Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

INSULIN RESISTANCE AND PATHOGENESIS OF POSTMENOPAUSAL OSTEOPOROSIS.

Osteoporosis (OP) is a disease predisposing postmenopausal women to fractures, and often accompanied by insulin resistance (IR) and metabolic syndrome (MetS). Previous studies provided contradictory results concerning prevalence of MetS in postmenopausal OP. To better understand the pathogenesis of IR, we reviewed cellular and molecular aspects and systematically reviewed studies providing homeostasis model assessment (HOMA) index. Bone is an active endocrine organ maintaining its integrity by orchestrated balance between bone formation and resorption. Both osteoblasts and osteoclasts contain receptors for insulin and insulin-like growth factor-1 (IGF-1) operating in skeletal development and in the adult life. Defects in this system generate systemic IR and bone-specific IR, which in turn regulates glucose homeostasis and energy metabolism through osteocalcin. Examination of genetic syndromes of extreme IR revealed intriguing features namely high bone mineral density (BMD) or accelerated growth. Studies of moderate forms of IR in postmenopausal women reveal positive correlations between HOMA index and BMD while correlations with osteocalcin were rather negative. The relation with obesity remains complex involving regulatory factors such as leptin and adiponectin to which the contribution of potential genetic factors and in particular, the correlation with the degree of obesity or body composition should be added.

VITAMIN D LEVEL AND ITS RELATIONSHIP WITH CANCER STAGE IN PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA.

Background: Differentiated thyroid carcinoma (DTC) has witnessed an increase in incidence and although it is considered to have a slow grow potential and a 90% 10-year survival rate, local or distant metastases can be observed in 20%. It is essential to recognize other factors associated with malignancy and poor prognosis. Vitamin D and its deficiency has proven useful as a prognostic biomarker for many types of cancer, including thyroid cancer. Aim: Evaluate the relationship between vitamin D status in DTC and benign thyroid disorders patients and correlation between vitamin D and histopathological findings in DTC group. Methods: Study included 170 patients with confirmed DTC and 200 with benign thyroid pathology. Evaluation included 25-hydroxy vitamin D [25(OH)D], ultrasound and histopathologic features. Results: In DTC patients, mean value of vitamin D was significantly lower (17.86 ng/mL ± 9.31 DS versus 20.26 ng/mL ± 9.31 DS, p=0.029). Statistical analysis confirmed a negative correlation between vitamin D levels and tumor size (T) according to TNM classification (r=-0.176, p=0.02). Conclusions: Vitamin D level was significantly lower in the DTC group and 25(OH)D levels may be correlated with histopathology features like tumor size and aggressiveness according to TNM classification.

THE LEARNING CURVE AND PERFORMANCE OF A NEWLY ESTABLISHED THYROID FINE-NEEDLE ASPIRATION CENTER.

Context: Thyroid fine-needle aspiration (FNA) cytology is the best tool for preoperative diagnosis of thyroid carcinoma; however, its learning curve is poorly described. Our aim was to assess the learning curve of a new thyroid FNA center involving unexperienced operator and pathologist. Methods: We retrieved from our tertiary endocrinology center database all thyroid FNA procedures done by a single operator (endocrinologist with no experience in FNA) between 2018 and 2021. Cytology was assessed by two pathologists with limited or no experience in thyroid cytology. We also got the corresponding sex, age, nodule diameter, EU-TIRADS score, Bethesda category and final pathology report. Results: There were 1872 FNA in 1618 patients. Proportion of Bethesda 1 nodules decreased significantly (p for trend=0.003) from 17% in the first 100 FNA procedures to 4% in the 401-500 group of procedures, and remained constant between 9% and 4% (p for trend=NS) for the rest of the study. Proportion of Bethesda 2 rose steady from 26% in the first 100 nodules to 80.1% in the last 241 nodules (p for trend<0.001). Indeterminate lesions (Bethesda 3 and 4) decreased significantly (p for trend=0.001) from 16% and 35% in the first 100 nodules to 2.5% and 5.8% in the last 241 lesions. Proportions of Bethesda 5+6 categories varied non-significantly over time. There were no time trends in the malignancy rate of surgically removed nodules. Conclusions: At least 300 procedures are needed to reach the standard performance. A steadily state for the whole center is obtained after about 500 procedures.

