Showing papers in "Journal of Endocrinological Investigation in 2018"

Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies

Abstract: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Six scientific Italian societies entitled to cure thyroid cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field. The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

Polyglandular autoimmune syndromes.

Abstract: In recent years, scientific knowledge pertaining to the rare ORPHAN polyglandular autoimmune syndrome (registered code ORPHA 282196) has accumulated. To offer current demographic, clinical, serological and immunogenic data on PAS. Review of the pertinent and current literature. Polyglandular autoimmune syndromes (PAS) are multifactorial diseases with at least two coexisting autoimmune-mediated endocrinopathies. PAS show a great heterogeneity of syndromes and manifest sequentially with a large time interval between the occurrence of the first and second glandular autoimmune disease. PAS cluster with several non-endocrine autoimmune diseases. In most endocrinopathies of PAS, the autoimmune process causes an irreversible loss of function, while chronic autoimmune aggressions can simultaneously modify physiological processes in the affected tissue and lead to altered organ function. The rare juvenile PAS type I is inherited in a monogenetic manner, whereas several susceptibility gene polymorphisms have been reported for the more prevalent adult types. Relevant for a timely diagnosis at an early stage is the screening for polyglandular autoimmunity in patients with monoglandular autoimmune disease and/or first degree relatives of patients with PAS. The most prevalent adult PAS type is the combination of type 1 diabetes with autoimmune thyroid disease. Early detection of specific autoantibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown PAS disease.

Thyroid diseases and bone health

Abstract: Thyroid hormones are essential for skeletal development and are important regulators of bone maintenance in adults. Childhood hypothyroidism causes delayed skeletal development, retarded linear growth and impaired bone mineral accrual. Epiphyseal dysgenesis is evidenced by classic features of stippled epiphyses on X-ray. In severe cases, post-natal growth arrest results in a complex skeletal dysplasia. Thyroid hormone replacement stimulates catch-up growth and bone maturation, but recovery may be incomplete dependent on the duration and severity of hypothyroidism prior to treatment. A severe phenotype characteristic of hypothyroidism occurs in children with resistance to thyroid hormone due to mutations affecting THRA encoding thyroid hormone receptor α (TRα). Discovery of this rare condition recapitulated animal studies demonstrating that TRα mediates thyroid hormone action in the skeleton. In adults, thyrotoxicosis is well known to cause severe osteoporosis and fracture, but cases are rare because of prompt diagnosis and treatment. Recent data, however, indicate that subclinical hyperthyroidism is associated with low bone mineral density (BMD) and an increased risk of fracture. Population studies have also shown that variation in thyroid status within the reference range in post-menopausal women is associated with altered BMD and fracture risk. Thus, thyroid status at the upper end of the euthyroid reference range is associated with low BMD and increased risk of osteoporotic fragility fracture. Overall, extensive data demonstrate that euthyroid status is required for normal post-natal growth and bone mineral accrual, and is fundamental for maintenance of adult bone structure and strength.

From inflammation to sexual dysfunctions: a journey through diabetes, obesity, and metabolic syndrome

Abstract: Metabolic diseases are associated with chronic low-grade inflammation, which has been indicated as a potential mediator of endothelial dysfunction and cardiovascular disease. Visceral adiposity is thought to be the starting condition of the inflammatory state through the release of inflammatory cytokines, including TNF-alpha, CRP, and IL-6, which in turn promote endothelial dysfunction, endothelial expression of chemokines (IL-1) and adhesion molecules (ICAM-1, VCAM-1, and P-selectin), and the inhibition of anti-atherogenic factors (adiponectin). Obesity, metabolic diseases, and diabetes, all conditions characterized by abdominal fat, are well-recognized risk factors for sexual dysfunction in both sexes. Evidence from randomized-controlled trials supports the association between inflammatory milieau and erectile dysfunction in men suffering from metabolic diseases, whereas, in women, this has to be confirmed in further studies. A healthy lifestyle based on dietary pattern with high content of whole grain, fruit, nuts and seeds, and vegetables and low in sodium and saturated fatty acids plus regular physical activity may help to modulate the pro-inflammatory state associated with metabolic diseases and the related burden of sexual dysfunctions.

