The Association Between Oxidative Stress and Sperm Parameters in Patients with Acromegaly.

OBJECTIVE: Spermatozoa are susceptible to oxidative radicals when antioxidant defenses are inadequate. The extent to which oxidative radicals contribute to sperm damage in patients with acromegaly remains unclear. This study aimed to investigate and elucidate this relationship. METHODS: The overall status of oxidants and antioxidants in both seminal plasma and serum of patients with acromegaly compared to a control group of healthy individuals was investigated. In addition, sperm parameters, including important measures such as growth hormone and insulin-like growth factor-1 concentrations. RESULTS: Twenty-two patients with acromegaly with controlled disease and 14 healthy controls were included. The total oxidant status was significantly higher in the semen samples of the patients with acromegaly. A negative correlation was found between sperm total oxidant status and total sperm count and sperm concentration. Similarly, a negative correlation was found between the total sperm count and the sperm oxidative stress index. In individuals diagnosed with acromegaly, there was a statistically significant increase in sperm growth hormone levels. Conversely, the level of insulin-like growth factor 1 was significantly increased in the sperm of the control group, which consisted of healthy individuals. The correlation analysis revealed a significant relationship between venous total oxidant status and growth hormone levels in semen. CONCLUSION: The elevated levels of reactive oxygen radicals in individuals with acromegaly suggest a possible link between oxidative stress and its effects on semen quality.

Machine Learning May Be An Alternative To BIPSS In The Differential Diagnosis Of ACTH-Dependent Cushing's Syndrome.

OBJECTIVE: This study aimed to develop machine learning (ML) algorithms for the differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) based on biochemical and radiological features. METHODS: Logistic regression algorithms were used for ML, and the area under the receiver operating characteristics curve (AUROC) was used to measure performance. We used Shapley Contributed Comments (SHAP) values, which help explain the results of the ML models to identify the meaning of each feature and facilitate interpretation. RESULTS: A total of 106 patients, 80 with Cushing's disease (CD) and 26 with ectopic ACTH syndrome (EAS), were enrolled in the study. The ML task was created to classify patients with ACTH-dependent CS into CD and EAS. The average AUROC value obtained in the cross-validation of the logistic regression model created for the classification task was 0.850. The diagnostic accuracy of the algorithm was 86%. The SHAP values indicated that the most important determinants for the model were the 2-day 2-mg dexamethasone suppression test, the > 50% suppression in the 8-mg high-dose dexamethasone test, late-night salivary cortisol, and the diameter of the pituitary adenoma. We have also made our algorithm available to all clinicians via a user-friendly interface. CONCLUSION: ML algorithms have the potential to serve as an alternative decision support tool to invasive procedures in the differential diagnosis of ACTH-dependent CS.

The Effect of Metformin Treatment on Disease Control in Patients with Acromegaly.

BACKGROUND: The increase in portal insulin levels has been shown to upregulate growth hormone receptor expression in the liver, leading to increased insulin-like growth hormone- 1 levels. Metformin inhibits hepatic gluconeogenesis and reduces fasting insulin. OBJECTIVE: We evaluated the effect of metformin treatment in patients with acromegaly on growth hormone, insulin-like growth hormone-1, and pituitary adenoma size. METHODS: Patients who were followed up with the diagnosis of acromegaly in Istanbul University- Cerrahpasa, Cerrahpasa Medical Faculty were evaluated. The patients were divided into three groups after pituitary adenectomy as those who received somatostatin receptor ligand and metformin treatment (group A), somatostatin receptor ligand treatment only (group B), and those who received metformin treatment only (group C). Groups A and B were compared with each other, and patients in group C were compared among themselves. RESULTS: While the median insulin-like growth factor-1 level decreased to 170 ng/ml in Group A after the treatment, the median insulin-like growth factor-1 level decreased to 229 ng/ml in Group B, and a statistically significant difference was found between the two groups (p =0.020). There was no significant difference in post-treatment growth hormone levels and residual adenoma sizes between groups A and B (p >0.005). In group C, there was no significant difference in growth hormone values pre-and post-metformin treatment (p =0.078); however, the median insulin-like growth factor-1 level decreased from 205 ng/ml to 168 ng/ml during metformin treatment and was found to be statistically significant (p =0.027). CONCLUSION: Due to the effect of metformin treatment on insulin-like growth factor-1 values in patients with acromegaly, it can be used in disease control, as well as diabetes treatment.

