GENERALIZED LIPODYSTROPHY: EFFECT OF CEREBRAL DOPAMINERGIC BLOCKING AGENT (PIMOZIDE)

Abstract

Generalized lipodystrophy (GLD), characterized by loss of subcutaneous and other fat, skeletal/muscle overgrowth, neutral fat hepatomegaly, genital enlargement, gonadal failure, hyper-pigmentation, acanthosis nigricans, hyperlipidemia, hyperglycemia, and hyperinsulinism, is associated with detectable hypothalamic regulatory hormones in plasma (J Pediat 82:625, 1973).Reasoning that GLD is a disorder of hypothalamic dysfunction dependent on catecholaminergic mechanisms, and using our earlier experience with chlorpromazine, we administered Pimozide to a 7-year-old girl with GLD (8 mg/day for 16 mo). Pimozide (a diphenylbutylpiperidine used as a neuroleptic) is a selective inhibitor of cerebral dopaminergic receptors.Effects over 16-months were: a) immediate and sustained diminution of luteinizing releasing hormone and corticotropin releasing hormone to zero or trace plasma levels, b) return of normal response to intravenous ACTH (Acta Endocr 73:437, 1973), c) return of liver function and size to normal or near normal with abatement of abdominal pain, d) reversal of skin and hair changes, e) return of subcutaneous fat to face and back as shown by appearance and biopsy (0.5 cm thick).These results 1) support the concept of diencephalic involvement in GLD, 2) indicate that Pimozide impairs the synthesis/release of hypothalamic regulatory hormones, and 3) suggest that GLD is amenable to meaningful treatment.