Testosterone deficiency in non-cancer opioid-treated patients

Abstract: The use of opioids in patients with chronic non-cancer pain is common and can be associated with opioid-induced androgen deficiency (OPIAD) in men. This review aims to evaluate the current literature regarding the prevalence, clinical consequence and management of OPIAD. A database search was performed in Medline, Embase and Cochrane using terms such as “analgesics”, “opioids” and “testosterone”. Relevant literature from January 1969 to March 2018 was evaluated. The prevalence of patients with OPIAD ranges from 19 to 86%, depending on the criteria for diagnosis of hypogonadism. The opioid-induced suppression of gonadotropin-releasing and luteinizing hormones represents the main important pathogenetic mechanisms. OPIAD has significant negative clinical consequences on sexual function, mood, bone density and body composition. In addition, OPIAD can also impair pain control leading to hyperalgesia, which can contribute to sexual dysfunction and mood impairment. OPIAD is a common adverse effect of opioid treatment and contributes to sexual dysfunction, impairs pain relief and reduces overall quality of life. The evaluation of serum testosterone levels should be considered in male chronic opioid users and the decision to initiate testosterone treatment should be based on the clinical profile of individuals, in consultation with the patient.

The role of microRNAs in different types of thyroid carcinoma: a comprehensive analysis to find new miRNA supplementary therapies.

Abstract: The most common endocrine malignancy is thyroid cancer, and researchers have made a great deal of progress in deciphering its molecular mechanisms in the recent years. Many of molecular changes observed in thyroid cancer can be used as biomarkers for diagnosis, prognosis, and therapeutic targets for treatment. MicroRNAs (miRNAs) are important parts in biological and metabolic pathways such as regulation of developmental stages, signal transduction, cell maintenance, and differentiation. Therefore, their dysregulation can expose individuals to malignancies. It has been proved that miRNA expression is dysregulated in different types of tumors, like thyroid cancers, and can be the cause of tumor initiation and progression. In this paper, we have reviewed the available data on miRNA dysregulation in different thyroid tumors including papillary, follicular, anaplastic, and medullary thyroid carcinomas aiming to introduce the last updates in miRNAs-thyroid cancer relation.

Thyroid dysfunctions secondary to cancer immunotherapy

Abstract: Immunotherapy is a firmly established pillar in the treatment of cancer, alongside the traditional approaches of surgery, radiotherapy, and chemotherapy. Like every treatment, also cancer immunotherapy causes a diverse spectrum of side effects, collectively referred to as immune-related adverse events. This review will examine the main forms of immunotherapy, the proposed mechanism(s) of action, and the incidence of thyroid dysfunctions. A comprehensive MEDLINE search was performed for articles published up to March 30, 2017. Following the pioneering efforts with administration of cytokines such as IL-2 and IFN-g, which caused a broad spectrum of thyroid dysfunctions (ranging in incidence from 1 to 50%), current cancer immunotherapy strategies comprise immune checkpoint inhibitors, oncolytic viruses, adoptive T-cell transfer, and cancer vaccines. Oncolytic viruses, adoptive T-cell transfer, and cancer vaccines cause thyroid dysfunctions only rarely. In contrast, immune checkpoint blockers (such as anti-CTLA-4, anti-PD-1, anti-PD-L1) are associated with a high risk of thyroid autoimmunity. This risk is highest for anti-PD-1 and increases further when a combination of checkpoint inhibitors is used. Cancer patients treated with monoclonal antibodies that block immune checkpoint inhibitors are at risk of developing thyroid dysfunctions. Their thyroid status should be assessed at baseline and periodically after initiation of the immunotherapy.

Energy expenditure in the etiology of human obesity: spendthrift and thrifty metabolic phenotypes and energy-sensing mechanisms.

Abstract: The pathogenesis of human obesity is the result of dysregulation of the reciprocal relationship between food intake and energy expenditure (EE), which influences daily energy balance and ultimately leads to weight gain. According to principles of energy homeostasis, a relatively lower EE in a setting of energy balance may lead to weight gain; however, results from different study groups are contradictory and indicate a complex interaction between EE and food intake which may differentially influence weight change in humans. Recently, studies evaluating the adaptive response of one component to perturbations of the other component of energy balance have revealed both the existence of differing metabolic phenotypes ("spendthrift" and "thrifty") resulting from overeating or underfeeding, as well as energy-sensing mechanisms linking EE to food intake, which might explain the propensity of an individual to weight gain. The purpose of this review is to debate the role that human EE plays on body weight regulation and to discuss the physiologic mechanisms linking EE and food intake. An increased understanding of the complex interplay between human metabolism and food consumption may provide insight into pathophysiologic mechanisms underlying weight gain, which may eventually lead to prevention and better treatment of human obesity.

NAFLD/NASH in patients with type 2 diabetes and related treatment options.

