[Lp(a) and weight loss in obese patients]. / Lp(a) et perte de poids chez l'obèse.

High concentrations of lipoprotein (a) (Lp(a)) are associated with an increased risk of atherosclerotic vascular disease. Lp(a) synthesis is mainly under genetic control but many endocrine disturbances may modulate Lp(a) plasmatic concentrations. There is no agreement upon Lp(a) variations in patients under a hypocaloric diet. This study was undertaken to assess this point in obese females subjected to a 1100 kcal/d diet. Ninety-two obese patients (42.4 +/- 10.4 yr old, BMI 33.9 +/- 5.6 kg/m2) came once a week as out patients during 9 weeks. Lp(a) concentrations distribution was highly skewed. The threshold Lp(a) concentration for a significant cardiovascular risk is estimated at 0.3 g/l. Concentrations above 0.3 g/l were found in 29/92 patients (31%). If the patients were distributed in 2 groups according to their Lp(a) values (< or = ou > 0.3 g/l), the BMI, total cholesterol or triglycerides were not different. There were no significant correlation between Lp(a) and age, total cholesterol or triglycerides. After 9 weeks BMI and total cholesterol values decreased (-1.6 +/- 3.4 kg/m2 and -0.17 +/- 0.68 mmol/l, respectively). Lp(a) concentrations were unchanged (0.3 +/- 0.3 vs 0.3 +/- 0.3 g/l). There were no significant correlation between Lp(a) variations and age, BMI or initial Lp(a) concentrations. No significant decrease of Lp(a) could be detected even in the sub-group of patients with initial concentrations of Lp(a) > 0.3 g/l or even in a sub-group with Lp(a) > 0.7 g/l (n = 7). Under our conditions, weight loss is not associated with a decrease of Lp(a) concentrations suggesting that in a given obese a single determination is enough to assess his Lp(a)-related atherosclerotic risk.

Pretibial myxedema and high-dose intravenous immunoglobulin treatment.

Seven patients affected by Graves' ophthalmopathy and pretibial myxedema (four patients with nodular form, two with diffuse, and one with elephanthiasic form) have been treated with high-dose intravenous immunoglobulins. We have observed (a) clinical improvement of pretibial myxedema and Graves' ophthalmopathy in all patients, (b) a reduction of pretibial skin thickness, by ultrasonography evaluation, in four patients, (c) a reduction of mucopolysaccharide skin content in three patients, (d) disappearance of lymphocytic skin infiltration and IgG deposition in two patients, and (e) a parallel reduction of the titer of circulating autoantibodies as antithyroglobulin, antimicrosomal, anti-TSH receptor, and of non-organ-specific antibodies as antinuclear, anti-smooth muscle cells, and anti-mitochondrial. In comparison two patients with Graves' ophthalmopathy and pretibial myxedema treated with systemic corticosteroids did not present any improvement of the cutaneous ailment. Therefore, this study suggests that intravenous immunoglobulins are effective in the treatment of pretibial myxedema and may have an immunomodulant action in patients with Graves' disease and related disorders.

Comparative value of plasma ACTH and beta-endorphin measurement with three different commercial kits for the etiological diagnosis of ACTH-dependent Cushing's syndrome.

Recent reports suggest that, contrary to radioimmunoassays (RIA), immunoradiometric assays (IRMA) artifactually decrease plasma ACTH levels in patients with the ectopic ACTH syndrome. Discrepancies between RIA and IRMA results may provide a means of discriminating this entity from Cushing's disease. We have compared the results of these two techniques, together with those of a beta-endorphin assay, in 17 patients with Cushing's disease, 9 with the ectopic ACTH syndrome and 30 controls. ACTH-RIA and ACTH-IRMA levels in patients with Cushing's disease were similar (17.5 +/- 2.5 vs 15.1 +/- 2.8 pmol/l) and were correlated (rs = 0.59, p less than 0.01). ACTH-RIA levels in patients with the ectopic ACTH syndrome were higher than ACTH-IRMA levels (27.3 +/- 2.9 vs 14.5 +/- 2.5, p less than 0.01) and these did not correlate. The ACTH-RIA and ACTH-RIA/ACTH-IRMA ratio levels in patients with the ectopic ACTH syndrome were higher than those of patients with Cushing's disease (p less than 0.01), but they overlapped with these in 27 and 31% of cases respectively. Plasma beta-endorphin level was higher in patients with the ectopic ACTH syndrome than in patients with Cushing's disease (81.9 +/- 19.4 vs 26.4 +/- 5.6 pmol/l, p less than 0.01) and was correlated with ACTH only in patients with Cushing's disease. The overlap in beta-endorphin and beta-endorphin/ACTH-IRMA molar ratio levels between the two groups were 19 and 27% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Biological and developmental aspects of macronodular adrenal hyperplasia in Cushing's disease]. / Aspects biologiques et évolutifs de l'hyperplasie surrénalienne macronodulaire au cours de la maladie de Cushing.

