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The aim of the study was to assess the cli­nical performance of the model combining areal bone mineral density (aBMD) at spine and microarchitecural texture (TBS) for the detection of the osteoporo­tic fracture. The Eastern European Study is a multicenter study (Serbia, Bulgaria, Romania and Ukraine) evaluating the role of TBS in routine clinical practice as a complement to aBMD. All scans were acquired on Holo­gic Disco­very and GE Prodigy densitometers in a routine clinical manner. The additional clinical values of aBMD and TBS were analyzed using a two steps classification tree approach (aBMD followed by TBS tertiles) for all type of osteoporotic fracture (All-OP Fx). Sensitivity, specifi­city and accuracy of fracture detection as well as the Net Reclassification Index (NRI) were calculated. This study involves 1031 women subjects aged 45 and older recrui­ted in east European countries. Clinical centers were cross-calibrated in terms of BMD and TBS. As expe­cted, areal BMD (aBMD) at spine and TBS were only mo­derately correlated (r2 = 0.19). Prevalence rate for All-OP Fx was 26%. Subjects with fracture have significant lower TBS and aBMD than subjects without fracture (p

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 nonfracture 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. [ABSTRACT FROM AUTHOR]

Introduction: The Fat Mass and Obesity-Associated ( FTO ) gene encodes a demethylase, which modulates RNA N6-methyladenosine (m6A) and plays a regulatory role in adipocyte differentiation and the pathogenesis of human obesity., Methods: To understand the potential role of FTO in osteoporosis (OP), we investigated five single nucleotide variations (SNVs) in intron 1 (rs8057044, rs8050136, rs9939609, rs62033406, and rs9930506) of the FTO gene, and a missense SNV i.e., rs3736228 (A1330V), located in exon 18 of the LRP5 gene, in a cohort of postmenopausal women ( n = 188) from Central Europe. Genotyping was performed with an allele discrimination assay, while haplotypes were reconstructed in the population by PHASE 2.1., Results: The rs9930506 was strongly associated with OP ( p < 0.0035), which was supported by Bonferroni correction ( p < 0.0175), and all SNVs located in the FTO gene were more strongly associated with severe OP with fragility fractures. Among seventeen haplotypes detected for the FTO gene, two haplotypes (H1 and H9) were frequent (frequency > 10%) and distributed in three main haplotypes pairs (H1/H1, H1/H9 and H9/H9, respectively). The pathogenic pair H1/H9 was associated with a leaner phenotype, increased fracture risk, and a lower bone mineral density (BMD), and carried the heterozygous GA of rs9930506, while the protective pair H9/H9 was associated with an increased obesity risk and carried AA alleles of rs9939609., Conclusions: Concordant associations with OP, an increased fracture risk, and a lower BMD at all skeletal sites indicate that the FTO gene is a promising candidate for OP, explaining the complex relationship with obesity and offering new perspectives for the study of the epigenetic regulation of bone metabolism.

Objectives: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients., Design: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb., Results: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4., Conclusions: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment., (© 2024 John Wiley & Sons Ltd.)

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., (© 2024. The Author(s).)