Abstract: Type 2 diabetes may reduce life expectancy and patients' quality of life due to its micro- and macro-vascular complications and to the higher risk of several types of cancer. An emerging important factor is represented by the hepatic involvement; it is recognized that excessive hepatic fat accumulation represents a typical feature of diabetic patients and that it also plays an important pathogenic role. It is now evident that non-alcoholic fatty liver disease (NAFLD), generally perceived as a benign condition, may have on the contrary an important deleterious impact for diabetic patients increasing the risk to develop cardiovascular complications but also serious hepatic diseases, in particular non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Lifestyle intervention, bariatric surgery and several drug therapies have now accumulated evidence of efficacy in treating NASH. On the other hand, their durability and safety in the long-term is yet to be proven and their use may be sometimes associated with side effects or higher risk of adverse events limiting the regular administration or contraindicating it. Professional health care providers, building awareness about the importance of these hepatic complications, should put more efforts in primary prevention using a behavioral therapy needing a multidisciplinary approach, in secondary prevention applying on a regular basis in the clinical setting available predictive algorithms to identify the patients at higher cardiovascular and hepatologic risk, and in tertiary prevention treating, when not contraindicated, the diabetic patients preferentially with drugs with proven benefit on NAFLD/NASH.

Von Hippel–Lindau disease: a single gene, several hereditary tumors

Abstract: The Von Hippel–Lindau (VHL) disease is an autosomal dominant disorder characterized by the predisposition for multiple tumors caused by germline mutations in the tumor suppressor gene VHL. This disease is associated with a high morbidity and mortality and presents a variable expression, with different phenotypes from family to family, affecting different organs during the lifetime. The main manifestations of VHL are hemangioblastomas of the central nervous system and retina, renal carcinomas and cysts, bilateral pheochromocytomas, cystic and solid tumors of the pancreas, cystadenomas of the epididymis, and endolymphatic sac tumors. The discovery of any of the syndrome components should raise suspicion of this disease and other stigmas must then be investigated. Due to the complexities associated with management of the various VHL manifestation, the diagnosis and the follow-up of this syndrome is a challenge in the clinical practice and a multidisciplinary approach is needed. The particular relevance to endocrinologists is the detection of pheochromocytomas in 35% and islet cell tumors in 17% of VHL patients, which can be associated with hypertension, hypoglycemia, cardiac arrhythmias, and carcinoid syndrome. The purpose of this review is to define the Von Hippel–Lindau syndrome addressing its clinical aspects and classification, the importance of genetic counseling and to propose a protocol for clinical follow-up.

Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients.

Abstract: To evaluate the efficacy of alpha-lipoic acid (ALA) administration on hormonal and metabolic parameters of obese PCOS patients. A group of 32 obese PCOS patients were selected after informed consent. 20 patients referred to have first grade relatives with diabetes type I or II. Hormonal and metabolic parameters as well as OGTT were evaluated before and after 12 weeks of ALA integrative administration (400 mg per os every day). ALA administration significantly decreased insulin, glucose, BMI and HOMA index. Hyperinsulinemia and insulin response to OGTT decreased both as maximal response (Δmax) and as AUC. PCOS with diabetes relatives showed the decrease also of triglyceride and GOT. Interestingly in all PCOS no changes occurred on all hormonal parameters involved in reproduction such as LH, FSH, and androstenedione. ALA integrative administration at a low dosage as 400 mg daily improved the metabolic impairment of all PCOS patients especially in those PCOS with familiar diabetes who have a higher grade of risk of NAFLD and predisposition to diabetes.

Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index

Abstract: Insulin resistance is a common feature among women with polycystic ovary syndrome (PCOS), especially in those patients with hyperandrogenism and chronic anovulation. PCOS women are at risk for developing metabolic syndrome, impaired glucose tolerance and type II diabetes mellitus (DM II). The aim of this review is to explore the existing knowledge of the interplay between androgen excess, pancreatic β-cell function, non-alcoholic fatty liver disease (NAFLD), intra-abdominal and subcutaneous (SC) abdominal adipocytes in PCOS, providing a better comprehension of the molecular mechanisms of diabetologic interest. A comprehensive MEDLINE® search was performed using relevant key terms for PCOS and DM II. Insulin-induced hyperandrogenism could impair pancreatic β-cell function, the SC abdominal adipocytes’ lipid storage capacity, leading to intra-abdominal adipocyte hypertrophy and lipotoxicity, which in turn promotes insulin resistance, and could enhance NAFLD. Fetal hyperandrogenism exposure prompts to metabolic disorders. Treatment with flutamide showed to partially reverse insulin resistance. Metabolic impairment seems not to be dependent only on the total fat mass content and body weight in women with PCOS and might be ascribed to the androgen excess.

Antithyroid drug treatment for Graves' disease: baseline predictive models of relapse after treatment for a patient-tailored management.

