Berardinelli-Seip Syndrome: Report of an Old Case Successfully Treated with Anti-Glucocorticoid Therapy Followed by Bilateral Adrenalectomy

Abstract

A female teenager was diagnosed in 1986 with Berardinelli-Seip syndrome (congenital generalized lipodystrophy). Following the predictable failure of the usual treatments for her severe type 2 diabetes and hypertriglyceridemia, we decided to treat her with a novel anti-glucocorticoid-centered approach. In 1988, we treated her with mifepristone alone (9 weeks), then with mifepristone combined with ketoconazole (1 week), and again, with mifepristone alone (2 weeks). Acanthosis nigricans, as well as eruptive xanthomas, experienced complete regression following the anti-glucocorticoid therapy. Moreover, the patient gained 7 kilograms. Besides, there was a striking metabolic amelioration with mifepristone therapy. The addition of ketoconazole strongly reduced the relevant mifepristone-induced hypercortisolemia within 1 week. Fasting serum glucose, insulin, and triglycerides fell from day 1 to day 7 without reaching values within the normal range. Two weeks after ketoconazole withdrawal (while keeping mifepristone administration), serum triglyceride and glucose values rose significantly. Eleven days after bilateral adrenalectomy, fasting glucose values were within normal limits or slightly above. An oral glucose tolerance test (75-g OGTT) performed 13 days after surgery showed insulin values within normal limits, fasting serum glucose values within the normal range, and a 2-h serum glucose value in the diabetic range. These findings were consistent with our working hypothesis proposing that Berardinelli-Seip syndrome is due to cortisol-mediated unrestrained lipolysis.