Central Diabetes Insipidus

OVERVIEW

Diabetes insipidus (DI) is a condition caused by loss of the effect of antidiuretic hormone on the collecting ducts of the kidneys, resulting in loss of free water.

• diabetes insipidus can be central or nephrogenic
• This article will focus on CDI

PATHOPHYSIOLOGY

Normal physiology

• ADH is produced in the hypothalamus and travels along nerve fibers to the posterior pituitary, where it is stored and released
• Increased plasma osmolality stimulates release of ADH
• ADH promotes reabsorption of water in the collecting duct of nephrons via translocation of aquaporins (water channels) to the plasma membrane from internal sites within the cells

Diabetes insipidus

• central DI (CDI) results from causes that impair the synthesis, transport, or release of ADH
• nephrogenic DI (NDI) results from receptor, or downstream, unrepsonsiveness to circulating ADH
• loss of ADH effect results in polyuria, dehydration, hypernatremia and a hyperosmolar state

CAUSES OF CENTRAL DIABETES INSIPIDUS

Acquired

• Surgery (transsphenoidal) – common
• TBI – common
• Idiopathic
• Autoimmune
• Tumours (suprasellar, lung, breast, lymphoma, leukaemia)
• Hypoxic brain injury
• Brain stem death
• Profound hyponatraemia -> cerebral oedema
• Radiotherapy
• Inflammatory conditions – sickle cell, sarcoid, Wegener’s, histiocytosis X
• Infections – Tb, abscess, encephalitis, meningitis
• Vascular disease – CVA, SAH, Sheehan’s syndrome, pituitary apoplexy

Congenital

• Autosomal dominant mutation in ADH production
• Wolfram syndrome

DIAGNOSIS

Key findings

• plasma hyperosmolality (can be mild in partial DI)
• hypernatraemia (na >155 mM)
• polyuria (>3L/24h)
• urine osmolality < 200 mOsm/kg

Water deprivation test

• rarely performed in the critical care setting
• usually 4-18h water deprivation with serial urine and plasma osmolality until:
  — 5% loss of body weight
  — 2 urine samples with <30 mOsm/kg
• then check ADH level
• then give 1mcg DDAVP and check urine osmolality at 30 min and 60 min
• results:
  — psychogenic polydipsia: urine osmolality > plasma osmolality; <10% increase in urine osmolality after ADH
  — CDI: urine osmolality < plasma osmolality; >50% increase in urine osmolality after ADH
  — NDI: urine osmolality < plasma osmolality; <50% increase in urine osmolality after ADH

Investigate for underlying cause

MANAGEMENT

(1) treat hypernatraemia
(2) address deficit in total body H2O (dehydration and hypovolaemia)
(3) supplement ADH
(4) consider associated anterior pituitary dysfunction
(5) treat underlying cause

• manage in a critical care environment
• measure Na+ frequently

Hypernatraemia

• replacement of the previous hours urine output with an appropriate fluid
• avoid a fall in Na+ concentration by more than 0.5mml/hr

Dehydration and Hypovolaemia

• use isotonic saline
• if hypernatraemia is > 155 -> then also use hypertonic saline to reduce the rate of reduction

ADH supplementation

• if patient is euvolaemic -> DDAVP (V2 receptor agonist) 1-4mcg/day IV/IM/SC/IN
• can infuse and titrate against urine output

PROGNOSIS

Post-traumatic diabetes insipidis is associated with:

• more severe trauma
• cerebral edema
• lower GCS scores
• higher mortality rate
  • 57-69% overall
  • 86-90% if early-onset (<3 days after injury)
• brain death (DI is present in ~80% of brain dead TBI patients)
• hypernatraemia correlates with higher mortality (e.g. Na >160 mmol/L)

References and Links

• CCC – Hypernatraemia
• CCC – Hypernatraemia Mind map (PDF)
• CCC – Hyponatraemia
• CCC – Hyponatraemia Mind map (PDF)
• CCC – Hyponatraemia Interpretation (PNG)
• CCC – SIADH – SIADH DDx
• CCC – Diabetes Insipidus Central – Diabetes Insipidus DDx
• Case – Exercise-associated Hyponatremia
• Case – Seizures, hyponatremia and ADH

Journals

• Di Iorgi N, Napoli F, Allegri AE, Olivieri I, Bertelli E, Gallizia A, Rossi A, Maghnie M. Diabetes insipidus–diagnosis and management. Horm Res Paediatr. 2012;77(2):69-84. PMID: 22433947
• Makaryus AN, McFarlane SI. Diabetes insipidus: diagnosis and treatment of a complex disease. Cleve Clin J Med. 2006 Jan;73(1):65-71. PMID: 16444918