Alterations of cardiometabolic risk profile in polycystic ovary syndrome: 13 years follow-up in an unselected population.

PURPOSE: Cardiometabolic risk factors are common in women with polycystic ovary syndrome (PCOS) during reproductive years. The aim of this study was to determine the impact of aging on cardiometabolic risk of the syndrome by examining women who had previously been diagnosed to have PCOS or to be healthy in an unselected population in 2009. PARTICIPANTS: Forty-one women with PCOS who were diagnosed and phenotyped according to the Rotterdam criteria and 43 age- and body mass index (BMI)-matched healthy women from the same unselected cohort. METHODS: All participants were evaluated by structured interview, physical examination, anthropometric, hormonal and biochemical measurements. Additionally, body composition analyses and echocardiographic assessments of 30 women with PCOS and 30 control women were conducted at 13 years of follow-up. RESULTS: There was no difference between the patient and the control groups in terms of anthropometric and body composition measures and metabolic parameters. Echocardiographic assessment showed similar systolic functions, strain measurements and epicardial fat measurements between the groups. PCOS patients still had higher levels of total testosterone, free androgen index (FAI) and dehydroepiandrosterone sulfate (DHEAS) levels compared to controls. Epicardial fat thickness showed positive correlations with BMI, total and truncal body fat, homeostatic model assessment for insulin resistance (HOMA-IR) and free androgen index (FAI). CONCLUSIONS: Aging women with PCOS in the population have higher androgen levels and similar cardiometabolic risk profile compared to age- and BMI-matched healthy women. Epicardial fat thickness, a marker of cardiometabolic risk, appear to be associated with hyperandrogenism. Further research is needed on larger community-based cohorts where older patients are assessed with a longer follow-up.

One year of the pandemic - how European endocrinologists responded to the crisis: a statement from the European Society of Endocrinology.

Changes that COVID-19 induced in endocrine daily practice as well as the role of endocrine and metabolic comorbidities in COVID-19 outcomes were among the striking features of this last year. The aim of this statement is to illustrate the major characteristics of the response of European endocrinologists to the pandemic including the disclosure of the endocrine phenotype of COVID-19 with diabetes, obesity and hypovitaminosis D playing a key role in this clinical setting with its huge implication for the prevention and management of the disease. The role of the European Society of Endocrinology (ESE) as a reference point of the endocrine community during the pandemic will also be highlighted, including the refocusing of its educational and advocacy activities.

COVID-19 and endocrine and metabolic diseases. An updated statement from the European Society of Endocrinology.

BACKGROUND: COVID-19 has completely changed our daily clinical practice as well as our social relations. Many organs and biological systems are involved in SARS-Cov-2 infection, either due to direct virus-induced damage or to indirect effects that can have systemic consequences. Endocrine system is not only an exception but its involvement in COVID-19 is so relevant that an "endocrine phenotype" of COVID-19 has progressively acquired clinical relevance. AIM: We have been appointed by the European Society of Endocrinology (ESE) to update with the current statement ESE members and the whole endocrine community on the emerging endocrine phenotype of COVID-19 and its implication for the prevention and management of the disease. CONCLUSIONS: Diabetes has a major role in this phenotype since it is one of the most frequent comorbidities associated with severity and mortality of COVID-19. Careful management including treatment modifications may be required for protecting our patients rather with known diabetes from the most dangerous consequences of COVID-19 or hospitalized with COVID-19, but also in patients with SARS-CoV-2 induced newly onset diabetes. Obesity increases susceptibility to SARS-CoV-2 and the risk for COVID-19 adverse outcome. Adequate nutritional management needs to be granted to patients with obesity or undernourishment in order to limit their increased susceptibility and severity of COVID-19 infection. Lack of vitamin D, hypocalcemia and vertebral fractures have also emerged as frequent findings in the hospitalized COVID-19 population and may negatively impact on the outcome of such patients. Also, in patients with adrenal insufficiency prompt adaptation of glucocorticoid doses may be needed. Moreover, in this updated statement role of sex hormones as well as peculiar pituitary and thyroid aspects of COVID-19 have been included. Finally, in view of the mass vaccination, potential implications for endocrine patients should be considered.

Prevalence and predictors of gestational diabetes mellitus: a nationwide multicentre prospective study.

