Synonyms: neurogenic diabetes insipidus
This is caused by hyposecretion of anti-diuretic hormone (ADH) - arginine vasopressin.¹

Pathogenesis

ADH is synthesised in the hypothalamus and transported as neurosecretory vesicles to the posterior pituitary. There it is released into the circulation, governed by plasma osmolality. Its deficiency or failure to act causes an inability to concentrate urine in the distal renal tubules; leading to the passage of copious volumes of dilute urine. Usually the sufferer passes >3litres/24 hours of low osmolality (<300 mOsmol/kg) urine.²

Aetiology

It is usually due to disease of the hypothalamus or surrounding tissues. Posterior pituitary disease tends not to cause diabetes insipidus, as secretion continues in the hypothalamus, unless pituitary tumour extends above the sella, putting pressure on the hypothalamus.

Acquired

• Idiopathic
• Tumours - craniopharyngioma, germinoma, hypothalamic metastases (especially breast carcinoma), hypothalamic glioma, large pituitary tumours with suprasellar extension, lymphoma
• Intracranial surgery
• Head injury
• Granulomata - sarcoidosis, tuberculosis (TB), Wegener's, histiocytosis
• Infections - TB, encephalitis, meningitis, cerebral abscess
• Vascular disorders - haemorrhage/thrombosis, aneurysms, sickle-cell disease, Sheehan's syndrome (post-partum pituitary necrosis)
• Post-radiotherapy

Inherited

• Autosomal recessive combination of diabetes insipidus, diabetes mellitus, optic atrophy, deafness (DIDMOAD) - Wolfram syndrome³
• Autosomal dominant mutations of vasopressin gene

Presentation

Symptoms

The predominant symptoms in older patients are polyuria (large output of urine with micturition up to every 30 minutes), polydipsia and nocturia.² Children may exhibit enuresis. Infants tend to suffer failure to thrive, irritability, protracted crying, anorexia and fatiguability.

Signs

Bladder enlargement may occur. Signs of dehydration may be present. Confirm that the urine volume output >3 l/24 hours.

Differential diagnosis

• Psychogenic polydipsia (PP)
• Osmotic diuresis (especially diabetes mellitus)
• Diuretic abuse

Investigations

• Biochemistry - plasma glucose, urea and electrolytes, and plasma and urine osmolality should all be measured.
• Fluid deprivation test with response to desmopressin - this should be used if glucose and electrolyte levels are normal.⁴ The patient is deprived of fluids for up to 8 hours or 5% loss of body weight, following which desmopressin (DDAVP®) 2 micrograms (IM) is given. See Table I for interpretation of the results.
• Plasma vasopressin levels and osmolality in response to infusion of 5% hypertonic saline at 0.05 ml/kg/min for 2 hours may be measured in cases of diagnostic difficulty.
• A therapeutic trial of low dose desmopressin is another option, with careful monitoring of plasma osmolality or serum sodium. Cranial diabetes insipidus (CDI) patients improve, and those with nephrogenic diabetes insipidus (NDI) are unaffected. Those with PP develop hyponatraemia and may stop drinking.
• MRI of the pituitary, hypothalamus and surrounding tissues, including pineal gland may be contributory in helping to determine the underlying cause.

Management⁵

• As the primary problem is a hormone deficiency, physiological replacement with desmopressin is usually effective. This can be given orally, intranasally or parenterally.
• Mild cases of DI (urine output 3-4 litres/24hrs) can be managed by ingestion of water to quench thirst.
• It is essential to avoid chronic overdosage with desmopressin, which will cause hyponatraemia.

Long-term management

• Because of the risk of hyponatraemia, occasional (1-3 monthly) measurements of serum sodium are advised.
• Some endocrinologists recommend missing desmopressin treatment one day each week to avoid the development of hyponatraemia.

Prognosis

Once diagnosed, the condition should respond well to appropriate therapy. This should be initiated and supervised by a physician with appropriate experience.

Complications

Patients with diabetes insipidus need careful monitoring of fluid balance and therapy following surgery, with multidisciplinary care.⁶

Document references

1. Fujiwara TM, Bichet DG; Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol. 2005 Oct;16(10):2836-46. Epub 2005 Aug 10. [abstract]
2. Cooperman M; Diabetes Insipidus (overview of CDI and NDI). eMedicine, 2008.
3. OMIM; Wolfram Syndrome. Online Mendelian Inheritance in Man.
4. Central Diabetes Insipidus; Merck Manuals 2007
5. Pituitary Foundation (UK); Diabetes Insipidus; Resources Page
6. Dumont AS, Nemergut EC 2nd, Jane JA Jr, et al; Postoperative care following pituitary surgery. J Intensive Care Med. 2005 May-Jun;20(3):127-40. [abstract]

Internet and further reading

• Charmandari E, Brook CG; 20 years of experience in idiopathic central diabetes insipidus. Lancet. 1999 Jun 26;353(9171):2212-3.

Acknowledgements