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Hypoparathyroidism is the only endocrine deficiency for which hormone replacement therapy is not the standard of care. Although conventional treatments may control hypocalcaemia, other complications such as hyperphosphatemia, kidney stones, peripheral calcifications, and bone disease remain unmet needs. This meta-analysis (PROSPERO registration number CRD42019126881) aims to evaluate and compare the efficacy and safety of PTH

Ailanthus altissima is an aggressive invasive tree worldwide, but the ecological factors that lead to the spread of this species in Mediterranean ecosystems are still unclear. Here we aim to identify such factors, focusing on the interaction of human activity with climatic conditions. We determined the occurrence and abundance of Ailanthus in 240 sites and studied their relationship with 20 variables representing climatic, geographic, and topographic factors, as well as land use, in the region of Campania (southern Italy). Overall, we found that temperature and rainfall in Campania are suitable for Ailanthus, with the only major constraint being the temperature at an altitude exceeding 900 m a.s.l.. We found that Ailanthus is unable to spread where the mean annual temperature is lower than 11.1 °C. By contrast, precipitation variables showed poor correlation with Ailanthus distribution, suggesting that rainfall in the selected study sites is suitable to sustain the growth of this tree. About land use variables, roads were the primary landscape feature along which this species spread and invaded new areas. Roads probably combine high propagule pressure and favorable growing conditions in terms of available resources i.e., light, water, and mineral nutrients, that allow Ailanthus to establish and spread along roadside edges in different ecosystems. In conclusion, we found that climate and human-associated variables are correlated with the current occurrence of Ailanthus, with the temperature being more influential at high elevation sites and road distance playing a prominent role in low elevation areas.

We present the case of a 65 years old patient with Graves disease associated with hyperthyroidism and a medical history of bipolar disorder treated with lithium. Hyperthyroidism was initially treated with high-dose methimazole monotherapy and later the patient developed overt hypothyroidism (clinical and biochemical), but without remission of the underlying autoimmune disease. A "block and replace" therapeutic regimen was then started with reduced methimazole doses in combination with levothyroxine, which resulted in a short time in normalization of the hormonal profile and significant improvement of the clinical picture. Therefore, the "block and replace" regimen represents a valid therapeutic alternative to anti-thyroid drugs monotherapy in the treatment of hyperthyroidism due to Graves disease in selected cases.

Context Significant uncertainty exists about the diagnostic accuracy of ultrasonographic (US) features used to predict the risk of thyroid cancer in the pediatric population. Moreover, there are no specific indications for thyroid nodule evaluation in patients during the transition age. Objective The meta-analysis aimed to address the following question: which thyroid nodule US features have the highest accuracy in predicting malignancy in the transition age. Methods We performed a meta-analysis of observational/cohort/diagnostic accuracy studies dealing with thyroid nodule sonography, reporting US features, and using histology as a reference standard for the diagnosis of malignancy and histology or cytology for the diagnosis of benignity in the transition age (mean/median age 12–21 years). Results The inclusion criteria were met by 14 studies, published between 2005 and 2020, including 1306 thyroid nodules (mean size 17.9 mm) from 1168 subjects. The frequency of thyroid cancer was 36.6%. The US features with the highest diagnostic odds ratio (DOR) for malignancy were the presence of suspicious lymph nodes (DOR: 56.0 (95% CI: 26.0–119.0)), a ‘taller than wide’ shape of the nodule (6.0 (95% CI: 2.0–16.0)), the presence of microcalcifications (13.0 (95% CI: 6.0–29.0)) and irregular margins (9.0 (95% CI: 5.0–17.0)). Heterogeneity among the studies was substantial. Conclusions Following the diagnosis of a thyroid nodule in the transition age, a thorough US examination of the neck is warranted. The detection of suspicious lymph nodes and/or thyroid nodules with a ‘taller than wide’ shape, microcalcifications, and irregular margins is associated with the highest risk of malignancy in the selection of nodules candidates for biopsy.

