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Purpose: Vertebral fractures (VFs), the hallmark of skeletal fragility, have been reported as an emerging complication in patients with pituitary diseases associated with hormonal excess and/or deficiency, independently from bone mineral density. Non-functioning pituitary adenoma (NFPA) is amongst the most frequent pituitary adenomas; however, skeletal health in this context has never been investigated. We aimed at assessing the prevalence and the determinants of morphometric VFs in patients with NFPA., Methods: We enrolled 156 patients (79 M/77F, mean age 55.75 ± 12.94 years) at admission in Neurosurgery Unit before trans-sphenoidal surgery and compared them with an age and sex-matched control group of subjects with neither history/risk factors for secondary osteoporosis nor pituitary disorders. We performed a vertebral morphometric evaluation of the thoracic spine on pre-operative X-ray images (MTRx) and collected biochemical, demographic, and clinical data from the entire cohort., Results: The prevalence of thoracic VFs in patients with NFPA was significantly higher than the control group (26.3% vs. 10.3%; p < 0.001). In the NFPA group, 20 patients (48.8% of the fractured patients) showed multiple VFs, 14 (34.1% of them) showed moderate/severe VFs. Patients with VFs were significantly older and had lower serum free triiodothyronine (fT3) levels than non-fractured ones (p = 0.002 and p = 0.004; respectively). The prevalence of secondary male hypogonadism was higher among men with VFs as compared to those with no VFs (72% vs. 48.1%; p = 0.047). Consistently, total testosterone levels in males were significantly lower in fractured patients than in non-fractured ones (p = 0.02). The prevalence of gonadotroph adenomas was significantly higher among patients with VFs (p = 0.02). In multiple logistic regression analysis, older age and lower serum fT3 levels were independent factors predicting the risk for VFs., Conclusions: For the first time, we reported a high prevalence of thoracic radiological VFs in patients with NFPAs. Our data should prompt clinicians to proceed with a clinical bone fragility evaluation already during the diagnostic work-up, particularly in those with concomitant hypogonadism, or in those with older age and/or with lower fT3., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The primary goal of acromegaly treatment is to normalize biochemical parameters as it significantly reduces the risks of complications and comorbidities associated with the disease. First-line medical treatment is commonly represented by injectable somatostatin analogues (SRLs) after surgery. In June 2020, with the integration of Transient Permeation Enhancer® technology, oral octreotide capsules (OOCs) received regulatory approval from the US Food and Drug Administration for long-term maintenance treatment in patients with acromegaly who have responded to and tolerated treatment with octreotide or lanreotide. We reviewed the clinical pharmacological data on the development and clinical use of OOCs. The pharmacokinetic and pharmacodynamic data on OOCs showed a dose-dependent increase in octreotide levels and remarkable suppression of growth hormone secretion. The efficacy and safety of OOCs were investigated in four clinical trials conducted on patients with complete or partially controlled acromegaly. The trials resulted in the maintenance of biochemical control after switching from injectable SRLs to OOCs, with a comparable side-effect profile. Moreover, the acromegaly symptoms improved in patients on OOC. The data showed a patient preference to continue in the OOC arm for the extension phase of the trials. From the clinical pharmacological perspective, oral formulation of octreotide has the advantage of efficacy and safety with respect to injectable octreotide., Competing Interests: Disclosures: Stefano Frara has received consultancy and speaker fees from Ipsen, Pfizer, Novartis and Recordati. Andrea Giustina is a consultant for Ipsen, Pfizer and Recordati, and has received research grants from Pfizer and Recordati. Meliha Melin Uygur and Marta Villanova have no financial or non-financial relationships or activities to declare in relation to this article., (© Touch Medical Media 2023.)

