon face), purple striae, proximal myopathy, thin skin/easy bruising, hypertension, diabetes, osteoporosis, and hirsutism. Diagnosis: late-night salivary cortisol (sensitive, convenient), 24-hour urinary free cortisol, and 1 mg overnight dexamethasone suppression test (DST). Low-dose DST: normally, 1 mg dexamethasone suppresses morning cortisol to < 50 nmol/L; failure to suppress suggests Cushing's syndrome.

Addison's disease is primary adrenal insufficiency due to autoimmune destruction of the adrenal cortex (most common in high-income countries). Features: fatigue, weight loss, hyperpigmentation (elevated ACTH stimulates MSH receptors — buccal, palmar creases, scars), postural hypotension, hyponatraemia, and hyperkalaemia (lack of aldosterone). Adrenal crisis is life-threatening: vomiting, collapse, hypotension, and shock, often precipitated by an intercurrent illness. Management: immediate IM or IV hydrocortisone 100 mg, IV fluids. Maintenance: hydrocortisone + fludrocortisone (for mineralocorticoid replacement). Sick day rules are critical: double or triple the hydrocortisone dose during illness, surgery, or major stress.

Primary hyperaldosteronism (Conn's syndrome): excess aldosterone from adrenal adenoma or bilateral adrenal hyperplasia. Presents with refractory hypertension and hypokalaemia (often mild or absent). Screening: aldosterone-to-renin ratio (ARR) — elevated in primary hyperaldosteronism because aldosterone is high and renin is suppressed.

Phaeochromocytoma is a catecholamine-secreting tumour of the adrenal medulla (or sympathetic ganglia — then called paraganglioma). Classic triad: episodic hypertension, headache, palpitations, and diaphoresis. Diagnosis: 24-hour urinary catecholamines and metanephrines (or plasma metanephrines). Surgical resection is the treatment; requires pre-operative alpha-blockade (phenoxybenzamine) before beta-blockade (to prevent unopposed alpha vasoconstriction).

Hypopituitarism: deficiency of one or more pituitary hormones. Causes: pituitary adenoma (most common), surgery/irradiation, apoplexy, infiltrative disease. A panhypopituitary screen includes: IGF-1 (GH axis), free T4 + TSH, morning cortisol/synacthen test (ACTH/cortisol axis), FSH/LH/testosterone or oestrogen, and prolactin.

Acromegaly results from excess GH secretion (usually from a pituitary somatotroph adenoma) causing elevated IGF-1. Diagnosis: elevated IGF-1 + failure of GH suppression during oral glucose tolerance test (OGTT) — normally GH falls to < 1 mcg/L; in acromegaly it does not. Features: acral enlargement, prognathism, macroglossia, carpal tunnel syndrome, hypertension, sleep apnoea, and diabetes. Treatments: transphenoidal surgery, SSAs (octreotide, lanreotide), pegvisomant (GH receptor antagonist), or radiotherapy.