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Histologically aggressive micropapillary thyroid carcinomas (PTMC) subtypes are thought to be associated with an aggressive clinical course. However, evidence for unfavorable clinical outcomes in patients with aggressive PTMC subtypes is not clear. In this study, we intended to determine the difference in clinical outcomes between patients with aggressive and non-aggressive PTMC subtypes. In this multicenter cohort study, the computer-recorded clinical and histopathological data of patients who underwent thyroid surgery between January 2000 - January 2021 in 9 referral centers and were diagnosed as PTMC were analyzed. A total of 1585 patients [female 1340 (84.5%), male 245 (15.5%), mean age 47.9±11.63 years), with a mean follow-up time of 66.55±37.16 months], were included in the study. Ninety-eight cases were diagnosed as aggressive and 1487 as non-aggressive subtypes. Persistent/recurrent disease was observed in 33 (33.7% )and 41 (2.8%) patients with aggressive and non-aggressive subtypes (p1 cm in size. Therefore, the histopathological subtype of PTMC should be taken into consideration to tailor a personalized management plan.

Context Dopamine agonist (DA)–induced impulse control disorder (ICD) represents a group of behavioral disorders that are increasingly recognized in patients with prolactinoma. Objective We aimed to examine the genetic component of the underlying mechanism of DA-induced ICD. Methods Patients with prolactinoma receiving dopamine agonist (cabergoline) treatment were included in the study. These patients were divided into 2 groups: patients who developed ICD due to DA and patients who did not. Patients were evaluated for polymorphisms of the DRD1, DRD3, COMT, DDC, GRIN2B, TPH2, OPRK1, OPRM1, SLC6A4, SLC6A3, HTR2A genes. Results Of the 72 patients with prolactinoma using cabergoline, 20 were diagnosed with ICD. When patients with and without ICD were compared according to genotype frequencies, OPRK1/rs702764, DRD3/rs6280, HTR2A/rs6313, SLC6A4/rs7224199, GRIN2B/rs7301328, TPH2/rs7305115, COMT/rs4680, DRD1/rs4532 polymorphisms significantly increased in patients with DA-induced ICD. Conclusion Our results show that multiple neurotransmission systems affect DA-induced ICD in patients with prolactinoma.

Purpose: Various problems related to the gender-affirming therapy (GAT) can adversely affect both the physical and mental health of people diagnosed with gender dysphoria (GD). In this study, we aimed to highlight the reasons for loss to follow-up during the gender-affirming hormone therapy (GAHT), which is an important component of GAT. Methods: People diagnosed with GD who were followed for GAHT between January 2014 and June 2019 (female-to-male: 349; male-to-female: 89) were enrolled. The prepared questionnaire was administered to participants at routine follow-up visits. We arranged tele-interviews for those who did not attend the follow-up visits. Results: During GAHT process, the health problems most frequently reported by people diagnosed with GD were related to mental health. The most important factors in regular follow-up were the completion of legal procedures in Turkey required for GAT and citizenship alteration, financial barriers, lack of time for clinical visits, and dissatisfaction with health care setting. In addition, we found that the frequency of desire for supervised GAHT and family support were higher in regularly followed people diagnosed with GD. On the contrary, self-initiation of GAHT and mental disorders were more common in people diagnosed with GD lost to follow-up. Conclusion: The present study provides important information regarding the reasons for loss to follow-up during GAT in Turkey. Elucidation of reasons for loss to follow-up can aid in identifying the gaps in medical care, improve compliance, and outcomes of people diagnosed with GD.

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing’s syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing’s disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation.

Hypophysitis is a heterogeneous condition that includes inflammation of the pituitary gland and infundibulum, and it can cause symptoms related to mass effects and hormonal deficiencies. We aimed to evaluate the potential role of machine learning methods in differentiating hypophysitis from non-functioning pituitary adenomas.The radiomic parameters obtained from T1A-C images were used. Among the radiomic parameters, parameters capable of distinguishing between hypophysitis and non-functioning pituitary adenomas were selected. In order to avoid the effects of confounding factors and to improve the performance of the classifiers, parameters with high correlation with each other were eliminated. Machine learning algorithms were performed with the combination of gray-level run-length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray-level co-occurrence entropy.A total of 34 patients were included, 17 of whom had hypophysitis and 17 had non-functioning pituitary adenomas. Among the 38 radiomics parameters obtained from post-contrast T1-weighted images, 10 tissue features that could differentiate the lesions were selected. Machine learning algorithms were performed using three selected parameters; gray level run length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray level co-occurrence entropy. Error matrices were calculated by using the machine learning algorithm and it was seen that support vector machines showed the best performance in distinguishing the two lesion types.Our analysis reported that support vector machines showed the best performance in distinguishing hypophysitis from non-functioning pituitary adenomas, emphasizing the importance of machine learning in differentiating the two lesions.

