Central lacks the hormone; nephrogenic cannot respond to it
Mnemonic
“Cranial has no ADH; nephrogenic ignores it”:
- Cranial (central) - failure to produce ADH. Responds to desmopressin
- Nephrogenic - renal resistance to ADH. Does not respond
Both give large volumes of dilute urine with a raised plasma osmolality, and the water deprivation test separates them.
Cranial causes: pituitary surgery, trauma, tumour, craniopharyngioma, infiltration (sarcoid, histiocytosis), and idiopathic.
Nephrogenic causes: lithium (much the commonest acquired cause), demeclocycline, hypercalcaemia, hypokalaemia, chronic kidney disease and inherited forms.
Primary polydipsia is the mimic: excessive drinking washes out the medullary gradient, producing a partial response that can look like partial cranial diabetes insipidus. The distinguishing feature is a low or low normal plasma sodium, whereas true diabetes insipidus runs a high normal or raised sodium.
Expansion
Both cause large volumes of dilute urine and thirst.
Central (cranial)
- Deficient antidiuretic hormone secretion
- Causes: pituitary surgery, trauma, tumour, infiltration such as sarcoid or histiocytosis, idiopathic
- Responds to desmopressin
Nephrogenic
- Kidney cannot respond
- Causes: lithium, hypercalcaemia, hypokalaemia, chronic kidney disease, congenital V2 receptor or aquaporin-2 defects
- Does not respond to desmopressin
Water deprivation test: in both, urine stays dilute during deprivation. Giving desmopressin then separates them, since only the central form concentrates.
The main differential is primary polydipsia, in which the patient concentrates normally with water deprivation, though a chronically washed-out medullary gradient may blunt the response.
Note that patients with an intact thirst mechanism and free access to water maintain a normal sodium; hypernatraemia appears when thirst is impaired or water is unavailable.