Abstract: Antithyroid drugs (ATDs) are first-line treatment for Graves’ hyperthyroidism worldwide, but relapses are frequent. The reliability of individual risk factors to predict at baseline subsequent relapse is poor. Predictive scores grouping single risk factors might help to select the best treatment (pharmacological vs. ablative). To assess the predictivity of a recently developed score (Clinical Severity Score, CSS) and to compare it with another score (GREAT score). A retrospective observational, single-center study was conducted of 387 consecutive, newly diagnosed Graves’ patients, who completed an 18–24 months ATD course and were followed for at least 2 years. Hyperthyroidism relapsed in 185 patients (48%). At diagnosis and before treatment, the relapse group had higher serum TSH-receptor antibody and free thyroxine levels and larger goiters than the remission group, with no differences in Graves’ orbitopathy prevalence and severity. In the multivariate analyses, only large goiter size was significantly associated with an increased recurrence hazard ratio. Using CSS, the risk of relapse increased from 36% in the mild category and 49% in the moderate category to 59% in the severe category, with quite a good area under the curve (AUC) (0.60; 95% CI: 0.55; 0.66). GREAT score showed an increase in relapse from 34% for class I (mild) and 49% for class II (moderate) to 64% for class III (severe) (AUC, 0.63; CI: 0.58; 0.68). Both CSS and GREAT score are useful, although imperfect, tools to predict at baseline relapse of hyperthyroidism after treatment. In real life they may help the clinician to tailor a treatment for newly diagnosed Graves’ hyperthyroidism.

Transoral thyroidectomy: a viable surgical option with unprecedented complications—a case series

Abstract: To report the clinical implications of an initial experience with transoral endoscopic thyroidectomy vestibular approach (TOETVA). From March to November 2017, five cases of TOETVA were performed. Data reported include patient demographics, indication for surgery, extent of surgery, operative time, the need to convert to cervicotomy, the length of hospital stay and post-operative pain and morbidity. Unconventional complications regarded as specific for TOETVA were reported. The burden of surgery on the patient’s quality of life was evaluated using the 36-item short form (SF-36) health survey 1 month after surgery. All patients were females with a mean age of 36 years. They all underwent a right-sided hemithyroidectomy for a solitary thyroid nodule measuring on average 3.5 cm in size. The nodule was reported as Bethesda category II (n = 3), III (n = 1), and IV (n = 1) on fine needle aspiration cytology. The mean operative time was 122 min. Conversion to a transverse cervicotomy was required in one case. None of the patients developed post-operative bleeding, and none experienced vocal fold or mental nerve palsy. Surgical site infection did not occur. All patients developed subcutaneous emphysema that resolved within 12–48 h. All patients reported a long-standing bothersome pulling sensation along the surgical track that resulted in a poor outcome in some scales of the SF-36 survey. Flap perforation occurred in one case. The median VAS score was 3. Patients strongly motivated to undergo a novel surgical procedure tailored to their needs and desires should be properly counselled particularly regarding unconventional procedure-related complications.

New perspectives on the definition and management of polycystic ovary syndrome.

Abstract: There is a growing debate on the opportunity of improving the understanding in the diagnosis and management of polycystic ovary syndrome (PCOS). This review article summarizes recent research related to the definition of polycystic ovary syndrome (PCOS). Review of the recent literature on the topic. New ideas on the definition of hyperandrogenism, based on new scientific data and clinical perspectives are presented. (i) In fact, recent studies have pointed out the need to improve the concept of androgen excess by using a larger androgen profile, rather than simply measuring the testosterone blood levels. (ii) Due to the poor correlation between androgen blood levels and the degree of hirsutism, it is proposed that the definition of hyperandrogenism should be based on the presence of blood androgen excess and hirsutism, considered separately, because their pathophysiological mechanisms may differ according to the different phenotypes of PCOS. (iii) The potential role of obesity in favoring the development of PCOS during adolescence is also discussed and the concept of “PCOS secondary to obesity” is developed. (iv) Finally, the need for greater appropriateness in the evaluation of possible coexistence is highlighted, in patients with PCOS who have fasting or glucose-stimulated very high insulin levels, or severe insulin-resistant states. Based on what was discussed in this review, we believe that there are margins for modifying some of the current criteria that define the various PCOS phenotypes.

Impact of perfluorochemicals on human health and reproduction: a male's perspective.