Introduction Cushing's disease caused by pituitary corticotropin (ACTH)-secreting tumors. These tumors are almost always benign and are usually microadenomas. In 30 to 40 percent, the microadenoma is so small that it is not detectable by magnetic resonance imaging (MRI). Primary therapy consists of transsphenoidal surgery or pituitary irradiation. Patients who fail this first approach can be treated either by repeat transsphenoidal surgery, medical therapy, radiotherapy, or, as a final resort, surgical or medical adrenalectomy. Clinical Case A 38-year-old male patient presented with headache and fatigue. The laboratory examinations reviewed ACTH depending Cushing's syndrome. A suspicious lesion in the pituitary with no contrast enhancement was observed in Sella MRI. Cavernous sinus sampling consistent with central sources. He was operated in 2018 for pituitary Cushing's disease. Reticulin framework disrupted compatible with adenoma but, ACTH could not be stained in immunohistochemical staining for technical reasons. Due to the high cortisol levels of the patient in the postoperative follow-up, the patient underwent bilateral adrenalectomy in 2019. Because of active Cushing's disease, patient was re-evaluated in 2022. In laboratory examinations, HGB 16.6 g/dL, WBC 6400 /uL, NEU 3200 /uL, PLT 228000 uL, cre 0.76 mg/dL, TSH 1.5 mIU/L, FT4 1.2 ng/dl, FSH 4.6 U/L, LH 7.98 U/L, PTH 23.7 ng/L, PRL 17 µg/L, Total Testosterone 571 ng/dl, Progesterone 0.06 µg/L, GH 0.04 ug/L, IGF1 83 µg/L were detected. Basal cortisol was 35 ug/dl and ACTH 67 ng/L. Cortisol with 1 mg of DST resulted in 28 ug/dl. 2 mg DST resulted in cortisol 38 ng/L. Free cortisol in the urine was found to be 281 mg/day (n The patient's pasireotide 0.3 mg 1×1 treatment was continued. Metyropane 250 mg 2×1 was added to the treatment. Conclusion In Cushing's disease, the ACTH-secreting adenoma may be too small to be detected.

To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.

To evaluate the effects of online group problem-solving therapy (PST) for reducing negative problem orientation (NPO), psychological distress, and increasing quality of life in patients with Cushing's disease (CD).In this randomized trial, we allocated 55 eligible patients to either PST (n = 28) or treatment as usual (TAU) (n = 27) groups. The analyses primarily relied on intent-to-treat (ITT) principle and were repeated with intervention completers (per-protocol analyses). Social problem-solving inventory-revised short form, Beck Depression Inventory (BDI), General Health Questionnaire-12 (GHQ-12), Perceived Stress Scale (PSS), The Satisfaction with Life Scale, and Cushing's Quality of Life scale were used. Pre-test, post-test, and follow-up measures were obtained. Linear mixed models were used to compare PST and treatment as usual (TAU) groups across time.Of the total 55 patients with CD, the mean age was 46 ± 12 years, 49 patients (89%) were female, and 41 patients (74.5%) were in remission. The patients within the PST and TAU groups were similar in terms of age, sex, and disease activity. ITT analyses showed a greater reduction of NPO scores in patients who received PST as compared to patients who received usual care (df = 45.9, p = 0.029, Cohen's d = 0.47). The decrease in NPO was sustained at follow-up (mean difference: - 2.2, p = 0.007). Results of the ITT analyses revealed no superior benefits of the intervention for psychological distress. However, per-protocol analyses demonstrated that PST provided a greater decrease in BDI, PSS, and GHQ-12 scores.PST may decrease NPO and improve the psychological well-being of patients with CD.

