COVID-19 and Vitamin D- a Systematic Review.

Introduction: The COVID-19 pandemic has strongly affected global healthcare systems. Prior epidemiological studies on different infectious diseases have shown a strong correlation between serum vitamin D levels and the incidence of certain infectious diseases. Vitamin D has an important immunomodulatory effect on innate immunity and exhibits several other mechanisms in the pathogenesis of the cytokine storm, which is one of the main contributing factors to fatality in COVID-19 patients. Methods: A keyword search was conducted in the PubMed and Google Scholar research databases. The abstracts and/or full texts of selected papers were further evaluated. Articles that fulfilled the inclusion criteria were included in the systematic review. Results: The 28 studies summarized in this review provide observational findings that vitamin D levels are related to the incidence, severity, and mortality rate of COVID-19 infection. The literature does not suggest that COVID-19 could be eliminated with supplementation of vitamin D, but there are implications that vitamin D deficiency might increase the risk for COVID-19 infection and severity of the disease progression. Discussion: Current literature and several guidelines support the supplementation of vitamin D as a reasonable strategy for correcting and preventing vitamin D deficiency. The recommended dose for maintaining normal 25(OH)D levels by consensus is 1000 to 2000 IU vitamin D daily for at-risk teens and adults. Conclusion: Vitamin D supplementation might play an important role in protecting from acute respiratory infections like the SARS CoV2, and in high-risk individuals with COVID 19 from progressing to critical clinical condition and reducing mortality.

Testosterone treatment longer than 1 year shows more effects on functional hypogonadism and related metabolic, vascular, diabetic and obesity parameters (results of the 2-year clinical trial).

OBJECTIVE: We evaluated long-term effects of testosterone undecanoate on glycemic control, metabolic syndrome, vascular function and morphology in obese men with functional hypogonadism (FH) and type 2 diabetes (T2D) in a 2-year prospective clinical trial. METHODS: A total of 55 participants were enrolled in this study; group P (n = 27) received placebo during first and testosterone therapy (TTh) during second year, group T (n = 28) received TTh both years. We pooled results after 1 year of TTh to obtain more statistical power. Results for group T after 2 years of TTh are also presented. We evaluated wide assortment of biochemical (fasting plasma glucose-FPG, glycated hemoglobin-HbA1c and lipid profile), hormonal, vascular (flow-mediated dilatation-FMD and intima-media thickness-IMT), anthropometrical and derived parameters (BMI, HOMA-IR, non-HDL cholesterol, bioavailable and calculated free testosterone). Quality of life was assessed using Aging Males' Symptoms (AMS) questionnaire. RESULTS: FPG, HbA1c, HOMA-IR and IMT decreased, FMD increased, lipid profile and AMS sexual sub-score improved, and testosterone levels fully normalized after 2 years of TTh. CONCLUSIONS: Two-year of TTh resulted in normalized serum testosterone levels, improved glycemia, endothelial function, lipids and insulin sensitivity, and quelled the symptoms of hypogonadism, potentially reducing cardiovascular risk in obese men with FH and T2D.

Adrenal failure and antiphospholipid syndrome.

We herein report two cases of primary adrenal insufficiency (AI) associated with antiphospholipid syndrome (APS). In both patients, the main finding that led to the diagnosis was hyponatraemia. The major difference between the two cases was the time at which AI evolved during the course of APS. In the first patient, AI developed acutely along with other presenting features of APS. In the second patient, the AI was unmasked during a stressful situation induced by severe inflammation that occurred 7 years after the first APS manifestation and had probably evolved slowly during the previous few years. These cases emphasise the importance of considering AI in patients with either suspected or newly diagnosed APS as well as in patients who have long been known to have APS. The symptoms and signs alerting the clinician to possible AI are general abdominal complaints, fever, hypotension, and hyponatraemia. Conversely, patients with primary AI should be questioned about the signs and symptoms of APS.

Adult growth hormone deficiency in CEE region: Heterogeneity of the patient pathway.

