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The objective of the present study was to assess the lipid-lowering efficacy and safety of a novel dietary supplement containing monacolin K combined with the coenzyme Q10 and grape seed and olive tree leaf extracts (Arichol®®) on the lipid profile of adults with moderate cholesterol elevations and an absence of concomitant risk factors. We recruited patients from our Endocrinology Clinics in Greece who had low-density lipoprotein cholesterol (LDL-C) 140–180 mg/dL, were on no medications affecting serum lipid concentrations, and consented to participate in the present study. All subjects received 8-weeks supplementation with Arichol®® once daily. We measured total cholesterol (TC), high-density lipoprotein cholesterol (HDL), LDL-C, triglycerides (TG), and liver enzymes with enzymatic colorimetric assays at baseline and at the end of the study, and documented complaints potentially attributable to muscle injury. We recruited a total of 37 subjects, 33 females and 4 males (with a mean age of 55.89 ± 1.50 [mean ± standard error mean, SEM]). The treatment resulted in a statistically significant reduction in TC (from 258.9 ± 4.0 mg/dL to 212.7 ± 4.5 mg/dL, p < 0.001), LDL-C (from 173.8 ± 3.5 to 129.0 ± 4.5 mg/dL, p < 0.001), and TG (from 127.0 ± 12.2 to 117.0 ± 9.2, mg/dL, p = 0.012) concentrations, while HDL-C concentrations remained unchanged. There were no alterations in liver enzymes or symptoms of muscle pain in any subject. These promising results suggest that supplementation with this nutraceutical mixture favorably influences lipid concentrations during a short period of administration while exhibiting an excellent safety profile. Larger controlled studies are required to assess the potential for cardiovascular risk reduction with the above compound.

Polycystic ovary syndrome (PCOS) often coexists with a wide spectrum of dysglycemic conditions, ranging from impaired glucose tolerance to type 2 diabetes mellitus (T2D), which occur to a greater extent compared to healthy body mass index-matched women. This concurrence of disorders is mainly attributed to common pathogenetic pathways linking the two entities, such as insulin resistance. However, due to methodological flaws in the available studies and the multifaceted nature of the syndrome, there has been substantial controversy as to the exact association between T2D and PCOS which has not yet been elucidated. The aim of this review is to present the best available evidence regarding the epidemiology of dysglycemia in PCOS, the unique pathophysiological mechanisms underlying the progression of dysglycemia, the most appropriate methods for assessing glycemic status and the risk factors for T2D development in this population, as well as T2D risk after transition to menopause. Proposals for application of a holistic approach to enable optimal management of T2D risk in PCOS are also provided. Specifically, adoption of a healthy lifestyle with adherence to improved dietary patterns, such the Mediterranean diet, avoidance of consumption of endocrine-disrupting foods and beverages, regular exercise, and the effect of certain medications, such as metformin and glucagon-like peptide 1 receptor agonists, are discussed. Furthermore, the maintenance of a healthy weight is highlighted as a key factor in achievement of a significant reduction of T2D risk in women with PCOS.

Adequate vitamin D levels are particularly important in pregnant women for both the maternal and neonatal health. Prior studies have shown a significantly high prevalence of vitamin D deficiency (VDD) among refugees. However, no study has addressed the prevalence of VDD in pregnant refugees and its effects on neonatal health. In this study, we examined the prevalence of VDD in refugee pregnant women living in Greece and compared our results with Greek pregnant inhabitants. Vitamin D deficiency was frequent in both groups but was significantly more common in refugees (92.2% vs 67.3% of Greek women, p=0.003) with 70.6% of refugees having severe hypovitaminosis D (

INTRODUCTION There is increasing evidence that vitamin D has widespread tissue effects. In addition to osteoporosis, vitamin D deficiency has been associated with cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However, the effect of vitamin D supplementation on non-skeletal outcomes requires clarification, especially in postmenopausal women. AIM This position statement provides an evidence-based overview of the role of vitamin D in the health of postmenopausal women based on observational and interventional studies. MATERIALS AND METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS Vitamin D status is determined by measuring serum 25-hydroxyvitamin D levels. Concentrations

Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women during the reproductive period. It is considered a complex metabolic disorder with long-term metabolic, as well as reproductive consequences. Main pathophysiological pathways are related to the increased androgen levels and insulin resistance. Nowadays, genetic origins of PCOS are acknowledged, with numerous genes involved in the pathogenesis of hyperandrogenemia, insulin resistance, inflammation, and disturbed folliculogenesis. Rotterdam diagnostic criteria are most widely accepted and four PCOS phenotypes have been recognized. Metabolic abnormalities are more common in phenotypes 1 and 2. Women with classic PCOS are more obese and typically have the central type of obesity, more prevalently displaying dyslipidemia, insulin resistance, and metabolic syndrome that could be associated with an increased risk of cardiovascular complications during life. Heterogeneity of phenotypes demands an individualized approach in the treatment of women with PCOS. Metabolic therapies involve a lifestyle intervention followed by the introduction of insulin sensitizers including metformin and inositols, glucagon-like peptide 1 receptor agonists (GLP-1 RA), as recently sodium-glucose cotransporter-2 (SGLT2) inhibitors. The addition of an insulin sensitizer to the standard infertility therapy such as clomiphene citrate improves ovulation and pregnancy rates. Our current review analyzes the contemporary knowledge of PCOS etiology and etiopathogenesis, its cardiometabolic risks and their outcomes, as well as therapeutic advances for women with PCOS.

‘Snow White and the Seven Dwarfs’, a fairytale that is widely known across the Western world, was originally written by the Brothers Grimm, and published in 1812 as ‘Snow White’. Though each dwarf was first given an individual name in the 1912 Broadway play, in Walt Disney’s 1937 film ‘Snow White and the Seven Dwarfs’, they were renamed, and the dwarfs have become household names. It is well known that myths, fables, and fairytales, though appearing to be merely children’s tales about fictional magical beings and places, have, more often than not, originated from real facts. Therefore, the presence of the seven brothers with short stature in the story is, from an endocrinological point of view, highly intriguing, in fact, thrilling. The diversity of the phenotypes among the seven dwarfs is also stimulating, although puzzling. We undertook a differential diagnosis of their common underlying disorder based on the original Disney production’s drawings and the unique characteristics of these little gentlemen, while we additionally evaluated several causes of short stature and, focusing on endocrine disorders that could lead to these clinical features among siblings, we have, we believe, been able to reveal the underlying disease depicted in this archetypal tale.

Introduction Chronic lymphocytic thyroiditis is an important risk factor for differentiated thyroid cancer (DTC) in surgical series, but the role of thyroid peroxidase antibodies (TPO) seems less clear in that regard. We designed the present study to evaluate that effect in our large patient population. Methods We recruited subjects operated with total thyroidectomy in 4 sites (USA: 1, Greece: 3) during a period of 14 consecutive years. We gathered data on TPO antibodies titers measured with commercially available radioimmunoassays, and reviewed data on surgical pathology. TPO≥34IU/ml was deemed high (TPO+). Odds ratios (OR) for DTC were calculated with Fischer's exact test. p Results We reviewed data on 8,425 thyroid surgeries, and TPO titers were available for 1,620 subjects: DTC n=702 (43.3%), benign pathology (BEN) n=918 (56.7%), TPO+ n=524 (32.3%) and TPO- (1000IU/ml n=28/144 (19.4%), p Conclusions High TPO Antibodies appear protective against DTC in our large multicentre cohort of patients operated with a total thyroidectomy. Rising preoperative TPO titers confer linearly increasing protection against DTC in the surgical specimen. More research is needed to fully understand the role of thyroid autoimmunity in the genesis of DTC. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Introduction Hashimoto's thyroiditis raises the risk for differentiated thyroid cancer (DTC) in surgical series, but the role of thyroid peroxidase antibodies (TPO) remains controversial in that regard. We designed the present study to evaluate the effect of preoperative TPO titers in the risk of DTC. Methods A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases in November 2021 for the terms "thyroid cancer" and "TPO" or "peroxidase antibodies". We characterized the differential risk found in patients with high titers of TPO (TPO+), as compared to those with low or undetectable titers (TPO-) with regard to DTC. Data are expressed as odds ratio (OR) with 95% confidence interval (CI). Results We retrieved and reviewed 408 records; 21 retrospective cohort studies (2006-2022) from 7 countries and n=30,5536 subjects, fulfilled the eligibility criteria: 15 studies in East Asia with n=25,125 subjects (82.2%) and 6 studies in the Western world with n=5,428 subjects (17.8%)]. These comprised n=17,684 subjects with benign disease (57.9%) and n=12,869 with DTC (42.1%). The reference used for TPO+ was 23.6±18.8 (Range 5.1-60.0 IU/ml); n=6,307 patients were TPO+ (20.6%) and n=24,246 were TPO- (79.4%). DTC was present in n=2,960 TPO+ patients (46.9%) and n=9,909 TPO- patients (40.9), OR 1.28, (95%CI 1.21-1.35), p A high titer of TPO was associated with increased risk for DTC in both Asian cohorts, [OR 1.36 (1.28-1.45, p Conclusions Thyroid peroxidase antibodies are an integral part of Hashimoto's thyroiditis, which is a well characterized risk factor for thyroid cancer and seem to increase that risk as well. That effect seems significantly higher in East Asia as compared to the Western World region. Further studies are needed to characterize the effects of the immune response, with regard to thyroid cancer risk. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m.

