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W. E. de Lange, M. C. Snoep and H. Doorenbos


Eight boys with severely delayed puberty without pathological cause were treated for 6 months with testosterone. This resulted in acceleration of skeletal maturation and a marked increase in height and weight. No adverse effects were found on hypothalamic-pituitary and gonadal maturation. Basal LH, FSH and testosterone levels rose to nearly adult values at follow-up within a year and pituitary responsiveness to LH-RH increased markedly.

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W. E. de Lange, M. C. Snoep and H. Doorenbos


LH-RH injection and infusion studies were performed in advanced puberty, delayed puberty and hypogonadotrophic hypogonadism. No differential diagnosis could be made between delayed puberty and hypogonadotrophic hypogonadism using LH-RH injection. In the LH-RH infusion studies evidence was obtained that stimulation of the pituitary during 4 h results in continuously rising LH levels in advanced puberty and in delayed puberty while in hypogonadotrophic hypogonadism the secretory capacity of the pituitary is gradually exhausted. This phenomenon can be used in the differential diagnosis between delayed puberty and hypogonadotrophic hypogonadism. Though the FSH data point in the same direction they are not useful in this connection as the overlap between the different categories was considerable.

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J. W. Janssen, I. W. L. de Lange-Berkhout, C. van Hardeveld and A. A. H. Kassenaar


Rats were made hyperthyroid by repeated sc injections of l-thyroxine (T4) in a two-week period. At several time-points after the last injection, the triiodothyronine (T3) and T4 concentrations in plasma and red and white skeletal muscle were determined by a radioimmunoassay. This was done to investigate the relationship between the change in thyroid-hormone concentration in plasma and muscle and to see whether this change was similar in both muscle types. The results show that:

1. Information about the T3 and T4 concentrations in the muscles of the hyperthyroid rats can only be obtained by direct measurement in the muscles and cannot be gathered from the plasma-T3 concentration at any time-point or from below-normal plasma-T4 concentrations.

2. In hyperthyroid rats T4 and T3 are cleared more rapidly from the plasma than from the skeletal muscle.

3. A proportionally higher T3 concentration is present in the red compared with the white skeletal muscle of hyperthyroid rats.

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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


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.


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.


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.


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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A C Gore, J Balthazart, D Bikle, D O Carpenter, D Crews, P Czernichow, E Diamanti-Kandarakis, R M Dores, D Grattan, P R Hof, A N Hollenberg, C Lange, A V Lee, J E Levine, R P Millar, R J Nelson, M Porta, M Poth, D M Power, G S Prins, E C Ridgway, E F Rissman, J A Romijn, P E Sawchenko, P D Sly, O Söder, H S Taylor, M Tena-Sempere, H Vaudry, K Wallen, Z Wang, L Wartofsky and C S Watson