The impact of obesity on hormonal parameters in hirsute and nonhirsute women.

The influence of obesity on sex hormone-binding globulin (SHBG) and androgen concentrations in hirsute and nonhirsute women has been evaluated. The study was performed in 226 hirsute women (88 obese and 138 non-obese) classified as being affected by polycystic ovarian syndrome (PCOS) or by idiopathic hirsutism (IH) and in 100 nonhirsute control women ([C] 60 lean and 40 obese). SHBG, free testosterone (fT), androstenedione (A), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and gonadotropin levels were measured during the first week of the menstrual cycle by radioimmunoassay (RIA). A significant negative correlation between SHBG and body mass index (BMI) was observed in PCOS, IH, and C women. In obese women--whether PCOS, IH, or C-fT levels were significantly higher and, conversely, SHBG levels were lower than in non-obese women. A negative correlation between SHBG and fT was evidenced in each group. Upper-body obesity was associated with lower SHBG and higher fT levels than lower-body obesity. In conclusion, obesity, particularly upper-body obesity, is associated with a reduction in SHBG and an increase in fT in both nonhirsute and hirsute women.

Increased 17 alpha-hydroxyprogesterone response to ACTH in silent adrenal adenoma: cause or effect?

OBJECTIVE: Recent studies suggest a possible connection between silent adrenal nodules and mild forms of 21-hydroxylase deficiency. It remains unclear whether the enzymatic deficiency is generalized or intrinsic to the adrenal mass. To help to clarify this, we have studied 17 alpha-OH-progesterone (17OH-P) response to ACTH stimulation in a group of patients with adrenal 'incidentaloma' in comparison with normal subjects. In patients who underwent surgical treatment, the test was repeated to evaluate possible modifications in 17OH-P behaviour after resection of the adrenal mass. SUBJECTS AND METHODS: Fifteen subjects with incidentally discovered asymptomatic adrenal masses were studied. Basal hormone evaluations were normal, with normal cortisol suppression after low-dose dexamethasone. Iodocholesterol scanning, performed in 12 patients, showed normal bilateral adrenal uptake in 2 subjects and an increased uptake on the side of the lesion in 10 subjects. In every patient, ACTH stimulation was performed to evaluate the secretory response of cortisol, 17OH-P, progesterone and dehydroepiandrosterone sulphate. An identical test was performed in 10 control subjects with normal adrenal glands, matched for age and sex. In six patients with an adrenal lesion > 3.5 cm, the ACTH stimulation test was repeated one month after surgery. RESULTS: The 17OH-P response to ACTH stimulation was significantly higher in subjects with adrenal 'incidentaloma' than in controls (P < 0.01). In particular, 10 subjects out of 15 (66%) evidenced a 17OH-P peak > 18 nmol/l at 60 minutes. No differences were seen in baseline 17OH-P or cortisol levels or in cortisol response to ACTH between the two groups. Dehydroepiandrosterone sulphate concentrations were significantly lower in patients with adrenal 'incidentaloma' than in normals. In six patients who had an increased 17OH-P response to ACTH on initial evaluation, the ACTH test was repeated one month after surgery. In five of these patients, 17OH-P response to ACTH was clearly reduced, suggesting that in these cases the enzymatic defect was restricted to the adenoma. In the other patient, however, stimulated 17OH-P levels remained unchanged. In this case, therefore, all of the adrenal tissue seems to be involved, suggesting a late-onset 21-hydroxylase deficiency. No significant modifications in cortisol response to ACTH were observed. CONCLUSION: It seems therefore that in some cases of incidentaloma the steroidogenic enzymatic defect may be secondary to the adenomatous proliferation, while in others such defects may induce the development of silent adrenal nodules.

Endocrine evaluation in patients treated with interferon-alpha for chronic hepatitis C.

The aim of our study was to evaluate the hormonal profile in a group of 31 subjects who underwent recombinant interferon-alpha therapy for chronic active hepatitis C. Hormonal determinations were performed before treatment began and at the end of the 3rd and 6th months of therapy. Free-T4 concentrations, though remaining in the normal range, showed a significant reduction (p < 0.05) after 3 and 6 months of therapy compared with pretreatment levels. A lesser decrease in free-T3 levels was also seen. TSH basal values did not show any variation, while an increased secretory response to TRH stimulation was observed at the end of the 6th month. Thyroglobulin and calcitonin levels remained normal, while an increase in antithyroglobulin and antithyreoperoxidase antibody levels was observed in 4 patients (12.9%). No modifications in the other pituitary hormones or in adrenal and sex steroid concentrations were noticed. A significant increase in IGF-I concentrations (p < 0.05) was observed during treatment, and an inverse correlation was seen between IGF-I and alanine aminotransferase levels (p < 0.01). This study supports the view that interferon treatment can influence thyroid function. The increase in IGF-I concentration observed during therapy may reflect an improvement in patients with hepatic disease, but a direct stimulatory effect of interferon on IGF-I secretion cannot be excluded.

The use of flutamide in the management of hirsutism.

The aim of our study was to evaluate the clinical efficacy of flutamide (Flu), when used alone, on the course of hirsutism and to assess its effect on hormonal secretion. Thirty-six hirsute women [11 patients were affected by polycystic ovarian syndrome (PCOs), and 25 were classified as having idiopathic hirsutism (IH)] were treated with Flu, 375 mg daily for a 4-month period. We found a marked clinical improvement in the degree of hirsutism in all patients. Testosterone and free testosterone fell significantly in both groups, while SHBG concentrations showed an increase in PCOs. In these patients, a reduction in androstenedione levels was also evident. Basal DHEAS concentrations showed a significant decrease only in PCO women. No significant modifications in gonadotropin response to LHRH nor in adrenal steroid response to ACTH stimulation were observed in 12 of the IH women before therapy and after the first month. Although the main action of flutamide is attributed to its peripheral antiandrogenic properties, the decrease in circulating androgen levels observed during treatment suggests that it can also modulate androgen production and/or metabolism.