Context Thyroid nodules’ size should not be the sole criterion for thyroidectomy; however, many patients undergo surgery for large or slowly growing nodules. Objective We evaluated risk for clinically significant thyroid cancer in patients with large or slowly growing nodules. Methods We reviewed data from 2 prospectively collected databases of patients undergoing thyroidectomies in tertiary referral centers in the USA and Greece over 14 consecutive years. We collected data on the preoperative surgical indication, FNA cytology, and surgical pathology. We included subjects operated solely for large or growing thyroid nodules, without any known or presumed thyroid cancer or high risk for malignancy, family history of thyroid cancer, or prior radiation exposure. Results We reviewed 5523 consecutive cases (USA: 2711; Greece: 2812). After excluding 3059 subjects, we included 2464 subjects in the present analysis. Overall, 533 thyroid cancers were identified (21.3%): 372 (69.8%) microcarcinomas ( Conclusion The risk of synchronous, clinically important thyroid cancers is small, but not null in patients with large or slow growing thyroid nodules. Therefore, more precise preoperative evaluation is needed to separate the patients who would clearly benefit from thyroid surgery from the vast majority of those who do not need to be operated.

Background Polycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear. Aim of the study To determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk. Subjects and methods The oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI. Results Dysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice. Conclusions One-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported.

Beyond being aging-related diseases, atherosclerosis and osteoporosis share common pathogenetic pathways implicated in bone and vascular mineralization. However, the contributory role of dyslipidemia in this interplay is less documented. The purpose of this narrative review is to provide epidemiological evidence regarding the prevalence of bone disease (osteoporosis, fracture risk) in patients with dyslipidemias and to discuss potential common pathophysiological mechanisms linking osteoporosis and atherosclerosis. The effect of hypolipidemic therapy on bone metabolism is also discussed. Despite the high data heterogeneity and the variable quality of studies, dyslipidemia, mainly elevated total and low-density lipoprotein cholesterol concentrations, is associated with low bone mass and increased fracture risk. This effect may be mediated directly by the increased oxidative stress and systemic inflammation associated with dyslipidemia, leading to increased osteoclastic activity and reduced bone formation. Moreover, factors such as estrogen, vitamin D and K deficiency, and increased concentrations of parathyroid hormone, homocysteine and lipid oxidation products, can also contribute. Regarding the effect of hypolipidemic medications on bone metabolism, statins may slightly increase BMD and reduce fracture risk, although the evidence is not robust, as it is for omega-3 fatty acids. No evidence exists for the effects of ezetimibe, fibrates, and niacin. In any case, more prospective studies are needed further to elucidate the association between lipids and bone strength.

Inconsistency exists across studies conducted in postmenopausal women regarding the effect of vitamin D deficiency (VDD) and supplementation on several aspects of menopausal health, such as fractures, vasomotor symptomatology, cardiovascular disease (CVD), cancer and infections, including coronavirus disease 2019 (COVID-19). The aim of this review is to critically summarize the evidence provided by observational studies and randomized controlled trials (RCTs) of vitamin D supplementation in postmenopausal women with VDD. Observational studies have found that VDD is associated with an increased risk of falls and fractures after the menopause. VDD also has a negative effect on menopausal symptomatology. VDD, especially its severe form, is associated with an increased risk of CVD risk factors and CVD events. VDD is associated with increased risk and mortality from several cancer types and risk of infections. The evidence from RCTs regarding the effect of vitamin D supplementation on falls, fractures, menopausal symptoms, cardiovascular disease, cancer and infections is not robust. Thus, skeletal health may benefit only when vitamin D is co-administered with calcium, especially in those ≥70 years old and with severe VDD. There is no evidence of a favorable effect on menopausal symptoms or risk of CVD or cancer, except for a modest reduction in cancer-related mortality. Inconsistency still exists regarding its effect on infection risk, disease severity and mortality due to COVID-19.