Introduction . Osteoporosis (OP) affects 30% of postmenopausal women, often complicated by metabolic syndrome (MetS) with a still controversial role. We aimed to characterize MetS and its components in relation to bone mineral density (BMD), body mass index (BMI), and insulin resistance. Methods . Patients ( n = 188) underwent DEXA scans, spine X-rays, and metabolic and hormonal investigations, including bone biomarkers, muscular strength, and physical performance tests, while insulin resistance was evaluated by the Homeostasis Model Assessment (HOMA-IR). Results . Patients with a normal BMD or osteopenia ( n = 68) and with OP ( n = 120) displayed 51.5% and 30.8% of MetS, but without differences in insulin resistance. When BMD was studied as a function of the cumulative MetS criteria and centiles of BMI, lower levels of BMD were observed beyond an inflection point of 27.2 kg/m 2 for BMI, allowing for further stratification as lean and overweight/obese (OW/OB) subjects. In contrast with lean individuals ( n = 74), in OW/OB patients ( n = 46), MetS was associated with HbA1c ( p < 0.0037, OR 9.6, 95% CI [1.64-55.6]) and insulin resistance ( p < 0.0076, OR 6.7, 95% CI [1.49-30.8]) in the context where BMD values were lower than those predicted from BMI in non-OP subjects. In OP patients with fragility fractures (31% of MetS), glycemia also appeared to be the dominant factor for MetS ( p < 0.0005, OR 4.1, 95% CI [1.63-10.39]). Conclusions . These data indicate a detrimental effect of insulin resistance in MetS on OP patients, while the prevalence of the syndrome depends on the proportion of obesity. These findings provide new insights into the pathogenic role of MetS and reveal the need to consider different strata of BMI and insulin resistance when studying postmenopausal OP.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Purpose: Insulin sensitivity (S i ) and its role in glucose intolerance of acromegaly has been extensively evaluated. However, data on insulin secretion is limited. We aimed to assess stimulated insulin secretion using an intravenous glucose tolerance test (IVGTT) in active acromegaly., Methods: We performed an IVGTT in 25 patients with active acromegaly (13 normal glucose tolerance [NGT], 6 impaired glucose tolerance [IGT] and 6 diabetes mellitus [DM]) and 23 controls (8 lean NGT, 8 obese NGT and 7 obese IGT). Serum glucose and insulin were measured at 20 time points along the test to calculate S i and acute insulin response (AIRg). Medical treatment for acromegaly or diabetes was not allowed., Results: In acromegaly, patients with NGT had significantly (p for trend < 0.001) higher AIRg (3383 ± 1082 pmol*min/L) than IGT (1215 ± 1069) and DM (506 ± 600). AIRg was higher in NGT (4764 ± 1180 pmol*min/L) and IGT (3183 ± 3261) controls with obesity than NGT (p = 0.01) or IGT (p = 0.17) acromegaly. S i was not significantly lower in IGT (0.68 [0.37, 0.88] 10 6 *L/pmol*min) and DM (0.60 [0.42, 0.84]) than in NGT (0.81 [0.58, 1.55]) patients with acromegaly. NGT (0.33 [0.30, 0.47] 10 6 *L/pmol*min) and IGT (0.37 [0.21, 0.66]) controls with obesity had lower S i than NGT (p = 0.001) and IGT (p = 0.43) acromegaly., Conclusion: We demonstrated that low insulin secretion is the main driver behind glucose intolerance in acromegaly. Compared to NGT and IGT controls with obesity, patients with NGT or IGT acromegaly had higher S i . Together, these findings suggest that impaired insulin secretion might be a specific mechanism for glucose intolerance in acromegaly., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Plurihormonal pituitary neuroendocrine tumors (PitNETs) are rare forms of tumors that express more than one hormone. The most common association is between growth hormone (GH) and prolactin (PRL), but other unusual combinations have been reported, such as GH and ACTH. Usually, the clinical dominance in these cases is related to GH hypersecretion. In these cases, immunohistochemistry (IHC) of transcription factors (TFs) is very useful for an accurate diagnosis. We included 42 patients diagnosed with pituitary neuroendocrine tumors (PitNETs): 37 patients with a confirmed diagnosis of acromegaly, and 5 patients with prolactinomas. All patients underwent transsphenoidal surgical intervention. We correlated the immunohistochemical features of plurihormonal PitNETs with clinical, hormonal, and imaging data. Tumor specimens were histologically and immunohistochemically examined. Based on the 2022 WHO classification, using IHC, 13 patients exhibited positive staining for more than one hormone, while unusual combinations like GH + ACTH and PRL + ACTH were also identified in other cases. Unusual cell combinations that produce hormones unrelated histogenetically, biochemically, or through regulatory mechanisms can appear and may display aggressive behavior, persistent disease, and high recurrence. We have not identified a clear correlation with the prognosis of these rare PitNETs.

Background: Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are associated with disturbed mineral homeostasis and serum bone biomarkers. The interplay between T2DM and CKD on serum bone turnover markers (BTM) is unclear. Our aim was to describe the BTM in patients with T2DM, CKD or both., Methods: In this observational, single-centre, prospective study, we included 320 patients over 40 years, divided into four groups: T2DM and normal kidney function (n=142), T2DM and CKD (n=36), CKD and normal glucose metabolism (n=29) and healthy controls (n=113). We excluded patients treated for osteoporosis and with secondary osteoporosis. Patients were compared by age, levels of glycated hemoglobin, PTH, alkaline phosphatase, osteocalcin (OC), CTx and 25 OH vitamin D., Results: Univariate analysis showed that GFR correlated significantly with PTH (r=0.37), OC (r=0.43) and CTX (r=0.45) in the diabetes group but only with PTH (r=0.34) in the non-T2DM group. Multivariate analysis showed that GFR remained significantly correlated with the same bone markers even after adjustment for age, sex or 25(OH)D levels. Diabetics seem to have lower levels of alkaline phosphatase (68±22.1 U/L) and CTX (0.37±0.24 ng/mL) than those without diabetes (76.7±29.6. U/L and 0.5±0.19 ng/mL, respectively). There was no correlation between BTM and glycated hemoglobin., Conclusions: Bone turnover markers correlate with GFR, particularly in patients with T2DM. However, alkaline phosphatase is lower in T2DM than in non-T2DM., Competing Interests: The authors declare that they have no conflict of interest., (©2024 Acta Endocrinologica (Buc).)

