What is diabetes insipidus?

What is Diabetes Insipidus

Diabetes insipidus is a rare endocrine disorder characterized by the inability to concentrate urine, resulting in the excretion of large volumes of dilute urine (polyuria), excessive thirst (polydipsia), and inappropriately low urine osmolality (<200 mOsm/kg H₂O) despite high-normal or elevated serum sodium. 1, 2

Pathophysiology and Classification

Diabetes insipidus occurs due to defects in the antidiuretic hormone (ADH, also called vasopressin) system, which normally regulates water reabsorption in the kidneys. 3, 4 The condition is classified into four distinct types based on the underlying mechanism:

Central (Cranial) Diabetes Insipidus

• Results from deficiency or inadequate secretion of ADH from the posterior pituitary gland or hypothalamus 5, 6
• Can be complete or partial, with partial forms showing some residual ADH production 6
• May be idiopathic or secondary to head trauma, pituitary surgery, tumors, or other pathology 5, 7

Nephrogenic Diabetes Insipidus

• Results from kidney resistance to ADH action in the distal convoluted tubule and collecting duct 3, 8
• The kidneys cannot respond appropriately to circulating ADH despite normal or elevated levels 2, 4
• Can be congenital (genetic) or acquired from medications, chronic kidney disease, or electrolyte disorders 2

Gestational Diabetes Insipidus

• Occurs during pregnancy due to increased placental vasopressinase enzyme that breaks down ADH 3, 7
• Typically resolves after delivery 3

Dipsogenic (Primary Polydipsia)

• Results from excessive fluid intake due to abnormal thirst regulation with a low osmotic threshold 3, 7
• ADH secretion and kidney response are normal, but excessive water intake suppresses ADH release 7

Clinical Presentation

The hallmark triad consists of:

• Polyuria: Urine output typically >2.5 L per 24 hours in adults, with volumes often exceeding 3-20 liters daily in severe cases 1, 4
• Polydipsia: Excessive thirst with craving for cold water 3
• Dilute urine: Urine osmolality <200 mOsm/kg H₂O combined with high-normal or elevated serum sodium 1, 2

In children, additional features include failure to thrive, hypernatremic dehydration, and growth failure if untreated. 1, 2

Diagnostic Approach

The American College of Physicians and European Society of Endocrinology recommend measuring serum sodium, serum osmolality, and urine osmolality simultaneously as the initial biochemical work-up. 1, 9

• The combination of urine osmolality <200 mOsm/kg H₂O with high-normal or elevated serum sodium confirms diabetes insipidus 1
• Plasma copeptin levels (a stable surrogate marker for ADH) should be used to distinguish between central and nephrogenic forms: levels <21.4 pmol/L indicate central DI, while levels >21.4 pmol/L suggest nephrogenic DI 1, 2, 9
• Traditional water deprivation testing followed by desmopressin administration remains the gold standard when copeptin testing is unavailable 4, 7
• Early genetic testing is strongly recommended for suspected nephrogenic diabetes insipidus 2, 9

Treatment Principles

Central Diabetes Insipidus

Desmopressin (synthetic ADH) is the treatment of choice and can be administered via multiple routes including intranasal, oral, subcutaneous, or intravenous. 1, 9, 5

• The intranasal route may be compromised by nasal congestion, discharge, atrophic rhinitis, or following transsphenoidal surgery, requiring alternative administration routes 5

Nephrogenic Diabetes Insipidus

The European Society of Endocrinology and European Society of Pediatric Nephrology recommend combination therapy with thiazide diuretics and prostaglandin synthesis inhibitors (NSAIDs) for symptomatic patients. 1, 2, 9

• Thiazide diuretics combined with low-salt diet (≤6 g/day) can reduce diuresis by up to 50% through mild volume depletion and increased proximal tubular reabsorption 2, 9
• NSAIDs enhance collecting duct water permeability and should be added to the regimen 9
• Amiloride should be added if hypokalemia develops from thiazide therapy 2
• Dietary modifications including protein restriction (<1 g/kg/day) are essential to reduce renal osmotic load 1, 2

Universal Management Principles

All patients with diabetes insipidus must have free access to fluid to prevent dehydration, hypernatremia, growth failure, and other complications. 1, 2, 9

• Patients capable of self-regulating should determine fluid intake based on thirst sensation rather than prescribed amounts 1, 2, 9
• Each patient should have an emergency plan including instructions for intravenous fluid management with 5% dextrose in water during illness or when oral intake is compromised 2

Important Clinical Pitfalls

• Desmopressin is ineffective for nephrogenic diabetes insipidus since the kidneys cannot respond to ADH 5
• Prostaglandin synthesis inhibitors are contraindicated during pregnancy 2
• In patients with idiopathic central DI, close follow-up is essential as it may be the first sign of underlying pathology such as tumors or infiltrative disease 7
• Regular monitoring of growth parameters in children, electrolytes, and kidney ultrasound (every 2 years) for urinary tract complications is recommended 2