Two hundred and sixty-three women with ultrasound-diagnosed polycystic ovary syndrome were studied of whom 91 (35%) were obese (BMI greater than 25 kg/m2). Obese women with PCOS had a greater prevalence of hirsutism (73% compared with 56%) and menstrual disorders than non-obese subjects. Total testosterone and androstenedione concentrations in serum were similar in the two subgroups but SHBG concentrations were significantly lower, and free testosterone levels higher, in obese compared with lean subjects. In addition, concentrations of androsterone glucuronide, a marker of peripheral 5 alpha-reductase activity, were higher in obese than in non-obese women with PCOS. There were no significant correlations of either SHBG or free testosterone with androsterone glucuronide suggesting that obesity has independent effects on transport and on metabolism of androgen. There were no significant differences between the subgroups in either baseline gonadotrophin concentrations or the pulsatile pattern of LH and FSH secretion studied over an 8-h period. There was, however, an inverse correlation of FSH with BMI, but only in the obese subgroup. In conclusion, the increased frequency of hirsutism in obese compared with lean women with PCOS is associated with increased bio-availability of androgens to peripheral tissues and enhanced activity of 5 alpha-reductase in obese subjects. The mechanism underlying the higher prevalence of anovulation in obese women remains unexplained.

Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 microg, 3 times daily, increased to 200 micro g three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 microg/liter). Five-point GH profiles were performed at 0, 4, 12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk. The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During sc Oct, serum GH fell to less than 5 mU/liter in 9 patients (38%), and IGF-I fell to normal in 8 patients (33%). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49% (range, 12-73), and for macroadenomas it was 43% (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/liter in 11 of 14 patients (79%), and IGF-I was normal in 8 of 15 patients (53%). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24%. At the end of the study 79% of patients had mean serum GH levels below 5 mU/liter, 53% had normal IGF-I levels, and 73% showed greater than 30% tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 microg/liter).

Objectives: Controversy persists with regard to the atherogenic risk associated with adult growth hormone deficiency (GHD). Endothelial dysfunction and enhanced oxidative stress are early features of atherogenesis. Therefore, we have studied the effect of three months of low dose GH replacement therapy (0.03 IU/kg/day) on these parameters in GHD adults. Subjects and Methods: Eight hypopituitary GHD adults (4 male, 4 female), who were receiving conventional hormone replacement therapy, were studied before and after 3 months of GH replacement (0.03 IU/kg/day). All observations obtained were compared with similar measurements made in 8 matched control subjects. All study subjects were non-smokers, normotensive and gave no personal or family history of premature vascular disease. Endothelial function was assessed using a specialised vessel wall tracking system to measure endothelium-dependent, flow-mediated, brachial artery dilatation (FMD). Measurements were repeated following glyceryl-trinitrate (GTN) (endotheliumindependent dilatation). Oxidative stress was assessed by directly measuring lipid-derived free radicals in venous blood by electron paramagnetic resonance spectroscopy. Fasting lipids, insulin, plasma glucose and IGF-I were also measured at baseline and following GH replacement. Results: FMD, expressed as a percentage change from resting base-line diameter, was significantly impaired in the pre-treatment GHD patients compared with controls (3.1 Ϯ 2.1% vs 6.1 Ϯ 0.9%, P < 0.001; means Ϯ S.D.) indicating endothelial dysfunction. Significant increase in FMD was noted following GH therapy (3.1 Ϯ 2.1% vs 6.5 Ϯ 1.9%, P < 0.001). Free radicals (arbitrary units) were elevated in the pre-treatment GHD patients compared with controls (0.36 Ϯ 0.09 vs 0.11 Ϯ 0.12, P < 0.05) and fell significantly following GH therapy (0.23 Ϯ 0.03 vs 0.36 Ϯ 0.09, P < 0.05), although they remained elevated compared with controls. Fasting insulin was significantly higher (25.9 Ϯ 18.8 vs 13.9 Ϯ 6.7 mu/l, P < 0.05) and IGF-I concentrations lower (10.8 Ϯ 4.7 vs 20.2 Ϯ 6.3 nmol/l, P < 0.05) in the pre-treatment GHD subjects. After treatment there were no changes in insulin concentration, although IGF-I levels were normalised (10.8 Ϯ 2.3 vs 23.6 Ϯ 11.4 nmol/l, P < 0.05). Conclusions: Endothelial dysfunction and enhanced oxidative stress are features of adult GHD. This study suggests plausible mechanisms underlying any proatherogenic tendency in adult GHD and demonstrates improvement of these factors following GH replacement.

