We found lower basal plasma cortisol concentrations in nonsurvivors compared with survivors of severe sepsis. In addition, the plasma cortisol response to a single CRH stimulation was impaired in nonsurvivors compared with survivors. Reduced responses to CRH stimulation may reflect a state of endocrinologic organ dysfunction in severe sepsis.

Radiotherapy can cause infertility in both men and women. However, few data are available concerning the effects of radioiodine therapy for thyroid carcinoma on testicular function. We investigated 25 men (age 23-73 years) with differentiated thyroid carcinoma in a longitudinal prospective trial. Follicle-stimulating hormone (FSH), inhibin B, luteinising hormone (LH) and testosterone were measured before (n = 25) and 3 months (n = 11), 6 months (n = 18), 12 months (n = 22), and 18 months (n = 18) after radioiodine therapy [radioiodine dose (mean +/- SEM): 9.8+/-0.89 GBq]. Before therapy, FSH was 5.4+/-0.77 IU/l; it increased significantly (P<0.001) to 21.3+/-2.4 IU/l after 6 months and fell to 7.4+/-1.3 IU/l after 18 months (normal range: 1.8-9.2 IU/l). Inhibin B was significantly decreased (P<0.001) from 178+/-25.3 pg/ml before therapy to 22.2+/-5.5 pg/ml after 3 and 29.4+/-5.7 pg/ml after 6 months and rose to 154+/-23.3 pg/ml after 18 months (normal range 75-350 pg/ml). LH and testosterone were within the normal range during the whole study (1.6-9.2 IU/l and 10.4-34.7 nmol/l, respectively). LH was significantly increased (P<0.001) from 2.8+/-0.33 IU/l before therapy to 5.9+/-0.69 IU/l 6 months after therapy and then fell slowly to 4.0+/-0.45 IU/l after 18 months. Total testosterone was significantly increased (P<0.01) from 12.8+/-0.99 nmol/l at baseline to 19.8+/-1.7 nmol/l after 12 months and 19.6+/-1.7 nmol/l after 18 months. The testosterone/LH ratio (normal range: 3.3-17.9 nmol/IU) fell from 5.8+/-0.66 nmol/IU to 3.0+/-0.36 nmol/IU after 3 months (P<0.01); it remained close to the latter value after 6 months (3.4+/-0.49 nmol/IU) and then rose to 5.5+/-0.6 nmol/IU after 18 months. In conclusion, 3 and 6 months after radioiodine therapy all patients showed elevated FSH and decreased inhibin B levels, reflecting severely impaired spermatogenesis. At the same time a compensated insufficiency of the Leydig cell function was observed. Eighteen months after the last radioiodine therapy, mean values of gonadal function had completely recovered.

HBY 097 [(S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4-dihydroquinoxaline-2(1H)-

Skewing of X inactivation may contribute to the manifestation of symptoms in adrenoleukodystrophy carriers. We observed highly skewed X inactivation in 32% of 22 symptomatic and asymptomatic carriers but not in 7 related and 35 unrelated controls. Skewing of X inactivation correlated with clinical neurological scores but not with the extent of very long-chain fatty acid accumulation. Transcript analysis in cultured fibroblasts revealed that skewing could occur both in favor of the mutant and the wild-type allele. Adrenoleukodystrophy carriers are more susceptible to develop skewing of X inactivation in favor of the mutant allele being associated with the manifestation of symptoms.

Dosages of 15, 20 or 30 mg hydrocortisone/day have equivalent effects on quality of life in patients with secondary hypocortisolism. With 15 or 20 mg hydrocortisone/day the patients feel nearly as well and content as normal healthy individuals. Since long-term treatment with a high replacement dose of glucocorticoids (hydrocortisone 30 mg/day) induces bone loss, this risk can be avoided with a substitution dosage of 20 mg or even 15 mg hydrocortisone/day, without influencing the well-being of the patient.