Transgender people are exposed to many health inequality practices while receiving healthcare. In this study, we aimed to investigate the levels of transphobia among physicians who play an active role in the gender-affirming treatment (GAT) in Turkey. In this cross-sectional study, 530 physicians from the disciplines of psychiatry, endocrinology, gynecology, urology, and plastic surgery were assessed. Respondents completed a web-based survey consisting of sociodemographic data form and Genderism and Transphobia Scale (GTS) from May to June 2020. Among the 530 physicians, 126 were psychiatrists, 107 were endocrinologists, 119 were gynecologists, 111 were urologists, and 67 were plastic surgeons. We concluded that the transphobic attitude was the lowest in psychiatrists and the highest in urologists. In addition, we found that males were more transphobic than females (for GTS, p

Purpose To evaluate the effectiveness of cabergoline and the parameters affecting cabergoline response as add-on treatment to somatostatin analaogues (SSA) in patients with acromegaly uncontrolled with SSAs. Material and Method One hundred and twenty-nine acromegalic patients uncontrolled with SSA who had cabergoline added to their treatment were included in this retrospective study. Patients were divided into the SSAs + cabergoline-responsive (group 1) and non-responsive groups (group 2), and biochemical, pathologic, and radiologic parameters were assessed. Results IGF-1 normalization was achieved in 75 of 129 patients (58%) when cabergoline was added to the SSA treatment. Female patients were significantly higher in group 1 compared to group 2 (p=0.006). Group 1 had significantly smaller pre- and post-cabergoline tumor size (p=0.011, p=0.007 respectively), lower levels of IGF-1 in pre-and post-operative period (p=0.040, p=0.001), and lower levels of IGF-1 in pre- and post-cabergoline treatment (p Conclusion Cabergoline can be added to the treatment of acromegalic patients uncontrolled with SSAs due to its ease of use and low economic cost, especially in patients with acromegaly who have small adenomas and no fibrous bodies.

Purpose To evaluate the expression of G-protein coupled estrogen receptor (GPER1), aromatase, estrogen receptor α (ERα), estrogen receptor β (ERβ), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) in GH-secreting and non-functioning adenomas (NFA). Methods Thirty patients with acromegaly and 27 patients with NFA were included. Gene expression was determined via quantitative reverse transcription polymerase chain reaction (QRT-PCR). Protein expression was determined via immunohistochemistry. Results There was no difference, in terms of gene expression of aromatase, ERα, PTTG, and FGF2 between the two groups (p>0.05 for all). ERβ gene expression was higher and GPER1 gene expression was lower in GH-secreting adenomas than NFAs (p0.05 for all). GPER1 gene expression was positively correlated to ERα, ERβ, PTTG, and FGF2 gene expression (p Conclusions GPER1 is expressed at both gene and protein level in a substantial portion of GH-secreting adenomas and NFAs. The finding of a positive correlation between GPER1 and ERα, ERβ, PTTG, and FGF2 gene expression and aromatase and GPER1 protein expression suggests GPER1 along with aromatase and classical ERs might mediate the effects of estrogen through upregulation of PTTG and FGF2.

Introduction Acromegaly is a chronic disease of increased growth hormone (GH) secretion and elevated insulin-like growth factor-I (IGF-I) levels induced by a pituitary adenoma. HMGA2 (high mobility group A2) and AIP (aryl hydrocarbon receptor-interacting protein) expression levels are related to GH-secreting adenomas, and also a response to Somatostatin Analogs (SSAs). We studied SNPs in miR-107 and miR-23b that related with AIP and HMGA2 genes respectively and control their expression, and also SNP in the 3'UTR of HMGA2 gene. Our aim was to investigate genotype distributions of the studied SNPs, as well as the possible relationship between disease and/or response to SSAs treatment in patients with acromegaly. Material and Methods Genotypes were determined by qRT-PCR method from DNA materials obtained blood samples of acromegaly patients (141) and healthy individuals (99). The genotype distributions of patients and healthy groups, as well as the relationship between the clinical data of the disease and genotypes were statistically compared. Results In acromegaly patients with T-allele, p53 expression (p=0.049) was significantly higher. In patients with CT+TT genotype and T-allele who were responder to SSA-treatment Ki-67 index (respectively p=0.019, p=0.020 respectively) was higher. We did not observe the genotypes for miR-23b and miR-107 polymorphisms in the patients and control group of Turkish population. Conclusion The genetic variations of the miRNAs genes related with HMGA2 and AIP genes were not seen in our study. Although there is no relationship between HMGA2-rs1351394 polymorphism and acromegaly disease, T allele was associated with some clinical features related to adenoma in patients with acromegaly.

© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Purpose: Our aim was to investigate the changes in the composition of oral and gut microbiota in patients with newly diagnosed acromegaly and their relationship with IGF-1 levels. Methods: Oral and fecal samples were collected from patients with newly diagnosed acromegaly without comorbidities and from healthy controls. The composition of the microbiota was analyzed. The general characteristics, oral and stool samples of the patients and healthy control subjects were compared. The changes in microbiota composition in both habitats, their correlations and associations with IGF-1 were statistically observed using machine learning models. Results: Fifteen patients with newly diagnosed acromegaly without comorbidities and 15 healthy controls were included in the study. There was good agreement between fecal and oral microbiota in patients with acromegaly (p = 0.03). Oral microbiota diversity was significantly increased in patients with acromegaly (p < 0.01). In the fecal microbiota, the Firmicutes/Bacteroidetes ratio was lower in patients with acromegaly than in healthy controls (p = 0.011). Application of the transfer learned model to the pattern of microbiota allowed us to identify the patients with acromegaly with perfect accuracy. Conclusions: Patients with acromegaly have their own oral and gut microbiota even if they do not have acromegaly-related complications. Moreover, the excess IGF-1 levels could be correctly predicted based on the pattern of the microbiome.

Aim To assess the effect of social function, motivation, support, and traumatic childhood experiences on follow-up behavior of patients with gender dysphoria (GD). Method: All the patients with GD who came to our clinic for endocrinological visit between September 2020 and July 2021 were asked to participate in this cross-sectional study. People with GD that provided consent were included in trans group. We also assigned age-matched cis-gender healthy controls. Data regarding gender transition process were collected retrospectively from medical charts. All the participants were administered Social Adaptation Self-evaluation Scale (SASS), Childhood Trauma Questionnaire (CTQ), and Multidimensional Scale of Perceived Social Support (MSPSS). The results were compared between groups. Results The study included 50 male-to-female with GD (MtF), 50 female-to-male with GD (FtM), 48 cis-females, 28 cis-males. The ratio of regular follow-up was higher in FtMs (n=48, 77.1%) than MtFs (n=39, 56.4%) (p Conclusion Childhood traumas, emotional and sexual abuse may serve the reason for the loss to follow-up of MtFs. Presentation: No date and time listed

Objective: Data about the impact of Cushing’s syndrome (CS) on thyroid is scarce. We aimed to identify the prevalence of thyroid diseases in patients with CS. Patients and Methods: Nineteen patients with CS and 40 healthy participants were included in the study. All patients were tested for free tri-iodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), anti-thyroglobulin (anti-Tg), and antithyroid peroxidase (anti-TPO) levels, and thyroid ultrasonography (US). Results: Overt hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was evident in 5.3%, 5.3%, and 21.1% of patients with CS; and 2.5%, 7.5%, and 15% of healthy subjects, respectively. fT3 and fT4 levels were lower in patients with CS. None of the patients with CS and 27.5% of the control group had autoimmune thyroid disease (AITD), which was demonstrated by both US findings and anti-TPO positivity (P=0.01). Frequency of thyroid nodule was 52.6% and 52.5% in patients with CS and controls, respectively (P=0.99). Conclusion: The prevalence of thyroid dysfunction, nodular thyroid disease, and goiter is comparable to healthy population. However, AITD is less prevalent among patients with CS. Although, hypercortisolism has an impact on hypothalamic-hypophyseal-thyroid axis, its clinical implication does not seem to be significant.

Despite receiving Gender-Affirming Hormone Therapy or Gender-Affirming Surgery, which may adversely impact their fertility, people with Gender Dysphoria (GD) may desire to form families. In this study, we aimed to quantitatively display fertility desire from the perspective of these individuals, despite all the legal challenges they face. The single center, cross-sectional comparative study included individuals with GD and cisgender volunteers. A Sociodemographic Data Form, the Fertility Desire Data Form, the Childbearing Motivations Scale and the Fertility Desire Scale were used. Of the 414 participants, 171 were individuals with GD (110 FtM; 61 MtF) and 243 were cisgender volunteers (142 cis-males; 101 cis-females). While 22% of the people with GD stated that they had regrets about not undergoing fertility preservation, 16% stated that they would like this process if it were legal. People with GD, particularly MtF, want to have children more than cisgenders. Moreover, people with MtF exhibited less negative motivations toward becoming parents, despite having reservations regarding the socioeconomic aspect of parenthood. Our findings indicate that fertility desire in people with GD is not less in comparison to cisgender people. Healthcare professionals should not forget to offer fertility preservation options as part of clinical practice before Gender-Affirming Therapy.

