Diabetes Insipidus (DI) vs Primary Polydipsia

• Both DI and primary polydipsia present with polyuria, polydipsia, and normal blood glucose

• Distinguishing between central DI, nephrogenic DI, and primary polydipsia is crucial for appropriate management

• Water deprivation test plus desmopressin challenge remains the gold standard for diagnosis

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Key Presentations

• Polydipsia, Polyuria, Nocturia

  • Typically large volumes of dilute urine (low urine osmolality)

• Normal Blood Glucose

  • Helps differentiate from diabetes mellitus

• Central and Nephrogenic DI

  • Inability to concentrate urine → low urine osmolality (<300 mOsm/kg) despite dehydration

• Primary Polydipsia

  • Excessive intake of water (often psychiatric or behavioural origin)

  • Kidneys are essentially normal but overwhelmed by high fluid intake

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Causes

• Central DI

  • Reduced ADH (vasopressin) production from posterior pituitary or hypothalamus

  • Common causes: tumours (craniopharyngioma, germinoma), head trauma, post-neurosurgery, infiltrative diseases (sarcoidosis), infections (encephalitis, TB), hereditary forms

• Nephrogenic DI

  • Kidneys unresponsive to ADH

  • Common causes: lithium toxicity (most frequent), hypercalcaemia, inherited mutations (aquaporin channels, vasopressin receptor), chronic kidney disease (e.g., autosomal dominant polycystic kidney disease)

  • Also consider electrolyte disturbances (severe hypokalaemia) that reduce ADH responsiveness

• Primary Polydipsia (Psychogenic Polydipsia)

  • Excessive fluid intake driven by psychiatric conditions (schizophrenia, bipolar), anxiety, or habit

  • Over time, leads to suppressed ADH release and decreased medullary concentration gradient

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Clinical Clues

• Central DI

  • Sudden onset of large-volume polyuria after pituitary surgery or head trauma

  • Possibly associated with other pituitary hormone deficiencies if damage is extensive

• Nephrogenic DI

  • History of lithium use or hypercalcaemia

  • Persistent polyuria despite normal ADH production

• Primary Polydipsia

  • Psychiatric history (e.g. psychosis, severe anxiety), normal serum electrolytes if fluid intake is not extreme

  • May show mild hyponatraemia or low serum osmolality if water intake is excessive

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Water Deprivation Test

• Differentiates central DI, nephrogenic DI, and primary polydipsia

• Procedure

  • Controlled fluid deprivation while monitoring body weight, urine output, urine osmolality, and serum sodium/osmolality

  • Test ended if significant hypotension, tachycardia, or serum sodium approaches dangerous levels

• Expected Results

  • Central DI

    • Inadequate ADH → low urine osmolality (<300 mOsm/kg) during deprivation

    • Serum osmolality rises (hypernatraemia risk)

    • After desmopressin (ADH analogue), urine osmolality increases significantly (>50% rise)

  • Nephrogenic DI

    • Low urine osmolality remains low during deprivation (<300 mOsm/kg)

    • Minimal or no response to desmopressin (kidneys cannot respond)

  • Primary Polydipsia

    • Gradual increase in urine osmolality (>600–800 mOsm/kg) once fluid intake is restricted

    • Desmopressin has minimal additional effect because ADH axis is intact

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Post-Desmopressin (DDAVP) Challenge

• Central DI

  • Marked increase in urine osmolality (often >50% rise)

• Nephrogenic DI

  • Little or no change in urine osmolality

• Primary Polydipsia

  • Minimal change, though baseline urine concentration may normalise when water intake is restricted

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Management

• Central DI

  • Desmopressin (DDAVP) as nasal spray or oral tablets

  • Address underlying cause (remove tumour, treat infection, manage autoimmune)

  • Monitor serum sodium and fluid balance to avoid hyponatraemia

• Nephrogenic DI

  • Correct offending agents (e.g. stop or reduce lithium if possible)

  • Adequate hydration and low salt/protein diet to reduce solute load

  • Medications such as hydrochlorothiazide or amiloride can paradoxically reduce urine output by modifying renal tubular handling

  • Evaluate for hypercalcaemia and correct as needed

• Primary Polydipsia

  • Behavioural or psychiatric intervention (counselling, managing psychosis or anxiety)

  • Restrict excessive fluid intake gradually

  • Monitor for electrolyte disturbances to avoid complications like water intoxication

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Additional Considerations

• Electrolyte Monitoring

  • Serum sodium and potassium to detect hypernatraemia or other imbalances

• Renal Function

  • eGFR to ensure correct interpretation of dehydration tests

• Long-Term Follow-Up

  • Regular assessment of fluid intake, serum sodium, and renal function

  • Adjust therapy based on changes in disease status or medication side effects

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Notes:

• Suspect DI or primary polydipsia in patients with persistent polyuria and polydipsia but normal blood glucose

• Water deprivation test + desmopressin challenge is definitive for differentiating central vs nephrogenic DI vs primary polydipsia

• Carefully manage underlying causes (discontinue nephrotoxic drugs, correct hypercalcaemia, address psychiatric drivers)

• In central DI, desmopressin dramatically improves symptoms if dosed and monitored correctly

• In nephrogenic DI, focusing on cause reversal (e.g. lithium cessation) and using diuretics like hydrochlorothiazide or amiloride can help reduce urine output

• Behavioural modification and mental health support are crucial in primary polydipsia to prevent complications of excessive water intake