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A variety of lesions can invade and destroy all or a large part of the hypothalamus These include sarcoid and other granulomatous diseases, an idiopathic in ammatory disease, and germ-cell and other tumors The hypothalamus is involved in approximately 5 percent of cases of sarcoidosis, sometimes as the primary manifestation of the disease, but more often in combination with facial palsy and hilar lymphadenopathy An elevation of angiotensin-converting factor, particularly in the cerebrospinal uid (CSF), con rms the diagnosis The lesions are visible by magnetic resonance imaging (MRI) (see Fig 32-2) Tumors that involve the hypothalamopituitary axis include metastatic carcinoma, lymphoma, craniopharyngioma, and a variety of germ-cell tumors The latter (reviewed by Jennings et al) include germinomas, teratomas, embryonal carcinoma, and choriocarcinoma They develop during childhood, tend to invade the posterior hypothalamus, and are accompanied in some instances by an increase in serum alpha fetoprotein or the beta subunit of chorionic gonadotropin A unique syndrome of gelastic epilepsy is caused by a hamartoma of the hypothalamus (see Chap 16) Among the in ammatory conditions, infundibuloneurohypophysitis, or infundibulitis, is a cryptogenic in ammation of the neurohypophysis and pituitary stalk, with thickening of these parts by in ltrates of lymphocytes (mainly T cells) and plasma cells (Imura et al) It is thought to be an autoimmune disorder Histiocytosis X a group of diseases comprising Letterer-Siwe disease, HandSchuller-Christian disease, and eosinophilic granuloma impli cates multiple organs, including the hypothalamus and neighboring structures and leptomeninges (often causing cells to appear in the CSF) These conditions of children pursue an indolent course The cell type is a proliferating histiocyte

Diabetes Insipidus (DI) This is a state of polyuria with dilute urine and polydypsia that results in 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 DI 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 posterior pituitary secretion 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 DuVigneaud and colleagues determined the chemical structure of the two neurohypophysial peptides, vasopressin and oxytocin, of which these granules were composed

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These observations opened up the entire eld of neuroendocrinology As already stated, the usual cause of DI is a lack of vasopressin (antidiuretic hormone, or ADH) as a result of a lesion of the neurohypophysis This leads to a reduction in its action in the kidneys, where it normally promotes the absorption of water As a consequence there is diuresis of low-osmolar urine (polyuria), 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 has a similar effect nephrogenic DI DI is also of interest to the neurologist because of its association with lithium toxicity, which impairs renal tubular water absorption Among the established causes of acquired DI, the most important are brain tumors, in ltrative granulomatous diseases, head injury, and intracranial surgical trauma (which has become less frequent with the transphenoidal approach to pituitary tumors) In a series of 135 cases of persistent DI reported by Moses and Streeten, 25 percent were idiopathic, 15 percent complicated primary brain tumors, 24 percent were postoperative (mostly after hypophysectomy or surgery for craniopharyngioma), 18 percent were due to head trauma, and fewer than 10 percent were associated with intracranial histiocytosis, metastatic cancer, sarcoidosis, and ruptured aneurysm Granulomatous in ltration of the base of the brain by sarcoid, eosinophilic granuloma, Letterer-Siwe disease, or Hand-Schuller-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 in ltrating processes generally exhibit other systemic manifestations before polydipsia and polyuria appear Metastatic tumors originating in the lung or breast or leukemic in ltration 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 is not always evident at the time brainstem re exes are lost Pituitary tumors are infrequently associated with DI unless they become massive and invade the stalk of the pituitary and the infundibulum This anatomic relationship has been substantiated by surgical sections of the stalk for metastatic carcinoma and for retinitis proliferans, which result in DI only if the section is high enough to produce retrograde degeneration of supraoptic neurons Among the idiopathic forms of DI, there also exists a congenital type of hypothalamic DI, of which only a small number of familial cases have been described The disorder is evident at an early age and persists throughout life, owing to a developmental defect of the supraoptic and paraventricular nuclei and smallness of the posterior lobe of the pituitary This defect has been related in some cases to a point mutation in the vasopressin-neurophysinglycopeptide gene It may be combined with other genetic disorders such as diabetes mellitus, optic atrophy, deafness (Wolfram syndrome), and Friedreich ataxia Acquired idiopathic DI may occur at any age, most often in childhood or early adult life and more often in males, and by definition has no apparent cause Other signs of hypothalamic or pituitary disease are lacking in 80 percent of such patients, but steps must be taken to exclude other disease processes by repeating the.

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