This is a state of production of excessively dilute urine that results from the loss of action of antidiuretic hormone. As long ago as 1913, Farini of Venice and von den Velden of Dusseldorf (quoted by Martin and Reichlin) independently discovered that diabetes insipidus was associated with destructive lesions of the hypothalamus. They showed, moreover, that in patients with this disorder, the polyuria could be corrected by injections of extracts of the posterior pituitary. Ranson elucidated the anatomy of the neurohypophysis; the Scharrers traced the substance secreted by the posterior pituitary to granules in the cells of the supraoptic and paraventricular nuclei and followed their passage to axon terminals in the posterior lobe of the pituitary. As mentioned in the introductory section, DuVigneaud and colleagues determined the chemical structure of the two neurohypophyseal peptides, vasopressin and oxytocin, of which these granules were composed.
As already stated, the usual cause of diabetes insipidus DI is a lack of vasopressin (ADH) secretion resulting from a lesion of the neurohypophysis. This leads to a reduction of absorption of water in the renal tubules. As a consequence, there is diuresis of low-osmolar urine, reduction in blood volume, and increased thirst and drinking of water (polydipsia) in an attempt to maintain osmolality. A congenital abnormality of renal tubular epithelium or destruction of the epithelium ultimately has a similar effect, but is termed nephrogenic DI. Notably, this type of DI may be provoked by lithium toxicity.
Among the established causes of acquired central DI, the most important are brain tumors, infiltrative granulomatous diseases, head injury, and intracranial surgical trauma (which has become less frequent with the transsphenoidal approach to pituitary tumors). In a series of 135 cases of persistent DI reported by Moses and Stretten, 25 percent were idiopathic, 15 percent complicated primary brain tumors, 24 percent were postoperative (mostly after hypophysectomy or surgery for craniopharyngioma), 18 percent were caused by head trauma, and fewer than 10 percent were associated with intracranial histiocytosis, metastatic cancer, sarcoidosis, and ruptured aneurysm. Granulomatous infiltration of the base of the brain by sarcoid, eosinophilic granuloma, Letterer-Siwe disease, or Hand-Schüller-Christian disease, is a more frequent cause of DI in young patients. Of the primary tumors, glioma, hamartoma and craniopharyngioma, granular cell tumor (choristoma), large chromophobe adenomas, and pinealoma are notable. The primary tumors can present with DI alone, whereas the granulomatous infiltrating processes generally exhibit other systemic manifestations before polydipsia and polyuria appear. Metastatic tumors originating in the lung or breast or leukemic and lymphomatous infiltration may also cause DI, sometimes in conjunction with pituitary disturbances and impairment of vision. The mild global hypothalamic dysfunction that often follows brain irradiation for glioma may occasionally include DI as a feature. The most extreme cases of hypothalamic destruction occur in brain death, in which DI is a regular component, although it may occur only hours after brainstem reflexes are lost, or it may not be apparent at all.
Pituitary tumors are infrequently associated with DI unless they become massive and invade the stalk of the pituitary and the infundibulum. This anatomic relationship was substantiated in past years by surgical sections of the stalk for metastatic carcinoma, which resulted in DI only if the section was high enough to produce degeneration of supraoptic neurons.