Clinical Endocrinology

Background  Pituitary adenomas (PAs) are associated with increased morbidity and mortality. The optimal delivery of services and the provision of care for patients with PAs require distribution of the resources proportionate to the impact of these conditions on the community. Currently, the resource allocation for PAs in the health care system is lacking a reliable and an up‐to‐date epidemiological background that would reflect the recent advances in the diagnostic technologies, leading to the earlier recognition of these tumours.

Objectives  To determine the prevalence, the diagnostic delay and the characteristics of patients with PA in a well‐defined geographical area of the UK (Banbury, Oxfordshire).

Patients and methods  Sixteen general practitioner (GP) surgeries covering the area of Banbury and a total population of 89 334 inhabitants were asked to participate in the study (data confirmed on 31 July 2006). Fourteen surgeries with a total of 81,449 inhabitants (91% of the study population) agreed to take part. All cases of PAs were found following an exhaustive computer database search of agreed terms by the staff of each Practice and data on age, gender, presenting manifestations and their duration, imaging features at diagnosis, history of multiple endocrine neoplasia type 1 and family history of PA were collected.

Results  A total of 63 patients with PA were identified amongst the study population of 81,149, with a prevalence of 77·6 PA cases/100,000 inhabitants (prolactinomas; PRLoma: 44·4, nonfunctioning PAs: 22·2, acromegaly; ACRO: 8·6, corticotroph adenoma: 1·2 and unknown functional status; UFS: 1·2/100,000 inhabitants). The distribution of each PA subtype was for PRLoma 57%, nonfunctioning PAs 28%, ACRO 11%, corticotroph adenoma 2% and UFS 2%. The median age at diagnosis and the duration of symptoms until diagnosis (in years) were for PRLoma 32·0 and 1·5, nonfunctioning PAs 51·5 and 0·8, ACRO 47 and 4·5 and corticotroph adenoma 57 and 7, respectively. PRLoma was the most frequent PA diagnosed up to the age of 60 years (0–20 years: 75% and 20–60 years: 61% of PAs) and nonfunctioning PA after the age of 60 years (60% of PAs). Nonfunctioning PAs dominated in men (57% of all men with PA) and PRLoma in women (76% of all women with PA). Five patients (7·9%) presented with classical pituitary apoplexy, with a prevalence of 6·2 cases/100,000 inhabitants.

Conclusions  Based on a well‐defined population in Banbury (Oxfordshire, UK), we have shown that PAs have a fourfold increased prevalence than previously thought; our data confirm that PAs have a higher burden on the Health Care System and optimal resource distribution for both clinical care and research activities aiming to improve the outcome of these patients are needed.

The aetiology of Polycystic Ovary Syndrome (PCOS) is complex and multifactorial. There is much evidence, however, to suggest that adipose tissue plays an important role in the development and maintenance of PCOS pathology. There is a close correlation between adiposity and symptom severity in women with PCOS, and even modest reductions in weight generally translate into significant improvements in menstrual regularity, fertility and hyperandrogenic features. This review article considers the various mechanisms that might underlie this link between excess adiposity and PCOS – including the effects of differential insulin sensitivity, abnormal steroid hormone metabolism and adipocytokine secretion. Greater attention to the therapeutic options available to reduce the impact of excess adiposity on ovarian and metabolic function is essential to the management of PCOS.

background  There are many reports that diagnostic accuracy of fine‐needle aspiration (FNA) of thyroid is improved with ultrasound guidance, especially for impalpable nodules. Despite its general acceptance, routine use of ultrasound‐guided fine‐needle aspiration (USGFNA) has been the source of much controversy due to the lack of large‐scale studies and lack of data on the natural course of well‐differentiated thyroid cancer of small size.

objective  The aim of our study was to define the rate of malignancy in relatively large numbers of patients with incidentally detected impalpable thyroid nodules and to assess the extent of disease in patients with suspicious or malignant cytology on USGFNA of thyroid nodules by surgery.

patients  We retrospectively reviewed the medical records of the 267 patients who underwent USGFNA of incidental thyroid nodules from January 2000 to December 2001.

results  Three hundred and seventeen nodules from 267 patients were aspirated. The average size of nodules was 0·9 ± 0·3 cm, a range of 0·2 cm to 1·5 cm. All 317 lesions were impalpable. Cytological diagnosis included 101 inadequate specimen (32%), 139 benign (44%), 29 indeterminate (9%), four suspicious of follicular or Hürthle cell neoplasm (1%), 42 papillary carcinoma (13%) and two others. The size of the nodule was not related to the probability of getting an adequate specimen for cytological diagnosis. Forty of 48 patients with suspicious or malignant cytology underwent surgery. All 35 patients with a cytological diagnosis of papillary carcinoma were confirmed to have papillary carcinoma on histological results. One of three patients with a cytological diagnosis of follicular neoplasm had a follicular carcinoma. In 36 patients with well‐differentiated thyroid cancer, extrathyroidal extension was observed in 44% (16/36), regional lymph node metastasis was found in 50% (18/36) and multifocal tumours were found in 39% (14/36).