The exact risk of type 2 diabetes mellitus (T2DM) in women with polycystic ovary syndrome (PCOS) is unknown. It is also unclear if obesity independently increases T2DM risk in this population. The aim of this study was to systematically review and synthesize the best available evidence regarding the association between PCOS and T2DM, stratified according to obesity status. A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to October 31, 2020. Data are expressed as relative risk (RR) with 95% confidence interval (CI). The I2 index was employed for heterogeneity. The eligibility criteria were fulfilled by 23 studies (319,780 participants; 60,336 PCOS and 8847 type 2 diabetes cases). Women with PCOS demonstrated a higher risk of T2DM than those without PCOS (RR 3.45, 95% CI, 2.95–4.05, p

Background Levothyroxine (LT4-Rx) is one of the most commonly prescribed drugs worldwide and the vast majority of patients receive long-term treatment. However, in a recent study of LT4-Rx withdrawal in 291 subjects, it was found that 60% of those remained biochemically euthyroid two months after LT4-Rx discontinuation1. Aim of the study A prospective clinical cohort follow-up study was carried out to address this issue. We registered all patients presented in our clinical practice who were not on LT4-Rx for a solid diagnosis of hypothyroidism and abruptly discontinued treatment. All subjects underwent weight, height, TSH, TPO, Tg-Abs and free T4 measurement and thyroid ultrasound on enrolment, 2-4 months later, and at the end of follow up. A TSH value of ≥4.5IU/mL was considered as underlying hypothyroidism. Results We enrolled 802 consecutive subjects (83% females) aged 48±16 (range 18-84 years) with 8.8±7.3 years on LT4-Rx. The treatment indications and corresponding percentage for LT4-Rx were classified as a nodule(s) (35%), indefinite (25%), post-partum (7%) and Hashimoto's (33%); 48% of subjects were part of Group A and long-term follow-up up to 5 years was achieved in the remaining. Among the entire cohort, n=182 subjects became hypothyroid, while the remaining n=620 remained euthyroid off LT4-Rx (23 vs. 77%, p3IU/mL vs. 5.2% with baseline TSH Conclusions These findings suggest considerable overuse of thyroxine therapy. In cases of uncertainty, the existence of nodules, a low-normal TSH value, a relatively small T4 dose, and the absence of ATA are strong predictors of euthyroidism, and accordingly a treatment discontinuation trial is recommended. Furthermore, if hypothyroidism does not ensue 2-4 months post-treatment discontinuation, the likelihood to develop hypothyroidism in the long term is minimal.1. Livadas S, et al. Thyroid 2018. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Introduction Thyroglossal duct (TGD) carcinoma is an uncommon entity, located in the TGD remnant, and is diagnosed in patients undergoing evaluation of the neck for midline swelling, or incidentally after removal of a TGD cyst. Despite the presence of multiple publications on the topic, no systematic characterization of these tumors has been performed to date. The present study aims to characterize the tumors found patients diagnosed with TGD remnant malignancies. Methods We performed a systematic search for the term "Thyroglossal duct" in Pubmed, Embase and Cochrane databases on December 1, 2021 and retrieved 1229 records. We included all manuscripts containing cohorts, case reports or case series, when the manuscript or its abstract was available in English, Italian, French or Spanish language. We reviewed the demographics, the histological report of the thyroglossal duct and the thyroidectomy specimen (when this was performed) and the features of tumor aggressiveness, when these were available. Results We incorporated data from 366 manuscripts, comprising 1202 patients operated for TGD disease. Out of these, n=550 cancers were identified, consisting of n=475 (86.4%) Papillary thyroid carcinomas (PTC), n=8 Follicular thyroid carcinomas (FTC) (1.5%), n=5 Hürthle cell carcinomas (HCC) (0.9%), n=27 Squamous cell carcinomas (SCC) (4.9%), n=2 poorly differentiated/anaplastic thyroid carcinomas (ATC) (0.4%), n=1 Adeno-SCC (0.18%), n=1 Adenocarcinoma (0.18%), n=12 synchronous PTC/FTC (2.2%), n=1 synchronous PTC/SCC (0.18%) and n=18 of unclear histological diagnosis (4.75%). N=173/446 (38.8%) patients were males and n=273/446 (61.2%) were females; gender was not available in n=104 cases. Mean cancer size was 1.4±1.4cm (range 0.01-7.0cm); n=88/173 (50.9%) were microcarcinomas ( Conclusions TGD remnant cancers include various tumors, with histology and features of aggressive behavior similar to what we see in thyroid cancer cases. More research is needed to enhance our understanding of the mechanisms involved in the pathogenesis and malignant behavior of these infrequently identified tumors. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women during the reproductive period. True PCOS phenotype is prone to develop metabolic consequences during life. Obese PCOS women with insulin resistance are carrying a risk for developing type 2 diabetes, and influencing liver function by generating liver steatosis and nonalcoholic fatty liver disease (NAFLD). Moreover, serum testosterone of over 3 nmol/L is associated with at least two-fold higher risk for the development of NAFLD in PCOS women. Numerous genes involved in the pathogenesis of hyperandrogenism, insulin resistance and inflammation are associated with the development of NAFLD in PCOS women. Liver biopsy is not considered as the first line procedure for the diagnosis of liver damage in a prevalent condition as PCOS. Therefore, simple and reliable surrogate markers as serum aminotransferases levels or surrogate indexes (i.e. fatty liver index and NAFLD-fatty liver score) could be used for the assessment of fatty liver in PCOS women. First line therapeutic approach for NAFLD in PCOS includes a change in lifestyle that implies dietary regiment and physical activity but without well-defined protocols. Second line therapy considers addition of drugs on the established lifestyle change. Metformin remains the drug of choice for reduction of insulin resistance and liver enzymes level. Liraglutide, glucagon-like peptide-1 receptor agonists, showed favorable effects on the reduction of liver fat content and visceral adipose tissue in overweight women with PCOS. Current review analyzes the impact of metabolic risk factors, diagnostic approach and management options on NAFLD in women with PCOS.