To evaluate the role of metformin on thyroid cancer risk in patients with acromegaly.Medical charts of 534 patients with acromegaly that were followed-up between 1983 and 2019 were reviewed. Patients with follow-up duration at least 6 months were included. Cohort entry was defined as first visit date. The date of each case's thyroid cancer diagnosis was defined as index date. Patients were followed until the index date, death, or last visit date, whichever came first. Nested case-control study design was selected to evaluate the association between metformin and the thyroid cancer risk in patients with acromegaly.291 patients with acromegaly were included into final analysis. The mean age at acromegaly diagnosis was 42.3 ± 1.3 years. The median follow-up duration was 76 [34-132] months. Among 291 patients, 13 patients (4.5%) had thyroid cancer. Thirty-one percent (n = 92) of the patients used metformin for 6 months or longer. One standard deviation (SD) increase in average growth hormone increased the odds of having thyroid cancer by 1.164 folds (p = 0.017). One SD increase of the average insulin-like growth factor 1 to upper limit of normal ratio increased the odds of having thyroid cancer by 1.201 folds (p = 0.004). If a patient used metformin for at least 6 months, the odds to have thyroid cancer was decreased, multiplied by 0.62 with a 95% confidence interval of [0.47, 0.83] (p = 0.0013). The risk of thyroid cancer decreased with increasing duration of metformin use.Metformin may decrease the thyroid cancer risk in patients with acromegaly.

Based on the possible effects of androgens on the course of COVID-19, it can be posited that Gender-Affirming Hormone Therapy (GAHT) may affect the course of the disease in people with GD. We aimed to investigate the relationship between GAHT and contracting COVID-19, as well as the severity of the disease in individuals with Gender Dysphoria (GD). The single center, cross-sectional, web-based survey was completed by people with GD who received GAHT. The questionnaire contained three parts: a sociodemographic data form; a GAHT data form; a COVID-19-related data form. Of the 238 participants, 179 were individuals with female-to-male (FtM) and 59 male-to-female (MtF) GD. We detected that the risk of contracting COVID-19 increased 3.46 times in people with FtM GD, who had received testosterone therapy, in comparison to people with MtF GD, who received estrogen and anti-androgen therapy. Additionally, people with FtM GD who contracted COVID-19 had received longer testosterone therapy when compared to those who did not contract COVID-19. Our findings indicate that individuals with FtM GD who receive testosterone treatment within the scope of GAHT are at higher risk of contracting COVID-19 and that the clinicians who follow-up on GAHT should be more careful about this issue.

Background: Acromegaly is a disease that occurs as a result of excessive growth hormone caused by pituitary adenomas. Some acromegaly patients show resistance to somatostatin analog (SSA) treatment. Filamin-A (FLNA) and β-arrestins are thought to play a role in the response to SSAs. We aimed to investigate the relationship between FLNA-rs782079491 and β-arrestin-2-rs34230287 single-nucleotide polymorphisms and disease risk, as well as treatment response in patients with acromegaly in the Turkish population. Methods: The genotypes of 110 acromegaly patients and 99 controls were determined by realtime PCR. The genotype distributions were compared with clinical data on the disease. Results: There was no association between the β-arrestin-2 gene polymorphism and the response to SSA treatment in acromegaly patients. For responder patients to SSAs, the β-arrestin-2-rs34230287 CT+TT genotype was associated with higher microadenoma as compared with the CC genotype (p = 0.017). The FLNA polymorphism was not observed in the study group. Conclusions: We showed that there was no association between the polymorphic genotypes of FLNA and β-arrestin-2 genes with acromegaly disease and SSAs response in the Turkish population. However, there was a relationship between β-arrestin-2 and some of the clinical characteristics. Furthermore, the CC genotype and the C allele are risk factors associated with tumor growth rate in acromegaly patients. 34669321

