Epidemiology

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Etiology

Central diabetes insipidus (CDI)

• Most common form: caused by insufficient or absent hypothalamic synthesis or posterior pituitary secretion of ADH
  • Primary (∼ ⅓ of cases)
  • Secondary (∼ ⅔ of cases)
    • Brain tumors (especially craniopharyngioma)
    • Neurosurgery
    • Traumatic brain injury, pituitary bleeding, subarachnoid hemorrhage
    • Pituitary ischemia (e.g., Sheehan syndrome, ischemic stroke)

Nephrogenic diabetes insipidus (NDI)

• Rare: caused by defective ADH receptors in the distal tubules and collecting ducts
• Hereditary (mutation in ADH receptor): very rare
• Acquired: typically reversible if the underlying cause is resolved
  • Adverse effect of medications (lithium, demeclocycline)
  • Hypokalemia, hypercalcemia

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Pathophysiology

Tip

Note that in central DI, ADH levels are decreased, while in nephrogenic DI, they are normal or increased to compensate for the high urine output.

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Clinical features

• Polyuria with dilute urine
• Nocturia → restless sleep, daytime sleepiness
• Polydipsia (excessive thirst)
• In cases of low water intake → severe dehydration (altered mental status, lethargy, seizures, coma) and hypotension
• Symptoms may worsen during pregnancy.

Tip

In the absence of nocturia, diabetes insipidus is very unlikely.

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Diagnostics

Serum sodium and plasma osmolality

• ↓ Na⁺ and/or ↓ plasma osmolality: primary polydipsia likely
• Normal values: diagnosis unclear; obtain subsequent studies to differentiate between polyuria-polydipsia syndromes.
• ↑ Na⁺ and/ or ↑ plasma osmolality: Diabetes insipidus likely; obtain subsequent studies to differentiate between CDI and NDI.

Water deprivation test (indirect assessment of ADH activity)

Urine concentrating capacity is assessed during a period of dehydration; desmopressin is then administered to assess response to a synthetic ADH analogue.

• Interpretation after period of water deprivation
  • Urine osmolality increases to > 800 mOsm/kg: Primary polydipsia is confirmed.
  • Urine osmolality remains ≤ 800 mOsm/kg: Administer desmopressin (a synthetic ADH analogue).
• Interpretation after desmopressin administration
  • Urine osmolality (300–800 mOsm/kg) and:
    • Significant increase (≥ 10%) after desmopressin: partial CDI
    • No or minimal increase (< 10%) after desmopressin: primary polydipsia
  • Urine osmolality (< 300 mOsm/kg) and:
    • Significant increase (> 50%) after desmopressin: complete CDI (indicating intact renal ADH receptors)
    • No or moderate increase (< 50%) after desmopressin: NDI (indicating defective renal ADH receptors)

Differential diagnostics

Primary polydipsia (psychogenic polydipsia)

• Mechanism
  • Compulsive water intake
• Etiology
  • Psychiatric diseases (e.g., schizophrenia, obsessive-compulsive disorder)
  • Lesions in the hypothalamic thirst center
• Features
  • Hyponatremia
  • Low plasma osmolarity, very low urine osmolarity
  • Water deprivation: plasma and urine osmolarity increase to normal level

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Treatment

Encourage adequate fluid intake and a low-sodium, low-protein diet.

Central diabetes insipidus

• Desmopressin (preferred): synthetic ADH analogue without vasoconstrictive effects
  • Intranasal administration is preferred.
• Chlorpropamide

Nephrogenic diabetes insipidus

• Treat the underlying cause, if applicable, e.g.:
  • Discontinue the causative agent (e.g., lithium, demeclocycline).
• Thiazide diuretics
  • Lead to sodium depletion, which increases sodium and water reabsorption in the proximal tubules
  • As a result, less water reaches the distal collecting tubules and urine volume decreases.
• NSAIDs (e.g., indomethacin)
  • Inhibit renal prostaglandins that act as ADH antagonists
• Amiloride

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