OBJECTIVES: Adult growth hormone deficiency (AGHD) is a rare disease characterised by abnormal body composition, reduced strength and exercise capacity and impaired psychological wellbeing. An advisory board of leading Central and Eastern European (CEE) endocrinologists was assembled to gain insights into the status of AGHD care in the CEE region. Topics of discussion included the position of adult hypopituitarism/AGHD in health system priorities, availability and affordability of treatments, awareness of AGHD, practice guidelines used in CEE countries and provisions for long-term care of patients. DESIGN: Prior to the meeting, the advisors were asked to summarise, using an itemised survey questionnaire, the usual standards of care for patients with AGHD in their country. At the meeting, the panel of experts discussed the findings and thereby elucidated similarities and differences among CEE countries; these were compared with international guideline-recommended practices for AGHD. RESULTS: All CEE countries involved reported having some type of infrastructure in place for care of patients with GHD transitioning from adolescence to adulthood. Most countries reported having at least one specialist centre for patients with AGHD. The main variations across the region included initial entry into healthcare systems, tests required to confirm AGHD diagnosis and medication reimbursement by health authorities. Most CEE countries relied on international society-led guidelines, while some countries have developed national guidelines. CONCLUSION: The CEE Adult Endocrinology Advisory Board meeting recognised considerable diversity in the care and patient pathways for AGHD across CEE countries. Additional work is needed to optimise care of patients with AGHD in the CEE region.

Genetic analysis of adult Slovenian patients with combined pituitary hormone deficiency.

PURPOSE: Among genetic causes of combined pituitary hormone deficiency (CPHD), mutations of genes coding for transcription factors involved in pituitary development have been implicated. Congenital CPHD is a rare disease; therefore, it is important to expand the knowledge about incidence and regional distribution of specific mutations. The aim of this paper is to report results of genetic analyses of adult Slovenian patients with CPHD. METHODS: Twenty-three adult Slovenian patients with early childhood onset CPHD were included in the study. Blood samples were collected through the GENHYPOPIT network to assess possible mutations of six genes (PROP1/HESX1/LHX4/LHX3/POU1F1) involved in the pituitary development following an established algorithm. RESULTS: In seven out of 23 patients (30%) a specific mutation in genes encoding pituitary transcription factors was discovered. In five patients, two different mutations of the PROP1 gene (c.150delA and c.301-302delAG) were identified. One patient was heterozygous for a missense variant in the LHX4 gene. Additionally, one patient was positive for a mutation in the gene coding for prokineticin receptor-2. CONCLUSIONS: Our study confirms that the two most common mutations of the PROP1 gene globally are also the most frequent mutations in the cohort of adult Slovenian patients with CHPD. Other mutations of pituitary transcription factor genes are extremely rare.

Cardiometabolic risk in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age. Besides hyperandrogenism, oligomenorrhea and fertility issues, it is associated with a high prevalence of metabolic disorders and cardiovascular risk factors. Several genetic polymorphisms have been identified for possible associations with cardiometabolic derangements in PCOS. Different PCOS phenotypes differ significantly in their cardiometabolic risk, which worsens with severity of androgen excess. Due to methodological difficulties, longer time-scale data about cardiovascular morbidity and mortality in PCOS and about possible beneficial effects of different treatment interventions is missing leaving many issues regarding cardiovascular risk unresolved.

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8 cm vs ≥2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

The impact of testosterone replacement therapy on glycemic control, vascular function, and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes.

OBJECTIVE: This study set out to assess effects of testosterone replacement therapy (TRT) on parameters of metabolic syndrome and vascular function in obese hypogonadal males with type 2 diabetes mellitus (DM2). STUDY DESIGN: Fifty-five obese hypogonadal diabetic males on oral hypoglycemic treatment were enrolled into this one-year, double-blind, randomized, placebo-controlled clinical study. Group T (n = 28) was treated with testosterone undecanoate (1000 mg i.m. every 10 weeks) while group P (n = 27) received placebo. METHODS: Anthropometrical and vascular measurements - flow-mediated dilatation (FMD) and intima media thickness (IMT) - biochemical and hormonal blood sample analyses were performed at the start of the study and after one year. Derived parameters (BMI, HOMA-IR, calculated free testosterone (cFT) and bioavailable testosterone (BT)) were calculated. RESULTS: TRT resulted in reduction of HOMA-IR by 4.64 ± 4.25 (p < .001), HbA1c by 0.94 ± 0.88% points (p < .001), and an increase in FMD by 2.40 ± 4.16% points (p = .005). CONCLUSION: TRT normalized serum testosterone levels, improved glycemic control and endothelial function while exerting no ill effects on the study population.