Less than a year ago, none of us had heard of novel coronavirus disease (COVID-19) Today, it has become the main topic of our daily conversations This disastrous disease has united the medical professions belonging to various specialties to fight against the disease in collaboration However, the exact role of endocrinologists still remains elusive The coronavirus could potentially infect organs other than the lungs, such as the pancreas, thyroid, adrenal glands, and pituitary, as reflected by various endocrinological manifestations The direct invasion of organ systems and indirect mechanisms such as induction of autoimmunity could be responsible for the endocrinological consequences A large body of literature on its pathophysiology, management, and associated conditions is growing, and its association with endocrinological diseases is increasingly being recognized However, data that would guide the proper management of these endocrinological disorders during this novel pandemic are still lacking This review presented a brief overview of the association of COVID-19 with endocrinological diseases and methods to ease the management of some frequently encountered endocrinological problems

Objectives\ud Many patients with Cushing's disease (CD) require chronic pharmacotherapy to control their hypercortisolism. We evaluated the efficacy and safety of long‐acting pasireotide during a long‐term extension study in patients with CD.\ud \ud Design\ud Open‐label extension to a 12‐month Phase III study of long‐acting pasireotide in CD (N = 150; NCT01374906).\ud \ud Patients\ud Patients with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) or receiving clinical benefit at core study end could continue long‐acting pasireotide during the extension.\ud \ud Results\ud Eighty‐one of 150 (54.0%) enrolled patients entered the extension. Median overall exposure to pasireotide at study end was 23.9 months; 39/81 (48.1%) patients completed the extension (received ≥ 12 months’ treatment during the extension and could transit to a separate pasireotide safety study). mUFC was ≤ULN in 42/81 (51.9%), 13/81 (16.0%) and 43/81 (53.1%) patients at extension baseline, month (M) 36 and last assessment. Median mUFC remained within normal limits. Median late‐night salivary cortisol was 2.6 × ULN at core baseline and 1.3 × ULN at M36. Clinical improvements were sustained over time. Forty‐two (51.9%) patients discontinued during the extension: 25 (30.9%) before M24 and 17 (21.0%) after M24. Hyperglycaemia‐related AEs occurred in 39.5% of patients. Mean fasting glucose (FPG) and glycated haemoglobin (HbA1c) were stable during the extension, with antidiabetic medication initiated/escalated in some patients. Sixty‐six (81.5%) and 71 (88.9%) patients were classified as having diabetes (HbA1c ≥ 6.5%, FPG ≥ 7.0 mmol/L, antidiabetic medication use, or history of diabetes) at extension baseline and last assessment.\ud \ud Conclusions\ud Long‐acting pasireotide provided sustained biochemical and clinical improvements, with no new safety signals emerging, supporting its use as an effective long‐term therapy for CD.

Objective Plurihormonal pituitary adenomas (PPAs) have recently been divided into 2 subtypes: pituitary specific transcription factor 1–positive plurihormonal pituitary adenomas (PIT-1+ PPAs) and plurihormonal adenomas with unusual immunohistochemical combinations (PAwUIC). The purpose of this study was to review patients with PPAs, elucidate their clinicopathologic characteristics, and present the surgical results. Methods Records were analyzed for 665 patients who underwent endoscopic endonasal transsphenoidal surgery for pituitary adenomas between 2007 and 2018. Data were reviewed for 27 patients who met the definition of PPAs and delineated regarding clinical, radiologic, pathologic features, and surgical outcomes. Results Of the 27 patients, 18 had PAwUIC, and 9 patients were diagnosed with PIT-1+ PPAs. Twenty-four patients (88.8%) had macroadenomas, including 6 giant adenomas (≥4 cm) (22.2%). Cavernous sinus invasion was found in 12 patients (44.4%). Pathologic examinations showed high aggressivity in nearly half of the patients. Most patients with PAwUIC (77.8%) had features of nonfunctioning pituitary adenomas, and only 4 had features of hormone-secreting pituitary adenomas. Gross total resection rates were 57.1% for PAwUIC and 77.8% for PIT-1+ PPAs. The remission rate for hormone-secreting pituitary adenomas was 100% in this case series. Mean follow-up was 74.4 ± 33 months (range, 6–121 months) for overall groups. Conclusions To our knowledge, this is the first study to describe the clinicopathologic features of newly classified PPAs, which are characterized by aggressive behavior with higher values of percentage of cavernous sinus invasion. Relevant pathologic diagnosis of PPAs is crucial for appropriate management and follow-up.