conclusions  The rate of malignancy in incidentally detected impalpable thyroid nodules was 12% in retrospective analysis of our patients. In this subgroup, 69% (25/36) of patients had either extrathyroidal extension or regional node involvement and 39% had multifocal tumours at surgery. This suggests that the small size alone does not guarantee low risk in incidentally found thyroid cancers. USGFNA is a useful diagnostic method in these patients.

Objectives  The role of androgen decline in the sexual activity of adult males is controversial. To clarify whether sexual function would benefit from testosterone (T) treatment in men with partially or severely reduced serum T levels, we conducted a systematic review and meta‐analysis of placebo‐controlled studies published in the past 30 years. The aim of this study was to assess and compare the effects of T on the different domains of sexual life.

Data source  A comprehensive search of all published randomized clinical trials was performed in MEDLINE, the Cochrane Library, EMBASE and Current Contents databases.

Review methods  Guided by prespecified criteria, software‐assisted data abstraction and quality assessed by two independent reviewers, a total of 17 randomized placebo‐controlled trials were found to be eligible. For each domain of sexual function we calculated the standardized mean difference relative to T and reported the results of pooled estimates of T treatment using the random effect model of meta‐analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta‐regression analysis.

Results  Overall, 656 subjects were evaluated: 284 were randomized to T, 284 to placebo (P) and 88 treated in cross‐over. The median study length was 3 months (range 1–36 months). Our meta‐analysis showed that in men with an average T level at baseline below 12 nmol/l, T treatment moderately improved the number of nocturnal erections, sexual thoughts and motivation, number of successful intercourses, scores of erectile function and overall sexual satisfaction, whereas T had no effect on erectile function in eugonadal men compared to placebo. Heterogeneity was explored by grouping studies according to the characteristics of the study population. A cut‐off value of 10 nmol/l for the mean T of the study population failed to predict the effect of treatment, whereas the presence of risk factors for vasculogenic erectile dysfunction (ED), comorbidities and shorter evaluation periods were associated with greater treatment effects in the studies performed in hypogonadal, but not in eugonadal, men. Meta‐regression analysis showed that the effects of T on erectile function, but not libido, were inversely related to the mean baseline T concentration. The meta‐analysis of available studies indicates that T treatment might be useful for improving vasculogenic ED in selected subjects with low or low‐normal T levels. The evidence for a beneficial effect of T treatment on erectile function should be tempered with the caveats that the effect tends to decline over time, is progressively smaller with increasing baseline T levels, and long‐term safety data are not available. The present meta‐analysis highlights the need, and pitfalls, for large‐scale, long‐term, randomized controlled trials to formally investigate the efficacy of T replacement in symptomatic middle‐aged and elderly men with reduced T levels and ED.

OBJECTIVE The evidence that some women with the polycystic ovary syndrome (PCOS) are hyperinsulinaemic has brought into question their risk of developing early coronary artery disease. We have focused on three cardiac risk factors which have been associated with hyperinsullnaemia by measuring glucose tolerance, fasting serum lipid concentrations and blood pressure in women with PCOS.

DESIGN Comparison of clinical and biochemical measurements in lean and obese women with PCOS and in women with normal ovaries. Determinants of the risk factors for coronary artery disease were assessed by multiple regression analysis.

PATIENTS One hundred and two women with ultrasound diagnosed PCOS and 19 lean women with normal ovaries were studied. Patients were recruited from a reproductive endocrine clinic.

MEASUREMENTS Fasting total cholesterol, triglycerides, high density lipoproteins (HDL), HDL₂, glucose tolerance, fasting and stimulated insulin, gonadotrophins, testosterone and androstenedione were measured during a 2‐hour oral glucose tolerance test. Recumbent blood pressure was measured automatically.

RESULTS Lean women with PCOS were found to be hyperinsulinaemic and have reduced serum HDL and HDL₂ concentrations compared to women with normal ovaries; serum insulin concentrations correlated positively with plasma glucose and blood pressure measurements in multiple regression analysis. Obese women with PCOS were in addition found to have higher systolic blood pressure, serum triglyceride and plasma glucose concentration than lean women with PCOS and controls.

CONCLUSIONS These results support the evidence that hyperinsulinaemic women with PCOS have an increased risk of developing cardiovascular disease and therefore form a population in whom metabolic screening is advisable.