Is There A Connection Between Primary Hypophysitis and Celiac Disease?

AIM: To investigate the autoimmune and genetic relationship between primary hypophysitis (PH) and celiac disease (CD). METHODS: The study was retrospective and patients with PH followed in our clinic between 2007 and 2022 were evaluated. Clinical, endocrinologic, pathologic, and radiologic findings and treatment modalities were assessed. Patients diagnosed with CD in the Gastroenterology outpatient clinic in 2020-2022 were included in the study as a control group. Information such as sociodemographic data, year of diagnosis, human leukocyte antigen (HLA) DQ2/8 information, CD-specific antibody levels, pathologic results of duodenal biopsy, treatment received, follow-up status, additional diseases, hormone use, and surgical history was obtained from patient records at PH.In patients diagnosed with PH, a duodenal biopsy was obtained, and the tissue was examined for CD by experienced pathologists. Anti-pituitary antibody (APA) and anti-arginine-vasopressin (AAVP) antibody levels of individuals with PH and CD were measured. RESULTS: The study included 19 patients with lymphocytic hypophysitis, 30 celiac patients, and 30 healthy controls. When patients diagnosed with lymphocytic hypophysitis were examined by duodenal biopsy, no evidence of CD was found in the pathologic findings. The detection rate of HLA-DQ2/8 was 80% in celiac patients and 42% in PH (p=0.044). (APA and AAVP antibodies associated with PH were tested in two separate groups of patients and in the control group. APA and anti-arginine vasopressin (AAVP) levels in PH, CD and healthy controls, respectively M [IQR]: 542 [178-607];164 [125-243]; 82 [74-107] ng/dL (p=0.001), 174 [52-218]; 60 [47-82]; 59 [48-76] ng/dL (p=0.008) were detected. The presence of an HLA-DQ2/8 haplotype correlates with posterior hypophysitis and panhypophysitis (r=0.598, p=0.04 and r=0.657, p=0.02, respectively). CONCLUSION: Although patients with PH were found to have significant levels of HLA-DQ2/8, no CD was found in the tissue. Higher levels of pituitary antibodies were detected in celiac patients compared with healthy controls, but no hypophysitis clinic was observed at follow-up. Although these findings suggest that the two diseases may share a common genetic and autoimmune basis, the development of the disease may be partially explained by exposure to environmental factors.

Serum Lipoprotein(a) Is Not Associated with Graves' Ophthalmopathy.

Aim: To investigate the relationship of serum lipoprotein(a) [Lp(a)] and other serum lipids with presence of Graves' ophthalmopathy (GO). Methods: A total of 99 consecutive patients diagnosed with Graves' disease (GD), aged 18-65 years, who had not received prior treatment for GO, thyroid surgery, or radioactive iodine therapy, were recruited between June 2020 and July 2022. In addition, 56 healthy controls (HCs) were included as the control group. All patients underwent an ophthalmological examination, and were classified based on the presence of GO into the GO group (n = 45) and no GO group (n = 54). Fasting blood samples were collected from all participants to analyze serum lipid parameters, including Lp(a), total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. Results: The median serum levels of Lp(a) were 5.7 [4.3-9.2] in the GO group, 6.7 [3.7-9.9] in the no GO group, and 4.7 [3-7.6] in the HC group. The intergroup comparisons of serum Lp(a) levels showed no significant result. The serum levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were also similar between the groups (P > 0.05 for all). However, when analyzing only euthyroid GD patients and the control group, the serum LDL cholesterol levels were found to be significantly higher in the euthyroid GO group [median: 132 interquartile range (IQR) (110-148) mg/dL] than in the HCs [median: 96 IQR (94-118) mg/dL] (P = 0.002). Conclusion: The findings of our study did not support the association between serum Lp(a) levels and GO.

Acromegaly increases depressive symptoms and reduces quality of life of cohabitants.