Patients with acromegaly may have balance abnormalities due to changes in body composition. We aim to compare static and dynamic balances in patients with acromegaly and healthy volunteers, and to evaluate the effects of exercise on balance in patients with acromegaly. This prospective study included 25 patients with acromegaly followed at endocrinology clinic of Cerrahpasa Medical Faculty and 13 healthy volunteers. The acromegalic patients were divided into 2 groups. Group A (n = 11) attended an exercise program 3 days/week for 3 months, whereas group B (n = 14) and healthy volunteers (Group C) were exercise-free. Bipedal and unipedal stance static and dynamic balance tests were performed using a Prokin 252N device. The ages, demographic characteristics, and body compositions were similar. In acromegalic patients, the static balance parameters of displacement of center-of-pressure in anterior–posterior direction (C.o.P.Y) while eyes open (p = 0.002) and on left leg (p = 0.001), in left–right direction (C.o.P.X) on right leg (p = 0.03), eyes-closed average medio-lateral velocity (AMLV) (p = 0.001) and the dynamic parameter of forward/backward front/right standard deviation (FBFRSD) (p = 0.02) were significantly different from healthy controls. When the exercise effect on balance was evaluated between group A and B, there were significant improvements in most parameters of dynamic balance measurements of both forward–backward and medial–lateral sway (FBFRSD, FBDME, and RLBLSD) (p = 0.02, p = 0.02, and p = 0.004, respectively) after exercise in group A. Patients with acromegaly had impairments at various static and dynamic balance parameters, especially in posterior direction. After a 3-month exercise program, the dynamic balance profoundly improved, but static balance was relatively preserved in patients with acromegaly.

To investigate the effects of preoperative somatostatin analogue (SSA) treatment on the annual cost of all acromegaly treatment modalities and on remission rates. The medical records of 135 patients with acromegaly who were followed at endocrinology clinic of Cerrahpasa Medical Faculty for at least 2 years after surgery between 2009 and 2016 were reviewed. The mean follow-up time was 50.9 ± 25.7 months. Early remission was defined according to 3rd month values in patients who didn’t achieve remission, and 6th month values in patients who achieved remission at the 3rd month after surgery. The early and late remission rates of the entire study population were 40% and 80.7%, respectively. The early remission of the preoperative SSA-treated group (61.5%) was significantly higher than SSA-untreated group (31.2%) (p = 0.002). The early remission of the preoperative SSA-treated patients with macroadenomas (52.2%) was also significantly higher than the SSA-untreated group (23.5%) (p = 0.02). In the subgroup analysis; this difference was much more pronounced in invasive macroadenomas (p = 0.002). There were no differences between the groups in terms of late remission.The median annual cost of all acromegaly treatment modalities in study population was €3788.4; the cost for macroadenomas was significantly higher than for microadenomas (€4125.0 vs. €3226.5, respectively; p = 0.03). Preoperative SSA use in both microadenomas and macroadenomas didn’t alter the cost of treatment. The increase in the duration of preoperative medical treatment had no effect on early or late remissions (p = 0.09; p = 0.8). Preoperative medical treatment had no effect on the costs of acromegaly treatment. There was a benefical effect of pre-operative SSA use on early remission in patients with macroadenomas; however, this effect didn’t persist long term.

Purpose: Vitamin B12 causes hematologic and neuropsychiatric disorders, so it is important to evaluate it in risky situations. In this study, we aimed to evaluate the association between somatostatin receptor ligands and vitamin B12 levels in patients with acromegaly.Methods: Patients who were followed up with the diagnosis of acromegaly in the Endocrinology and Metabolism outpatient clinic of Istanbul University-Cerrahpaşa Medical Faculty were evaluated. Patients were divided into groups according to their somatostatin receptor ligand use status. The groups were evaluated according to their vitamin B12 levels, demographic data, and biochemical parameters.Results: One hundred fifty-two patients were evaluated. Thirteen patients had vitamin B12 deficiency. The majority (11/13) of patients with vitamin B12 deficiency were patients using somatostatin receptor ligand. In addition, the number of patients with vitamin B12 deficiency who received lanreotide autogel treatment was significantly higher compared with patients who did not use somatostatin receptor ligand (p = 0.011). Vitamin B12 levels were higher in patients who received lanreotide autogel treatment than in patients who did not use somatostatin receptor ligand treatment (p = 0.040). There was a negative correlation between vitamin B12 levels and lanreotide autogel use time, cumulative lanreotide autogel dose.Conclusion: It is important to evaluate the level of vitamin B 12 in the follow-up of patients with acromegaly using somatostatin receptor ligand treatment.