Introduction: Osteopathy in patients with acromegaly is characterized by increased prevalence of vertebral fragility fractures (VF). However, the diagnostic criteria for osteoporosis are seldomly met in terms of bone mineral density (BMD), as patients with acromegaly frequently present normal BMD for age and gender., Methodology: We performed a cross-sectional study on 71 patients with acromegaly and 75 patients with hypogonadism. Turnover markers comprised alkaline phosphatase, osteocalcin, the C-terminal telopeptide of type I collagen and total procollagen type-1 amino-terminal propeptide; imaging comprised dual x-ray absorptiometry for BMD, T and Z scores of the lumbar spine, femoral neck and total hip, trabecular bone score (TBS), and x-ray scans of the thoracic and lumbar spine., Results: Vertebral fractures (VF) in subjects with acromegaly were significantly more frequent than in subjects with hypogonadism, with a prevalence of 29.6% compared to 9.3%. Patients with acromegaly had significantly higher BMD at all skeletal sites but lower TBS than hypogonadal subjects. This difference remained statistically significant after grouping patients with acromegaly according to gonadal status and comparing them with patients with hypogonadism. However, presence of hypogonadism in patients with acromegaly did not influence BMD, TBS or VF prevalence. Moreover, patients with active acromegaly did not have significantly different BMD, TBS and VF prevalence compared to patients with controlled disease. Patients with acromegaly with VF had significantly lower BMD at all skeletal sites than those without VF, but no difference in TBS., Conclusions: Vertebral fractures are frequent in acromegaly, and are associated with lower BMD but not with TBS. Patients with acromegaly, regardless of gonadal status, have significantly higher BMD but lower TBS than hypogonadal patients. Moreover, disease activity and hypogonadism do not influence BMD, TBS or VF in acromegaly., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Pituitary neuroendocrine tumors (PitNETs) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Despite their benign evolution, in some cases, prolactin (PRL) and growth hormone (GH)-secreting PitNETs may have aggressive behavior. In this study, we investigated the potential predictive role of ER∝, alongside the clinicopathological classification of PitNETs (tumor diameter, tumor type, and tumor grade). A retrospective study was conducted with 32 consecutive cases of PRL- and mixed GH- and PRL-secreting PitNETs (5 patients with prolactinomas and 27 with acromegaly, among them, 7 patients with GH- and PRL- co-secretion) who underwent transsphenoidal intervention. Tumor specimens were histologically and immunohistochemical examined: anterior pituitary hormones, ki-67 labeling index, CAM 5.2, and ER∝; ER∝ expression was correlated with basal PRL levels at diagnosis (rho = 0.60, p < 0.01) and postoperative PRL levels (rho = 0.58, p < 0.001). In our study, the ER∝ intensity score was lower in female patients. Postoperative maximal tumor diameter correlated with Knosp grade ( p = 0.02); CAM 5.2 pattern (densely/sparsely granulated/mixed densely and sparsely granulated) was correlated with postoperative PRL level ( p = 0.002), and with ki-67 ( p < 0.001). The IGF1 level at diagnosis was correlated with the postoperative GH nadir value in the oral glucose tolerance test (OGTT) (rho = 0.52, p < 0.05). Also, basal PRL level at diagnosis was correlated with postoperative tumor diameter ( p = 0.63, p < 0.001). At univariate logistic regression, GH nadir in OGTT test at diagnostic, IGF1, gender, and invasion were independent predictors of remission for mixed GH- and PRL-secreting Pit-NETs; ER∝ can be used as a prognostic marker and loss of ER∝ expression should be considered a sign of lower differentiation and a likely indicator of poor prognosis. A sex-related difference can be considered in the evolution and prognosis of these tumors, but further studies are needed to confirm this hypothesis.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors., Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita)., Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01)., Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study., Competing Interests: LH, PP, EP, EN received consultancy fees from IBSA Biochimique SA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer PM declared a shared affiliation with the author TB to the handling editor at the time of review., (Copyright © 2023 Žarković, Attanasio, Nagy, Negro, Papini, Perros, Cohen, Akarsu, Alevizaki, Ayvaz, Bednarczuk, Berta, Bodor, Borissova, Boyanov, Buffet, Burlacu, Ćirić, Díez, Dobnig, Fadeyev, Field, Fliers, Frølich, Führer, Galofré, Hakala, Jiskra, Kopp, Krebs, Kršek, Kužma, Lantz, Lazúrová, Leenhardt, Luchytskiy, McGowan, Melo, Metso, Moran, Morgunova, Mykola, Beleslin, Niculescu, Perić, Planck, Poiana, Puga, Robenshtok, Rosselet, Ruchala, Riis, Shepelkevich, Unuane, Vardarli, Visser, Vrionidou, Younes, Yurenya and Hegedüs.)