PURPOSE: To assess how living with patients with acromegaly affects people's psychology and quality of life (QoL). METHODS: Acromegaly patients and their cohabitants included in this study. Patients were administered Acromegaly Quality of Life Questionnaire (AcroQoL), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI). Cohabitants were administered quality of life questionnaire (SF-36), BAI, BDI, and Zarit Caregiver Burden Interview (ZBI). RESULTS: This study included 84 patients with acromegaly and 84 cohabitants. Sixty-nine patients (n = 84, 82.1%) had an acromegalic appearance. Cohabitants who were affected by the acromegalic appearance had higher BAI, BDI, and ZBI scores than those who were not affected (p < 0.001 for all). Cohabitants who were affected by the acromegalic appearance had a significantly lower SF-36 score (p = 0.015). The BAI (r=-0.535, p < 0.001), BDI (r=-0.592, p < 0.001), and ZBI (r=-0.465, p < 0.001) scores of the cohabitants showed a negative correlation with AcroQoL. SF-36 scores showed correlation with AcroQoL (r = 0.387, p < 0.001). CONCLUSION: The chronic process of acromegaly and the external appearance of patients with this disease can negatively affect both the patients and the people living with them. Physicians being aware of this effect and taking counteractive measures may contribute positively to the course of acromegaly.

Promising Outcomes in Acromegaly Patients Receiving CyberKnife Stereotactic Hypofractionated Radiotherapy.

BACKGROUND: The primary treatment for patients with acromegaly has traditionally been transsphenoidal surgery, with decreasing reliance on radiotherapy (RT) due to advancements in pharmacotherapy (PT). Despite these advancements, a substantial portion of patients still face persistent acromegaly, necessitating novel treatment approaches. This study investigates the role of CyberKnife Stereotactic Hypofractionated Radiotherapy (CK-HFRT) in persistent acromegaly. OBJECTIVE: The primary objective was to assess the impact of CK-HFRT on endocrine remission (ER) rates while maintaining acceptable toxicity levels. METHODS: The study retrospectively analyzed 31 consecutive patients with acromegaly who received CK-HFRT following multiple unsuccessful surgeries and prolonged PT without ER. Various CK-HFRT dose fractionation regimes were administered, and dose volume histograms were evaluated. Tumor control, cured disease (CD), endocrine remission (ER) rates, and overall survival were estimated at a median follow-up of 62 months. Acute and late toxicity, including pituitary insufficiency and radiation-induced optic neuropathy (RION), were also assessed. RESULTS: At 62 months of follow-up, the study group demonstrated excellent tumor control with 100% nonprogressive adenomas. Endocrine remission was achieved in 86.7% of patients, with a 22.4% CD rate at five years. Pituitary insufficiency occurred in 32.3% of patients, and no cases of RION were reported. The study observed three deaths related to cardiovascular diseases, all in patients receiving PT. Overall survival at five years was 79.2%. CONCLUSION: CyberKnife stereotactic hypofractionated radiotherapy, as an adjunct to PT, provides a viable treatment option for patients with persistent acromegaly following unsuccessful surgeries. The therapy results in substantial ER rates and tumor control while minimizing the risk of permanent radiation-induced optic neuropathy. However, the decision to administer CK-HFRT should be individualized, considering the patient's overall condition and treatment history.

Efficacy of blood parameters as indicators of the need for overdue urgent cholecystectomy in elderly patients with acute cholecystitis.

BACKGROUND: Although early cholecystectomy is recommended for patients with acute cholecystitis, conservative treatment followed by delayed cholecystectomy (DC) is a highly preferred modality, especially in older adult patients. However, some severe cases require overdue urgent cholecystectomy (OC). This study aimed to evaluate the ability of laboratory findings and Tokyo severity classification (TokyoSC) to differentiate those with the need for OC among elderly patients. METHODS: Laboratory/radiological/clinical findings of geriatric patients with acute cholecystitis on admission and TokyoSC were retrospectively analyzed. The DC and OC groups were compared. RESULTS: The mean age of the 164 patients was 72.3±6.4 years. White blood cell, neutrophil (NEU), immature granulocyte (IG), C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), and TokyoSC parameters were all significant at P<0.001 in differentiation. NLR had a specificity of 98%, and TokyoSC had a sensitivity of 98%. CONCLUSION: NLR, NEU, IG, and TokyoSC were effective in differentiating patients who needed OC while planning conservative treatment + DC for older adult patients who were followed up due to acute cholecystitis. If the NLR is >9.9 and TokyoSC is moderate/high, early cholecystectomy should be preferred instead of conservative treatment + DC in aged patients.