Abstract: Perfluoroalkyl compounds (PFCs) are a class of organic molecules used in industry and consumer products. PFCs are non-biodegradable and bioaccumulate in the environment and for these reasons they have been a major subject of research regarding their toxicity, environmental fate, and sources of human exposure, since they have been shown to induce severe health consequences, such as neonatal mortality, neurotoxicity and immunotoxicity. The aim of this review is to explore the existing knowledge of the interplay between PFCs exposure and human health, with a focus on male reproductive health, given the emerging gender differences in PFCs clearance and their interaction with sex hormones receptors. A comprehensive PUBMED search was performed using relevant key terms for PFCs and male fertility. Different degrees of evidence suggest an impairment of semen parameters and sex hormones in relation to PFCs exposure. These preliminary results point towards a sex-dependent pharmacodynamics and clearance, with males having a much higher tendency to accumulation. Moreover, because of the widespread environmental occurrence of these chemicals, along with their ability to cross the placental barrier, exposure of the foetus to these compounds is inevitable. This is of concern because foetal development of the male reproductive organs may be disturbed by exposure to exogenous factors. These findings clearly suggest an antiandrogenic potential of PFCs and a link between endocrine disruptors and disorders of male health.

The use of follicle stimulating hormone (FSH) for the treatment of the infertile man: position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS).

Abstract: Abbreviations ART Assisted reproductive technologies FSH Follicle stimulating hormone FSHR FSH receptor GnRH-a Gonadotropin-releasing hormone agonist hCG Human chorionic gonadotropin hMG Human menopausal gonadotropin hpFSH Highly purified follicle stimulating hormone ICSI Intracytoplasmic sperm injection IUI Intrauterine insemination IVF In vitro fertilization IVF-ET In vitro fertilization-embryo transfer OAT Oligo/astheno/teratozoospermia pFSH Purified follicle stimulating hormone RCT Randomized controlled trial rhFSH Recombinant human follicle stimulating hormone

Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution

Abstract: Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors. 52 patients (30 F; age 61 ± 13 years) with advanced melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2 weeks) or pembrolizumab (2 mg/kg i.v./3 weeks). Thyroid function and autoimmunity were assessed before, after 6 weeks, at the end of ipilimumab, as well as before and every 3 months during nivolumab/pembrolizumab treatment. During ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1 associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7 patients (3 F) developed hypothyroidism with severe manifestations in 6 of them; 3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean follow-up after anti-CTLA4 inhibitors treatment was 36 ± 28 months. Thyroid disorders occurred 45.1 ± 20.8 and 151 ± 67 days after the initiation of CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation were associated with a better clinical response to CTLA4 followed by PD1 treatment. Immune checkpoint blockade is burdened by a high incidence of autoimmune thyroid dysfunction, which is often severe. Therefore, early and careful monitoring and, eventually, treatment are crucial to prevent the negative impact of thyroid dysfunction on the clinical outcome.

Phosphaturic mesenchymal tumors: what an endocrinologist should know

Abstract: Tumor-induced osteomalacia (TIO), also known as "oncogenic osteomalacia", is a rare cause of osteomalacia. TIO often has an insidious onset characterized clinically by progressive muscle weakness and bone pain with fractures. The hallmark biochemical finding is a persistent low serum phosphorus concentration due to renal phosphate wasting. The vast majority of cases of TIO result from production of the phosphaturic hormone fibroblast growth factor 23 (FGF23) by a histologically distinctive mesenchymal tumor, termed "phosphaturic mesenchymal tumor" (PMT). Circulating FGF23 induces internalization of renal sodium/phosphate co-transporters resulting in reduced proximal tubular phosphate reabsorption. FGF23 also inhibits production of 1α,25-dihydroxyvitamin D which is inappropriately low or normal in the context of hypophosphatemia. Diagnosis is often delayed owing to the rarity of the condition and an underappreciation for the role of phosphorus as a cause for the constellation of symptoms. Primary treatment for TIO is identification of the offending tumor and surgical removal. However, these tumors are notoriously difficult to find, precluding the opportunity for a curative surgery in many. In such cases, phosphate and calcitriol therapy is used to improve symptoms and heal the osteomalacia. Recently, molecular genetic studies have shown recurrent genetic events in PMT, including the novel fusions FN1-FGFR1 and less commonly FN1-FGF1. These fusion events are hypothesized to result in autocrine/paracrine signaling loops within the tumor, spurring tumorigenesis. This review will cover the clinical features, imaging characteristics, pathologic features, molecular genetic aspects, and therapy of PMT, with a brief discussion of other neoplasms that may cause TIO.