Objective Neurosurgery is the first-line treatment for acromegaly. Whether metabolic disorders are reversible after neurosurgery is still debated. The meta-analysis aimed to address the following questions: (i) Does neurosurgery affect glycolipid metabolism? (ii) Are these effects related to disease control or follow-up length? Design A meta-analysis and systematic review of the literature. Methods Three reviewers searched databases until August 2019 for prospective trials reporting glycometabolic outcomes after neurosurgery. Three other extracted outcomes, all assessed the risk of bias. Results Twenty studies were included. Neurosurgery significantly reduced fasting plasma glucose (FPG) (effect size (ES): −0.57 mmol/L, 95% CI: −0.82 to −0.31; P < 0.001), glucose load (ES: −1.10 mmol/L, 95% CI: −1.66 to −0.53; P < 0.001), glycosylated haemoglobin (HbA1c) (ES: −0.28%, 95% CI: −0.42 to −0.14; P < 0.001), fasting plasma insulin (FPI) (ES: −10.53 mU/L, 95% CI: −14.54 to −6.51; P < 0.001), homeostatic model assessment of insulin resistance (HOMA-IR) (ES: −1.98, 95% CI: −3.24 to −0.72; P = 0.002), triglycerides (TGDs) (ES: −0.28 mmol/L, 95% CI: −0.36 to −0.20; P < 0.001) and LDL-cholesterol (LDLC) (ES: −0.23 mmol/L, 95% CI: −0.45 to −0.02 mmol/L); P = 0.030) and increased HDL-cholesterol (HDLC) (ES: 0.21 mmol/L, 95% CI: 0.14 to 0.28; P < 0.001). Meta-regression analysis showed that follow-up length – not disease control – had a significant effect on FPG, with the greatest reduction in the shortest follow-up (beta = 0.012, s.e. = 0.003; P = 0.001). Conclusions Neurosurgery improves metabolism with a significant decrease in FPG, glucose load, HbA1c, FPI, HOMA-IR, TGDs, and LDLC and increase in HDLC. The effect on FPG seems to be more related to follow-up length than to disease control.

The classification of indeterminate cytopathology at thyroid fine-needle-aspiration (FNA) has been updated to reduce the number of unnecessary surgery; the 2014 Italian classification introduced the low-risk (TIR3A) and high-risk (TIR3B) subcategories. Aim of this study was to identify the ultrasonographic (US), clinical and cytological predictors of malignancy among TIR3B nodules from a single institution. A prospective observational study including 1844 patients who underwent thyroid FNA from June 2014 to January 2019. Ultrasonographic, clinical and cytological features were recorded. All TIR3B diagnoses were referred to surgery. According to final histology, patients were divided into thyroid cancer (TC) or benign nodules. Chi-square test, or Fisher exact test when appropriate, were used to compare groups and logistic regression analyses were used to determine independent predictors of malignancy. Of 1844 FNAs, 96 (5.2%) were TIR3B. Histology report was available in 65. Among them, 25 (38.5%) were TC. Predictors of TC were nodule size

Central hypogonadism, also defined as hypogonadotropic hypogonadism, is a recognized complication of hypothalamic-pituitary-gonadal axis damage following treatment of sellar and parasellar masses. In addition to radiotherapy and surgery, CTLA4-blocking antibodies and alkylating agents such as temozolomide can also lead to hypogonadism, through different mechanisms. Central hypogonadism in boys and girls may lead to pubertal delay or arrest, impairing full development of the genitalia and secondary sexual characteristics. Alternatively, cranial irradiation or ectopic hormone production may instead cause early puberty, affecting hypothalamic control of the gonadostat. Given the reproductive risks, discussion of fertility preservation options and referral to reproductive specialists before treatment is essential. Steroid hormone replacement can interfere with other replacement therapies and may require specific dose adjustments. Adequate gonadotropin stimulation therapy may enable patients to restore gametogenesis and conceive spontaneously. When assisted reproductive technology is needed, protocols must be tailored to account for possible long-term gonadotropin insufficiency prior to stimulation. The aim of this review was to provide an overview of the risk factors for hypogonadism and infertility in patients treated for parasellar lesions and to give a summary of the current recommendations for management and follow-up of these dysfunctions in such patients. We have also briefly summarized evidence on the physiological role of pituitary hormones during pregnancy, focusing on the management of pituitary deficiencies.

