Diabetes Insipidus

A decrease of >75% in the secretion or action of Arginine Vasopressin usually results in DI, a syndrome characterized by the production of abnormally large volumes of dilute urine.

• The 24-h urine volume exceeds 50 mL/kg body weight, and the osmolarity is less than 300 mosmol/L.
• Cause: results from agenesis or irreversible destruction of the neurohypophysis. It is referred to variously as neurohypophyseal DI, neurogenic DI, pituitary DI, cranial DI, or central DI. 50% idiopathic.

Causes of DI

• Pituitary diabetes insipidus:
  • Acquired:
    • Head Injury
    • Pituitary surgery
    • Neoplasms - primary (Pit. adenoma, meningioma), seconary (lung, breast), hematological (lymphoma, leukemia)
    • Granulomas: Sarcoidosis, Histiocytosis.
    • Infections: Chr. meningitis, viral encephalitis, Toxoplasmosis.
    • Inflamatory: SLE, scleroderma
    • Toxins: Snake poison
    • Vascular: Sheehan’s syndrome, Aneurysm (internal carotid), Hypoxic encephalopathy
    • Idiopathic
  • Congenital
  • Genetic
• Gestational DI: 2nd, 3rd trimester
• Nephrogenic diabetes insipidus: Primary deficiency in AVP action.
  • Drugs: Lithium, Demeclocycline, Methoxyflurane, Amphotericin B, Aminoglycosides, Cisplatin, Rifampin.
  • Metabolic: Hypercalcemia, hypercalciuria, Hypokalemia
  • Obstruction (ureter or urethra)
  • Vascular: Sickle cell disease and trait, Ischemia (acute tubular necrosis)
  • Granulomas: Sarcoidosis
  • Neoplasms: Sarcoma
  • Infiltration: Amyloidosis
  • Idiopath
  • Genetic
• Secondary deficiencies of AVP secretion (Primary Polydipsia):
  • Dipsogenic DI: Inappropriate thirst caused by a reduction in the set of the osmoregulatory mechanism. It sometimes occurs in association with multifocal diseases of the brain such as neurosarcoid, tuberculous meningitis, and multiple sclerosis but is often idiopathic.
  • Psychogenic polydipsia: Not associated with thirst, and the polydipsia seems to be a feature of psychosis or obsessive compulsive disorder.
  • Iatrogenic polydipsia: Results from recommendations to increase fluid intake for its presumed health benefits.

Diagnosis:

If 24-h urine volume > 50 mL/kg BW, and the osmolarity is < 300 mosmol/L, then proceed as below:

Basal plasma AVP >1 pg/mL	Nephrogenic DI
Basal plasma AVP <1 pg/mL	Brain MRI	Pituitary bright spot - Present	Primary polydipsia
		Pituitary bright spot - Absent	Pituitary DI

DI Treatment

• Desmopressin (DDAVP), a synthetic analogue. DDAVP can be given by IV or SC injection, nasal inhalation, or orally.
• Dose: usually range from 1–2 μg qd or bid by injection, 10–20 μg bid or tid by nasal spray, or 100–400 μg bid or tid orally. The onset of antidiuresis is rapid, ranging from as little as 15 min after injection to 60 min after oral administration.
• Primary polydipsia cannot be treated safely with DDAVP or any other antidiuretic drug because eliminating the polyuria does not eliminate the urge to drink.
• Nephrogenic DI: is not affected by treatment with standard doses of DDAVP. If resistance is partial, it may be overcome by tenfold higher doses, but this treatment is too expensive and inconvenient for long-term use. Treatment with conventional doses of a thiazide diuretic and/or amiloride in conjunction with a low-sodium diet and a prostaglandin synthesis inhibitor (e.g., indomethacin) usually reduces the polyuria and polydipsia by 30–70% and may eliminate them completely in some patients.
• Brands:
  D-Void Nasal Spray 0.01% (1 mcg) (Sun Pharma)
  D-Void 0.1mg, 0.2mg tablet (Sun Pharma)

Hypodispic Hypernatremia

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Hyponatremia

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