The epidemiology of osteoporosis in Italian postmenopausal women according to the National Bone Health Alliance (NBHA) diagnostic criteria: a multicenter cohort study

Abstract: The study was aimed at evaluating the prevalence of osteoporosis, defined by BMD and the National Bone Health Alliance (NBHA) criteria, and the prevalence of clinical risk factors for fractures in Italian postmenopausal women. This is a cross-sectional, multicenter, cohort study evaluating 3247 postmenopausal women aged ≥ 50 and older in different areas of Italy in the period 2012–2014. All the participants were evaluated as far as anthropometrics; questionnaires for FRAX® and DeFRA calculation were administered and bone mineral density was measured at lumbar spine, femoral neck and total hip by DXA. The prevalence of osteoporosis, as assessed by BMD and NBHA criteria was 36.6 and 57%, respectively. Mean ± SD values of FRAX® and DeFRA were: 10.2 ± 7.3 and 11 ± 9.4 for major fractures, and 3.3 ± 4.9 and 3.9 ± 5.9 for hip fractures, respectively. Among clinical risk factors for fracture, the presence of previous fracture, particularly non-spine/non-hip fracture, parental history of hip fracture and current smoking were the most commonly observed. Our study showed that more that the half of postmenopausal women aged 50 and older in Italy has osteoporosis on the basis of the NBHA criteria. There is a relevant high risk of femur fracture, as assessed by the FRAX® and DeFRA and previous fracture, parental history of hip fracture and current smoking are the most common risk factors. The data should be considered particularly in relation to the need to increase prevention strategies on modifiable risk factors and therapeutic intervention.

Thyroid ultrasonography reporting: consensus of Italian Thyroid Association (AIT), Italian Society of Endocrinology (SIE), Italian Society of Ultrasonography in Medicine and Biology (SIUMB) and Ultrasound Chapter of Italian Society of Medical Radiology (SIRM)

Abstract: Thyroid ultrasonography (US) is the gold standard for thyroid imaging and its widespread use is due to an optimal spatial resolution for superficial anatomic structures, a low cost and the lack of health risks. Thyroid US is a pivotal tool for the diagnosis and follow-up of autoimmune thyroid diseases, for assessing nodule size and echostructure and defining the risk of malignancy in thyroid nodules. The main limitation of US is the poor reproducibility, due to the variable experience of the operators and the different performance and settings of the equipments. Aim of this consensus statement is to standardize the report of thyroid US through the definition of common minimum requirements and a correct terminology. US patterns of autoimmune thyroid diseases are defined. US signs of malignancy in thyroid nodules are classified and scored in each nodule. We also propose a simplified nodule risk stratification, based on the predictive value of each US sign, classified and scored according to the strength of association with malignancy, but also to the estimated reproducibility among different operators.

Efficacy and safety of long-term management of patients with chronic post-surgical hypoparathyroidism

Abstract: To evaluate adherence to European Society of Endocrinology guidelines and risk of renal complications in patients with chronic post-operative hypoparathyroidism (PO-HypoPT) treated with calcium and activated vitamin D metabolites. We evaluated 90 adult patients (68 females and 22 males) with chronic (3 years) PO-HypoPT. Total albumin-corrected (Alb-Ca) and ionized serum calcium, phosphate, creatinine, PTH, and 24-h urinary calcium were measured; renal ultrasound was also performed. Healthy hospital employers (n = 142) were used as control. Complete data were available in 82 patients. Twenty-eight (34.1%) met four targets (Alb-Ca, phosphate, calcium phosphate product and 24-h urinary calcium), 36 (43.9%) three, 17 (20.7%) two, and 1 (1.2%) one. Thirteen (14.4%) had Alb-Ca value below and 18 (20.0%) above the target range and 54.9% 24-h urinary calcium above the upper normal limit. Seven (7.7%) has increased serum phosphate and none an increased calcium phosphate product. Eleven (12.2%) patients had eGFR 50% of cases, 18 in > 75%, and only 2 in 100%. Two patients never had values in the target range. Treatment of chronic PO-HypoPT with calcium and activated vitamin D metabolites is suboptimal and associated with an increased risk of renal complications.

Clinical and pathologic predictors of central lymph node metastasis in papillary thyroid microcarcinoma: a retrospective cohort study.

Abstract: To identify the clinical and pathological predictors of central lymph node metastasis (CLNM) in patients with clinically lymph node-negative papillary thyroid microcarcinoma (PTMC). Data pertaining to 541 clinically lymph node-negative PTMC patients who underwent thyroid surgery at the Shanghai General Hospital between January 2010 and December 2013 were retrospectively analyzed. According to histopathological evidence of central lymph node involvement, patients were divided into central lymph node metastasis (CLNM)-positive and CLNM-negative groups; risk factors for CLNM were identified statistically. LNM was found in 148 (27.4%) patients. Gender (P = 0.002), age (P 0.575 cm (OR = 2.105), gross extrathyroidal extension (OR = 14.605) and multifocality (OR = 2.084) were independent risk factors for CLNM. Among patients who did not have any of these five risk factors, only 3.9% were found to have CLNM. A relatively high prevalence of CLNM was observed in patients with clinically lymph node-negative PTMC. CLNM was associated with male sex, younger age, larger tumor size, extrathyroidal extension and multifocal PTMC.