Objective Registry data show that Cushing's syndrome (CS) and adrenal insufficiency (AI) increase mortality rates associated with infectious diseases. Little information is available on susceptibility to milder forms of infections, especially those not requiring hospitalization. This study aimed to investigate infectious diseases in patients with glucocorticoid disorders through the development of a specific tool. Methods We developed and administered the InfeCtions in pAtients with endocRinOpathies (ICARO) questionnaire, addressing infectious events over a 12-month observation period, to 1017 outpatients referred to 4 University Hospitals. The ICARO questionnaire showed good test–retest reliability. The odds of infection (OR (95% CI)) were estimated after adjustment for confounders and collated into the ICARO score, reflecting the frequency and duration of infections. Results In total, 780 patients met the inclusion criteria: 43 with CS, 32 with adrenal incidentaloma and mild autonomous cortisol secretion (MACS), and 135 with AI, plus 570 controls. Compared to controls, CS was associated with higher odds of urinary tract infections (UTIs) (5.1 (2.3–9.9)), mycoses (4.4 (2.1–8.8)), and flu (2.9 (1.4–5.8)). Patients with adrenal incidentaloma and MACS also showed an increased risk of UTIs (3.7 (1.7–8.0)) and flu (3.2 (1.5–6.9)). Post-dexamethasone cortisol levels correlated with the ICARO score in patients with CS. AI was associated with higher odds of UTIs (2.5 (1.6–3.9)), mycoses (2.3 (1.4–3.8)), and gastrointestinal infections (2.2 (1.5–3.3)), independently of any glucocorticoid replacement dose. Conclusions The ICARO tool revealed a high prevalence of self-reported infections in patients with glucocorticoid disorders. ICARO is the first of its kind questionnaire, which could be a valuable tool for monitoring infections in various clinical settings.

Chronotype is the attitude of subjects to carry out their daily activities mainly in the morning ("lark") or in the evening ("owl"). The intermediate chronotype is located between these two categories. It has been demonstrated that chronotype can influence the incidence, course and response to treatments of tumors. In particular patients diagnosed with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and evening chronotype are characterized by unhealthy lifestyle, obesity, metabolic syndrome, a worsen cardiometabolic profile, a poor prognosis with a progressive disease and the development of metastasis. In addition, evening chronotype has been associated with sleep disturbances, which in turn have been related to tumor development and progression of tumors. There is a strict connection between sleep disturbances and NENs because of the hyperactivation of proangiogenic factors that caused aberrant neoangiogenesis. A nutritional tailored approach could represent a tool to align subjects with evening chronotype to physiological biological rhythms based on the properties of some macro and micronutrients of being substrate for melatonin synthesis. Thus, we aimed to provide an overview on the association of chronotype categories and sleep disturbances with NENs and to provide nutritional advices to manage subjects with NENs and these disturbances of circadian rhythm.

Sorafenib and lenvatinib are the only multikinase inhibitors (MKIs) approved for the treatment of radioactive iodine refractory differentiated thyroid cancer (RR-DTC). Although they have been demonstrated to improve progression free survival and overall response rate, the risk of toxicities is very high, worsening patients’ quality of life. Therefore, predicting MKI treatment outcomes in the setting of RR-DTC is very challenging for optimizing patients’ management. The current review provides an overview of the predictive factors for the response and survival of sorafenib and lenvatinib in RR-DTC. In this setting, a systemic therapy should be considered after conducting a multidisciplinary discussion aimed at evaluating the risk-benefit ratio of the treatment and taking into account several clinical, biochemical, and molecular factors. Age, performance status, and cancer-related symptoms are the most important clinical markers to be considered prior to starting MKI treatment, together with tumor burden. Some tissue and circulating biomarkers have been investigated, those involved in the angiogenic pathways being the most promising. Finally, prospective clinical trials aimed at evaluating predictive markers for therapeutic response are needed for tailoring patient management and allowing more appropriate treatment choices.