Risk of impulse control disorders in patients with Cushing's disease: do not blame cabergoline but do not give up caution.

PURPOSE: To asses risk of new-onset impulse control disorders (ICDs) in patients with Cushing's disease (CD) who initiated cabergoline (CBG) and to determine frequency of ICDs in CBG-treated patients with CD. METHODS: This naturalistic observational study had prospective and cross-sectional arms which included patients at five referral centers based in Istanbul. Patients who were scheduled for CBG were assigned to prospective arm. These patients underwent neuropsychological tests (Barratt Impulsiveness Scale, Minnesota Impulsive Disorders Interview, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Go/No-Go Task, Iowa Gambling Task, and Short Penn Continuous Performance Test) for assessment of impulsivity and psychiatric evaluations at baseline, 3, 6, and 12 months of CBG treatment. Impulsivity and new-onset ICDs were prospectively assessed. Patients with CD with current CBG treatment for ≥ 3 months and matched CBG-naïve patients with CD were included in cross-sectional arm. These patients underwent the same neuropsychological and psychiatric assessments. The impulsivity and frequency of ICDs were compared between CBG-treated and CBG-naïve patients with CD. RESULTS: The follow-up duration of prospective cohort (n = 14) was 7.3 ± 2.3 months. One patient developed major depressive episode and another patient developed compulsive gambling after CBG. We observed no significant changes in impulsivity scores during follow-up. In cross-sectional arm, CBG-treated (n = 34) and CBG-naïve patients (n = 34) were similar in impulsivity scores and frequency of ICDs [3 patients (8.8%) vs. 2 patients (5.9%) respectively, p = 1.0]. CONCLUSION: CBG-treated patients with CD appeared to have a low risk of ICDs, suggesting that CBG still holds promise as a safe agent in CD.

Changing presentation of acromegaly in half a century: a single-center experience.

OBJECTIVE: Investigate the changes in the characteristics of presentation, in patients with acromegaly over a period of approximately half a century. METHODS: The medical records of patients diagnosed with acromegaly between 1980 and 2023 were retrospectively reviewed. The collected data were examined to assess any changes observed over the years and a comparison was made between the characteristics of patients diagnosed in the last decade and those diagnosed in previous years. RESULTS: A total of 570 patients were included in the study, 210 (37%) patients were diagnosed in the last decade. Patients diagnosed before 2014 had longer symptom duration before diagnosis, advanced age, larger pituitary adenomas, higher incidence of cavernous sinus invasion, and higher GH and IGF-1 levels than those diagnosed last decade (p < 0.05, for all). Furthermore, the patients diagnosed before 2014 had a lower rate of surgical remission (p < 0.001), and a higher prevalence of comorbidities such as diabetes, hypertension, colon polyps, and thyroid cancer at the time of diagnosis (p < 0.05, for all). CONCLUSION: There may be a trend for earlier detection of patients with acromegaly.

The Effects of Gender-Affirming Hormone Therapy on Body Satisfaction, Self-Esteem, Quality of Life, and Psychopathology in People with Female-to-Male Gender Dysphoria.

Purpose: Gender-affirming hormone therapy (GAHT) is one of the most important therapeutic interventions sought by people with gender dysphoria (GD). In the present study, we aimed to examine the effects of GAHT on body satisfaction, self-esteem, quality of life, and psychopathology in people with female-to-male (FtM) GD. Methods: Thirty-seven FtM GD participants who did not receive any gender-affirming therapy, 35 FtM GD participants who received GAHT for over 6 months, and 38 cisgender women were included in the study. The Body Cathexis Scale (BCS), Rosenberg Self Esteem Scale (RSES), World Health Organization's Quality of Life Questionnaire Brief Form (WHOQOL-BREF), and Symptom Checklist-90-Revised (SCL-90-R) were completed by all participants. Results: The BCS scores of the untreated group were significantly lower than both the GAHT group and the female controls (p<0.001); while the WHOQOL-BREF-psychological health scores of the untreated group were significantly lower than those of the female controls (p=0.003). The psychoticism subscale scores on the SCL-90-R of the untreated group were higher than those of the GAHT group (p=0.04) as well as the female controls (p=0.003). With regard to the RSES, there were no significant differences between the groups. Conclusion: Our findings suggest that people with FtM GD who receive GAHT are more satisfied with their bodies and have less psychopathological problems compared to those who do not receive GAHT, but their quality of life and self-esteem do not change as a result of GAHT.

