What are the different forms of Diabetes Insipidus (DI)?

Types of Diabetes Insipidus

Diabetes insipidus (DI) is classified into two main types: central diabetes insipidus (vasopressin deficiency) and nephrogenic diabetes insipidus (vasopressin resistance), with two less common forms being dipsogenic DI and gestational DI. 1, 2

Main Types of Diabetes Insipidus

1. Central Diabetes Insipidus (CDI)

• Also recently proposed to be renamed "vasopressin deficiency" 2
• Characterized by deficiency in the synthesis or release of antidiuretic hormone (ADH/vasopressin) from the posterior pituitary gland 1
• Causes include:
  • Tumors in the hypothalamic-pituitary region
  • Head trauma or surgery
  • Infiltrative diseases
  • Idiopathic (no identifiable cause)
• Responds to treatment with desmopressin (synthetic ADH) 3

2. Nephrogenic Diabetes Insipidus (NDI)

• Also proposed to be renamed "vasopressin resistance" 2
• Characterized by kidney resistance to the effects of ADH 4
• Causes include:
  • Genetic mutations in AVPR2 (X-linked, 90% of cases) or AQP2 genes (autosomal, <10% of cases) 4
  • Acquired forms (medication-induced, especially lithium)
  • Secondary forms related to other conditions (Bartter syndrome, distal renal tubular acidosis)
• Does not respond to desmopressin treatment 3
• Requires different management approaches including thiazide diuretics, NSAIDs, and amiloride 4

Less Common Types

3. Dipsogenic Diabetes Insipidus

• Characterized by excessive thirst due to a low osmotic threshold 1
• Primary polydipsia with abnormal thirst regulation
• Treatment focuses on behavioral therapy and sometimes antipsychotic medications 1

4. Gestational Diabetes Insipidus

• Occurs during pregnancy due to increased concentration of placental vasopressinase 1
• Usually resolves after delivery
• Can be treated with desmopressin during pregnancy 1

Special Clinical Variants

Adipsic Diabetes Insipidus

• A rare and dangerous variant where DI occurs with dysfunction of the thirst center 5
• Often follows brain surgery involving the hypothalamic region
• Requires careful management with fixed desmopressin dosing and scheduled fluid replacement 5

Partial Central Diabetes Insipidus

• Characterized by partial deficiency of ADH 6
• Milder symptoms compared to complete CDI
• May still require treatment with desmopressin 6

Diagnostic Approach

The diagnosis of DI type requires:

• Essential laboratory tests: serum sodium, serum osmolality, and urine osmolality 4
• Water deprivation test followed by desmopressin administration (gold standard) 7
• Emerging diagnostic tool: copeptin (surrogate marker for ADH) measurement during hypertonic saline infusion 7, 2
• Genetic testing for suspected nephrogenic DI 4
• MRI imaging of the hypothalamic-pituitary region 2

Management Differences by Type

1. Central DI: Desmopressin (DDAVP) is the mainstay of treatment 3
2. Nephrogenic DI:
   • Unrestricted access to water/fluids
   • Low-salt diet (<6 g/day)
   • Low-protein diet (<1 g/kg/day)
   • Thiazide diuretics, NSAIDs, and amiloride (particularly for lithium-induced NDI) 4
   • Desmopressin is ineffective and not indicated 4, 3

Clinical Pearls and Pitfalls

• All forms of DI share the common symptoms of polyuria and polydipsia but require different management approaches 1
• Paradoxically, thiazide diuretics can be beneficial in both central and nephrogenic DI 1
• Regular monitoring of electrolytes, renal function, and urine osmolality is essential for all DI patients 4
• Hypernatremia correction should be limited to <8 mmol/L/day to prevent osmotic demyelination syndrome 4
• Adipsic DI represents a particularly dangerous form requiring specialized management due to the absence of thirst mechanism 5

The recent proposal to rename diabetes insipidus as "vasopressin deficiency" (central) and "vasopressin resistance" (nephrogenic) aims to reduce confusion with diabetes mellitus and better reflect the underlying pathophysiology 2.