Background: Levothyroxine (LT4) is one of the most prescribed drugs worldwide. Once started, approximately 90% of patients continue treatment long term. However, accumulating evidence suggests that...

PURPOSE To compare the effects of insulin sensitizers metformin (MET) and myo-inositol (MI) on adiponectin levels and metabolic characteristics in women with polycystic ovary syndrome (PCOS) with respect to their body mass index (BMI). METHODS In this open label, parallel randomized clinical trial, 66 women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of adiponectin, hormonal and metabolic laboratory outcomes and clinical assessment of BMI, body composition and Ferriman-Gallwey score (FG score) were evaluated before and after treatment. RESULTS After the 6-month intervention, comparison between MET and MI in time to treatment analysis showed no significant differences between the two treatments for all analyzed parameters. Only borderline significantly lower AUC glucose was found in the MET group in comparison to the MI group (p = 0.071). The main effect of treatment was shown for glucose concentration at 120 min OGTT (p = 0.032) and testosterone (p = 0.002). The main effect of time was shown for body mass (p = 0.004), waist circumference (p

The exact risk of type 2 diabetes mellitus (T2DM) in women with polycystic ovary syndrome (PCOS) is unknown. It is also unclear if obesity independently increases T2DM risk in this population. The aim of this study was to systematically review and synthesize the best available evidence regarding the association between PCOS and T2DM, stratified according to obesity status.A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to October 31, 2020. Data are expressed as relative risk (RR) with 95% confidence interval (CI). The IThe eligibility criteria were fulfilled by 23 studies (319,780 participants; 60,336 PCOS and 8847 type 2 diabetes cases). Women with PCOS demonstrated a higher risk of T2DM than those without PCOS (RR 3.45, 95% CI, 2.95-4.05, p 0.001; IWomen with PCOS present an increased risk of T2DM compared with non-PCOS women only if they are obese/overweight.

Introduction: Despite the current state of evidence suggesting that thyroid nodules’ size should not be the sole criterion for the decision to undergo thyroidectomy, many patients are still operated for large, or growing nodules. In order to ascertain whether this is a justifiable approach, we performed the present study. Methods/ Subjects: We reviewed the data from two prospectively collected databases of patients undergoing thyroid surgery in two tertiary referral centers, one in the USA (A) and the other one in Greece (B) over 14 consecutive years. We collected data on the preoperative surgical indication, FNA cytology and surgical pathology. We included subjects with multinodular goiters, operated solely for large or growing thyroid nodules, who did not have any known or presumed thyroid cancer, or indications of high risk for malignancy (FNA suspicious for thyroid cancer, follicular neoplasm, suspicious for follicular neoplasm, FLUS/AUS, cellular specimen), family history of thyroid cancer or prior neck radiation exposure. Results: We reviewed 5523 consecutive cases of thyroid surgery (A:2711, B:2812). After excluding n=3059 subjects, we included n=2464 subjects in the present analysis. Overall 535 thyroid cancers were identified (21.7%): 349 (65.2%) were microcarcinomas ( Conclusions: Although the likelihood of identifying a clinically relevant thyroid cancer in a large or growing nodule, in the absence of risk enhancing features, is low; the risk of synchronous, clinically important, thyroid cancers is high in patients with large multinodular goiters. Therefore, more precise screening strategies are urgently needed to identify the patients, who would clearly benefit from thyroid surgery and protect those who do not need to be operated on.