Osteoporotic Hip Fracture Incidence Rates in the Main Urban Area of Romania.

CONTEXT: Estimation of osteoporotic hip fracture incidence and Romanian FRAX model were based on nationally reported hospital ICD 10 coding admissions of all hip fractures (without a validation process). OBJECTIVE: We aimed to calculate, based on individual hospital charts analysis, the incidence of osteoporotic hip fracture in the main urban area of Romania and compare it with data reported to the National Institute of Public Health (NIPH). DESIGN: We retrospectively analyzed the charts of all patients (>40 years old) admitted for hip fracture in a 12-month period in hospitals with an Orthopedic Department in Bucharest and surrounding Ilfov County (11.8% of Romania population). SUBJECTS AND METHODS: All ICD 10 fracture and event/fall codes were validated against the charts. We calculated the age and sex adjusted incidence of osteoporotic hip fracture and used the national reported hip fracture data base for comparison. RESULTS: There were 2203 hip fractures of which 1997 (90.65%) were fragility fractures. The crude incidence of low-energy hip fractures was 171/100,000 (225/100,000 in women, 103/100,000 in men). The incidence rose with age to a maximum rate of 1902/100,000 in women >85 years. The NIPH-reported incidence of hip fracture was 181/100,000 for the region of interest and 176/100,000 at the national level. CONCLUSION: The incidence of osteoporotic hip fracture was lower than the incidence based on hip fractures reported codes in the national database, but the incidence of fragility fractures calculated by our group was higher than the incidence reported in previous national studies. Nationwide studies are warranted.

FAMILY HISTORY - BMD INDEPENDENTLY - INFLUENCES FRACTURE RISK.

Context: Parental history of osteoporosis is associated with an increased risk of fracture. However, there are not many data on the mechanism of action.Our objective was to determine if heredity influences fracture rate: independently or through the bone mineral density; to identify also the strongest independent risk factors of osteoporotic fractures among our study population. Methods: We processed data of 541 women outpatients with an average age of 55 years, participating in an osteoporosis screening program.Our results confirm that the presence of family history significantly increases fracture prevalence, (37% vs. 17%, p<0.001, OR 2.853, p=0.001) and decreases BMD scores. Fractures occur at higher (better) T and Z-scores. The risk of having T values in the range of (0- -1) and Z values in (-1--2) is much higher in the positive group. The logistic regression analysis confirms the BMD-independent influence of heredity on fracture risk. Conclusions: Parental history of osteoporosis negatively affects bone density and significantly increases the incidence of fractures. The latter happens also independently of the bone density values. Timely intervention in these easy-to-detect cases may be the most effective prevention of osteoporotic fractures.

Dopamine Agonists in the Management of Non-Functioning Pituitary Adenomas.

Non-functioning pituitary tumors (NFPA) are usually large at the time of diagnosis and present with symptoms caused by compression on the neighbouring structures. Transsphenoidal resection of the tumor is the first-line treatment but in many cases complete tumor resection cannot be attained. Close follow-up with repeated hormonal assessment and pituitary imaging is recommended after surgery. During follow-up of the tumor remnant sometimes radiotherapy is used to stop or prevent tumor progression. Medical treatment with dopamine agonists (DA) is the mainstay in the management of prolactinomas. For NFPA several small series or case reports suggested beneficial effects with tumor shrinkage in some cases. The aim of the current paper is to summarize the available evidence related to the potential efficacy of DA medical treatment in NFPA while underlining that in the absence of randomized, placebo-controlled studies, no final conclusion on the efficacy of these drugs in the treatment of NFPA can be drawn.

UPDATES IN AGGRESSIVE PITUITARY TUMORS.

Aggressive pituitary tumors lie between pituitary adenomas and carcinomas, displaying a particular behavior, with invasion, resistance to conventional therapy and early recurrence. The radiological grading, along with prognostic markers such as Ki-67 proliferation index, p53, MGMT and transcription factors are important factors in establishing the benign, aggressive, or malignant nature of pituitary tumors, with a more accurate treatment strategy. In this article, we report the novelties in defining, classifying, and managing aggressive pituitary tumors and their malignant potential, focusing on clinicopathological, histological, molecular and radiological data.