The pathophysiology of macronodular adrenocortical hyperplasia (MNH) associated with Cushing's diseases remains debatable. Some authors have claimed that MNH represents an autonomous condition that has to be treated by surgical adrenalectomy while others advocate the use of pituitary surgery. We have compared the biochemical features, before and after pituitary surgery, between 7 cases of MHN and 22 cases of diffuse hyperplasia (DH) associated with Cushing's disease. In addition, the diameter of the adrenal nodules after surgery was evaluated in 6 cases. The mean ACTH level in MNH and DH subjects was similar. Dexamethasone suppressibility and the stimulatory effect of metyrapone on ACTH secretion were less in MNH than in DH subjects, suggesting a greater degree of adrenal autonomy in the former. The cortisol responses to metyrapone and CRF tests suggested an increased responsiveness of the adrenals to endogenous ACTH in the MNH group. Only one MNH patient had biochemical features suggesting a primary adrenal disease. The use of a sensitive ACTH assay and the results of inferior petrosal sinus sampling identified the ACTH-dependency of the disease. A short to medium term remission of the disease was obtained in all cases of MNH and in 87% of cases of DH after surgery. The diameter of the adrenal nodules significantly decreased in only 43% of cases. Our results suggest that the adrenal autonomy in MNH is incomplete and that, despite the persistence of the adrenocortical nodules, the disease can be cured with pituitary microsurgery in most cases.

[Isolated osteoporosis in a case with Cushing's disease: development after treatment]. / Ostéoporose isolée dans un cas de maladie de Cushing: évolution après traitement.

The unusual case of a 37 year old woman with Cushing's disease in whom the only feature of hypercortisolism was a clinically asymptomatic osteoporosis is presented. After successful treatment of the disease, serial bone biopsy examinations and bone mineral density measurements (BMD) were performed up to 31 months. 27 months after cessation of hypercortisolism, BMD remained unchanged and histomorphometric examination showed no improvement of the osteopenia in addition to focal osteomalacia. Despite 5 months of calcium and vitamin D therapy, BMD did not improve. This case report emphasizes the importance of routine evaluation of adrenal function in unexplained isolated osteoporosis. Long-term follow-up studies, leaded in a large number of patients are necessary to elucidate the course of osteoporosis in Cushing's syndrome and the usefulness of a specific treatment.

Use of ketoconazole in the treatment of Cushing's disease and ectopic ACTH syndrome.

Ketoconazole, an imidazole derivative which inhibits adrenal steroidogenesis, has been used with success for the metabolic control of Cushing's disease. Few data are available about the use of ketoconazole in the management of the ectopic ACTH syndrome. We have used ketoconazole in eight patients: four patients with Cushing's disease, two patients with overt and two with occult ectopic ACTH syndrome. Among patients with Cushing's disease, reversible hypoadrenalism occurred once. All had full clinical and biochemical regression of the disease for more than 6 months with 400-1200 mg ketoconazole per day. Patients with ectopic ACTH syndrome received 1200 mg ketoconazole per day for at least 2 months. Partial biochemical regression was observed in two and a secondary escape to adrenal blockade in two others. These findings further indicate that ketoconazole is a valuable tool for the metabolic control of Cushing's disease. On the contrary, in ectopic ACTH syndrome, this aim can be impossible to reach with ketoconazole although the reasons for its ineffectiveness remain to be determined.

[Efficacy and long-term tolerance of ketoconazole in the treatment of Cushing's disease]. / Efficacité et tolérance à long terme du kétoconazole dans le traitement de la maladie de Cushing.

Successful short term treatment of patients with Cushing's disease by Ketoconazole without adverse effects is now well established. Little data are available about prolonged treatment of this disease with ketoconazole. We report herein our experience of ketoconazole therapy in four patients with Cushing's disease treated for 9 to 38 months. One patient rapidly developed adrenal hypofunction and required transient steroid therapy adjunction. In the other patients, cortisol overproduction was reduced to normal levels within two months and their urinary free cortisol remained within the normal range throughout the study. In two patients ketoconazole dose could be decreased but had to be increased after ten months of therapy in one patient. None of the patients had clinical or biochemical signs of drug toxicity. Thus, ketoconazole seems to be a useful drug for the prolonged metabolic control of Cushing's disease. However, in this circumstance, ketoconazole daily dose adaptation can be necessary in order to maintain normal urinary cortisol levels and the ability of ketoconazole to cure Cushing's disease still remains to be determined.

[Systemic urticaria associated with autoimmune thyroiditis]. / Urticaire systémique associée à une thyroïdite auto-immune.

A case of chronic urticaria associated with thyroiditis is described. The diagnosis of autoimmune thyroid disease (Hashimoto's disease) rested on the presence of nodular goiter, thyroid dysfunction and significantly elevated thyroid microsomal antibodies (greater than 6,400). Skin biopsy showed changes suggestive of leucocytoclastic vasculitis. Immunological studies showed few abnormalities (low titers of antinuclear antibodies and rheumatoid factor) but a search for circulating immune complexes was negative, and serum complement levels were within normal range. The patient complained of severe pruritus and polyarthralgia but no systemic involvement occurred. Urticaria vasculitis has never previously been described in association with thyroid autoimmunity. This suggests the possibility of an autoimmune cause of urticaria. The urticaria improved and disappeared after treatment with levothyroxine. The frequent clinical latency of thyroiditis warrants systematic testing for circulating anti-microsome antibodies in women presenting with an apparently idiopathic chronic urticaria.