Endocrinological aspects of HIV infection.

Abstract: Patients with human immunodeficiency virus (HIV) are living longer with effective antiretroviral therapies and are enjoying near normal life span. Therefore, they are encountering endocrine issues faced by the general population along with those specific to HIV infection. The purpose of this article is to review the common endocrine aspects of HIV infection, and the early detection and management strategies for these complications. Recent literature on HIV and endocrine disease was reviewed. HIV can influence endocrine glands at several levels. Endocrine glandular function may be altered by the direct effect of HIV viral proteins, through generation of systemic and local cytokines and the inflammatory response and via glandular involvement with opportunistic infections and HIV-related malignancies. Endocrine disorders seen in people with HIV include metabolic issues related to obesity such as diabetes, hyperlipidemia, lipohypertrophy, lipoatrophy and lipodystrophy and contribute significantly to quality of life, morbidity and mortality. In addition, hypogonadism, osteopenia and osteoporosis are also more prevalent in the patients with HIV. Although disorders of hypothalamic–pituitary–adrenal axis resulting in adrenal insufficiency can be life threatening, these along with thyroid dysfunction are being seen less commonly in the antiretroviral therapy (ART) era. ARTs have greatly improved life expectancy in people living with HIV but can also have adverse endocrine effects. Clinicians need to have a high index of suspicion for endocrine abnormalities in people with HIV as they can be potentially life threatening if untreated. Endocrine evaluation should be pursued as in the general population, with focus on prevention, early detection and treatment to improve quality of life and longevity.

Clinical presentation and management of patients with primary hyperparathyroidism in Italy

Abstract: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. From January 2014–January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. Over the first year we enrolled 604 patients (age 61 ± 14 years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13 years), the remaining 38 (6.3%, age 41 ± 17 years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2–81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1–37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24 h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.

Identification of key genes of papillary thyroid cancer using integrated bioinformatics analysis

Abstract: To identify novel clinically relevant genes in papillary thyroid carcinoma from public databases. Four original microarray datasets, GSE3678, GSE3467, GSE33630 and GSE58545, were downloaded. Differentially expressed genes (DEGs) were filtered from integrated data. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, followed by protein–protein interaction (PPI) network construction. The CentiScape pug-in was performed to scale degree. The genes at the top of the degree distribution (≥ 95% percentile) in the significantly perturbed networks were defined as central genes. UALCAN and The Cancer Genome Atlas Clinical Explorer were used to verify clinically relevant genes and perform survival analysis. 225 commonly changed DEGs (111 up-regulated and 114 down-regulated) were identified. The DEGs were classified into three groups by GO terms. KEGG pathway enrichment analysis showed DEGs mainly enriched in the PI3K–Akt signaling pathway, pathways in cancer, focal adhesion and proteoglycans in cancer. DEGs’ protein–protein interaction (PPI) network complex was developed; six central genes (BCL2, CCND1, FN1, IRS1, COL1A1, CXCL12) were identified. Among them, BCL2, CCND1 and COL1A1 were identified as clinically relevant genes. BCL2, CCND1 and COL1A1 may be key genes for papillary thyroid carcinoma. Further molecular biological experiments are required to confirm the function of the identified genes.

Varicocele and semen quality: a retrospective case–control study of 4230 patients from a single centre

Abstract: The aim of the present study is to assess impairment of spermatogenesis induced by varicocele in, to our knowledge, the largest single-centre caseload available to date. We conducted a retrospective study on 4230 consecutive patients attending our Department for andrological outpatient assessment and preconception check-ups between 2011 and 2014. A total of 2113 patients had varicocele (Group V), while the remaining 2117 were selected as the control group (Group C). All patients were divided into age classes (<17, 18–28, 29–39 and ≥40 years), and Group V patients were classified as “low” (I–II) or “high” (III–IV) grade. Varicocele patients had a higher mean height than controls, as well as lower BMI. There was also a statistically significant reduction in the concentration/mL and the total sperm number in Group V against Group C. When stratified by age, values for all semen parameters were significantly worse in the older than in the younger age classes in both Group V and Group C, except for concentration/mL and total sperm number in the 29–39 and ≥40 age classes in both groups. A multivariable logistic regression analysis showed that factors independently predicting the presence of varicocele were older age, higher BMI and smoking for more than 10 years. Varicocele patients show worse semen parameters compared to controls, although their values were still within WHO reference limits. Semen quality is further worsened by increased age, grade and chronic smoking.