AIM: Prevalence rates of gestational diabetes mellitus (GDM) show considerable variation among different countries and regions of the world. The primary aim of this study was to determine the nationwide prevalence and predictors of GDM in Turkey. METHODS: We conducted prospective nationwide screening among pregnant women. Between August 2016 and November 2017, a total of 2643 pregnant women from 51 centres in 12 different regions were enrolled. A two-step screening method and Carpenter and Coustan criteria were used in the diagnosis of GDM. Clinical and biochemical data were obtained using electronic database software. RESULTS: The national prevalence of GDM was found to be 16.2% [95% confidence intervals (CI) 15.0% to 17.4%] without a significant difference between urban and rural regions. Women with GDM were older (mean age: 32 ± 5 vs. 28 ± 5 years, P < 0.001) and heavier (mean BMI: 27.2 ± 5.1 vs. 24.7 ± 4.7 kg/m2 , P < 0.001) than their counterparts without GDM. The prevalence of GDM tended to increase with age (< 25 years, 6.9%; 26-35 years, 15.6%; and 36-45 years, 32.7%; P < 0.001). Maternal age, maternal BMI, history of previous GDM and family history of diabetes mellitus were independent predictors of developing GDM (P < 0.05 for all). Low-risk women (age < 25 years, BMI < 25 kg/m2 , no family history of diabetes) comprised 10.7% of the total population and the prevalence of GDM in these women was 4.5% (95% CI 2.4% to 7.8%). CONCLUSION: The results of this nationwide study indicate that GDM is very common, affecting one in seven pregnancies in Turkey. Implementation of international guidelines on screening and management of this public health problem is required.

Comparison of adrenocortical steroidogenesis in women with post-adolescent severe acne and polycystic ovary syndrome.

BACKGROUND: Increased adrenocortical production appears to be associated with acne and hirsutism in acne and polycystic ovary syndrome (PCOS). However, the aetiological role of androgens in the pathogenesis of acne per se is far from being clear. OBJECTIVE: We aimed to evaluate adrenocortical function in women with post-adolescent severe acne in comparison with patients with PCOS and healthy women. METHODS: The study included 32 women with post-adolescent severe acne, 32 women with PCOS and 32 age and body mass index (BMI)-matched healthy controls (age 17-34 years, BMI: 20.8 ± 1.9 kg/m²). Women with acne did not have hirsutism or ovulatory dysfunction whereas all PCOS patients had androgen excess and ovulatory dysfunction. Measurements included basal testosterone (T), sex hormone-binding globulin (SHBG) and dehydroepiandrosterone sulphate (DHEAS) levels and serum 17-hydroxyprogesterone (17-OHP), androstenedione (A4), DHEA and cortisol levels in response to corticotropin (ACTH) stimulation. RESULTS: T, free androgen index, DHEAS levels, basal and AUC (area under the curve) values for A4 were significantly higher in PCOS than women with acne and controls (P < 0.05 for all), whereas three groups did not differ for basal or AUC values of DHEA and cortisol. Women with PCOS and those with severe acne had significantly and similarly higher AUC values of 17-OHP compared to controls (P < 0.05). CONCLUSION: Women with isolated post-adolescent severe acne do not have increased levels of adrenal androgens basally or in response to ACTH. However, these women have similar secretion pattern of 17-OHP with PCOS patients suggesting increased enzymatic activity in this pathway.

Oral contraceptives in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women of reproductive age and combined oral contraceptives (OCs) are often the first-line treatment of the syndrome by improving hyperandrogenism and regulating menstrual cycles. Oral contraceptives have some cardiovascular and metabolic effects that varies among different formulations depending upon the dose and type of the both estrogen and progestin components. These cardiometabolic effects of OCs raise some concerns about their long-term use in PCOS, but available data suggest that the benefits outweigh the risks. More studies are needed to clarify the safety of long-term use of OCs in PCOS.

Autoimmune polyendocrine syndrome with atrial septal defect.

Atrial septal defect is frequently reported with genetic syndromes. But, to the best of our knowledge, it has not been reported with autoimmune polyendocrine syndrome. Here, the case of a 44-year-old-woman with concomitant involvement of the salivary gland, thyroid, intestines, and, possibly endocrine pancreas, diagnosed with autoimmune polyendocrine syndrome type II, is reported with accompanying atrial septal defect. Celiac disease, Hashimoto thyroiditis, and Sjögren syndrome were symptomatic and laboratory confirmed diagnosis; anti-glutamic acid decarboxylase antibody was positive but asymptomatic for type-1 diabetes. She was known to have sinus venosus type atrial septal defect diagnosed at 38 years old, when she had tiredness and chest pain.

Prevalence of glutamic acid decarboxylase antibody positivity and its association with insulin secretion and sensitivity in autoimmune thyroid disease: A pilot study.