65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma.

Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm.

Preoperative medical treatment in Cushing's syndrome: frequency of use and its impact on postoperative assessment: data from ERCUSYN.

BACKGROUND: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. OBJECTIVE: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). PATIENTS AND METHODS: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). RESULTS: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. CONCLUSIONS: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.

Diagnostic tests for Cushing's syndrome differ from published guidelines: data from ERCUSYN.

OBJECTIVE: To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing's syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. PATIENTS AND METHODS: We analyzed data on the diagnostic tests performed in 1341 patients with Cushing's syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). RESULTS: Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (P < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (P < 0.05). CONCLUSIONS: Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.

MOD-4023, a long-acting carboxy-terminal peptide-modified human growth hormone: results of a Phase 2 study in growth hormone-deficient adults.

OBJECTIVE: Growth hormone (GH) replacement therapy currently requires daily injections, which may cause distress and low compliance. C-terminal peptide (CTP)-modified growth hormone (MOD-4023) is being developed as a once-weekly dosing regimen in patients with GH deficiency (GHD). This study's objective is to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of MOD-4023 administered once-weekly in GHD adults. DESIGN: 54 adults with GHD currently treated with daily GH were normalized and randomized into 4 weekly dosing cohorts of MOD-4023 at 18.5%, 37%, 55.5% or 123.4% of individual cumulative weekly molar hGH dose. The study included 2 stages: Stage A assessed the effectiveness and PK/PD profiles of the 4 dosing regimens of MOD-4023. Stage B was an extension period of once-weekly MOD-4023 administration (61.7% molar hGH content) to collect further safety data and confirm the results from Stage A. RESULTS: Dose-dependent response was observed for both PK and PD data of weekly MOD-4023 treatment. Insulin-like growth factor I (IGF-I) SDS levels were maintained within normal range. The 18.5% cohort was discontinued due to low efficacy. MOD-4023 was well tolerated and exhibited favorable safety profile in all dose cohorts. The reported adverse events were consistent with known GH-related side effects. CONCLUSIONS: Once-weekly MOD-4023 administration in GHD adults was found to be clinically effective while maintaining a favorable safety profile and may obviate the need for daily injections. Weekly GH injections may improve compliance and overall outcome. The promising results achieved in this Phase 2 study led to a pivotal Phase 3 trial, which is currently ongoing.

Comparison of different methods investigating functional and morphological markers of early atherogenesis in obese women with polycystic ovary syndrome.

BACKGROUND: The prognostic importance of preclinical markers of atherosclerosis and their interrelationship are inconclusive. In this study interrelationship between different methods investigating endothelial function and intima media thickness (IMT) was investigated in patients with polycystic ovary syndrome (PCOS). METHODS: Endothelial function was assessed by endothelium-dependent flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), low-flow-mediated constriction (L-FMC) and peripheral arterial tonometry (PAT). Arterial stiffness was determined by pulse wave velocity (PWV) and the Augmentation Index (AI). The IMT of carotid arteries was measured. RESULTS: Twenty-eight obese women were recruited with the diagnosis of PCOS, mean age 27±7.2 years and Body Mass Index 38.8±6.3 kg/m2. A relationship between FMD and NMD (r=0.44, P=0.02) was shown. FMD as well as NMD of the brachial artery were not correlated with L-FMC or PAT. The AI and PWV, indicators of arterial stiffness were not interrelated with FMD, and there was no significant interrelationship between IMT and FMD or NMD. The AI was related only to IMT (r=0.45, P=0.30). CONCLUSIONS: The relationship between available methods for evaluation of endothelial function/dysfunction is weak in PCOS. This indicates that different methods investigate different mechanisms and various sections of the circulatory system.