If circulating adrenal androgens levels rise before the age of 8 years in girls, this phenomenon is termed premature adrenarche (PA), while the concomitant appearance of pubic hair is called premature pubarche (PP). Girls with PA-PP display an unfavorable hormonal profile compared to their normal peers and have an increased risk of developing polycystic ovary syndrome (PCOS) features peripubertally. However, the sequelae of premature adrenarche remains unclear. We assessed metabolic, hormonal, psychologic profiles, and ovarian morphology in 21 women of mean age (±SD) 21.3±3.3 years, BMI: 23.6±4.4 kg/m2 with PA-PP, 45 women with PCOS and 26 controls, matched for age and BMI. PA-PP women displayed a favorable lipid profile compared to PCOS and controls. Insulin resistance index (HOMA-IR), however, were similar in PA-PP and PCOS women (2.09±1.42, 2.08±0.83) and higher than controls (1.13±0.49, p

Polycystic ovary syndrome (PCOS), considered a lifelong condition, manifests mainly as a cluster of hyperandrogenic symptoms during the early reproductive years, with the affected woman gradually developing an adverse cardiometabolic profile over the years. However, some data point to the possibility of differences in the evolution of PCOS according to a woman’s weight. The aim of the present study was to evaluate the metabolic and hormonal profiles of women with PCOS over time. A total of 763 lean women with PCOS (BMI 20–25 kg/m2) and 376 controls were included. The study group was further divided into three age groups representing women post-adolescence, of reproductive age, and of late reproductive age. All subjects were assessed clinically, biochemically, and hormonally. Waist circumference, lipids, androgens, and insulin resistance index (homeostasis model assessment of IR index (HOMA-IR)) were significantly higher in the PCOS group compared with controls. Age subgroup analysis showed a progressive decrease of HOMA-IR and waist circumference, and lipid levels were comparable between PCOS and controls in all age groups. Androgens remained significantly higher in PCOS, but they gradually decreased through time. A significant negative association of age with waist circumference, androgens, insulin, and HOMA-IR was revealed. Univariate and multivariate regression analysis disclosed a strong correlation of HOMA-IR with age (p = 0.014, β − 0.19, SE coefficient 0.008) as a single parameter or in combination with total cholesterol (TC) (p

Background: Incidental finding of differentiated thyroid microcarcinomas (DTMc) in patients undergoing thyroid surgery for benign indications has become increasingly common. Even though carcinogene...

The mechanisms underlying the initiation of puberty, one of the cornerstones of human evolution, have not been fully elucidated as yet. However, recently, an accumulating body of evidence has helped unravel several critical aspects of the process. It is clear that a change in the pattern of pituitary gonadotropin secretion serves as a hormonal trigger for puberty induction. This change is directly guided by the hypothalamic GnRH pulse generation, a phenomenon regulated by the Kisspeptin-Neurokinin-Dynorphin (KNDy) system also in the hypothalamus. This represents the kisspeptin molecule, which is crucial in augmenting GnRH secretion at puberty, whose secretion is fine-tuned by the opposing signals neurokinin B and dynorphin. Recently, the novel kisspeptin inhibitory signal MKRN3 was described, whose role in puberty initiation provided further insight into the mechanistic aspects of pubertal onset. Furthermore, the description of higher inhibitory and stimulatory signals acting upstream of the KNDy neurons suggested that the trigger point of puberty is located upstream of the KNDy system and the GnRH pulse generator. However, the mechanism of pubertal onset should not be considered as an isolated closed loop system. On the contrary, it is influenced by such factors as adipose tissue, gastrointestinal function, adrenal androgen production, energy sensing, and physical and psychosocial stress. Also, fetal and early life stressful events, as well as exposure to endocrine disruptors, may play important roles in pubertal initiation, the latter primarily through epigenetic modifications. Here we present the available data in the field and attempt to provide an integrated view of this unique and crucial phenomenon.

Background/Aims: Polycystic ovary syndrome (PCOS) is associated with disordered carbohydrate metabolism and an increased risk for T2D. However, there are limited data on the magnitude of this risk. Furthermore, 50-80% of women with PCOS are obese and obesity is known to have a synergistic deleterious effect on glucose tolerance in affected women. We systematically reviewed the literature regarding the association between PCOS, obesity and T2D risk. Methods: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases. Data are expressed as relative risk (RR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. The available data, did not allow us to analyze the impact of weight status as normal, overweight and obese and as a consequence the studied subjects were stratified as obese (BMI>30 kg/m2) and non-obese (BMI3-fold increased risk of T2D compared to women without PCOS, but this risk is substantially increased by the presence of obesity. Accordingly, weight reduction should be pursued in these women. References: 1. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989;38(9):1165-1174.2. Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. 1999;84(1):165-169.3. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. 1999;22(1):141-146.4. Rubin KH, Glintborg D, Nybo M, Abrahamsen B, Andersen M. Development and risk factors of type 2 diabetes in a nationwide population of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2017;102(10):3848-3857.