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A Thesis* Questionnaire Survey of Romanian Physicians *Thesis: Treatment of Hypothyroidism in Europe by Specialists: an International Survey.

OBJECTIVE: Romania has no national guidelines for hypothyroidism treatment, nor are there any recommendations from national societies to adhere to international guidelines. Our aim was to identify the attitudes of Romanian physicians relating to hypothyroidism treatment focusing on available formulations of levothyroxine (LT4). METHODS: All 748 members of the Romanian Society of Endocrinology were invited to participate in a web-based survey. A total of 316 (42.24%) members responded, of whom 222 (70.2%) completed all questions. RESULTS: Half of the respondents recommended LT4 treatment in euthyroid patients, from 3.6% in euthyroid patients with obesity to 36.4% in euthyroid females with infertility associated with high levels of thyroid antibodies. LT4 was considered the preferred treatment for hypothyroidism (compared to combination treatment of LT4 with LT3 or LT3 alone) by 98.6% of respondents. LT4 in liquid solution was preferred over tablets if malabsorption is suspected (56.5% vs. 27.3%), for patients with unexplained poor biochemical control (52.5% vs. 22.9%) and for patients not able to adhere to ingesting LT4 fasted (74.0% vs. 9.8%). The most and least probable explanations for persistent symptoms in patients with hypothyroidism who achieve a normal TSH under medication were "psychosocial factors" and "burden of having to take medication", respectively. CONCLUSION: A significant proportion of Romanian physicians would use LT4 in some groups of euthyroid patients, contrary to current evidence. The preferred treatment for hypothyroidism was LT4. Alternative LT4 formulations (liquid solution) are considered in specific clinical conditions. Diversification of available thyroid hormone formulations was readily incorporated into everyday practice.

OSTEOPOROSIS AND FRACTURE RISK IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fragility fractures compared to the general population. The pathogenesis of the elevated fracture risk is multifactorial and still largely elusive. In contrast to primary osteoporosis, in T2DM the bone mineral density (BMD) is increased compared to controls, suggesting that specific alterations in bone quality occur in diabetic patients. Even more, the specific increase in BMD observed in these patients impairs at least in part both the classical diagnosis of osteoporosis by dual-energy X-ray absorptiometry (DXA) and the current fracture risk estimation by FRAX (fracture risk assessment tool). Trabecular bone score (TBS) and TBS-adjusted FRAX could improve fracture risk estimation in patients with T2DM but improved tools are needed in the future as well as specific risk stratification criteria. Decreases in the fracture risk of patients with T2DM can be obtained by optimal diabetes control and standard treatment of osteoporosis (most drugs appear to have similar efficacy in patients with T2DM and primary osteoporosis).

HYPOVITAMINOSIS D IN HIV-INFECTED PATIENTS.

INTRODUCTION: Vitamin D (VD) deficiency is highly prevalent worldwide. AIM: To assess the prevalence of hypovitaminosis D in HIV-positive Romanian patients compared to controls. METHODS: Serum 25OHD concentration was measured in HIV-infected patients and a control sample, matched by age, sex and menopausal status. The 25OHD status was defined as: deficiency < 20 ng/mL (severe deficiency <10 ng/mL), insufficiency 20-30 ng/mL, normal >30 ng/mL. RESULTS: We evaluated 118 HIV-positive patients (72 males, 46 females), aged 36.9±12.2 years. 98.14% of them were on complex antiviral regimens. The B/C hepatitis coinfection rate was 9.3%. The control sample consisted of 119 subjects, (74 males, 45 women). The median and interquartile range for serum 25OHD concentration in patients was 17.6 (9.7, 26.9) ng/mL and 23.7 (18.4, 27.5) ng/mL in controls (p=0.001). Only 15.96% of HIV-positive cases and 12.71% of controls had normal VD status. The percentage of cases with severe VD deficiency was significantly higher in HIV positive cases (23.52%) compared to HIV-negative controls (4.2%, p=0.001). CONCLUSIONS: Hypovitaminosis D was identified in 84.04% of HIV-infected patients, but the serum 25OHD concentration was not associated with specific HIV-related factors in our sample. Clinical guidelines regarding VD status determination and supplementation in HIV patients are needed.

CRANIOPHARYNGIOMA - CLINICAL AND THERAPEUTIC OUTCOME DATA IN A MIXED COHORT OF ADULT AND PAEDIATRIC CASES.