Altered thalamic volume in patients with mild autonomous cortisol secretion: a structural brain MRI study.

PURPOSE: To compare thalamic volume and cognitive functions of patients with mild autonomous cortisol secretion (MACS) with control subjects and patients with overt Cushing's syndrome (CS). METHODS: In this cross-sectional study, volumes of regions of interest were assessed using 3 T magnetic resonance imaging and a voxel-based morphometry approach in 23 patients with MACS, 21 patients with active CS, 27 patients with CS in remission, and 21 control subjects. Cognitive functions were assessed using validated questionnaires. RESULTS: Patients with MACS had smaller left thalamic (F = 3.8, p = 0.023), left posterior thalamic (F = 4.9, p = 0.01), left medial thalamic (F = 4.7, p = 0.028), and right lateral thalamic (F = 4.1, p = 0.025) volumes than control subjects. Patients with active CS also had smaller left thalamic (F = 3.8, p = 0.044), left posterior thalamic (F = 4.9, p = 0.007), left medial thalamic (F = 4.7, p = 0.006), and right lateral thalamic (F = 4.1, p = 0.042) volumes compared to controls. Patients with CS in remission had smaller left medial (F = 4.7, p = 0.030) and right lateral thalamic (F = 4.1, p = 0.028) volumes than controls. Neuropsychological tests showed no difference between the groups. CONCLUSION: MACS may decrease thalamic volume.

Does the Association of Hashimoto's Thyroiditis with Differentiated Thyroid Cancer Really Have a Protective Role?

The study is an investigation of aggressive tumor features, prognosis, and disease-specific mortality rates of differentiated thyroid cancer (DTC) in the presence of concomitant Hashimoto's Thyroiditis (HT). The data of patients with DTC followed in our tertiary care center between 2000-2022 were analyzed. Variables such as patient age, gender, preoperative serum autoantibody levels, tumor characteristics, and treatment modalities were obtained from medical records. The diagnosis of HT was based either on the presence of a positive result in the pathological examination and/or on antibody positivity. A total of 637 patients [mean±SD age, 44.9±13.5 years; 485 women [76.1%)] were included in the analysis. The overall prevalence of coexistent HT was 22.9% (n=146). The disease-specific mortality associated with DTC was 2.9%. DTC patients with HT compared to those without; have more positive lymphovascular invasion (p<0.001), and lymph node metastases (p<0.001). According to the Kaplan-Meier curves, disease-specific survival rates among DTC patients without HT were significantly higher than patients with HT (log-rank p=0.002). The disease-specific mortality rate was 4.79% in DTC patients with HT, it was 1.43% in those without HT. Hashimoto thyroiditis was not associated with a 10-year recurrence-free survival (p=0.059). Differentiated thyroid cancers with concomitant HT are associated with some aggressive tumor features (such as lymphovascular invasion and nodal metastasis) and lower survival. In staging systems based on tumor risk factors, it may be useful to evaluate the presence of concomitant HT as a prognostic factor.

A Genetic Assessment of Dopamine Agonist-Induced Impulse Control Disorder in Patients With Prolactinoma.

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.

Pasireotide treatment in Cushing's disease: A single tertiary center's experience.

