Anti-androgen treatment increases circulating ghrelin levels in obese women with polycystic ovary syndrome.

In a previous study we were the first to describe a negative correlation between circulating ghrelin concentrations and androgen levels in human plasma, suggesting an interaction between ghrelin and the endocrine regulation of reproductive physiology. We now investigated a potential direct regulatory influence of circulating androgens on plasma ghrelin levels. Fourteen obese women with polycystic ovary syndrome (PCOS) on a hypocaloric diet were randomly assigned to treatment groups (open-labeled design), receiving either placebo (no.=7) or the antiandrogen flutamide (no.=7) for 6 months. Anthropometry, visceral (VAT) and subcutaneous (SAT) adipose tissue (quantified by computerized tomography), plasma hormone levels, insulin sensitivity indexes (Quantitative Insulin-Sensitivity Check Index-QUICKI) and Homeostatic Model Assessment applied to the oral glucose tolerance test (HOMA(OGTT)) were evaluated at baseline and at the end of the study. Body weight decreased and insulin resistance indexes improved in both groups. A tendency toward a greater loss of VAT was observed in the flutamide group. Only in the flutamide group was a significant reduction of androgens levels observed. Plasma ghrelin levels significantly increased following treatment with flutamide, while ghrelin remained unchanged in the placebo group. We observed a negative correlation between changes of ghrelin levels and changes of androgen plasma concentration in the flutamide-treated group. In the same group a positive correlation was found between plasma ghrelin changes and insulin sensitivity as expressed by HOMA(OGTT). Analysis in a multiple regression model, however, showed that plasma ghrelin changes were mainly due to changes of androgen levels rather than improved insulin sensitivity. We, therefore, conclude that androgens are independent modulators of circulating ghrelin concentrations.

Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in women with visceral and subcutaneous obesity: effects of the corticotropin-releasing factor/arginine-vasopressin test and of stress.

In a previous study, we demonstrated that premenopausal women with visceral obesity have hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, characterized by an exaggerated hormone response to corticotropin-releasing factor (CRF) and corticotropin (ACTH) stimulation. The hypothalamic peptide flow that stimulates the pituitary, particularly after a physiological stress challenge, involves not only CRF, but also arginine-vasopressin (AVP), which synergizes the CRF capacity to stimulate pituitary hormone secretion. Previous studies in humans have demonstrated that combining AVP with CRF permits maximal stimulation of the pituitary, providing a more appropriate method of assessing pituitary hormone reserve. We therefore investigated the response of the HPA axis to combined CRF and AVP stimuli in obese women with different obesity phenotypes. Moreover, we examined hormonal and cardiovascular responses to several mental stress tasks, according to previously standardized procedures. Two groups of age-matched premenopausal eumenorrheic obese women with visceral (V-BFD) or subcutaneous (S-BFD) body fat distribution and a group of normal-weight healthy controls were investigated. All women randomly underwent the following protocol: (1) a combined CRF/AVP test (100 micrograms plus 0.3 IU intravenously [IV], respectively); (2) a standardized stress test, which consisted of completing two puzzles and a mental arithmetic test; and (3) a control saline test. Blood samples for ACTH and cortisol determinations were obtained before and during each test, and measurements of arterial blood pressure and pulse rate were made at regular intervals during the stress test. After combined CRF/AVP administration, ACTH and cortisol were significantly higher in V-BFD than in the other two groups. In contrast, no significant hormonal variation was found in either group during stress tasks. During the stress test, pulse rate (but not arterial blood pressure) significantly increased after 8 and 15 minutes in the V-BFD group, whereas no significant variation was found in S-BFD and control women. A significant correlation was present between the pulse rate and change in cortisol level during the stress test at minutes 8 (r=.54, P<.05) and 15 (r=.57, p<.01) in all women considered together. Subjective emotional involvement during stressful tasks was measured by a two-dimensional short verbal scale, which revealed that the stress section had a more significant impact in obese V-BFD than in S-BFD and control women. These data therefore confirm that women with visceral obesity have hyperactivity of the HPA axis, and that the combined CRF/AVP stimulation may offer a good tool for investigating pituitary reserve in this obesity phenotype. Moreover, the results indicate that these women probably have a hyperreactive sympathetic response to acute stress that seems interrelated to that of the HPA axis.

[Pseudodiverticula of the ureter: a precancerous lesion?]. / Pseudodiverticoli dell'uretere: una lesione precancerosa?

Ureteral diverticula belong to the group of acquired diverticula even though their pathogenesis and clinical significance are still debated. They are occasionally detected during urography or retrograde pyelography and appear as small spicular or saccate wall outpouchings, single or more often multiple, mostly limited to the upper third of the ureter. The frequent association of these lesions with transitional cell carcinoma of the urinary tract is a problem of great clinical interest since they might represent a preneoplastic manifestation. The authors report on 16 patients with pseudodiverticula, 6 of whom (37.5%) affected with benign prostatic hyperplasia, 4 (25%) with synchronous or metachronous vesical neoplasm and 3 with renal stones. The remaining three patients were affected respectively with vesicoureteral reflux, neurogenic bladder and ureteropelvic junction obstruction. All patients were men over 46 years old. Ureteral involvement was bilateral in 50% of patients. The radiologic pattern consisted of small marginal outpouchings 1-3 mm in diameter, whose demonstration requires good contrast opacification and ureter distension. Pseudodiverticula were always localized in the upper third of the ureter and were multiple in 15/16 cases. Anatomical-histologic studies showed that pseudodiverticula result from hyperplastic-type proliferation of lung epithelium in the ureteral submucosa. Our observations do not confirm literature data on the frequent association between pseudodiverticula and transitional cell carcinoma because of the common presence, in our patients, of other non-neoplastic urinary conditions. The patients with benign hyperplasia of the ureteral epithelium cannot be excluded to be a risk group for cancer, even though no precise confirmation exists. The best advice is to carefully follow-up the patients with ureteral pseudodiverticula, clinically and with IVP.

[Diagnostic images of renal angiomyolipoma]. / Diagnostica per immagini dell'angiomiolipoma renale.

The authors report 26 cases of renal angiomyolipomas (AML) detected in a three-years period (1983-85). In all cases echography, in 6 renal arteriography and in 13 CT were performed. The review of the pathway and of literature stress some new aspects in diagnostic problems of AML. The extensive use of diagnostic ultrasound shows an higher rate of tumors than in the pre-echographic period. Most of these lesions are asymptomatic and incidentally detected as small nodules. Ultrasound, combined with CT, can resolve the diagnostic dilemma of benign lesion. An echographic follow-up is sufficient to confirm this evaluation in typical cases. In large or bleeding tumors and when there is a prevalence of connective and/or muscular tissue, a diagnostic and ablative surgery is mandatory.