The syndromes of anorexia nervosa and bulimia have been difficult to classify and are mentioned in this chapter only because they are associated with alterations in several hypothalamic functions, including appetite, temperature control, and menstruation. In all likelihood, these alterations do not stem from a primary dysfunction of hypothalamic nuclei, but rather are a result of the extreme weight loss that is the primary feature of the disease. However, a causal link between these idiopathic diseases and hypothalamic dysfunction has been suggested by the rare patients with an anorexia nervosa syndrome who were later found to have hypothalamic tumors (Bhanji and Mattingly; Berek et al; and Lewin et al).
Anorexia nervosa and bulimia are probably best regarded as disorders of behavior, in this case an obsession with thinness; consequently, they are discussed with the psychiatric disorders (see Anderson and Chap. 47). But the developmental nature of the disease (arising in early adolescence), its virtual absence in men, and the hypothalamic alterations mentioned previously do not allow the dismissal of a primary disorder of the brain’s appetite centers (Scheithauser).
Abnormalities of Growth
Some instances of growth retardation relate to a deficiency of either GHRH or GH. In the Prader-Willi syndrome (obesity, hypogonadism, hypotonia, mental retardation, and short stature), Bray and Gallagher found the deficiency to be one of GHRH. In other congenital and developmental diseases, the hypothalamus appears to be incapable of releasing GH. This appears to be the case in the de Morsier septooptic defect of the brain (median facial cleft, cavum septum pellucidum, optic defect), where Stewart and colleagues found an isolated deficiency of GH. In children with idiopathic hypopituitarism in whom stunting of growth is associated with other endocrine abnormalities, the deficiency is probably in the synthesis or release of GHRH (Brazeau). In some dwarfs (Laron dwarf, Seckel bird-headed dwarf), there are extremely high levels of circulating GH, suggesting either a defect in the GH molecule or an unresponsiveness of target organs. Many patients with the more severe forms of mental retardation are subnormal in height and weight, but the explanation for this has not been ascertained. It has not been reducible to changes in the level of GHRH or GH.
Of course, the vast majority of unusually short children who are otherwise healthy do not have a recognizable defect in GH or GHRH. Often their parents are short. The therapeutic use of GH in such children is a controversial matter. The hormone affects a spurt in growth during the first year of its administration, but whether it significantly influences growth in the long term is still under investigation. There is concern about the risk of transmitting prion or viral diseases through administration of the biologically derived hormone; this problem is obviated if a genetically produced hormone is used.
In gigantism, most reported cases have been caused by pituitary adenomas that secrete an excess of GH. This must occur prior to closure of the epiphyses. Hypersecretion of GH after closure of the epiphyses results in acromegaly. The notion of a purely hypothalamic form of gigantism or acromegaly (hypothalamic acromegaly) has been affirmed by Asa and associates, who described six patients with hypothalamic gangliocytomas that produced GHRH. The possibility of an ectopic source of GH must also be considered. The mentally retarded individuals with gigantism described by Sotos and coworkers were found to have no abnormalities of GHRH, GH, or somatomedin.
Systemic Effects and Other Disorders of Hypothalamic Disease
Disturbances of Temperature Regulation