Context: The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism., Methods: This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups., Results: Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism., Conclusion: Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pituitary hormones regulate skeletal physiology, and excess levels affect bone remodeling and alter bone microstructure. Vertebral fractures (VFs) are an early phenomenon of impaired bone health in secreting pituitary adenomas. However, they are not accurately predicted by areal bone mineral density (BMD). Emerging data demonstrate that a morphometric approach is essential for evaluating bone health in this clinical setting and is considered to be the gold standard method in acromegaly. Several novel tools have been proposed as alternative or additional methods for the prediction of fractures, particularly in pituitary-driven osteopathies. This review highlights the novel potential biomarkers and diagnostic methods for bone fragility, including their pathophysiological, clinical, radiological, and therapeutic implications in acromegaly, prolactinomas, and Cushing's disease., Competing Interests: Declaration of interests A.G. is a consultant for Abiogen, Ipsen, Recordati, and Pfizer and received grants to institution from Pfizer and Recordati. S.F. has received consultant and speaker fees from Ipsen, consultant fees from Novartis, and served on advisory boards from Recordati and Novo Nordisk., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: An imbalance of inflammatory factors can stimulate obesity by inducing chronic inflammation in adipose tissue. Interleukin-6 (IL-6) is a cytokine with both inflammatory and anti-inflammatory functions. Suppressor of cytokine signaling 3 (SOCS3) acts as an inhibitor for a number of cytokine signals. The IL-6 and SOCS3 genes are known to be involved in lipid and energy metabolism, although it is unclear how these genes relate to obesity. The aim of this study is to determine whether the obesity risk is associated with the IL-6 (rs1800795, rs1800796) and SOCS3 (rs4969170) gene polymorphisms., Methods and Results: Based on their body mass index (BMI) scores, 185 people were determined, of whom 90 were from the control group and 95 were obese. Anthropometric measurements and biochemical parameters of the study subjects were documented during the examination. Genomic DNA isolation was performed from the blood samples of all participants. IL-6 (rs1800795, rs1800796) and SOCS3 (rs4969170) polymorphisms were detected by real-time quantitative polymerase chain reaction (qRT-PCR) from genomic DNA samples. The IL-6 rs1800795 and rs1800796 variants showed a significant difference between the control and obese groups (p = 0.027; p = 0.013). The SOCS3 rs4969170 variation did not substantially differ between the control and obese groups (p = 0.825)., Conclusion: In our study, IL-6 rs1800795(G/C) and rs1800796(G/C) polymorphisms appeared to be a risk factor for obesity. The C allele was associated with the obesity phenotypes. However, the SOCS3 rs4969170 (A/G) polymorphism was not linked to an increased risk of obesity. IL-6 polymorphisms may be new targets for obesity treatment., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: An increased prevalence of vertebral fractures (VFs) has been reported in previous studies. The aim of this study was to evaluate the association between bone mineral density (BMD), bone turnover markers, serum sclerostin levels, and vertebral fractures (VFs) in acromegaly patients. We also evaluated the effects of gonadal status, disease activity, treatment modality, age, sex, and body mass index (BMI) on skeletal endpoints., Design: Case-control study., Patients and Measurements: Seventy acromegaly patients (M/F:36/34, mean age 45.5 ± 11.9 years) and 70 controls (M/F:31/39; mean age 45.66 ± 11.9 years) were included. VFs, BMD, calcium metabolism, markers of bone turnover, and sclerostin levels were evaluated. BMD was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500). Conventional lateral radiography of the spine was performed and the Genant method was used for the assessment of fractures of T4-L5 vertebrae., Results: The prevalence of vertebral fractures was higher in acromegalic patients as compared with the control group (72.9 vs. 20%; p < 0.001). Serum phosphate (P) levels (3.46 ± 0.59 mg/dl vs. 3.11 ± 0.44 mg/dl; p < 0.001) and b-cross laps (CTx) levels (0.47 µg/l, range 0.04-2.38 vs. 0.28 µg/l, range 0.11-0.80; p < 0.001) were significantly higher in acromegaly patients than control subjects. Serum sclerostin levels were similar between either acromegaly patients and control subjects or acromegaly patients with VF and without VF. In the means of treatment modality, VFs were more frequent in patients treated with adjuvant gamma knife radiosurgery (GKS) (p = 0.07). In the binary logistic regression analysis, the age of the acromegaly patients, the presence of hypogonadism, and GKS treatment were the factors significantly correlated with the occurrence of spinal fractures., Conclusions: The prevalence of VFs in patients with acromegaly is higher than in control subjects. Since advanced age, the presence of hypogonadism and GKS treatment were the factors predicting VFs in acromegaly; radiological evaluations should be considered as an emerging tool especially in those patients. Although markers of bone turnover elevated in acromegaly, they were not useful for the prediction of fractures. Serum sclerostin levels showed no discrepancy between the two groups and further studies are required for assessment of sclerostin role in this form of secondary osteoporosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Advanced glycation end product (AGE) is a marker of metabolic memory. Accumulated AGEs in skin collagen measured with skin autofluorescence (SAF) was found to be associated with subclinical atherosclerosis. We aimed to evaluate SAF and carotid intima-media thickness (CIMT) and its association with clinical and biochemical parameters in severely obese patients before and after bariatric surgery., Materials and Methods: In this observational study, 432 morbid obese patients evaluated before and after 6 and 12 months of bariatric surgery for metabolic and anthropometric parameters, CIMT and SAF. SAF was assessed in the forearm with an AGE Reader., Results: SAF measurements were higher in diabetic (2.04 ± 0.52 AU) obese patients compared to non-diabetic (1.78 ± 0.40 AU) obese patients (p < 0.0001). Although bariatric surgery-induced weight loss resulted in a decrease in CIMT in the 6th and 12th months compared to baseline, weight loss and metabolic improvements were not associated with a parallel decrease in SAF measurements. SAF measurements were positively correlated with body mass index (r 0.527, p < 0.0001), HbA1c (r 0.362, p < 0.0001), and CIMT (r 0.319, p < 0.0001). Multivariate analysis showed the presence of diabetes (but not BMI, age, and sex) was independently associated with SAF (R 2  = 7.62%), and the presence of diabetes, low-density cholesterol, and systolic blood pressure were independently associated with CIMT measurements (R 2  = 21.7%)., Conclusion: Bariatric surgery-induced weight loss and metabolic improvement were found to be associated with improvement in CIMT, while skin AGE accumulation was not regressed in the first year of surgery.

