Complete aromatase deficiency in four adult men: detection of a novel mutation and two known mutations in the CYP19A1 gene

The abstracts descibes four new cases of patients with aromatase deficiency. Both the clinical features and the results of the molecular studies are reported

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS

Non polycystic ovary syndrome-related endocrine disorders associated with hirsutism

Background Hyperandrogenism refers to classical androgen-dependent signs such as hirsutism, acne and androgenetic alopecia. Hirsutism is the main hyperandrogenic symptom, defined as an excess of body hair in the androgen-sensitive skin regions of the women. In this review, we attempt to focus on the pathogenesis of hirsutism related to disorders other than polycystic ovary syndrome (PCOS). Also, we will discuss their clinical and biochemical features as well as therapeutic options. Design Several original articles, meta-analysis and reviews have been screened in the field of hirsutism and hyperandrogenic disorders. Results Current English literature including our studies suggests that PCOS is the most common cause of hirsutism. The most important purpose for investigation is to identify those women with androgen-secreting tumours because of their life-threatening potential. In approximately 1-8% of the women with hirsutism, the underlying cause is nonclassical adrenal hyperplasia because of 21-hydroxylase deficiency. Depending on ethnicity and the geographic area, idiopathic hirsutism constitutes 5-17% of the patients with hirsutism. Approximately 3% of hyperandrogenic women were observed to suffer from hyperandrogenic-insulin-resistant acanthosis nigricans syndrome. More rare causes are glucocorticoid resistance syndrome, hyperprolactinemia, acromegaly, Cushing's syndrome and some drugs. Specific causes of hirsutism such as Cushing's syndrome and adrenal/ovarian tumours should be treated specifically. In other patients, pharmacological approach is the mainstay of therapy. Conclusions A number of patients presenting with hirsutism and exhibiting similar features to PCOS may have other underlying diagnoses. Unlike PCOS, some of these disorders can occasionally be life threatening and require prompt diagnosis and treatment. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation

Posterior pituitary function in Sheehan's syndrome

Objective: We studied posterior pituitary function in 27 patients with Sheehan's syndrome and 14 controls. Design: All patients were investigated by water deprivation test and 26 of them by 5% hypertonic saline infusion test. None of the patients had symptoms of diabetes insipidus and all patients were on adequate glucocorticoid and thyroid hormone replacement therapy before testing. Results: According to dehydration test, 8 (29.6%) patients had partial diabetes insipidus (PDI group) and 19 (70.3%) had normal response (non-DI group). During the 5% hypertonic saline infusion test, the maximal plasma osmolality was higher in PDI (305±4.3) and non-DI (308±1.7) groups when compared with controls (298±1.7 mOsm/kg; P < 0.005), but the maximal urine osmolality was lower in PDI group (565±37) than in non-DI (708±45) and control (683±17 mOsm/kg) groups (P<0.05). The osmotic threshold for thirst perception was higher in PDI (296±4.3) and non-DI (298±1.4) groups when compared with control group (287±1.5 mOsm/kg) (P<0.005). Basal plasma osmolalities were also higher in PDI (294±1.0) and non-DI (297±1.1) groups than in controls (288±1.2 mOsm/kg; P<0.001). Conclusions: Our findings demonstrated that patients with Sheehan's syndrome have an impairment of neurohypophyseal function. The thirst center may be affected by ischemic damage and the osmotic threshold for the onset of thirst in patients with Sheehan's syndrome is increased. © 2007 Society of the European Journal of Endocrinology

Investigation of adrenal functions in patients with idiopathic hyperandrogenemia

Objective: Some patients with hyperandrogenemia had no identifiable cause, which was named as idiopathic hyperandrogenemia (IHA). The role of the adrenal glands in these patients was investigated. Design: Clinical study in patients with IHA at the Endocrinology Department of a University Hospital. Patient(s): In this study, 26 pre-menopausal women with IHA and 20 healthy women were included. Basal hormonal investigations, ACTH test and a 75 g oral glucose tolerance test (OGTT) were performed. Basal levels of total testosterone, free testosterone, androstenedione (A4), sex hormone-binding globulin, DHEA sulfate (DHEAS), cortisol, 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (11-S) and ACTH-stimulated levels of cortisol, A4, DHEAS, 17-OHP, and 11-S were measured. Additionally, glucose and insulin responses to OGTT were obtained. Results: The patients and the control subjects had similar age and body mass index. Peak and area under the curve (AUC) responses of 11-S (P &lt; 0.05), DHEAS (P &lt; 0.005), and A4 (peak, P &lt; 0.005; AUC, P &lt; 0.00 1) to ACTH test were significantly higher in the patients with IHA than in the control subjects. There was a significant correlation between the basal DHEAS levels, peak 11-S, and AUC,11-s, in response to ACTH-stimulation test in patients with IHA (P &lt; 0.005, r, 0.6). Four (16.6%) patients with IHA had glucose intolerance. Conclusion: Our data suggest that adrenal androgen excess may play an important role in patients with IHA and these patients exhibit increased prevalence of glucose intolerance. © 2006 Society of the European Journal of Endocrinology

Do we still need the TRH stimulation test?