Impact of risk factors for gestational diabetes (GDM) on pregnancy outcomes in women with GDM.

Abstract: In this study, we evaluated the impact of risk factors for gestational diabetes on clinical/biochemical parameters and maternal/fetal outcomes. One hundred eighty-three (n 183) women (age 33.8 ± 5.5 years, 59% Caucasians, 41% non-Caucasians) with gestational diabetes were included in the study. Anamnestic information, anthropometric and laboratory parameters, and maternal and fetal outcomes at delivery were collected. Insulin therapy prevalence was higher in Asians vs Caucasians (p = 0.006), despite lower pre-pregnancy BMI in Asians (p = 0.0001) and in pre-pregnancy overweight vs normal weight patients (p = 0.04). Insulin-treated patients had higher fasting OGTT glucose than patients on diet therapy (p = 0.003). In multivariate analysis, Asian ethnicity, age ≥ 35 years and pre-pregnancy BMI ≥ 25 kg/m2 were independent predictors of insulin therapy. Cesarean section occurred more in women aged ≥ 35 years than < 35 years (p = 0.02). Duration of pregnancy and age showed inverse correlation (r − 0.3 p = 0.013). Week of delivery was lower in patients ≥ 35 years vs patients < 35 years (p = 0.013). Fasting OGTT glucose was higher in overweight than in normal weight patients (p = 0.016). 1-h OGTT glucose was lower in obese vs normal weight (p = 0.03) and overweight patients (p = 0.03). Prevalence of prior gestational diabetes was higher in overweight/obese women (p = 0.002). Ethnicity, age, and BMI have the heaviest impact on pregnancy outcomes.

Up-regulation of miR-340-5p promotes progression of thyroid cancer by inhibiting BMP4.

Abstract: The incidence of thyroid cancer is increasing and the proliferation of thyroid cancer cells is incompletely understood. microRNAs may play key roles in thyroid cancer progression. We analyzed miR-340-5p in thyroid cancer tissue and normal tissue, and using informatics to predict its target. Cell lines and a mouse model were used to study the role of miR-340-5p in cancer proliferation. Overexpression of miR-340-5p was found in thyroid cancer specimens. Tumors with higher pathological grade had higher levels of miR-340-5p. Overexpression of miR-340-5p significantly enhanced cell viability and colony formation. Treatment of anti-miR-340-5p, however, showed opposite alterations. We predicted that bone morphogenetic protein 4 (BMP4) is a possible target, and found a negative correlation between miR-340-5p and BMP4 levels in thyroid cancer tissue. miR-340-5p reduced BMP4 expression. BMP4 overexpression attenuated the effects of miR-340-5p in cell viability and colony formation. In addition, using a xenograft mouse model we proved that anti-miR-340-5p was able to inhibit tumor growth. miR-340-5p promotes thyroid cancer proliferation by inhibiting BMP4. Anti-miR-340-5p can be a promising strategy to control thyroid cancer.

The association between circulating fetuin-A levels and type 2 diabetes mellitus risk: systematic review and meta-analysis of observational studies

Abstract: Fetuin-A is a liver-derived circulating protein that is associated with insulin resistance and diabetes. The objective of this systematic review and meta-analysis of published observational studies was to investigate mean levels of fetuin-A in T2D patients and the relationship between blood fetuin-A levels and T2D risk. PubMed, Embase, Google Scholar, Web of Science, and The Cochrane Library were systematically searched for potential relevant studies up to 1 December 2016. Natural logarithm-transformed estimate risks, standard mean differences on the basis of Hedges’s adjusted g, and 95% confidence intervals (CIs) were calculated for all eligible studies and were combined to measure the pooled data using random-effects model. A total of 32 studies including 27 case–control and 5 cohort studies were included in the current study. Fetuin-A levels in T2D patients were significantly higher than control groups [Hedges’ g = 1.73, 95% CI (1.25–2.22), P < 0.001], with significant heterogeneity across studies (P < 0.001, I 2 = 98.46%). Findings from meta-analyses of cohort studies showed a statistically significant association between fetuin-A levels and T2D risk [rate ratio = 1.62, 95% CI (1.26–2.08), P < 0.001], with no significant heterogeneity (P = 0.10, I 2 = 46.06%). We found a significant relationship between the fetuin-A levels with T2D risk. Although fetuin-A may be as a potential screening and prediction biomarker or a therapeutic target in T2D patients, further studies are required in this regard.