BACKGROUND: Craniopharyngiomas are benign but locally invasive tumours of the sellar region that arise from ectopic embryonic remnants of Rathke's pouch, affecting both children (adamantinomatous type -aCP) and adults (papillary type -pCP) and associated with significant morbidity. OBJECTIVE: To study the clinical presentation of CRF as well as the posttreatment evolution of craniopharyngioma in children versus adults in a large mixed cohort. MATERIAL AND METHODS: We performed a retrospective review of CRF patients evaluated in the National Institute of Endocrinology in Bucharest between 1990 and 2016. RESULTS: A total of 107 patients (72 adults, 35 children) with a mean follow-up of 6.2 years were included. The presenting symptoms were mostly headache, visual impairment, symptoms of hypopituitarism, diabetes insipidus. Some symptoms or hormonal abnormalities were significantly more prevalent in the children group (p<0.05): nausea/ vomiting (47.8% vs 16.7%), photophobia (21.7% vs 5.6%), diabetes insipidus(28.5% vs 8.3%), GH deficiency (68.8% vs 17.1%). Impaired visual acuity (67.6%of cases) or visual fields (71.4%) were more frequent in adults compared to children (44.1%; 51.6%). The tumor dimensions were similar in both groups (3.05± 1.05 cm in children; 2.7± 1.07 cm in adults). Massive suprasellar extension reaching the third ventricle was frequently present in all cases. All cases underwent surgery but only a minority of those not cured received postoperative adjuvant radiotherapy. Frequent postoperative complications were: aggravation of the endocrine deficit (>80% of cases in both groups needed chronic replacement therapy), central diabetes insipidus (68.2% children, 34.3% of adults). CONCLUSIONS: Despite similar tumor dimensions and extension compared to adults, craniopharyngioma in children is more frequently associated with signs of intracranial pressure. The results and complications of treatment are similar in adults and children.

Increased copeptin levels in metabolic syndrome from a Romanian population.

Rationale: Arginine vasopressin (AVP) is secreted under conditions of water deprivation. Since AVP has a low half-life in the plasma, the C-terminal fragment of AVP-precursor (copeptin) was used to estimate the AVP levels. High copeptin levels increase the risk for the development of diabetes mellitus. Aim: This study was aimed to measure copeptin levels in the metabolic syndrome (MetS) in Romanians using a competitive enzyme immunoassay. Methods and results: Patients prone to present MetS (n = 63) were compared to controls (n = 42). In the MetS group, the syndrome was confirmed in 93.6%. Affected patients displayed 85.7% obesity and insulin resistance (HOMAIR of 4.9 ± 0.4 versus 1.1 ± 0.8 in controls). Low HDL-cholesterol was less represented (47.5%). Copeptin levels were 0.6 ± 0.0 in MetS versus 0.42 ± 0.0 ng/ mL in controls (P < 0.004). Higher copeptin (0.79 to 1.83 ng/ mL) was associated with MetS, P < 0.0018, OR 20, 95%CI [3.03 - 131.7]. In ANOVA, high copeptin was equally explained by MetS or obesity (P < 0.05,α = 3.8). The best correlation was found with high triglyceride levels (P < 0.013,α = 6.3) while the correlation with HOMAIR remained not significant. Discussion: These data indicated a concordant correlation between increased copeptin and MetS or its components. In the light of epidemiological data, indicating that more than 50% of the European population has a lower daily water intake and a fraction of 25% displaying high copeptin, our data further sustained that copeptin may be a good biomarker for MetS and/ or obesity, which should be further investigated with other members of the osmoregulation pathway at both pathogenesis and genetic levels.

Short-term Administration of Alphacalcidol is Associated with More Significant Improvement of Muscular Performance in Women with Vitamin D Deficiency Compared to Native Vitamin D.

