Types of Diabetes Insipidus
Diabetes insipidus is classified into four distinct types based on the underlying pathophysiological defect: central (neurogenic), nephrogenic, gestational, and dipsogenic (primary polydipsia). 1, 2, 3
The Four Main Types
1. Central Diabetes Insipidus (CDI)
- Results from deficient production or secretion of antidiuretic hormone (ADH/vasopressin) from the posterior pituitary gland or hypothalamus 1, 3, 4
- Characterized by low or absent plasma ADH levels despite appropriate physiological stimuli 5
- Responds effectively to desmopressin (synthetic ADH) replacement therapy 1, 6
- Can occur following head trauma, pituitary surgery, or may be idiopathic 6, 4
2. Nephrogenic Diabetes Insipidus (NDI)
- Characterized by kidney resistance to ADH despite normal or elevated plasma ADH levels 1, 5, 3
- The distal nephron fails to respond appropriately to circulating vasopressin 5, 3
- Plasma copeptin >21.4 pmol/L is diagnostic in adults, indicating significantly elevated ADH levels 1, 5
- Does NOT respond to desmopressin administration, which is the key diagnostic distinction from central DI 5, 6
- Can be congenital (genetic mutations in aquaporin-2 or vasopressin receptor genes) or acquired (lithium toxicity, chronic kidney disease) 1, 7, 3
3. Gestational Diabetes Insipidus
- Results from increased placental vasopressinase enzyme activity during pregnancy, which degrades circulating ADH 3, 8
- Typically resolves after delivery when placental vasopressinase is no longer present 8
- Treated with desmopressin, which is resistant to vasopressinase degradation 3
4. Dipsogenic (Primary Polydipsia)
- Caused by excessive water intake due to either a defect in the thirst mechanism (dipsogenic) or compulsive water drinking (psychogenic) 2, 3, 4
- ADH secretion and kidney response are both normal 2, 4
- The low osmotic threshold for thirst drives inappropriate fluid consumption 3
- Distinguished from true DI by normal ADH secretion capacity when properly tested 2, 4
Critical Diagnostic Distinctions
The fundamental difference between central and nephrogenic DI lies in plasma ADH levels and response to desmopressin:
- Central DI: Low/absent ADH → positive response to desmopressin 5, 6
- Nephrogenic DI: Normal/elevated ADH → minimal or no response to desmopressin 5, 6
- Both present with dilute urine (osmolality <200 mOsm/kg), polyuria, and elevated serum sodium 1, 5
Common Diagnostic Pitfall
Do not confuse diabetes insipidus with diabetes mellitus—they are completely unrelated conditions. The evidence provided includes diabetes mellitus classification 9, which is irrelevant to diabetes insipidus. Diabetes insipidus involves water balance and ADH, while diabetes mellitus involves glucose metabolism and insulin 2, 3.
Treatment Implications by Type
- Central DI and Gestational DI: Desmopressin is first-line therapy 1, 6, 3
- Nephrogenic DI: Thiazide diuretics, low-salt diet, and ad libitum fluid access (desmopressin is ineffective) 5, 3
- Dipsogenic DI: Behavioral therapy to regulate water intake, possible antipsychotic therapy if psychogenic 3
- All types require unrestricted access to water to prevent life-threatening hypernatremia 1, 5