Although the present data were not obtained in a formal study we conclude that cabergoline is an effective and well-tolerated treatment for macroprolactinoma patients.

Pheochromocytoma is rare in pregnancy, with an estimated incidence of 0.007%. Diagnosis is difficult owing to the variety of presentations and nonspecific symptoms. Nevertheless, unsuspected disease accounts for a significant proportion of morbidity and mortality. Currently, there appears to be no consensus on management with regard to the need for and timing of medical vs. surgical management. In this case report, we describe two patients who underwent different modes of treatment based on careful consideration of disease-related and nondisease-related factors. We emphasise that good outcomes can be achieved through individualized management within the context of a multidisciplinary team, involving close collaboration among physicians, surgeons, obstetricians, and anesthetists. We also illustrate the importance of genetic testing in all patients with pheochromocytoma in pregnancy, especially with the emergence of new predisposing genes (succinate dehydrogenase B and D) and the recognition that germline mutations in these and more established genes (VHL and RET) account for over a quarter of all apparently sporadic cases.

The results provide evidence for the long-term effectiveness and safety of cabergoline in the treatment of hyperprolactinaemia. Its ability to normalize PRL and restore gonadal function compares favourably with reported data on reference compounds while its tolerability profile and simple administration schedule offer potential advantages in terms of patient acceptability.

Adenosine receptors are widely distributed in most species and mediate a diverse range of physiological and pathological effects. Although adenosine receptors have been identified in the pituitary gland, the distribution of the individual subtypes (A 1 , A 2A , A 2B , A 3 ) has not been well defined. Furthermore, the effects of adenosine on pituitary trophic activity and function are not well established despite good evidence for growth-and immunemodulating properties of the nucleoside elsewhere.Recent advances have provided a more detailed description of adenosine receptor distribution and function in the anterior pituitary and this commentary reviews these observations and highlights some of the possible implications in relation to the control of the hypothalamicpituitary-adrenal axis and the regulation of inflammation and pituitary cell growth.

The Fibroid Registry for Outcomes Data (FIBROID) was founded in 1999 to serve as a prospective multicenter database of women undergoing uterine embolization for leiomyomata. This paper presents an analysis of the short-term outcomes of patients enrolled at 72 participating sites. Of a total 3005 patients, 2729 had a 30-day follow-up interview, which provided information on any further medical care, adverse events, time to return to work, and time to return to normal activities. The Registry defined an adverse event as an unexpected problem that required an unanticipated clinic visit or unanticipated therapy.Seventy-four percent of all patients received preprocedure antibiotics and one fourth was also given antibiotics postprocedure. Uterine embolizations were generally carried out under intravenous conscious sedation and supplemented with narcotics, two thirds of which were patient-controlled. In one participating center, regional analgesia was used in 12% of cases. Overall, 5% of patients had postprocedure deep vein thrombosis (DVT) prophylaxis with automated intermittent compression boots.Seventy-four percent of procedures were technically successful. Technical failures occurred when only one uterine artery could be identified for embolization or when bilateral uterine artery catheterization was unsuccessful.The average hospital stay was 1.68 days. During hospitalization, 90 patients experienced 94 adverse events, of which 20 were major. Eleven of these prolonged the hospital stay. Pain and nausea were the most common conditions, but one patient had a femoral nerve injury, which resulted in permanent leg pain. Other problems included drug reaction, urinary retention, and contrast reaction. Of 74 minor complications, groin hematomas were the most common (n ϭ 22). Other minor complications included less severe nausea, pain, vessel injury, drug reaction, urinary retention, and contrast reaction, as well as device-related problems and nontarget embolization. Patients generally resumed normal activities after 2 weeks.Major and minor adverse events were combined for univariate analysis. Possible predictors for perioperative complications, including patient demographic variables, medical history variables, presenting signs and symptoms, medications used, procedure-related variables, and site-related variables, were included. Only length of procedure, site status (ie, core registry sites vs participating sites), and size of leiomyomata were found to have predictive value for operative complications (odds ratio [OR], 1.012; 95% confidence interval [CI], 1.005-1.019; OR, 0.334; 95% CI, 0.15-0.76; OR, 1.0173; 95% CI, 1.0131-0138; respectively). After multivariate analysis, site status was no longer predictive of perioperative adverse advents.By the 1-month postprocedure evaluation, 710 patients had reported adverse events. Major complications (n ϭ 111; 4%) were persistent bleeding in 7 patients, infection or possible infection in 17, new hot flashes in 2, thromboembolism GYNECOLOGY Volume 60, Number 11 OBSTETRICAL AND GYN...