central diabetes insipidus
Summary
Central diabetes insipidus (CDI) is caused by insufficient secretion of antidiuretic hormone (ADH/vasopressin) from the posterior pituitary/hypothalamus, leading to impaired renal water reabsorption. This results in polyuria with dilute urine and compensatory polydipsia. Common causes include head trauma, pituitary surgery, tumors, and idiopathic autoimmune destruction of ADH-producing neurons.
Detail
Central DI results from decreased production or release of arginine vasopressin (AVP) by the hypothalamic supraoptic and paraventricular nuclei, or damage to the posterior pituitary (neurohypophysis) where ADH is stored and released. Without adequate ADH, the renal collecting ducts fail to insert aquaporin-2 water channels, causing excretion of large volumes of dilute urine (polyuria) and secondary polydipsia to compensate for water loss.
Etiologies include: idiopathic (autoimmune destruction of vasopressinergic neurons), traumatic brain injury, neurosurgery (especially pituitary/hypothalamic surgery), tumors (craniopharyngioma, germinoma, metastases), infiltrative diseases (Langerhans cell histiocytosis, sarcoidosis), infections (meningitis, encephalitis), and genetic causes (rare, autosomal dominant AVP gene mutations).
Clinical presentation: polyuria (>3L/day), nocturia, polydipsia, and if water intake is restricted or impaired (e.g., in infants or altered mental status), can lead to hypernatremia and hyperosmolar dehydration.
Diagnosis: Water deprivation test shows failure to concentrate urine despite dehydration; administration of desmopressin (DDAVP, synthetic ADH analog) leads to significant increase in urine osmolality (>50% increase) in central DI, differentiating it from nephrogenic DI (where the kidney is unresponsive to ADH and there is minimal response to desmopressin). Serum sodium and osmolality are typically high-normal or elevated; urine osmolality is inappropriately low relative to serum osmolality.
Treatment: Desmopressin (DDAVP) is the mainstay of treatment, given intranasally, orally, or parenterally. It's important to differentiate from primary polydipsia (psychogenic) and nephrogenic DI, as management differs significantly.
Key Step 1/2 associations: Compare with SIADH (opposite pathophysiology - excess ADH), differentiate central vs nephrogenic DI using desmopressin challenge test, and know that lithium and demeclocycline can cause nephrogenic DI as an important pharmacology correlation.
Sources
- First Aid for the USMLE Step 1
- Harrison's Principles of Internal Medicine
- UpToDate: Diagnosis of diabetes insipidus
- Guyton and Hall Textbook of Medical Physiology
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.