There is increased interest related to the impact of coronavirus disease 19 (COVID-19) on the endocrine system and in particular on the pituitary gland. Over the course of the severe infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are both acute and delayed effects on the pituitary, related to infection and/or treatment. Hypopituitarism, pituitary apoplexy and hypophysitis have been all reported, as well as arginine vasopressin deficiency (diabetes insipidus) and syndrome of inappropriate antidiuretic hormone secretion. Furthermore, patients with acromegaly, Cushing's disease and hypopituitarism are theoretically at increased risk of complications with COVID-19 and require close monitoring. Evidence regarding pituitary dysfunction in patients with COVID-19 continues to be gathered, as the breadth and depth of knowledge also continues to rapidly evolve. This review summarizes data analysis to date on the possible effects of COVID-19 and COVID-19 vaccination on patients with normal pituitary function and patients with known pituitary pathology. Though clinical systems were significantly affected, it seems there is no overall loss of biochemical control in patients with certain pituitary pathologies., Competing Interests: Disclosures The authors have no conflict of interest(s) to report regarding this topic., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Growth-hormone (GH)- and prolactin (PRL)-secreting PitNETs (pituitary neuroendocrine tumors) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Proliferation markers alone have a questionable degree of prediction, so we try to identify validated prognostic models as accurately as possible. (1) Background: The data available so far show that the use of staging and clinical-pathological classification of PitNETs, along with imaging, are useful in predicting the evolution of these tumors. So far, there is no consensus for certain markers that could predict tumor evolution. The application of the WHO (World Health Organisation) classification in practice needs to be further evaluated and validated. (2) Methods: We performed the CRD42023401959 protocol in Prospero with a systematic literature search in PubMed and Web of Science databases and included original full-text articles (randomized control trials and clinical trials) from the last 10 years, published in English, and the search used the following keywords: (i) pituitary adenoma AND (prognosis OR outcome OR prediction), (ii) growth hormone pituitary adenoma AND (prognosis OR outcome OR prediction), (iii) prolactin pituitary adenoma AND (prognosis OR outcome OR prediction); (iv) mammosomatotroph adenoma AND (prognosis OR outcome OR prediction). (3) Results: Two researchers extracted the articles of interest and if any disagreements occurred in the selection process, these were settled by a third reviewer. The articles were then assessed using the ROBIS bias assessment and 75 articles were included. (4) Conclusions: the clinical-pathological classification along with factors such as GH, IGF-1, prolactin levels both preoperatively and postoperatively offer valuable information.

Radiotherapy, conventional or radiosurgery, has been used to control prolactin secretion and tumour growth in prolactinomas both as part of multimodal therapy or rarely as primary treatment. However, considering the radiotherapy side effects, notably hypopituitarism, as opposed to the high efficacy and low toxicity of dopamine agonists (DA) treatment and neurosurgery, radiotherapy is recommended mostly for patients with aggressive or high-risk prolactinomas or in those resistant or intolerant to medical therapy, usually after surgical failure. We provide an overview of the published literature on the efficacy and toxicity of radiotherapy (conventional fractionated or radiosurgery), in aggressive, high-risk, or DA resistant prolactinomas. Radiotherapy has shown a good efficacy and a reasonable toxicity profile in prolactinomas where other treatment modalities failed. In aggressive and high-risk prolactinomas, the cumulative percentage for tumour control (reduction plus stable) ranged from 68% to 100%. Most studies reported global hormonal control rates over 50%. In resistant prolactinomas, the global secretion control rate (on, but also off DA) ranged from 28% to 89%-100%; in most studies over 80%. The 5-year rate of hypopituitarism was around 12%-25%. To date there are no controlled study on the use of radiotherapy as a prophylactic treatment in patients with clinical, radiological or pathological markers of aggressiveness. In conclusion, our review supports the use of radiotherapy in patients with growing, clinically aggressive or truly DA resistant prolactinomas. In patients with high-risk or invasive prolactinomas or in those harboring pathological markers of aggressiveness, the prophylactic use of radiotherapy should be individualized., Competing Interests: Conflicts of interests We declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Introduction: Acromegaly is characterized by a very particular alteration of bone microarchitecture, leading to increased vertebral fragility. However, due to inconsistent and insufficient evidence, no guidelines are available for the evaluation of this osteopathy., Methods: We performed a literature review of studies published between 1968 and January 2022 on the PubMed and SCOPUS databases using the terms "acromegaly" and "vertebral fractures". Twenty-four studies were found eligible for inclusion, published between June 2005 and November 2021. Included studies evaluated acromegaly patients, who were assessed for the presence of vertebral fractures. We excluded case reports, reviews, meta-analyses, letters to the editor, articles not written in English, and research performed on the same set of patients without significant differences in study design. Risk of bias was avoided by following the ROBIS risk of bias recommendations. We executed rigorous data collection, and the results are depicted as a narrative overview, but also, as statistical synthesis. Limitations of the evidence presented in the study include study heterogeneity, small sample sizes, and a small number of prospective studies with short follow-up., Findings: Data regarding vertebral fractures (VFs) in acromegaly and their influencing factors are variable. Twenty-four studies were included, nine out of which had a prospective design. The smallest group of acromegaly patients had 18 subjects and the largest included 248 patients. Prevalence ranges between 6.5% and 87.1%, although most studies agree that it is significantly higher than in controls. VFs also have a higher incidence (between 5.6% and 42%) and are more frequently multiple (between 46.15% and 71%). Evidence shows that disease activity and active disease duration are influencing factors for the prevalence and incidence of VFs. Nonetheless, hypogonadism does not seem to influence the frequency of VFs. While reports are conflicting regarding the use of bone mineral density in acromegaly, evidence seems to be slightly in favor of it not being associated with VFs. However, trabecular bone score is significantly lower in fractured patients, although no prospective studies are available., Interpretation: Vertebral fractures evaluation should be performed with regularity in all acromegalic patients, especially in the presence of active disease. Disease activity is an important determinant of vertebral fracture incidence and prevalence, although hypogonadism is less so. To clarify the predictive value of both BMD and TBS for vertebral fractures, additional, larger, prospective studies are necessary.