Identifying the Deleterious Effect of Rare LHX4 Allelic Variants, a Challenging Issue.

LHX4 is a LIM homeodomain transcription factor involved in the early steps of pituitary ontogenesis. To date, 8 heterozygous LHX4 mutations have been reported as responsible of combined pituitary hormone deficiency (CPHD) in Humans. We identified 4 new LHX4 heterozygous allelic variants in patients with congenital hypopituitarism: W204X, delK242, N271S and Q346R. Our objective was to determine the role of LHX4 variants in patients' phenotypes. Heterologous HEK293T cells were transfected with plasmids encoding for wild-type or mutant LHX4. Protein expression was analysed by Western Blot, and DNA binding by electro-mobility shift assay experiments. Target promoters of LHX4 were cotransfected with wild type or mutant LHX4 to test the transactivating abilities of each variant. Our results show that the W204X mutation was associated with early GH and TSH deficiencies and later onset ACTH deficiency. It led to a truncated protein unable to bind to alpha-Gsu promoter binding consensus sequence. W204X was not able to activate target promoters in vitro. Cotransfection experiments did not favour a dominant negative effect. In contrast, all other mutants were able to bind the promoters and led to an activation similar as that observed with wild type LHX4, suggesting that they were likely polymorphisms. To conclude, our study underlines the need for functional in vitro studies to ascertain the role of rare allelic variants of LHX4 in disease phenotypes. It supports the causative role of the W204X mutation in CPHD and adds up childhood onset ACTH deficiency to the clinical spectrum of the various phenotypes related to LHX4 mutations.

A 12-week treatment with the long-acting glucagon-like peptide 1 receptor agonist liraglutide leads to significant weight loss in a subset of obese women with newly diagnosed polycystic ovary syndrome.

OBJECTIVE: The long-acting glucagon-like peptide 1 receptor agonist liraglutide is linked to progressive and sustained weight loss in obese people with diabetes. However, its efficacy and safety in women with polycystic ovary syndrome (PCOS) has not yet been addressed. DESIGN: Thirty-two obese women (aged 27.6±7.2 years, BMI 39.5±6.2 kg/m(2)) with newly diagnosed PCOS were randomized to receive either liraglutide 1.2 mg QD sc (n=17) or metformin 1000 mg BID po (n=15) for 12 weeks; 28 patients completed the study (14 on liraglutide and 14 on metformin). The main outcome was change in body weight. RESULTS: Intention-to-treat analysis showed significant BMI (-0.98 kg/m(2); p<0.001), body weight (-2.52 kg; p<0.001), waist circumference (-3.38 cm; p<0.001) and whole-body fat mass (-1.26%; p<0.001) reduction in both treatment arms without significant differences between therapeutic groups. However, in a subgroup of patients (n=9) with insulin resistance (HOMA(IR) >2), severe obesity and higher odds ratio for the metabolic syndrome (OR=3.9), the patients fared much better with liraglutide than with metformin (mean BMI decreased 2.13 kg/m(2) vs. 0.62 kg/m(2), respectively). CONCLUSIONS: Short-term liraglutide treatment was associated with significant weight loss in a subset of obese patients with newly diagnosed PCOS and a higher metabolic risk profile.

Short-term intervention with liraglutide improved eating behavior in obese women with polycystic ovary syndrome.

AIM: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) stimulate satiety leading to reductions in food intake and body weight. The effects of long- acting GLP-1 RA liraglutide on eating behavior of women with PCOS have not been investigated yet. METHODS: Thirty-six obese women with PCOS (mean ± SD, aged 31.2 ± 7.8 years, with BMI 38.7 ± 0.1 kg/m(2)), pretreated with metformin (1000 mg BID) were switched to liraglutide 1.2 mg QD sc for 12 weeks. Adiposity parameters and eating behavior as assessed by Three-Factor Eating Questionnaire (TFEQ-R18) were examined at baseline and after 12 weeks. RESULTS: Subjects treated with liraglutide lost on average 3.8 ± 0.1 kg (p < 0.001). Significant reductions of waist circumference and visceral adipose tissue (VAT) mass, volume and area were demonstrated from liraglutide induction to the end of the study. TFEQ-R18 scores were significantly different pre- and post-liraglutide intervention. After treatment with liraglutide the uncontrolled eating (UE) score decreased from 36.8 ± 24.5 to 19.6 ± 18.4 (p < 0.001) and emotional eating (EE) score decreased from 49.9 ± 33.3 to 28.5 ± 26.9 (p < 0.001). Scores for cognitive restraint (CR) were not changed. CONCLUSIONS: Short-term liraglutide treatment was associated with weight loss and significantly improved eating behavior in obese women with PCOS.

