Recent data suggest that insulin is a modulator of ovarian and adrenal steroidogenesis and that, in the ovary of hyperandrogenic women, hyperinsulinemia might cause dysregulation of cytochrome P450c17 alpha activity. To further assess in vivo the effects of insulin on adrenal steroidogenesis, ACTH stimulation was carried out in 21 hyperandrogenic women during a 3-h hyperinsulinemic (80 mU/m2-min) euglycemic clamp. In all of these women the procedure was repeated during saline infusion as n control. In nonamenorrheic patients, the tests were performed in the early follicular phase of two different menstrual cycles. Serum cortisol, progesterone, 17-hydroxypregnenolone (17-OHJPREG). 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), and androstenedione (A) were measured after 2 h of insulin or saline infusion (zero time) and, subsequently, 30 and 60 min after an iv bolus of 0.25 mg ACTH-(1-24). At zero time, no difference was found in the serum steroid concentrations between the two protocols. ACTH-stimulated serum 17-OHPREG and, to a lesser extent, 17-OHP were significantly higher during insulin than during saline infusion (peaks, 60.6 +/- 9.0 vs. 40.7 +/- 7.9 and 7.7 +/- 7.7 vs. 6.6 +/- 0.6 nmol/L; P < 0.005 and P < 0.01, respectively). Serum DHEA was also slightly higher during hyperinsulinemia, although only after 30 min (54.5 +/- 3.0 vs. 48.2 +/- 4.2 nmol/L; P < 0.05). No statistically significant difference in the cortisol, progesterone, or androstenedione response to ACTH was found between the two protocols. ACTH-stimulated 17-OHPREG/DHEA and 17-OHP/A molar ratios, indexes of apparent 17,20-lyase activity, were significantly higher during the clamp studies than during saline infusion (by ANOVA, F = 12.8; P < 0.001 and F = 6.7; P < 0.005, respectively), suggesting an impaired enzyme activity. These in vivo data support the hypothesis that insulin potentiates ACTH-stimulated steroidogenesis. This effect of insulin seems to be associated with a relative impairment of 17,20-lyase activity.

We examined the effects of biosynthetic growth hormone (GH) on biochemical indices of bone turnover and on bone mineral density in a group of GH-deficient adults. Thirteen patients (eight males and five females) aged 24 +/- 5 years (range 16-35) were studied before and 12 and 24 months after GH treatment (0.1 IU.kg-1 day-1, 6 days a week). Serum levels of insulin-like growth factor I (IGF-I), calcitonin, parathyroid hormone, alkaline phosphatase, intact osteocalcin, fasting urinary hydroxyproline/creatinine ratio and bone mineral density (BMD), measured at the lumbar spine by dual-photon absorptiometry, were evaluated. After 12 months of treatment, IGF-I, alkaline phosphatase, osteocalcin and the fasting urinary hydroxyproline/creatinine ratio increased significantly. However, after 24 months of therapy, serum levels of osteocalcin decreased to pretreatment values while IGF-I, fasting urinary hydroxyproline/creatinine ratio and alkaline phosphatase remained elevated significantly. No changes were found in parathyroid hormone and calcitonin plasma levels or in BMD either after 12 or 24 months of treatment. These data demonstrate that GH, at the dosage that we used, activates bone turnover during 24 months of therapy in adults with panhypopituitarism, even if a downward trend for osteocalcin became apparent at 24 months. However, this activation in bone turnover was not accompanied by an increase in BMD. We can hypothesize that GH, at the relatively high dosage used, may stimulate osteoclastic activity to a greater extent than osteoblastic activity. It is probable that the dose of GH replacement therapy in adults plays a key role.

Three sisters with male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency are described. On the basis of a 46 XY karyotype and female phenotype all subjects were thought to have the testicular feminization syndrome. At puberty the two older patients developed signs of virilization and gynaecomastia. In these patients the plasma androstenedione level was 4-5 times higher than normal, whilst the plasma testosterone level was low compared to the normal range and, under basal conditions, their plasma androstenedione to testosterone ratio was 20-25 times higher than normal. Interestingly, in the third, prepubertal case, the basal androstenedione to testosterone ratio was normal but became six times higher than normal after hCG stimulation. These data support the diagnosis of male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency and underline the diagnostic value of the hCG stimulation test prepubertally.

No abstract

To evaluate the effect of growth hormone on testicular response to human chorionic gonadotropins (hCG) in vivo in humans, we selected patients with combined deficits of GH and gonadotropins who were in substitution treatment with both GH (from the time of diagnosis) and gonadotropins (from the time of induction of puberty). Testicular response to gonadotropin therapy was then evaluated during and six months after the cessation of GH treatment. Blood samples were collected before and 2, 4 and 6 days after hCG administration. hCG responses were calculated and expressed as the areas under the response curve. We studied four hypogonadotropic patients (aged 18–19 years) with associated GH deficiency. Their gonadotropin treatment consisted of hCG 1500IU every six days, and FSH 75 IU every three days. The GH therapy replacement consisted of 4 IU thrice weekly. Testosterone, androstenedione, 17α-hydroxyprogesterone and estradiol were measured. In all subjects the testosterone area during GH treatment was significantly higher compared to the testosterone area obtained without GH administration (2993±1091 vs 2310±751; M±sd; p<0.04). The androstenedione area followed a similar pattern (708±377 vs 402±248; M±sd; p<0.05). The 17α-hydroxyprogesterone area, on the contrary, was significantly higher during GH withdrawal (542±307 vs 235±190; M±sd; p<0.05). As far as the estradiol area is concerned, no significant differences were found (22860±10082 vs 25697±13640; M±sd). In conclusion, GH administration seems to improve testosterone production induced by human chorionic gonadotropins. The finding of the inverse response pattern of 17α-hydroxyprogesterone with respect to testosterone led us to suppose that the increased testosterone area during GH treatment may be due to an increased activity of C17,20-lyase enzyme.