Introduction: Positive relationships between muscle function and vitamin D (VD) status, defined by serum 25-hydroxy VD (25OHD) levels have been reported and muscle strength is generally improved with VD supplementation in deficient individuals. The effects of active VD analogs have been less studied. Aim: We aim to investigate the effect of short-term treatment with native VD (cholecalciferol) or alphacalcidol on the muscular function and physical performance in women with vitamin D deficiency. Material and methods: We analysed 178 women with VD deficiency, defined as serum 25-hydroxyVD-25OHD concentration below 30 ng/ml. We recorded the grip-strength and the results of the chair-rise test (CRT) and timed-up-and-go test (TUG). We randomised the patients to receive cholecalciferol 1 000 IU daily or alphacalcidol 1 µg daily, for 6 months. Results: The mean baseline 25OHD concentration was 14.47±6.57 ng/ml. After treatment the serum 25OHD level rose to 20.85±8.88 ng/ml, significantly higher in cases supplemented with cholecalciferol (22.7±8.32 ng/ml) compared to those treated with alphacalcidol (13.5±7.29 ng/ml, p=0.000). After treatment, significant improvements of TUG and CRT test results (- 6.48 and-5.05% compared to baseline, respectively, p=0.000) and gripstrength (7.85% compared to baseline, p=0.000) occurred. The benefit was more significant in cases treated with alphacalcidol for gripstrength (p=0.001), TUG (p=0.002), CRT (p=0.033). After treatment, the gripstrength increased significantly more in patients with severe baseline VD deficiency. Conclusions: VD status improvement is associated with an increase in muscular performance in women with VD deficiency. Alphacalcidol exerts significantly better effects compared to cholecalciferol, and this can not be explained by a larger increase in serum 25OHD concentration.

SPONTANEOUS CONCEPTION AND TERM DELIVERY IN A WOMAN WITH UNCONTROLLED ACROMEGALY AND HYPOGONADOTROPIC HYPOGONADISM.

BACKGROUND: Patients with acromegaly (caused by growth-hormone-secreting pituitary adenomas) are at increased risk of hypopituitarism, in particular hypogonadotropic hypogonadism, before and after multimodal therapy. In affected women of reproductive age, fertility is impaired and complex fertility treatments are needed to achieve conception. CASE PRESENTATION: We present the case of a young woman with acromegaly caused by a GH-secreting macroadenoma with suprasellar and bilateral cavernous sinus extension; hypogonadotropic hypogonadism and secondary hypothyroidism were present from the initial evaluation. Neurosurgical intervention was repeatedly recommended but the patient refused it initially; also she was non-compliant to the medical treatment of acromegaly. Transsphenoidal tumor debulking with adjuvant gamma-knife radiotherapy was eventually performed. Following treatment persistent active acromegaly and hypogonadotropic hypogonadism were diagnosed. Under chronic estroprogestative replacement therapy, the patient conceived and delivered a full-term healthy newborn without any complications. Possible mechanisms are discussed. CONCLUSIONS: Secondary hypogonadotropic hypogonadism in pituitary patients, even when considered permanent (after surgery and radiotherapy), can exceptionally allow spontaneous conception and normal course of pregnancy.

Current therapies and mortality in acromegaly.

UNLABELLED: Acromegaly is a rare disease most frequently due to a GH secreting pituitary adenoma. Without an appropriate therapy, life of patients with acromegaly can be shortened with ten years. Pituitary surgery is usually the first line therapy for GH secreting pituitary adenomas. A meta-analysis proved that mortality is much lower in operated patients, even uncured, than the entire group of patients and is similar with the general population in patients with GH<1 µg/ L. For the patients with hypersecreting postoperative remnant tumor, those with low chance of surgical cure or with life-threatening comorbidities, medical therapies are available: somatostatin receptor analogues (SRA), dopamine agonists (DA) and GH receptor antagonists. Studies with >30% utilization of SRAs reported a lower mortality ratio than studies with lower percentages of SRA administration. Although therapy with DA has long been used in patients with acromegaly, there are no studies reporting its effect on mortality, but its efficacy is limited by the low remission rate obtained. The use of conventional external radiotherapy, although with good remission rate in time, was linked with increased mortality, mostly due to cerebrovascular diseases. CONCLUSION: Mortality in acromegaly can be reduced to expected levels from general population by using modern therapies either in monotherapy or by using multimodal approaches in experienced centers.

Prevalent osteoporotic fractures in 622 obese and non- obese menopausal women.