OBJECTIVE: Type 1 diabetes and autoimmune thyroid disease are commonly associated. Few studies have addressed islet-cell autoimmunity and its relation with glucose homeostasis in Hashimoto's thyroiditis. The aims of this study were: (1) to determine the prevalence of islet-cell autoimmunity, and (2) to compare insulin sensitivity and secretion patterns between normal glucose tolerant glutamic acid decarboxylase antibodies (GA-D-Ab) positive and negative patients with Hashimoto's thyroiditis. METHODS: Two hundred fifty-three consecutive patients with Hashimoto's thyroiditis were recruited. After excluding 38 patients with diabetes mellitus, 215 were screened for presence of GAD-Ab. Nine GAD-Ab positive and 8 age, sex and body mass index (BMI) matched GAD-Ab negative patients from the same cohort were included. Frequently sampled intravenous glucose tolerance tests (FSIGTT) were applied. Using glucose and insulin data from FSIGTT, fasting glucose to insulin ratio, HOMA-IR and HOMA-beta-cell function, using the minimal model analysis (MIN-MOD) program, the first phase insulin secretion in response to glucose, the insulin sensitivity index and glucose sensitivity index were calculated. RESULTS: Eleven patients were positive for GAD-Ab (5.1%). There was no difference in any insulin sensitivity or secretion parameters between the GAD-Ab positive and negative patients. CONCLUSIONS: Our results suggest that the prevalence GAD-Ab in Hashimoto's thyroiditis is around 5%. GAD-Ab antibody positivity per se does not appear to be associated with any disturbances in insulin sensitivity or insulin secretion in this specific population. The presence of islet-cell autoimmunity does not seem to influence insulin secretion or action in normal glucose tolerant subjects with Hashimoto's thyroiditis in this pilot study. Whether the presence of GAD-Ab per se or along with other antibodies impairs insulin dynamics or predicts the development of diabetes in autoimmune thyroiditis remains to be determined in future studies.

A patient presenting with spinal cord compression who had two distinct follicular cell type thyroid carcinomas.

A 61-yr-old woman presented with complaints of weakness and pain in her legs. A magnetic resonance imaging showed a 3 x 5.6 x 7.8 cm mass lesion destructing the T1 and T2 vertebral bodies and compressing the spinal cord. The mass was excised surgically. It was follicular carcinoma metastasis of the cervicodorsal region. Then, she underwent a total thyroidectomy. Pathological examination showed two different types of carcinomas in two different focuses; follicular carcinoma in the left lobe and follicular variant papillary carcinoma in the isthmic lobe. After the operation she was given 100 mCi 131I. This is the first report of a patient who had both metastatic follicular carcinoma and follicular variant papillary carcinoma together.

Polycystic ovary syndrome and ovulation induction.

Polycystic ovary syndrome (PCOS) is likely the most common cause of anovulatory infertility. Although many options are available for ovulation induction in these patients, there is currently no evidence-based algorithm to guide the initial and subsequent choices of ovulation induction methods. In obese women with PCOS, mild to moderate weight loss results in improvement of ovulatory dysfunction, and should be advocated at the onset of the evaluation. Clomiphene citrate is currently the 1st line medical therapy for ovulation induction. Glucocorticoids do not result in consistent ovulation and have significant side effects. Exogenous pulsatile GnRH treatment has low ovulation and pregnancy rates with a high risk of miscarriage. The most commonly used medical agents for ovulation induction in clomiphene-resistant women with PCOS are parenteral gonadotropins. Various gonadotropin preparations and different protocols are available; however the risk of multiple pregnancy and ovarian hyperstimulation is high with gonadotropin therapy. The frequent association between PCOS and insulin resistance has prompted recent studies on the effect of insulin-sensitizing agents on spontaneous and as an adjuvant to conventional ovulation induction therapies. Overall, the improvement in ovulation with insulin sensitizing drugs is modest, and unresolved issues such as variability in ovarian response remain to be addressed in future studies. Nevertheless, these agents may be beneficial in a subset of PCOS patients. Surgical ovulation induction methods such as ovarian diathermy have been reported to be moderately effective. However, due to the inherent associated risks and unknown effect on long-term reproductive potential, this modality should be reserved for patients who are clomiphene-resistant and unable or unwilling to proceed to gonadotropin therapy.

Insulin resistance in polycystic ovary syndrome: hyperandrogenemia versus normoandrogenemia.

OBJECTIVE: The goal of this study was to evaluate the insulin resistance and glucose tolerance in hyperandrogenemic and normoandrogenemic groups of patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: In this cross-sectional study, 17 hyperandrogenemic and 14 normoandrogenemic, age and weight-matched non-obese women with PCOS were studied. All patients had clinical hyperandrogenism and chronic anovulation with polycystic ovaries on ultrasound. Insulin resistance and glucose tolerance were determined by measuring insulin and glucose concentrations following a 75 g oral glucose tolerance test (OGTT). Fasting glucose to insulin ratio (FG:I ratio), insulin area under the curve (AUC(insulin)) during OGTT, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. RESULTS: Hyperandrogenemic group of patients had fasting hyperinsulinemia, lower FG:I ratio, higher AUC(insulin), and HOMA-IR compared with normoandrogenemic group. The differences between two groups were statistically significant. CONCLUSION: PCOS has variable biochemical features. Hyperandrogenemia associated with insulin resistance differs from normoandrogenemia in this syndrome. Fasting insulin concentrations, FG:I ratio, AUC(insulin), and HOMA-IR are convenient markers for determining insulin resistance in PCOS.