Optimal scan time for evaluation of parathyroid adenoma with [(18)F]-fluorocholine PET/CT.

BACKGROUND: Parathyroid adenomas, the most common cause of primary hyperparathyroidism, are benign tumours which autonomously produce and secrete parathyroid hormone. [(18)F]-fluorocholine (FCH), PET marker of cellular proliferation, was recently demonstrated to accumulate in lesions representing enlarged parathyroid tissue; however, the optimal time to perform FCH PET/CT after FCH administration is not known. The aim of this study was to determine the optimal scan time of FCH PET/CT in patients with primary hyperparathyroidism. PATIENTS AND METHODS: 43 patients with primary hyperparathyroidism were enrolled in this study. A triple-phase PET/CT imaging was performed five minutes, one and two hours after the administration of FCH. Regions of interest (ROI) were placed in lesions representing enlarged parathyroid tissue and thyroid tissue. Standardized uptake value (SUVmean), retention index and lesion contrast for parathyroid and thyroid tissue were calculated. RESULTS: Accumulation of FCH was higher in lesions representing enlarged parathyroid tissue in comparison to the thyroid tissue with significantly higher SUVmean in the second and in the third phase (p < 0.0001). Average retention index decreased significantly between the first and the second phase and increased significantly between the second and the third phase in lesions representing enlarged parathyroid tissue and decreased significantly over all three phases in thyroid tissue (p< 0.0001). The lesion contrast of lesions representing enlarged parathyroid tissue and thyroid tissue was significantly better in the second and the third phase compared to the first phase (p < 0.05). CONCLUSIONS: According to the results the optimal scan time of FCH PET/CT for localization of lesions representing enlarged parathyroid tissue is one hour after administration of the FCH.

European survey of diagnosis and management of the polycystic ovary syndrome: results of the ESE PCOS Special Interest Group's Questionnaire.

BACKGROUND: There is evidence for differences between endocrinologists and other specialists in their approach to diagnosis and management of the polycystic ovary syndrome (PCOS). OBJECTIVE: A mailed survey consisting of a simple questionnaire aiming to understand current practice for diagnosis and management of the PCOS by specialists across Europe. METHODS: The questionnaire consisted of 23 questions grouped to achieve information on i) the general characteristics of the respondents, ii) patients with PCOS seen by endocrinologists, iii) the main diagnostic criteria, iv) biochemical parameters used in the differential diagnosis of hyperandrogenism, v) long-term concerns, and, finally vi) treatment choices. A total of 357 questionnaires representing 13.3% of the members of European Society of Endocrinology (ESE) were available for final analysis; 93% of the respondents were endocrinologists RESULTS: In relation to the diagnostic criteria, respondents were most likely to select menstrual irregularity as the most frequent criteria used for the diagnosis of PCOS although very high rates were achieved for the use of hirsutism and biochemical hyperandrogenism. It therefore appears that the NIH criteria were followed by the majority of respondents. The most frequent biochemical parameters in the differential diagnosis of hyperandrogenism were total testosterone or free androgen index. Obesity and type 2 diabetes were regarded as the principal long-term concerns for PCOS. The most common treatments for patients with PCOS were metformin (33%), lifestyle modification (25%), and oral contraceptives (22%). More direct treatments of infertility include clomiphene citrate alone or in combination with metformin, prescribed by 9 and 23%, respectively, whereas only 6% used other methods for induction of ovulation. CONCLUSION: The survey produced by ESE is a good start for evaluating the perspective in the diagnosis and treatment of PCOS by endocrinologists in Europe.