Hypothesis. The osteoporotic fractures represent a worldwide economical issue. In order to prevent them, we need to understand the risk factors constellation. Although obesity was traditionally considered as protective against osteoporosis, recent data exposed an increased risk of falling and thus a high risk of some fractures. Objective. We aimed to analyze the body mass index (BMI) in relationship with the bone mineral density (BMD) and the prevalent fractures. Methods and Results. Between 2008 and 2014, a cross-sectional observational study included Romanian menopausal Caucasian women without a previous diagnosis of bone maladies, or specific anti-osteoporotic therapy. Prevalent fragility fractures were both self-declared and incidental vertebral. All the subjects had lumbar BMD (GE Lunar Prodigy DXA machine). Out of 622 females (mean age of 58.65 years, mean BMI of 30.30 kg/ m2), 39.22% were obese (BMI ≥ 30kg/ m2). The fracture prevalence was 1.35% versus 1.67% in obese versus non-obese patients. The correlation coefficient between lumbar BMD and BMI was r=0.165, p<0.005. BMI in the fracture group was 31.68 kg/ m2 vs. 30.04 kg/ m2 in the non-fracture group (p=0.08). 15.91% of the entire cohort had prevalent fractures. Obesity prevalence among females with fractures was 30.3% versus 40.73% in the non-fracture group. The most frequent sites were distal forearm (42.42%) and vertebral (21.21%). Discussions & Conclusions. Although the vertebral fractures might be underdiagnosed in our study and despite the fact that we enrolled a relatively young menopausal population, BMI positively correlated with BMD, regardless of the fractures' prevalence. In early menopause, the most frequent fracture is distal forearm. BMI is higher in patients with prevalent fractures vs. non-fractures (borderline significance). Obesity might not protect from any type of fracture but future evidence is necessary since one third of osteoporotic fractures are met in women with a BMI ≥ 30kg/ m2.

Features of Polycystic Ovary Syndrome in adolescence.

RATIONALE: To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman's life. OBJECTIVE: To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood. METHODS AND RESULTS: A systematic review of literature was performed through electronic database searches (Pubmed, Medline and Embase). Studies published in English-language, peer-reviewed journals from 1996 to 2013 were included. The selected studies focused on the risk factors, the unique features and treatment options of the PCOS in puberty. The pathogenesis of the PCOS was hypothesized to be based on interactions between genetic and certain environmental factors. The diagnosis was usually difficult in young girls. The syndrome was related to a greater risk of future infertility, type II diabetes mellitus, the metabolic syndrome and cardiovascular disease. Early treatment was crucial to prevent the long-term complications of the syndrome, especially infertility and cardiovascular disease. DISCUSSION: The recognition of the early signs of PCOS during or even before adolescence is of great importance. It is essential to establish the correct diagnosis for PCOS and rule out other causes of androgen excess in young women with hyperandrogenism. The type of treatment applied should be considered on an individual basis. ABBREVIATIONS: PCOS = Polycystic Ovary Syndrome.

Phenotypic spectrum and hormonal profile in hypogonadotropic hypogonadism.

BACKGROUND: Hypogonadotropic hypogonadism (HH) is characterized by inappropriately low serum concentration of LH (luteinizing hormone) and FSH (follicle-stimulated hormone) in the setting of hypogonadism. A number of pathologic processes cause Hypogonadotropic hypogonadism but it can also occur as a part of various congenital syndromes. Objectives. To characterize the morphotypes and the hormonal profile of the HH patients enrolled in the COST Action BM1105 within "C.I. Parhon" National Institute of Endocrinology from May 2012 onward. Methods. The eligible patients were selected by using a general protocol that included: a detailed familial and personal history; a clinical evaluation focusing on genital development; a hormonal evaluation that aimed to exclude the acquired causes of HH and to characterize the basal/stimulated (triptoreline) profile of gonadotropins; a DNA extraction for genetic studies. RESULTS: We examinated the medical records of patients admitted in our institute with the diagnosis of hypogonadotropic hypogonadism from May 2012 onward. There were 19 patients: 12 males and 7 females, age at diagnosis 28.03 ± 11.45 years (13.4-56 years). The phenotypic expressions were variable and the hormonal evaluation showed low values of basal and stimulated gonadotropins. CONCLUSIONS: Although hypogonadotropic hypogonadism is a rare disease, the monospeciality profile of National Institute of Endocrinology enable the enrolment of a high number of patients in order to create clinical guidelines for evaluation/diagnosis and for treating GnRH deficient patients.