Objective: To evaluate the diagnostic value of the thyrotropin-releasing hormone (TRH) stimulation test in the diagnosis of central hypothyroidism in patients with Sheehan's syndrome. Design: TRH stimulation test was performed in 72 patients with Sheehan's syndrome. Basal free triiodothyronine (fT 3) and free thyroxine (fT4) levels were measured. Serum thyrotropin (TSH) concentration was determined before and 30, 60, 90, and 120 minutes after 200 µg TRH IV bolus injection. The peak TSH values &lt;5.5 µIU/ml were defined as inadequate response. A peak TSH at 60 minutes or later was considered as delayed response. If TSH (60 minutes after peak), was more than 40% of the peak value it was considered as prolonged response. The diagnosis of central hypothyroidism (CH) was made if either serum fT4 concentration was subnormal with an inappropriately low serum TSH concentration or inadequate response to TRH stimulation test and/or a delayed or prolonged response to TRH stimulation test. Main outcome: Fifty-six (77.7%) of the patients had low serum fT4 and fT3 levels with an inappropriately low serum TSH levels were defined as CH (CH0 group). Ten (13.8%) patients with normal and low-normal fT4 levels had no response and/or delayed or prolonged response to TRH stimulation test (CHlgroup). Six (8.3%) patients had fT 3, fT4, and TSH levels within normal limits and peak TSH responses ?5.5 µIU/ml consistent with euthyroidism (euthyroid group). Thus, 66 (91.6%) of 72 patients with Sheehan's syndrome had CH. Although fT 4 levels were within normal reference range, TRH stimulation test revealed that 10 (13.8%) of these had CH. Conclusion: TRH stimulation test is useful in the diagnosis of central hypothyroidism, especially in whom fT 4 and/or TSH is low-normal and known to have hypothalamo-pituitary pathology. © Mary Ann Liebert, Inc

Prevalence of polycystic ovarian changes and polycystic ovary syndrome in premenopausal women with treated type 2 diabetes mellitus

Objecti{dotless}ve: To investigate the prevalence of polycystic ovary syndrome (PCOS) and polycystic ovary (PCO) among premenopausal women with type 2 diabetes mellitus (DM). Desi{dotless}gn: Case-control study of women with type 2 DM. Setti{dotless}ng: Tertiary referral university hospital. Pati{dotless}ent(s): Ninety-two premenopausal women with DM, ?30 years of age, and 20 age- and body mass index-matched healthy premenapousal eumenorrheic women were recruited into the study. Interventi{dotless}on(s): An oral glucose tolerance test was performed according to the American Diabetes Association criteria for each healthy woman. After an overnight fasting, blood samples were obtained for the determination of fasting blood glucose, LH, FSH, free T, androstenedione (A4), 17-hydroxyprogesterone (17-OHP), DHEAS, PRL, free T4, TSH, E2, and sex hormone-binding globulin (SHBG) levels. A GnRH analog (buserelin) test was carried out in 36 patients with DM and PCO (including PCOS subjects), 20 patients with DM without PCO or PCOS, and 20 healthy subjects. Mai{dotless}n Outcome Measure(s): The prevalence of PCO and PCOS in women with type 2 DM. Result(s): Fifty-seven (62%) of diabetic patients had normal ovaries, 31 (33.7%) had PCO, and 4 (4.3%) had PCOS. The women with DM (n = 92) and healthy women (n = 20) had similar basal A4, FSH, E2, 17-OHP, free T, and DHEAS levels. The LH and SHBG levels were lower and the hirsutism score higher in diabetic patients than in healthy women (P&lt;.05). Peak and area under the curve LH and FSH levels after buserelin testing were significantly higher in healthy women than in the patients (P&lt;.05). Peak A4 levels after buserelin were significantly higher in the patients than in the healthy women (P&lt;.05). Ovarian volume was significantly greater in the patients with PCO (10.1 ± 0.7 mL) than in the healthy women (7.0 ± 0.9 mL) (P&lt;.05). Conclusion(s): We conclude that PCO but not PCOS is a common finding in premenopausal women with type 2 DM. Suppression of gonadotropins, particularly LH secretion, may play a role in the absence of increased PCOS prevalence among type 2 diabetic patients. © 2006 American Society for Reproductive Medicine