Purpose To investigate the relationship of Fibroblast Growth Factor Receptor-4 (FGFR-4) expression with radiologic, pathologic, and clinical parameters in pituitary adenomas. Methods Among 307 patients who underwent pituitary surgery for a pituitary adenoma between 2000 and 2015, we included 161 patients (53 gonadotroph, 26 corticotroph, 25 null cell, 22 lactotroph, 13 somatotroph, 8 adenomas with unusual combination, 7 Pit-1 positive adenomas, and 7 lactosomatotroph) based on availability of pathology specimens. Patients’ radiologic, pathologic, and clinical parameters were determined. FGFR-4 immunostaining was evaluated using a semi-quantitative histologic score (H-score). Results The mean follow-up period was 61 (IQR=32–84) months. The median H-scores for FGFR-4 were higher in patients without remission, those with residual lesion, and T2-hyperintense adenoma (p0.05). There was no significant difference (p>0.05) when the H-score and Ki-67 levels were assessed in terms of sex, sellar-dural invasion, Knosp and a grading system for superior, inferior, parasellar, anterior and posterior tumor extension Classification, tumor function or presence of poor subtype. Adenomas with Ki-67 expression ≥3% had higher FGFR4 expression levels than those with Conclusions Higher levels of FGFR-4 in pituitary adenomas could be use a marker for more aggressive tumor behavior.

Although the age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on differentiated thyroid carcinoma (DTC) recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA 3-tiered risk stratification system in patients with DTC with at least 5 years of follow-up.In this study, the computer-recorded data of the patients diagnosed with DTC between January 1985 and January 2016 were analyzed. Only patients with proven structural persistent/recurrent disease were selected for comparisons.This study consisted of 1691 patients (female, 1367) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (P = .045). Nevertheless, a markedly longer DFS was observed in patients aged45 years in the ATA low- and intermediate-risk categories (P = .004 and P = .009, respectively), whereas in patients aged55 years, DFS was markedly longer only in the ATA low-risk category (P.001). In the Cox proportional hazards model, ages of ≥45 and ≥55 years at diagnosis and the ATA risk stratification system were all independent predictors of persistent/recurrent disease.Applying the age cutoff of 45 years in the ATA intermediate- and low-risk categories may identify patients at a higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system, whereas sex may improve the performance of only the ATA low-risk category.

Background Any preoperative diagnostic assessment that can predict the success of the operation in acromegaly will provide a positive impact on overall remission rates. The aim of this study is to present whether signal intensity on T2-weighted Magnetic Resonance Imaging could predict postoperative results in acromegaly patients. Methods We analyzed our surgical results in regard to T2-weighted images in newly diagnosed consecutive 124 patients with acromegaly, operated between 2014 and 2019. The T2-intensity of the pure somatotroph adenomas was correlated with the clinical, radiological, surgical and histopathological characteristics of the acromegaly patients. Results We found a predominance of T2-hyperintensity in our series (45%) and the T2-hypointense pure somatotroph adenomas were detected in only 34% of our patients. Total resection was performed in 72% of newly diagnosed acromegaly patients in this series. Accordingly, total resection was achieved in 69% of the T2-hyperintense group, 77% of the T2-hypointense group and 69% of the T2-isointense group. The surgical remission rates for the T2-hyper-, hypo- and isointense groups were 55%, 80%, and 69%, respectively. The surgical remission rate in the T2-hyperintense group was significantly lower than those of hypo- and isointense groups in newly diagnosed acromegaly patients. Conclusions This study demonstrates a close relationship between the T2 signal intensity and the surgical remission rates in acromegaly. T2 signal intensity seems to be an indicator of the degree of surgical resection completeness in pure somatotroph adenomas. The implications suggest that preoperative T2-intensity may directly predict the probability of post-surgical remission as an important independent factor in patients with newly diagnosed acromegaly.