Background and objective Pituitary apoplexy (PA) is a possible life-threatening disorder due to spontaneous hemorrhage or impaired blood supply in the pituitary gland. It may present as an acute or subclinical form, and treatment options include either surgery or a conservative approach. The purpose of this study was to retrospectively analyze the clinical, imaging, and hormonal features, as well as the therapeutic outcomes, in a relatively short period of time in a series of consecutive patients with pituitary apoplexy (PA). Results Thirty-six patients were included, 50% presenting typical symptoms of PA. The presenting symptoms were headache (44.4%), visual abnormalities (44.4%), and digestive symptoms (22.2%). At diagnosis, hormonal deficiency was observed in 22 (61.1%) patients. Of the evaluated patients, 78.2% of the 23 operated cases and all unoperated cases presented tumor remnants. Vision improved in 81.8% of the operated and 100% of conservatively managed cases. Of all cases, 69.4% remained with long-term hypopituitarism. Conclusion Complex management of PA frequently leads to visual improvement but long-standing hypopituitarism., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Arbunea-Ghenoiu et al.)

Background/aim: Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms are involved in a variety of biological processes including cell proliferation, apoptosis, and adhesion in malignant tumors. This study investigated whether vitamin D levels and genetic variations of VDR are risk factors for thyroid cancer., Patients and Methods: Patients who underwent surgery for differentiated thyroid carcinoma (n=113) and those with benign thyroid pathology (n=150) were genotyped for VDR gene polymorphisms (ApaI, TaqI, FokI, and BsmI) and their 25(OH)D levels were simultaneously measured. Demographic data and histopathologic reports were also acquired for all patients., Results: Vitamin D levels were significantly lower in the thyroid cancer group (p=0.03). FokI and TaqI polymorphisms were more frequent in the thyroid cancer patients (p<0.001). Compared to control, the proportion of the FokI Ff genotype was increased (p<0.0006) and the proportion of the TaqI Tt genotype was also higher among patients with thyroid cancer (p<0.0001). The Ff genotype of FokI was also associated with multifocality, invasive pattern, and risk for local metastasis., Conclusion: The VDR gene polymorphism FokI may be associated with the risk of thyroid cancer and its more aggressive forms., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., Competing Interests: All authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (©2022 Acta Endocrinologica (Buc).)

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., Competing Interests: The authors declare that they have no conflict of interest., (©2022 Acta Endocrinologica (Buc).)

Acromegaly is a rare condition typically caused by benign pituitary adenomas, resulting in excessive production of growth hormone. Clinical manifestations of acromegaly are diverse, varying from the overgrowth of body tissue to cardiovascular, metabolic, and osteoarticular disorders. Symptoms may emerge slowly, overlapping with other diseases and often involve many different healthcare specialists. In the last decade, efforts to provide an accurate and timely diagnosis of acromegaly have improved disease management and clinical experience. Despite this progress, marked differences in the diagnosis, treatment, and management of acromegaly exist from country-to-country. To address these inconsistencies in the region comprising Central and Eastern Europe, Israel, and Kazakhstan, a panel of acromegaly experts from 13 of these countries was convened. Acromegaly experts from each country provided available information on the approaches from their country, including regional treatment centers and multidisciplinary teams, treatment access, reimbursement and availability, and physician education, disease awareness, and patient advocacy. Across several areas of acromegaly management, divergent approaches were identified and discussed, including the provision of multidisciplinary care, approved and available treatments, and disease awareness programs. These were recognized as areas of potential improvement in the management of acromegaly, in addition to participation in national and regional acromegaly registries. Further experience exchange will facilitate the identification of specific strategies that can be adapted in each country, and widespread participation in acromegaly registries will enable their evaluation. It is anticipated that this approach will support the optimization of acromegaly patient care across this region., Competing Interests: The authors declare competing interests as follows: MB reports personal fees and non-financial support from Novartis; grants, personal fees and non-financial support from Ipsen; personal fees, non-financial support and other from Pfizer; and personal fees from Recordati outside the submitted work. MD reports personal fees from Pfizer and personal fees from Novartis outside the submitted work. MG reports personal fees from Pfizer and personal fees from Novartis outside the submitted work. VH reports personal fees and non-financial support from Pfizer and Ipsen outside the submitted work. II reports lectures’ fees from Pfizer and Ipsen outside the submitted work. DK reports personal fees from Pfizer outside the submitted work. TK reports personal fees from Pfizer and personal fees from Novartis outside the submitted work. MK reports personal fees from Pfizer outside the submitted work. CP reports personal fees from Pfizer, Novartis and Ipsen outside the submitted work. SV reports personal fees from Pfizer outside the submitted work. RG reports employment with Pfizer. SP reports employment with Pfizer. DS reports employment with Pfizer. IS reports personal fees and other from Pfizer; personal fees and other from Medison Pharma; and grants, personal fees and other from Novartis outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This project received funding from Pfizer. The funder had the following involvement with the study: supported the face-to-face advisory board meeting and funded medical writing and editorial assistance., (Copyright © 2022 Bolanowski, Adnan, Doknic, Guk, Hána, Ilovayskaya, Kastelan, Kocjan, Kužma, Nurbekova, Poiana, Szücs, Vandeva, Gomez, Paidac, Simoneau and Shimon.)