Non-classical congenital adrenal hyperplasia (NCCAH) is considered to be a common monogenic inherited disease, with an incidence range from 1:500 to 1:100 births worldwide. However, despite the high incidence, there is a low genotype-phenotype correlation, which explains why NCCAH diagnosis is usually delayed or even never carried out, since many patients remain asymptomatic or are misdiagnosed as suffering from other hyperandrogenic disorders. For affected adolescent and adult women, it is crucial to investigate any suspicion of NCCAH and determine a firm and accurate diagnosis. The Synacthen test is a prerequisite in the event of clinical suspicion, and molecular testing will establish the diagnosis. In most cases occurring under 8 years of age, the first symptom is premature pubarche. In some cases, due to advanced bone age and/or severe signs of hyperandrogenism, initiation of hydrocortisone treatment prepubertally may be considered. Our unifying theory of the hyperandrogenic signs system and its regulation by internal (hormones, enzymes, tissue sensitivity) and external (stress, insulin resistance, epigenetic, endocrine disruptors) factors is presented in an attempt to elucidate both the prominent genotype-phenotype heterogeneity of this disease and the resultant wide variation of clinical findings. Treatment should be initiated not only to address the main cause of the patient's visit but additionally to decrease abnormally elevated hormone concentrations. Goals of treatment include restoration of regular menstrual cyclicity, slowing the progression of hirsutism and acne, and improvement of fertility. Hydrocortisone supplementation, though not dexamethasone administration, could, as a general rule, be helpful, however, at minimum doses, and also for a short period of time and, most likely, not lifelong. On the other hand, in cases where severe hirsutism and/or acne are present, prescription of oral contraceptives and/or antiandrogens may be advisable. Furthermore, women with NCCAH commonly experience subfertility, therefore, there will be analysis of the appropriate approach for these patients, including during pregnancy, based mainly on genotype. Besides, we should keep in mind that since the same patient will have changing requirements through the years, the attending physician should undertake a tailor-made approach in order to cover her specific needs at different stages of life.

Background: Polycystic ovary syndrome (PCOS) constitutes one of the most common endocrine diseases that should be considered as a continuum. This life span disease is originating in foetal life and through long reproductive period falling into long-term consequences extending beyond menopause. Hence, it is considered to increase diabetes risk as well cardiovascular risk and outcomes. However, the natural course of the disorder is not completely understood, and recent data suggest differences in the evolution of the disease between normal-weight and obese patients, indicating that the cardiometabolic effects may be an epiphenomenon of the obesity and not of PCOS per se. We aimed to define the evolution of normal-weight Caucasian women with PCOS through the years. Materials and Methods: In this multicenter cross-sectional case control study 763 normal-weight women with PCOS according to Rotterdam criteria and 376 age and BMI-matched controls were included. The study group was further divided into three age groups, representing women post-adolescence, of reproductive age, and of late reproductive age to menopause. All the subjects were assessed clinically, biochemically, hormonally, and with the means of pelvic ultrasound. Results: Waist circumference, WHR, FG score, glucose, lipids, gonadotropin, androgen levels as well as HOMA-IR and ovarian volume were significantly higher in the PCOS group in comparison to controls. No statistical difference was noted among PCOS women diagnosed with the Rotterdam criteria vs. those who met the NIH criteria. Age subgroup analysis showed that androgens remained significantly higher among PCOS and controls, whereas insulin and lipid levels, as well as HOMA-IR, were comparable between PCOS and controls in all age groups. Pearson correlations of studied parameters with age revealed a significant negative association of age with waist circumference, FG score, androgens (testosterone, FAI, DHEAS, D4), insulin, FSH, and HOMA-IR. Finally, multiple regression analysis of factors affecting HOMA-IR disclosed a negative association with age (r:-0.123, p: 0.001) and a positive association with BMI (r: 0.105, p: 0.004) and DHEAS (r: 0.175, p: 0.001). Conclusions: Lipids, androgens, insulin resistance, and menstrual cyclicity are gradually improved in an age-dependent manner in PCOS lean patients and age and BMI matched controls. Normal-weight PCOS women exhibit a higher degree of IR and dyslipidaemia compared to their healthy peers, but these aberrations improve gradually. If PCOS women retain their normal weight over the years, they may develop a metabolic and hormonal profile comparable to that of their peers without PCOS later in life.

