Clomiphene citrate is the treatment of first choice in the management of infertility in normally oestrogenized, anovulatory women (WHO group II). The majority of women with 'pure' anovulatory infertility respond to treatment with clomiphene citrate. The rates of pregnancy and miscarriage are close to those expected in a normal fertile population. Basal hormone concentrations do not predict outcome. An increased body mass index is the only factor which is consistently associated with a decreased response to clomiphene citrate; it follows therefore, that weight reduction should be an important part of therapy in anovulatory women. According to our data, only an increased luteinizing hormone value immediately post clomiphene citrate predicted an adverse pregnancy outcome in women who conceived. Clomiphene citrate, along with other ovulation induction therapies, can cause multiple follicular development, with a risk of ovarian hyperstimulation and multiple pregnancy. Ultrasound monitoring of treatment is important in order to choose the appropriate dose of clomiphene citrate in subsequent cycles and to minimize the risks of hyperstimulation and multiple pregnancy. When couples with other factors contributing to subfertility are excluded, the cumulative conception rate continues to rise after 6 months of treatment with clomiphene citrate, reaches a plateau by treatment cycle 12 and approaches that of the normal population. It has been reported that prolonged use of clomiphene citrate may be associated with an increased risk of a borderline or invasive ovarian tumour. Taking into consideration these observations, we recommend that anovulatory women responsive to clomiphene citrate should be treated for at least 6 cycles before considering more complex or invasive methods of ovulation induction, and that treatment should probably be limited to a maximum of 12 cycles.

ObsectIve: chronic autoimmune thyroiditis (At) is the most common cause of thyroid disease in children. the aim of the study was to define the epidemiological clinical and laboratory characteristics of children and adolescents with At. DesIGN: various parameters including thyroid ultrasonography of 228 children and adolescents aged 10.2±2.5yrs (mean±sD) with At, who attended our Pediatric endocrine Unit during a 5-year period were retrospectively analysed. resULts: 191 (83.8%) were female and 142 (62.3%) were pubertal. At At diagnosis, 130 children (57.0%) were euthyroid, 75 (32.9%) had subclinical hypothyroidism, 19 (8.3%) had hypothyroidism and 4 (1.8%) had hyperthyroidism. there was a positive correlation between thyroid stimulating hormone (tsH) levels and thyroid volume sDs (r=0.15, p=0.02). sixtythree children (28%) had a goiter and 32 (14%) had thyroid nodules. three children (1.3%) had papillary thyroid carcinoma. compared to euthyroid children, children with hypothyroidism were younger (9.2±1.8 vs 10.6±2.4yrs, p<0.05) and had higher thyroid volume sDs (3.1±1.9 vs 1.2±1.2, p<0.05) and higher prevalence of goiter [11(57.9%) vs 29(22.3%), p<0.05]. cONcLUsIONs: children and adolescents with At are mostly asymptomatic; the majority are female, pubertal and euthyroid. Hypothyroid children with At have higher thyroid volume, higher prevalence of goiter and higher antithyroid antibodies titers compared to euthyroid children. Diagnosing At at an early stage offers the opportunity for a timely intervention. the potential association of At with papillary thyroid carcinoma is an additional reason for a careful follow-up of the patients with At.

Objective: Although androgenic alopecia is recognised to be a symptom of polycystic ovary syndrome (PCOS), it is not known whether polycystic ovaries (PCO) and associated endocrine abnormalities are present in patients who present with alopecia as a primary complaint. We therefore set out to determine the strength of the association between androgenic alopecia and PCO. We examined the prevalence of ultrasound-based polycystic ovarian morphology and associated clinical and biochemical features in a large multiethnic group of women whose presenting complaint was of alopecia, and in a control group. Subjects and methods: We studied 89 women of mixed ethnic origin with androgenic alopecia and compared them to 73 control women. A detailed history was taken, anthropometry was performed and assessment of body-hair distribution was made. The presence of PCO was established by pelvic ultrasound scan. Serum gonadotrophins, testosterone, androstenedione, dihydrotestosterone and sex hormone binding globulin concentrations were measured. Results: Women with alopecia had a higher prevalence of PCO and hirsutism than the control population (PCO: 67% vs 27%, P , 0.00001; hirsutism: 21% vs 4%, P ¼ 0.003). Women with alopecia (with or without PCO) had higher testosterone, androstenedione and free androgen index than controls, even though few had frankly abnormal androgens. Conclusions: These findings confirm an association between androgenic alopecia and PCO, and other symptoms of hyperandrogenaemia. Thus most women who present with androgenic alopecia as their primary complaint also have PCO and have indices of abnormal androgen production. Since PCO is a well known risk factor for development of type 2 diabetes, this association has important implications for long-term management.

European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced beta-cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.

Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter is a rare entity. We present a 27-year old asymptomatic woman with a recent history of a painless mass in the left side of her lower neck. Thyroid function tests were normal. An ultrasound of her neck showed a multinodular goiter and a 3.4 cm solid mass in the left lower cervical area. These findings were confirmed by an MRI scan of her neck. The Tc99m Pertechnetate scan showed the presence of a functioning area under the left lobe of the thyroid gland. The patient underwent surgery. The cervical mass was identified as a structure separate from the left lobe of the thyroid, without any attachments to the body of the gland and was uniformly resected. A subtotal thyroidectomy was also performed. The histology revealed that the separate structure represented ectopic thyroid tissue. The patient had an uneventful postoperative recovery, subsequent to which she was euthyroid and had normal calcium levels.