Prolactinomas are the most frequent pituitary adenomas. Prolactinoma may occur in different clinical settings and always require an individually tailored approach. This is the reason why a panel of Italian neuroendocrine experts was charged with the task to provide indications for the diagnostic and therapeutic approaches that can be easily applied in different contexts. The document provides 15 recommendations for diagnosis and 54 recommendations for treatment, issued according to the GRADE system. The level of agreement among panel members was formally evaluated by RAND-UCLA methodology. In the last century, prolactinomas represented the paradigm of pituitary tumors for which the development of highly effective drugs obtained the best results, allowing to avoid neurosurgery in most cases. The impressive improvement of neurosurgical endoscopic techniques allows a far better definition of the tumoral tissue during surgery and the remission of endocrine symptoms in many patients with pituitary tumors. Consequently, this refinement of neurosurgery is changing the therapeutic strategy in prolactinomas, allowing the definitive cure of some patients with permanent discontinuation of medical therapy.

Maintenance dialysis is associated with almost universal changes in bone metabolism collectively known as chronic kidney disease-mineral and bone disorder (CKD-MBD). These are accompanied in various proportions by bone loss and altered bone quality that led to an increased risk of fracture. Osteoporosis, age-related or postmenopausal, a condition that often coexists with CKD, is also a leading cause of fracture. Dual-energy X-ray densitometry (DXA) is the main tool for assessing the bone quantity and bone loss and the associated fracture risk. It has been validated in both CKD-MBD and osteoporosis. Trabecular bone score (TBS) is a DXA-derived algorithm for the evaluation of bone microarchitecture, and its clinical value has been repeatedly demonstrated in large cohorts of osteoporotic patients. However, its utility in patients on maintenance dialysis has not been conclusively shown. Published studies showed a lower TBS score and implicitly an altered bone microarchitecture in patients on maintenance dialysis, even after adjusting for various variables. Moreover, FRAX-based fracture risk is higher after adjusting for TBS, showing promise on an algorithm better estimating the clinical fracture risk in dialysis patients. However, TBS has not been demonstrated to independently predict clinical fractures in prospective studies on dialysis patients. Also, aortic calcifications and altered fluid balance could significantly affect TBS score and could hamper the widespread clinical use in patients on maintenance dialysis. In this mini-review, we focus on the benefits and pitfalls of TBS in the management of CKD-MBD and fracture risk assessment in patients on maintenance dialysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Poiana, Dusceac and Niculescu.)

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., Competing Interests: The authors declare that they have no conflict of interest., (©2021 Acta Endocrinologica (Buc).)

Purpose: The evaluation of acromegalic osteopathy is a subject of current interest as there is a lack of evidence concerning proper evaluation techniques and clear diagnostic criteria. The aim of this study was to evaluate lumbar spine trabecular bone score (TBS) and bone mineral density (BMD) in acromegaly patients compared to healthy controls., Methods: We conducted a cross-sectional study on 43 acromegaly patients recruited between 2018 and 2020 and a healthy control group matched 1:1 for age, gender, and body mass index (BMI). All subjects underwent DXA, lumbar spine TBS, and bone turnover markers measurement., Results: Acromegaly patients showed significantly decreased lumbar spine TBS (1.244 ± 0.117 vs. 1.343 ± 0.124, p < 0.001) and no difference regarding BMD compared to control patients. In the subgroup analysis, TBS was significantly lower in both males and females (1.282 ± 0.075 vs. 1.366 ± 0.113, p = 0.01 and 1.222 ± 0.132 vs. 1.329 ± 0.130, p = 0.005) and, also, in hypogonadal and eugonadal acromegaly subjects compared to their healthy controls (1.231 ± 0.130 vs. 1.306 ± 0.125, p = 0.04 and 1.280 ± 0.065 vs. 1.381 ± 0.113, p = 0.008). Femoral neck BMD was higher in acromegalic hypogonadal patients [1.027 (IQR: 0.939-1.135) vs. 0.876 (IQR: 0.737-1.014), p = 0.004]., Conclusion: Our study indicates that TBS, but not BMD, is significantly decreased in acromegaly patients, regardless of gender and gonadal status. This data suggests that TBS could be a valuable tool in the assessment of acromegalic osteopathy., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Next-generation sequencing (NGS) is a fast and relatively inexpensive method to sequence a large number of genes with crucial importance in cancer medicine. Nowadays, NGS is frequently used in diagnostic and therapeutic decisions in oncology; however, recently, it was demonstrated that only a few cancer sites actually benefit from this assessment. Moreover, the association of a mutant gene with a targeted drug is not always as predicted during in-vitro trials and is often not associated with tumor response. To predict the efficacy of such an association several classification systems have been developed. The present review aims to analyze the most important tumor agnostic treatment trials and assess how they shape selecting cancer patients for NGS. Moreover, it aims to determine how mutation-drug associations can be classified by their targetability and level of evidence of efficacy in non-small-cell lung cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Orlov-Slavu et al.)