Introduction: Incidental finding of differentiated thyroid microcarcinomas (DTMc) in patients with thyroid nodules, undergoing thyroid surgery for benign indications, have become increasingly common. Even though carcinogenesis might relate to the background disease of the gland, the incidence of DTMc in the setting of various thyroid disorders remains unclear. We designed the present study to address this question. Methods/ Subjects: We reviewed the data from two prospectively collected databases of patients undergoing thyroid surgery in two high-volume tertiary care referral centers, one in the USA (A) and the other one in Greece (B) over 14 consecutive years. We collected data on the preoperative surgical indication, FNA cytology and surgical pathology. We excluded subjects operated for thyroid cancer or indications at high risk for malignancy (FNA suspicious for thyroid cancer, follicular neoplasm, suspicious for follicular neoplasm, FLUS/AUS, cellular specimen or sonographic features of malignancy), and those with post-surgical pathology consistent with PTC >9mm in largest diameter. We split our subjects based on pathology data in those with chronic lymphocytic thyroiditis (CLT), Graves disease (GR) or multinodular goiter (MNG). Incidence of DTMc or features of tumor aggressiveness were compared among groups, using Fischer’ s exact test and odds ratios (OR) were calculated. Categorical values were compared with Kruskal Wallis test. P values

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women during reproductive age. It was shown that PCOS women are with high risk for dyslipidemia, glucose intolerance, type 2 diabetes and metabolic syndrome. These factors are considered to represent traditional risk factors for the occurrence of cardiovascular disease. Observed increased risk for hypertension in PCOS women seems to be associated with insulin resistance and hyperinsulinemia. Both conditions interfere with the endothelium-dependent vasodilatation mechanisms causing vascular muscle wall hypertrophy. Obesity and insulin resistance are considered key factors for the alteration of blood pressure in PCOS women. Higher cardiovascular risk is implicated in PCOS with aging and its consequent association with both systolic and diastolic blood pressure. The elements of renin-angiotensin-aldosterone system (RAAS) have an impact on endothelial dysfunction as a marker of cardiovascular damage that could be modified is women with PCOS. Androgens and components of RAAS are involved in the process of atherogenesis in PCOS women. Therefore, it is hypothesized that spironolactone treatment could ameliorate endothelial dysfunction in PCOS women. Recently it was shown that telmisartan, angiotensin II receptor antagonist poses insulinsensitizing capacity to activate PPAR gamma and mediate favorable metabolic and reproductive effects in hypertensive PCOS women.

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.

The role of nonselective beta-blockers in cirrhotic patients with ascites has been recently questioned; however, definitive evidence in this regard is still lacking. To analyze published data on the influence of nonselective beta-blockers as compared to control group on survival of cirrhotic patients with ascites. Computerized bibliographic search on the main databases was performed. Hazard ratios from Kaplan–Meier curves were extracted in order to perform an unbiased comparison of survival estimates. Secondary outcomes were mortality in patients with refractory ascites, pooled rate of nonselective beta-blockers interruption, spontaneous bacterial peritonitis and hepato-renal syndrome incidence. Three randomized controlled trials and 13 observational studies with 8279 patients were included. Overall survival was comparable between the two groups (hazard ratio = 0.86, 0.71–1.03, p = 0.11). Study design resulted as the main source of heterogeneity in sensitivity analysis and meta-regression. Mortality in refractory ascites patients was similar in the two groups (odds ratio = 0.90, 0.45–1.79; p = 0.76). No difference in spontaneous bacterial peritonitis (odds ratio = 0.78, 0.47–1.29, p = 0.33) and hepato-renal syndrome incidence (odds ratio = 1.22, 0.48–3.09; p = 0.67) was observed. Pooled rate of nonselective beta-blockers interruption was 18.6% (5.2–32.1%). Based on our findings, nonselective beta-blockers should not be routinely withheld in patients with cirrhosis and ascites, even if refractory.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder with a significant psychological burden throughout the life course of affected women. Thus, use of mindful awareness may be beneficial as an adjunct to conventional medical management of women with PCOS. A randomized, controlled trial was conducted at the Evgenideion Hospital of the Athens University Medical School to explore the impact of an 8-week mindfulness stress management program on measures of depression, anxiety and stress as well as on the quality of life in reproductive age women with PCOS. The study was approved by the Research Ethics Committee. Twenty-three and 15 women with PCOS were randomly allocated to the intervention or control group, respectively. All participants were administered DASS21, PSS-14, PCOSQ, Daily Life and General Life Satisfaction Questionnaires and provided three-timed daily samples of salivary cortisol, before and after the intervention. Intervention group participants were provided with the Credibility/Expectancy Questionnaire at the day of enrolment, to check for possible placebo effect on the outcome. Post-intervention, between-group results revealed statistically significant reductions in stress, depressive and anxiety symptoms, as well as in salivary cortisol concentrations, along with an increase in Life Satisfaction and Quality of Life scores in the intervention group only. There was no significant "placebo" effect on the outcome measures. Mindfulness techniques seem promising in ameliorating stress, anxiety, depression and the quality of life in women with PCOS and could be used as an adjunct method to the conventional management of these women.