Objective To date, no systematic reviews and meta-analysis on the global epidemiology of acromegaly are available in the literature. The aims of this study are to provide a systematic review and a meta-analysis of the global epidemiology of acromegaly and to evaluate the quality of study reporting for the identified studies. Methods MEDLINE, EMBASE and The Cochrane Library databases were searched for studies assessing the epidemiology of acromegaly from inception until 31 January 2020. We included original observational studies written in English, reporting acromegaly prevalence and/or incidence for a well-defined geographic area. Two reviewers independently extracted data and performed quality assessments. Prevalence and incidence pooled estimates were derived by performing a random-effects meta-analysis. Results A total of 32 studies were included in the systematic review, and 22 of them were included in the meta-analysis. The pooled prevalence of acromegaly was 5.9 (95% CI: 4.4–7.9) per 100 000 persons, while the incidence rate (IR) was 0.38 (95% CI: 0.32–0.44) cases per 100 000 person-years. For both prevalence and IR, considerable between-study heterogeneity was found (I2 = 99.3 and 86.0%, respectively). The quality of study reporting was rated as the medium for 20 studies and low for 12 studies. Conclusions Although the largest amount of heterogeneity was due to the high precision of the studies’ estimates, data source and geographic area could represent relevant study-level factors which could explain about 50% of the total between-study variability. Large-scale high-quality studies on the epidemiology of acromegaly are warranted to help the public health system in making decisions.

Purpose To assess Strain Ratio (SRE) and Shear Wave Elastography (SWE) accuracy alone and with TIRADS classification, for the risk stratification of indeterminate thyroid nodules. Materials and methods 128 Patients with 128 indeterminate nodules candidates for thyroidectomy underwent preoperative staging neck ultrasound and were classified according to K-TIRADS score. After TIRADS evaluation, semi-quantitative (SRE) and quantitative (SWE expressed in kPa) elastosonography were performed and relative diagnostic performances, alone and in combination, were compared through ROC curves analysis. In order to maximize the SRE and SWE sensitivity and specificity, their cut-off values were calculated using the Liu test. Bonferroni test was used to evaluate statistically significant differences with a p value Results Sensitivity, specificity, PPV and NPV were, respectively, 71.4%, 82.4%, 62.5%, 87.5% for K-TIRADS baseline US, 85.7%, 94.1%, 85.7%, 94.1% for SRE and 57.1%, 79.4%, 53.3%, 81.8% for SWE (kPa expressed). SRE evaluation showed the best diagnostic accuracy compared to the SWE (kPa expressed) (p p > 0.05). The association of SRE with conventional ultrasound with K-TIRADS score increased sensitivity (92.9% vs 71.4%) but decreased the specificity than conventional US alone (76.5% vs 82.4%). Conclusion Strain Elastosonography can be associated with K-TIRADS US examination in the thyroid nodule characterization with indeterminate cytology; in fact, adding the SRE to K-TIRADS assessment significantly increases its sensitivity and negative predictive value. However, further multicenter studies on larger population are warranted.

Context Somatostatin analogs (SSAs) effectively control growth hormone secretion in first- and second-line treatment of acromegaly. Their effect on glucose metabolism is still debated. Objective To address the following questions: (1) Do SSAs affect fasting plasma glucose (FPG), fasting plasma insulin, glycosylated hemoglobin (HbA1c), glucose load (glucose levels after 2-hour oral glucose tolerance test), homeostatic model assessment of insulin resistance (HOMA-I), homeostatic model assessment of pancreatic β-cell function (HOMA-β), triglycerides, weight, or body mass index? (2) Do lanreotide and octreotide affect metabolism differently? (3) Does their effect depend on disease control? Design We performed a meta-analysis of prospective interventional trials treating acromegaly with SSAs. Inclusion criteria: all studies reporting glycometabolic outcomes before and after SSAs with a minimum 6-month follow-up. Results The inclusion criteria were met by 47 studies treating 1297 subjects (631 females). SSA treatment effectively lowered fasting plasma insulin [effect size (ES), −6.67 mU/L; 95% confidence interval (CI), −8.38 to −4.95 mU/L; P < 0.001], HOMA-I (ES, −1.57; CI, −2.42 to −0.72; P < 0.001), HOMA-β (ES, −47.45; CI, −73.15 to −21.76; P < 0.001), and triglycerides (ES, −0.37 mmol/L; CI, −0.47 to −0.27 mmol/L; P < 0.001). SSAs worsened glucose levels after a 2-hour oral glucose tolerance test (ES, 0.59 mmol/L; CI, 0.05 to 1.13 mmol/L; P = 0.032), but not FPG. A mild but significant increase in HbA1c (ES, 0.12%; CI, 0.00% to 0.25%; P = 0.044) was found in subjects treated with octreotide. Conclusions SSA treatment in acromegaly patients, while improving disease control, reduces insulin levels, increases after-load glucose, and, ultimately, increases HbA1c levels without affecting FPG. The findings suggest that clinicians treating acromegaly with SSAs should consider targeting postprandial glucose.