Purpose: The number of international acromegaly related registries is increasing; however, heterogeneity of acromegaly symptoms and signs across countries is not well described. We compared clinical disease manifestations at diagnosis between two large University referral centers from two continents., Methods: Retrospective, comparative epidemiological study of acromegaly patients at two centers: (i) C. I. Parhon National Institute of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy Bucharest, Romania (Parhon), and (ii) Pituitary Center, Oregon Health & Science University, Portland, Oregon, United States (OHSU) from approved data repositories was undertaken. Data were extracted from medical charts and questionnaires. Binary logistic regression analysis was undertaken for the most frequently noted symptoms and clinical signs., Results: The study included 216 patients (87 Parhon, 129 OHSU). Age, sex, and median delay in diagnosis were similar between centers. IGF-1 index was higher in patients at Parhon (3.3 vs 2.1, P < 0.001). The top five symptoms at both centers were enlarged hands/feet, headache, arthralgia, fatigue, and irregular menses in women. A significant difference was noted for multiple signs and symptoms frequency, often > 20 percentage points between centers. Center was a predictor of many signs and symptoms, independent of acromegaly biochemical severity or disease duration., Conclusion: We show in the first comparative study that differences in medical practice, documentation, and likely cultural differences can influence patients' symptom(s) reporting and screening patterns in geographically different populations. Pooling data into large multicenter international registry databases may lead to loss of regional characteristics and thus a mixed overall picture of combined cohorts.

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., (©2021 Acta Endocrinologica (Buc).)

Background: Vitamin D status and renal function are well-known independent predictors of serum parathyroid hormone (PTH) levels. We aimed to describe the combined effects of 25-hydroxy vitamin D (25(OH)D), glomerular filtration rate (GFR) and age on serum PTH levels across the whole clinical spectrum., Methods: We retrieved from our endocrinology center database all PTH measurement between 2012 and 2020 for which a simultaneous measurement of serum 25(OH)D, calcium and creatinine was available. Age, sex and diagnosis were available for all subjects. Intact PTH was measured using the same electrochemiluminescence assay., Results: There were 6,444 adults and 701 children without a diagnosis of hyper- or hypoparathyroidism or abnormal serum calcium levels. In adults with 25(OH)D≥12 ng/mL multiple regression models showed that serum PTH was negatively correlated with both 25(OH)D and GFR. Regression (-0.68 and -1.59 vs. -0.45 and -0.22 respectively), partial correlation (-0.16 and -0.35 vs. -0.12 and -0.10 respectively) and determination coefficients (0.14 vs. 0.031) were higher in CKD than in normal renal function. In subjects with 25(OH)D<12 ng/mL, GFR was the only significant predictor in those with CKD (β-coefficient=-2.5, r=-0.55) and 25(OH)D was the only significant predictor in those with normal renal function (β-coefficient=-2.05, r=-0.11). Increasing age was associated with higher PTH levels only in those with normal renal function and 25(OH)D≥12 ng/mL., Conclusions: We showed that declining vitamin D and renal function have additive effects on serum PTH in subjects without vitamin D deficiency. In vitamin D deficient subjects this dependency is stronger but is not additive anymore., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Niculescu, Deacu, Caragheorgheopol, Popescu, Ghemigian, Procopiuc, Rosca and Poiana.)

We calculated in-hospital, 30-day, and 1-year mortality rates and analyzed potential mortality risk factors in 2742 patients with low-trauma hip fractures. We found a high mortality rate at 30 days and 1 year after hip fracture. The high mortality can be explained by a very high number of conservatively treated fractures., Purpose: Data on mortality after low-trauma hip fracture in Romania is scarce and comes from a single-hospital study. Our aim was to calculate mortality rates and risk factors in all patients admitted for low-trauma hip fracture in the largest university medical center of Romania., Methods: 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, Romania, and surrounding Ilfov County and calculated the crude in-hospital, 30-day, and 1-year mortality rates after low-trauma hip fractures. A number of potential clinical risk factors for mortality were evaluated., Results: We analyzed 2742 low-trauma hip fractures. The in-hospital, 30-day, and 1-year all-cause mortality rates were 4.26% (n=117), 9.59% (n=263), and 29.72% (n=815) respectively. Four hundred and fifty (16.41%) fractures were managed conservatively with a 1-year mortality HR of 3.05 (p<0.001) compared to surgically treated fractures. The 1-year mortality rate in conservatively treated fractures was 56.44% compared to 24.47% in surgically treated fractures. Age, male sex, length of stay in hospital, day of surgery, post-surgical complications, and late surgery were significantly associated (p<0.001) with mortality after hip fracture. The lowest 1-year mortality rate was in surgically treated patients with a length of stay in hospital between 6 and 10 days., Conclusion: We found a high mortality rate at 30 days and 1 year after low-trauma hip fracture. The high mortality rates can be attributable, in part, to the high number of conservatively treated fractures.