Background: We aimed to evaluate the association of serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3) levels with clinicopathological parameters in patients with breast cancer (BC) and their efficiency for the prediction of recurrence., Methods: The records of 482 female patients with breast cancer diagnosis followed in Medical Oncology and Radiation Oncology clinics of Kartal Dr. Lutfu Kirdar Education and Research Hospital were evaluated retrospectively., Results: The median age of the patients was 49. CEA levels were significantly higher in postmenopausal patients (p = 0.022). There was no association between CEA and CA 15-3 levels and nodal involvement (p = 0.689, 0.379; respectively). CEA levels were significantly higher in hormone receptor-positive patients (p = 0.007). HER2 negative patients had significantly higher levels of CEA and CA 15-3 (p = 0.017 and 0.011, respectively). The evaluation of metastatic patients showed that CEA and CA 15-3 levels before metastasis were significantly elevated (p = 0.016 ve 0.008, respectively). There was no relation between the metastasis site and CEA, CA 15-3 levels (p = 0.936, 0.201, respectively). Receiver operating characteristic (ROC) analysis was performed to determine the role of CEA and CA 15-3 levels in the prediction of metastasis, and cut-off values were 1.39 ng/ml and 14.54 U/ml, respectively. Sensitivities of CA 15-3 and CEA levels were 82.1% and 88.3%; specificities were 47.3% and 46.2%, respectively., Conclusions: CEA and CA 15-3 are useful as tumor markers for early diagnosis of metastases, and their elevations were associated with unfavorable clinicopathological parameters of breast cancer patients. Since these markers are considered a cheap and accessible way of predicting breast cancer prognosis, there is an increasing interest in the prognostic value of serum levels of tumor markers in recent years. More sensitive cut-off values for each marker are needed to be validated with further studies., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: This study aims to examine the prevalence of Cushing's syndrome (CS) in class 3 obese patients before bariatric surgery., Materials and Methods: The data of 1037 class 3 obese patients admitted to the endocrinology outpatient clinic for endocrinological evaluation before bariatric surgery between 2012 and 2019were reviewed retrospectively. One milligram dexamethasone suppression test (DST) was used for the evaluation of hypercortisolism in all cases and cutoff accepted as 1.8 μg/dL., Results: The mean body mass index (BMI) was 48 ± 8.9 kg/m 2 and age was 42 ± 10 years with female preponderance (F/M: 799/238] being observed in this cohort. Insufficient cortisol suppression was found in 40 patients; confirmed hypercortisolemia was detected in 8 patients. The prevalence of pathologic DST was 3.85% and 0.77% in confirmed hypercortisolism. The specificity for 1-mg DST with the cutoff 1.8 μg/dL was calculated as 96.8%., Conclusion: Hypercortisolism prevalence was found to be low, and 1 mg DST is a sufficient test for the screening of CS in class 3 obese patients evaluated before bariatric surgery.

Gamma knife radiosurgery (GKS) is a treatment option for recurrent or persistent disease in patients with acromegaly., Objective: We aimed to retrospectively evaluate acromegaly patients who had undergone GKS in terms of pituitary hormone status, efficacy of GKS, and prognostic factors., Method: One-hundred and ten acromegaly patients who underwent GKS, and who were referred to our outpatient endocrinology clinic between 2007 and 2017, were included in the study. Anterior pituitary hormones and radiology imaging during follow-up were recorded. Remission for acromegaly was defined as a normal insulin-like growth factor 1 (IGF-1) level adjusted for age and gender, and a random growth hormone (GH) level < 1 ng/ml. Endocrine control was defined as normal GH and IGF-1 levels under medication., Results: After a mean follow-up of 6.5 ± 4.7 years; remission, endocrine control, and uncontrolled status was observed in 16.4%, 60%, and 23.6% of patients; respectively. Adenoma volume was decreased after GKS (P < .0001). Remnant adenoma diameter was higher in the uncontrolled group compared to the remission and endocrine control group. The presence of tumor extension was associated with disease status (P = .03) and higher initial GH and IGF-1 levels. The mean time after GKS to remission was 26.5 months. Six (5.4%) patients had new-onset pituitary deficiency after GKS. In the multivariate analysis, pre-GKS IGF-1 levels and patient's age were associated with disease status., Conclusion: GKS is an effective adjuvant treatment with minimal side effects to control GH and IGF-1 levels, increase remission rates, endocrine control, and reduce tumor diameter in persistent acromegaly patients after surgery., (Copyright © 2020. Published by Elsevier Ltd.)