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A. B. Abou-Samra, M. Fevre-Montange, M. Pugeat, H. Dechaud, D. Chalendar, B. Estour and J. Tourniaire

Abstract. Serum 11-deoxycortisol (S) determination has been used to evaluate the pituitary adrenal response to the short metyrapone (MTP) test. The validity of this indirect evaluation of corticotrophin ACTH reserve has been questioned since the MTP-induced S elevation may reflect a passive accumulation rather than an ACTH activated adrenal response. The purpose of this study was to evaluate the usefulness of serum β-lipotrophin (β-LPH) measurement during the short midnight MTP test (30 mg/kg body weight) in patients with pituitary diseases (n = 36) and in patients with Cushing's syndrome (n = 8). In 28/36 patients with pituitary diseases both S and β-LPH concentrations were increased normally by MTP. In 8/36 patients the β-LPH response was lacking, while their serum S concentrations increased significantly. The absence of β-LPH response to MTP in these 8 patients was in good agreement with the diagnosis of ACTH insufficiency because in 7 of them the cortisol response to insulin induced hypoglycaemia was also insufficient.

In the 8 patients with Cushing's syndrome serum S concentration increased following MTP administration in all the cases. In 2 with adrenal adenoma the increase of S level was an ACTH-independent phenomenon, since β-LPH level was undetectable both before and after MTP administration. In 2 patients with ectopic ACTH secretion, the basal β-LPH concentrations were high and remained unmodified by MTP administration. In the 4 patients with Cushing's disease, MTP administration resulted in a dramatic increase of β-LPH concentration. We conclude that β-LPH measurement improves the utility of the short MTP test for investigation of pituitary adrenal function.

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F Bonnet, B Balkau, J M Malécot, P Picard, C Lange, F Fumeron, R Aubert, V Raverot, H Déchaud, J Tichet, P Lecomte, M Pugeat and for the DESIR Study Group

Objective

Previous evidence has suggested that a low sex hormone-binding globulin (SHBG) concentration is associated with insulin-resistance and a low adiponectin concentration. We investigated the association between SHBG and the risk of hyperglycemia in each sex and we determined potential interactions between SHBG and adiponectin levels in the development of dysglycemia.

Design

We used a nested case–control design in the large prospective study, Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR). We studied 227 men and women who were normoglycemic at baseline but hyperglycemic at 3 years (glycemia≥6.1 mmol/l or type 2 diabetes). They were matched for sex, age, and body mass index with 227 subjects who remained normoglycemic at 3 years.

Results

At baseline, the concentration of SHBG was significantly lower in women who subsequently developed hyperglycemia than in those who remained normoglycemic, with no difference for men. In multiple regression, SHBG at baseline was as an independent determinant of plasma adiponectin levels, in both women (P<0.0001) and men (P=0.002). In multivariate conditional logistic regression taking into account physical activity and changes in waist circumference over the follow-up, plasma SHBG remained significantly associated with the development of hyperglycemia in women but not in men. These associations persisted after adjustment for fasting insulinemia, high fasting glucose, and adiponectin levels.

Conclusions

These findings suggest that a low SHBG level is a strong risk marker for dysglycemia in women, independently of both adiponectinemia and insulinemia. SHBG may therefore improve the identification of women at risk of diabetes.

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Elodie Fiot, Delphine Zénaty, Priscilla Boizeau, Jérémie Haignere, Sophie Dos Santos, Juliane Léger and the French Turner Syndrome Study Group

Objective

Turner Syndrome is associated with several phenotypic conditions associated with a higher risk of subsequent comorbidity. We aimed to evaluate the prevalence of congenital malformations and the occurrence of age-related comorbid conditions and to determine whether the frequencies of congenital and acquired conditions depend on X chromosome gene dosage, as a function of karyotype subgroup.

Design and methods

This national retrospective observational cohort study includes 1501 patients. We evaluated the prevalence of congenital malformations and the cumulative incidence of subsequent specific comorbidities at five-year intervals, from the ages of 10 to 30 years, with stratification by karyotype subgroup: 45,X (n = 549), 45,X/46,isoXq (n = 280), 46,X,r(X)/46,XX (n = 106), 45,X/46,XX (n = 221), presence of Y (n = 87).

Results

Median age was 9.4 (3.7–13.7) years at first evaluation and 16.8 (11.2–21.4) years at last evaluation. Congenital heart (18.9%) malformations were more frequent in 45,X patients, and congenital renal (17.2%) malformations were more frequent in 45,X, 45,X/46,isoXq and 46,X,r(X)/46,XX patients than in those with 45,X/46,XX mosaicism or a Y chromosome (P < 0.0001). The cumulative incidence of subsequent acquired conditions, such as thyroid disease, hearing loss, overweight/obesity, dyslipidemia and, to a lesser extent, celiac disease, glucose intolerance/type 2 diabetes, hypertension and liver dysfunction increased with age, but less markedly for patients with mosaicism than for those with other karyotypes. Patients with a ring chromosome were more prone to metabolic disorders.

Conclusion

These data suggest that X gene chromosome dosage, particularly for Xp genes, contributes to the risk of developing comorbidities.