On the occasion of a new case of congenital generalized lipodystrophy the clinical features of this disease are reviewed. Furthermore, the frequent association of type V hypertriglyceridemia is emphasized. Various pathogenic hypotheses guide the therapeutic attempts, which are often unsuccessful.
This article outlines a systematic treatment for patients on combined oral contraceptives (OCs) in whom hyperlipidism is induced or aggravated by the OCs. 36 women aged 20-40 years who used OCs containing 50 mcg of ethinyl estradiol (EE) and Norgestrel were treated by the same team of physicians with an identical protocol. 9 of the 36 women had elevated triglyceride (TG) levels, 5 had elevated total cholesterol (TC) levels, and 22 had both. The average level of TG was 1.56 and of TC 2.88 g/l. When the EE dosage of the 1st group was reduced to 30 mcg, the average TG level fell from 1.44 to l g/l. In a 2nd group, in which either lipid levels were very high or predisposing factors were present, the use of combined OCs was discontinued; the average level of TG declined from 1.64 to .95. Some patients were treated successively in both groups. In patients receiving reduced dosages of EE, the average TC level declined from 2.80 to 2.22. The average TC level for those discontinuing OC therapy declined form 2.89 to 2.40. Despite high initial values in those for whom OC therapy was stopped, most cases were normalized with these procedures. In 2 cases of elevated TG, 5 of TC, and 5 of both, the levels were not normalized within 3 months of discontinuing OC therapy. In 9 of 10 cases of elevated TC or TC and TG, predisposing factors were present. The experience suggests the existence of 2 categories of lipid anomales, those induced by the OCs, which tend to be moderate and subject to improvement or disappearance with reduced dosage of EE or discontinuation of OCs, and probably preexisting cases which are aggravated by the OCs. Such cases are of greater significance and are likely to persist longer. In cases of preexisting lipid anomalies when genetic factors are involved, OCs should be stopped to avoid the risk of vascular accidents.
In the present work, the presence of gastric inhibitory polypeptide (GIP) receptors and their functional role in the adrenal cells of three patients with food-dependent Cushing’s syndrome were studied. RT-PCR and in situ hybridization studies demonstrated the presence of GIP receptor in the adrenals of the three patients. The presence of this receptor was also demonstrated in two human fetal adrenals, but not in two normal adult human adrenals or in the adrenals of one patient with nonfood-dependent Cushing’s syndrome. Freshly isolated cells from patient adrenals responded in a dose-dependent manner to the steroidogenic action of both ACTH and GIP, whereas cells from normal adrenals responded only to ACTH. Treatment of cultured normal adrenal cells with ACTH, but not with GIP, increased the messenger ribonucleic acid (mRNA) levels of cholesterol side-chain cleavage cytochrome P-450, P450c17, and 3β-hydroxysteroid dehydrogenase, whereas both hormones enhanced these mRNAs in patients’ adrenal cells, although the effects of ACTH were greater than those of GIP. Moreover, pretreatment with ACTH enhanced the steroidogenic responsiveness of both normal and patient adrenal cells, whereas GIP caused homologous desensitization, and this was associated with a marked reduction of GIP receptor mRNA levels, as demonstrated by RT-PCR and in situ hybridization. Finally, both ACTH and GIP inhibited DNA synthesis in one patient’s adrenal cells, whereas in normal adrenal cells only ACTH had this effect. In conclusion, the present data demonstrate that ectopic expression of functional GIP receptors is the main cause of food-dependent Cushing’s syndrome.