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., (©by Acta Endocrinologica Foundation.)

Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia & Banach.)

Cardiovascular risk (CVR) is a broad term that includes traditional factors like hypertension, hyper lipidemia, abdominal obesity, hyperinsulinemia or overt type 2 diabetes mellitus (T2DM), and emerging ones such as hypothyroidism or inflammatory diseases. In epidemiologic studies, all of these factors are associated with atherogenesis and have complex interactions between them. They have in common an increased prevalence in the general population beginning in childhood, and are correlated with endothelial damage as demonstrated by echocardiographic modifications of the left ventricle or carotid intima-media thickness. Adolescence is a transition period where behavioural eating patterns develop and have a major impact on cardiovascular risk. To address these patterns, weight-loss programmes under medical supervision for overweight and obese adolescents are developed. It was observed that those who control the quality and quantity of their carbohydrates, by consuming more fruits and vegetables, associated with increased physical activity reduce their CVR. Some limited studies have shown that low carbohydrate diet (LCD) is safe and effective, but one should take into consideration the limited duration and the structure of the LCD. If there is a proper adherence to this type of nutritional intervention, it results in weight loss, improvement in insulin resistance, lipid profile and subclinical hypothyroidism reversal. We reviewed the literature starting from 2009 by searching all the observational, randomised clinical trials and meta-analyses on MEDLINE and SCOPUS databases regarding obesity and related metabolic diseases (dyslipidemia, type 2 diabetes, hypertension, hypothyroidism, LCD) in adolescents and synthesized the nutritional interventions for this population that could decrease CVR., (Copyright © 2020, Spandidos Publications.)

Background: Literature suggests that high body mass index can be correlated with better response to immune checkpoint inhibitors. On the other hand, sarcopenia seems to be a negative predictive marker. Materials and methods: The present analysis is a retrospective, multicenter trial that included patients with metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma treated with nivolumab between 2018 and 2020. Patients were stratified by creatinine levels both at treatment initiation and at first follow-up (at three months) and by BMI for the same intervals, as recorded in the patients' charts. Creatinine was considered a surrogate marker for sarcopenia. IBM SPSS version 20 was used for statistical analysis. Results: A total of 57 (n = 57) patients were included in the trial. Overall response rate (ORR) for the entire population was 38.59% ( p = 0.02). Patients with BMI lower than 25 had an ORR of 28.5% ( p = 0.003), whereas patients with BMI higher than 25 had an ORR of 42.3% ( p = 0.002). Patients who gained weight during treatment had a lower probability of having progressive disease (OR = 0.4 [95% CI; 0.4-1.2]), as did patients with creatinine higher than 0.9 (OR = 0.39 [95% CI: 0.13-1.14]). No superiority was found in progression-free survival (PFS) when patients were dichotomized for BMI = 25 or BMI = 18.5. Mean PFS in the BMI under 18.5 group was 10.2 months [95% CI: 5.8-23.1], versus 11.2 for BMI over 18.5 [95% CI: 5.3-25.3], p < 0.03. Mean PFS for the BMI under 25 was 11.2 months [95% CI: 7.2-20.1], vs. 13.3 months [95% CI: 6.4-22] for the BMI over 25, p < 0.001. There were also differences in PFS in the patients with baseline creatinine over 0.9 when compared with under 0.9 values. Mean PFS in the first group was 19.78 months [95% CI: 16.23-22.9] vs. 16.1 [95% CI: 12.2-20.3], p < 0.001. Conclusion: Patients treated with nivolumab who have weight gain during treatment have a better PFS than the ones who do not. Creatinine levels of over 0.9 at treatment initiation also have positive predictive value.

Evidence regarding the relation between SARS-CoV-2 mortality and the underlying medical condition is scarce. We conducted an observational, retrospective study based on Romanian official data about location, age, gender and comorbidities for COVID-19 fatalities. Our findings indicate that males, hypertension, diabetes, obesity and chronic kidney disease were most frequent in the COVID-19 fatalities, that the burden of disease was low, and that the prognosis for 1-year survival probability was high in the sample. Evidence shows that age-dependent pairs of comorbidities could be a negative prognosis factor for the severity of disease for the SARS-CoV 2 infection.