DIENCEPHALIC INVOLVEMENT IN GENERALIZED LIPODYSTROPHY: RATIONALE AND TREATMENT WITH THE NEUROLEPTIC AGENT, PIMOZIDE

Abstract

ABSTRACT Our results indicate that generalized lipodystrophy (GLD) possesses as one of its manifestations, diencephalic neuroendocrinopathy. It has been postulated that deranged hypothalamic catecholaminergic mechanisms lead to the hypersecretion of hypophysiotrophic hormones that are detectable in the peripheral circulation. Initial treatment of a pre-puberal GLD patient with chlorpromazine was unrewarding. Chronic treatment of the same patients with the selective dopaminergic blocking agent, pimozide, eliminated corticotrophin releasing factor and luteinizing hormone releasing factor activities from the general circulation. Pimozide treatment ameliorated most of the distorted blood chemistry profile, led to return of facial subcutaneous fat, and elimination of cutaneous hyperpigmentation, fever, abdominal pain, hypertrichosis, oilness of hair, scaliness of skin and to a state of general well-being. The results of these studies, structured within the framework of our present knowledge concerning hypothalamic neurotransmitter/releasing hormone physiology, support the concept of diencephalic involvement in GLD and may provide a guideline to effective therapy.