The rising prevalence of Type II (non-insulin-dependent) diabetes and obesity worldwide poses a serious challenge to human health and incomplete understanding of the aetiological basis of these closely related metabolic conditions is a major impediment to improved management. There is considerable evidence to suggest that primary abnormalities in energy balance contribute to the pathogenesis of diabetes and obesity [1]. Reduced energy expenditure is correlated with subsequent weight gain [2] and normoglycaemic women at increased risk of future diabetes have defective post-prandial thermogenesis [3,4]. Diabetologia (2000) Abstract Aims/hypothesis. Uncoupling proteins are mitochondrial transmembrane carriers implicated in the regulation of energy balance. Dysfunction of UCP3 (the predominant uncoupling protein in skeletal muscle) might therefore be expected to reduce thermogenic capacity, alter energy homeostasis and influence predisposition to obesity and Type II (non-insulin-dependent) diabetes mellitus. A variant in the putative promoter region of UCP3 (±55 c®t) has recently been identified, and an association with obesity reported in French subjects. Our aim was to study the pathophysiological role of this variant in diabetes-related and obesity-related traits using two distinct ethnic populations. Methods. The ±55 c®t variant was genotyped in 85 South Indian and 150 European parent-offspring trios ascertained through Type II diabetic probands and in 455 South Indian subjects initially recruited to an urban survey into the prevalence of diabetes. Results. In South Indian and European parent-offspring trios there was no preferential transmission of either allele at the ±55 c®t polymorphism to diabetic offspring (South Indians, p = 0.60; Europeans, p = 0.15). When family members were analysed for intermediate traits, the t-allele was associated with increased waist-to-hip ratio but only in females (South Indian mothers p = 0.036, daughters p = 0.032: European mothers p = 0.037, daughters p = 0.14). These findings were replicated in South Indian females from the population-based survey (p = 0.039). Conclusion/interpretation. The consistent association between the t-allele at this locus and increased waist-to-hip ratio in women from three separate data sets indicates that variation at this polymorphism (or another locus with which it is in linkage disequilibrium) influences fat distribution but that this effect is restricted to females. [Diabetologia (2000)

There have been considerable advances concerning understanding of the early and later stages of ovarian development; a number of genes have been implicated and their mutations have been associated with developmental abnormalities. The most important genes controlling the initial phase of gonadal development, identical in females and males, are Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF1). Four genes are likely to be involved in the subsequent stages of ovarian development (WNT4, DAX1, FOXL2 and RSPO1), but none is yet proven to be the ovarian determining factor. changes in nomenclature and classification were recently proposed in order to incorporate genetic advances and substitute gender-based diagnostic labels in terminology. The term "disorders of sex development" (DsD) is proposed to substitute the previous term "intersex disorders". Three main categories have been used to describe DsD in the 46,XX individual: 1) disorders of gonadal (ovarian) development: ovotesticular DsD, previously named true hermaphroditism, testicular DsD, previously named XX males, and gonadal dysgenesis; 2) disorders related to androgen excess (congenital adrenal hyperplasia, aromatase deficiency and P450 oxidoreductase deficiency); and 3) other rare disorders. In this mini-review, recent advances concerning development of the genital system in 46,XX individuals and related abnormalities are discussed. basic embryology of the ovary and molecular pathways determining ovarian development are reviewed, focusing on mutations disrupting normal ovarian development. Disorders of sex development according to the revised nomenclature and classification in 46,XX individuals are summarized, including genetic progress in the field.

Aims/hypothesis: We assessed the impact of ethnic origin on metabolism in women following gestational diabetes mellitus (GDM). Materials and methods: Glucose regulation and other features of the metabolic syndrome were studied at 20.0 (18.2-22.1) months (geometric mean [95% CI]) post-partum in women with previous GDM (185 European, 103 Asian-Indian, 80 African-Caribbean). They were compared with the same features in 482 normal control subjects who had normal glucose regulation during and following pregnancy. Results: Impaired glucose regulation or diabetes by WHO criteria were present in 37% of women with previous GDM (diabetes in 17%), especially in those of African-Caribbean and Asian-Indian origin (50 and 44%, respectively vs 28% in European, p=0.009). BMI, waist circumference, diastolic blood pressure, fasting triglyceride and insulin levels, and insulin resistance by homeostatic model assessment (HOMA), were increased following GDM (p<0.001 for all, vs control subjects).Where glucose regulation was normal following GDM, basal insulin secretion (by HOMA) was high (p<0.001 vs control subjects). Irrespective of glucose regulation in pregnancy, Asian-Indian origin was associated with high triglyceride and low HDL cholesterol levels, and AfricanCaribbean with increased waist circumference, blood pressure, and insulin levels, together with insulin resistance and low triglyceride concentrations. Nonetheless, the GDMassociated features were consistent within each ethnic group. The metabolic syndrome by International Diabetes Federation criteria was present in 37% of women with previous GDM, especially in non-Europeans (Asian-Indian 49%, African-Caribbean 43%, European 28%, p=0.001), and in 10% of controls. Conclusions/interpretation: Following GDM, abnormal glucose regulation and the metabolic syndrome are common, especially in non-European women, indicating a need for diabetes and cardiovascular disease prevention strategies.