The dopamine D2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D2 receptor. D2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as “intermediate zone”. This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D2 receptors. D2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

A phase III study has demonstrated that 6-month pasireotide treatment induced disease control with good safety in 15–26% of patients with Cushing’s disease (CD). The aim of the current study was to evaluate the 6-month efficacy and safety of pasireotide treatment according to the real-world evidence. Thirty-two CD patients started pasireotide at the dose of 600 µg twice a day (bid) and with the chance of up-titration to 900 µg bid, or down-titration to 450 or 300 µg bid, on the basis of urinary cortisol (UC) levels or safety. Hormonal, clinical and metabolic parameters were measured at baseline and at 3-month and 6-month follow-up, whereas tumour size was evaluated at baseline and at 6-month follow-up. At baseline, 31 patients had very mild to moderate disease and 1 patient had very severe disease. Five (15.6%) patients discontinued treatment for adverse events; the remaining 27 patients (26 with very mild to moderate disease and 1 with very severe disease), reached 6-month follow-up. Considering the group of patients with very mild to moderate disease, responsiveness, defined by the normalization (1 and ≤1.1 ULN) of UC levels, was registered in 21 patients (full control in 19 and near control in 2), corresponding to 67.7% and 80.8% according to an “intention-to-treat” or “per-protocol” methodological approach, respectively. Weight, body mass index, waist circumference, as well as total and LDL-cholesterol significantly decreased, whereas fasting plasma glucose and glycated haemoglobin significantly increased. Hyperglycaemia was documented in 81.2%, whereas gastrointestinal disturbances in 40.6% of patients. In conclusion, in the real-life clinical practice, pasireotide treatment normalizes or nearly normalizes UC in at least 68% of patients with very mild to moderate disease, with consequent improvement in weight, visceral adiposity and lipid profile, despite the occurrence or deterioration of diabetes in the majority of cases, confirming the usefulness of this treatment in patients with milder disease and without uncontrolled diabetes.

Introduction Pegvisomant (PEG) in monotherapy or combined with somatostatin analogs (SSAs) is used to control acromegaly, improving metabolism. However, the metabolic changes induced by PEG have not been systematically reviewed. Objective To address the following questions: does PEG or the combination of PEG and SSAs affect fasting plasma glucose (FPG), glycosylated Hb (HbA1c), glucose load (2-hour oral glucose tolerance test), insulin levels [fasting plasma insulin (FPI)], homeostatic model assessment of insulin resistance (HOMA-I), homeostatic model assessment of β-cell function, lipid profile, or body mass index? Are the effects disease-related or drug-related? Data sources Indexed databases up to January 2019. Study selection Prospective interventional trials reporting glycometabolic outcomes under PEG or PEG plus SSAs for a minimum of 6 months. Data extraction Three reviewers screened eligible publications (7248), three others extracted the outcomes, and all assessed the risk of biases. Data synthesis Thirteen studies were included in the PEG and 5 in the PEG plus SSAs analysis (overall 550 subjects). PEG significantly decreased FPG [effect size (ES) -0.80 mmol/L (95% CI, -1.06 to -0.55); P = 0.000], HbA1c [ES -0.43% (95% CI, -0.56 to -0.31); P = 0.000], FPI [ES -5.31 mU/L (95% CI, -10.23 to -0.39); P = 0.034], and HOMA-I [ES -0.61 (95% CI, -1.17 to -0.04); P = 0.034]. Effects on FPG and FPI were not correlated to IGF-1 changes. The addition of PEG to SSAs mitigated the effects of SSAs on metabolism, producing an overall neutral effect. Conclusions Independently of disease control, PEG in monotherapy or combined with SSAs seems to improve glucose metabolism, reducing FPG, HbA1c, FPI, and HOMA-I.