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Diabetes Insipidus (DI)

Overview Table

Overview of Water Balance Disorders

These 2 tables act as an overview to allow comparison between confusing water balance disorders. They do not contain all the information about these disorders; please review their separate articles for full details.
Feature SIADH Primary Polydipsia Diabetes Insipidus
Pathophysiology Excess ADH secretion causes water retention Excess water intake suppresses ADH secretion Deficiency (central) or resistance (nephrogenic) to ADH
Typical causes CNS disorder, malignancy, drugs Psychogenic Central: brain tumour
Nephrogenic: drugs, renal disease
Serum sodium (baseline) Hyponatraemia Hypernatraemia
Serum osmolality (baseline) Low (<275 mOsm/kg) High (>295 mOsm/kg)
Urine osmolality (baseline) High (concentrated) (>100 mOsm/kg) Low (diluted) (<100 mOsm/kg)
Diagnosis Diagnosis by exclusion + supported by:

  • Euvolaemic isotonic hyponatraemia
  • Paired serum and urine osmolality findings (as above)
Fluid intake history + water deprivation test:

  • Urine concentrates with fluid deprivation (urine osmolality increases)

Paired serum and urine osmolality findings (as above)

Water deprivation test:

  • Urine osmolality does not change with fluid deprivation

Desmopressin test (central vs nephrogenic):

  • Central: urine concentrates with desmopressin
  • Nephrogenic: no changes

Paired serum and urine osmolality findings (as above)

Some key trends, but presented in a different way:

Disorder Trends (at baseline)
SIADH
  • Hyponatraemia
  • ↓ Serum osmolality
  • ↑ Urine osmolality (concentrated urine)
Primary polydipsia
  • Hyponatraemia
  • ↓ Serum osmolality
  • ↓ Urine osmolality (diluted urine)
Diabetes insipidus
  • Hypernatraemia
  • ↑ Serum osmolality
  • ↓ Urine osmolality

Background Information

Definition

DI is characterised by the excretion of abnormally large volumes of diluted urine.

Pathophysiology

There are 2 types of DI: [Ref1][Ref2]

  • Central DI: impaired synthesis / secretion of ADH from the hypothalamus / posterior pituitary
  • Nehprogenic DI: resistance to ADH action in the kidney (collecting duct)

Both results in impaired renal water reabsorption, thus inability to concentrate urine and subsequent polyuria.

Aetiology

Central ID is more common than nephrogenic DI.

Both can be hereditary, but it is rare.

Central DI

Main acquired causes: [Ref1][Ref2]

  • Idiopathic – most common
  • Intracranial tumours (esp. craniopharyngioma)
  • Damage to hypothalamus / pituitary stalk (e.g. traumatic brain injury, neurosurgery)
  • Infiltrative diseases (e.g. sarcoidosis, Langerhans cell histiocytosis)

Nephrogenic DI

Main acquired causes: [Ref1][Ref2]

  • Lithium – most common
  • Demeclocycline
  • Polycystic kidney disease
  • Urethral obstruction
  • Electrolyte imbalance (hypercalcaemiahypokalaemia)

Clinical Features

Key presentation: [Ref1][Ref2]

  • Polyuria (nocturia is common)
  • Polydipsia

Complication

The main complication is dehydration and hypernatraemia[Ref1][Ref2]

Diagnosis and Management

Investigation and Diagnosis

Step 1 – Biochemical Confirmation

Gold standard test to confirm DI and determine the type is water deprivation test followed by desmopressin administration [Ref1][Ref2]

  • The test is aimed at differentiating between central DI vs nephrogenic DI vs primary polydipsia
  • Key principle: Interpretation is based primarily on changes in urine osmolality, not serum osmolality

The test is a 3-step process: [Ref1][Ref2]

Step Central DI Nephrogenic DI Primary polydipsia
Step 1 (baseline)
  • Hypernatraemia
  • ↑ Serum osmolality
  • ↓ Urine osmolality
  • Hyponatraemia
  • ↓ Serum osmolality
  • ↓ Urine osmolality
Step 2 (post-water deprivation)
  • Urine osmolality remains the same (low) / minimally increased
  • Serum and urine osmolality increase significantly
Step 3 (post-desmopressin administration)
  • Urine osmolality increases significantly
  • Urine osmolality remains the same
  • Minimal change (urine is already concentrated)

Central vs nephrogenic DI:

  • Central DI results from deficient ADH production / secretion, therefore by giving desmopressin (a synthetic ADH analogue) will restore ADH’s effect and thus concentrate the urine
  • Nephrogenic DI results from renal resistance to ADH (there is no problems with ADH production / secretion), therefore by giving more ADH would not change anything.

Step 2 – Neuroimaging

MRI of the hypothalamic-pituitary region after biochemical confirmation of central DI[Ref1][Ref2]

Management

Management depends on the type of DI: [Ref]

Type of DI Management
Central DI
  • Desmopressin therapy (synthetic ADH analogue)
Nephrogenic DI
  • Identify and manage any reversible causes (e.g. stop causative medication)
  • Ensure adequate hydration and dietary modifications (low-sodium and low-protein diet to reduce urine output)
  • Thiazide diuretics (paradoxically reduce polyuria by inducing mild volume depletion and increasing proximal tubular reabsorption of sodium and water)

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