Diabetes Insipidus & SIADH

Passage of large volumes of dilute urine from a lack of, or resistance to, vasopressin (ADH) — unrelated to diabetes mellitus. (Now increasingly renamed arginine vasopressin deficiency/resistance.)

• Central — deficiency of vasopressin release: head trauma, neoplastic or inflammatory conditions affecting the posterior pituitary, congenital, idiopathic (~50%), or gestational (placental vasopressinase degrades vasopressin).
• Nephrogenic — renal resistance to vasopressin: genetic; drug-induced (lithium, demeclocycline, amphotericin B); hypercalcaemia/hypokalaemia; renal damage.

Clinical features

Polyuria (typically >3.5 L/day, up to 10–20 L/day in complete DI), excessive thirst and polydipsia. Dehydration occurs if water access is limited.

Investigations

• Urine osmolality lower than serum osmolality (dilute urine despite concentrated plasma).
• Primary-care work-up of polyuria/polydipsia: measure 24-hour urine volume — >5 L → refer to endocrinology; 2.5–5 L → overnight fluid deprivation test (no fluids from 9 pm, measure urine osmolality at 9 am): >600 mOsm/kg suggests primary polydipsia (excess water intake); <600 → refer.
• The formal fluid deprivation test shows an inappropriately low urine osmolality against a high serum osmolality.

Management

• Central DI — desmopressin (SC, intranasal, or oral); drink to thirst; specialist management. (Desmopressin dose not separately re-verified against current AMH.)
• Nephrogenic DI — thiazide or amiloride; low-sodium diet; prostaglandin synthesis inhibitors (e.g. indomethacin); address the cause (e.g. lithium).

Polyuria / polydipsia (broader differential)

Urine output >3 L/day (adult) or >2 L/day (child). Causes beyond DI: diabetes mellitus, hypercalcaemia (>2.75 mmol/L), hypokalaemia (<3.0), drugs (lithium, diuretics, aminoglycosides, calcium channel blockers), and renal disease (Sjögren, sickle cell, post-obstructive, cystic kidney disease, amyloidosis). Serum sodium/osmolality separates excess water loss (Na >142, osmolality >285) from excess water intake (Na <137, osmolality <270).

SIADH

Syndrome of inappropriate antidiuretic hormone secretion — too much ADH (effectively the opposite of DI), causing water retention and euvolaemic hyponatraemia.

Causes: neoplasms (e.g. small-cell lung cancer), lung infections, CNS disorders, and drugs.

Clinical features

Often asymptomatic. If hyponatraemia develops quickly: headache, nausea/vomiting, anorexia, confusion, and — when severe — seizures and coma.

Investigations

• Hyponatraemia with low serum osmolality and inappropriately high urine osmolality
• High urinary sodium (in a euvolaemic, non-diuretic patient)

A diagnosis of exclusion — confirm clinical euvolaemia and exclude hypothyroidism and adrenal insufficiency.

Management

• Fluid restriction first-line (e.g. to ~500 mL less than urine output).
• Treat the underlying cause.
• Severe symptoms (seizures, coma) — hospital for hypertonic saline.
• Correct sodium slowly — over-rapid correction causes osmotic demyelination syndrome (central pontine myelinolysis).