BACKGROUND: Patients who were followed up for CD and treated with pasireotide between 2014-2020 at Cerrahpasa Medical Faculty, were evaluated retrospectively. The efficacy and adverse effects of pasireotide were evaluated in this study. METHODS: Thirty-two patients were evaluated. The mean duration of treatment was 26.5 [range, 12.0-37.0] months. The 24-h urinary free cortisol (UFC) decreased 46% during the treatment and normalized in 37.5% of patients. A significant decrement was found between pretreatment and last follow-up UFC (p = 0.001). Plasma ACTH decreased by 21%. A significant decrement was found between pre-treatment and the 3rd month, 6th month, and last follow-up ACTH levels (p = 0.014, p = 0.017, and p = 0.017, respectively). Serum cortisol levels decreased by 18% and a significant decrement was found between pretreatment and the 3rd month, and between pretreatment and the last follow-up (p = 0.034 and p = 0.013, respectively). While fasting blood glucose at the 3rd month was significantly higher than pretreatment fasting blood glucose, no significant difference was found between pretreatment fasting blood glucose and 6th month and last follow-up fasting blood glucose. Although there was a significant difference between pretreatment HbA1c levels and the HbA1c levels at the 3rd month (5.9% vs. 6.6% p = 0.007), 6th month (5.9% vs. 6.7% p = 0.003), and the last follow-up (5.9% vs. 7.1% p = 0.001), in the last follow-up, the majority (77%) of patients had adequate glycemic control (HbA1c ≤ 7.0 %). The authors declare that there is no conflict of interest. DISCUSSION: Pasireotide treatment is an alternative treatment in CD, remission is obtained in the first months of treatment, and continues for an extended period. Although hyperglycemia is the most common adverse effect, it can be successfully controlled.

Evaluation of the voluntary deep inspiration breath-hold reproducibility in left-sided breast radiotherapy.

PURPOSE: Voluntary deep inspiration breath hold (v-DIBH) reduces cardiac dose during left-sided breast irradiation. The purpose of this study is to evaluate the reproducibility and variability of breath-hold level (BHL) using breath-hold curves and lateral kV setup images together. MATERIAL/METHOD: A retrospective analysis of 30 left breast cancer patients treated using the v-DIBH technique in our department is performed. The BHL difference is measured from breath hold curves and lateral (LAT) kilo-Voltage (kV) setup images. The planning CT image and the selected treatment fraction data are collected. If the changes in BHL relate to the displacement of various bones in the kV setup, images are assessed. Furthermore, the maximum heart distance inside the treatment field is compared from LAT MV portal images. RESULTS: The median and mean values of the BHL are nearly identical in different fractions (good reproducibility). However, the mean BHL values between planning and all measured fractions are statistically different; 16.3 vs. 20.8 mm for the planning and measured fractions (p < 0.001), which indicates that the variability of BHL is significantly different. CONCLUSION: While reproducibility testing shows good agreement for inter-fractional breath-hold level, the variability between planning and fractions is relatively poor.

Effect of metformin on thyroid cancer risk in patients with acromegaly: A preliminary observational study.

PURPOSE: To evaluate the role of metformin on thyroid cancer risk in patients with acromegaly. METHODS: 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. RESULTS: 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. CONCLUSION: Metformin may decrease the thyroid cancer risk in patients with acromegaly.

Status of Weight Change, Lifestyle Behaviors, Depression, Anxiety, and Diabetes Mellitus in a Cohort with Obesity during the COVID-19 Lockdown: Turk-Com Study Group.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to a lockdown period. Confinement periods have been related to unhealthy lifestyle behaviors. Our study aimed to determine weight change, changes in eating and exercise habits, the presence of depression and anxiety, and diabetes mellitus (DM) status in a cohort of patients with obesity. METHODS: The study was undertaken in nine centers of Collaborative Obesity Management (COM) of the European Association for the Study of Obesity (EASO) in Turkey. An e-survey about weight change, eating habits, physical activity status, DM status, depression, and anxiety was completed by patients. The International Physical Activity Questionnaire (IPAQ) score was used to determine physical activity in terms of metabolic equivalents (METs). A healthy nutrition coefficient was calculated from the different categories of food consumption. The Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7) Questionnaire  were used for determining depression and anxiety, respectively. RESULTS: Four hundred twenty-two patients (age 45 ± 12.7 years, W/M = 350/72) were included. The healthy nutrition coefficient before the pandemic was 38.9 ± 6.2 and decreased to 38.1 ± 6.4 during the pandemic (p < 0.001). Two hundred twenty-nine (54.8%) patients gained weight, 54 (12.9%) were weight neutral, and 135 (32.3%) lost weight. Patients in the weight loss group had higher MET scores and higher healthy nutrition coefficients compared with the weight gain and weight-neutral groups (p < 0.001). The PHQ and GAD scores were not different between the groups. Percent weight loss was related to healthy nutrition coefficient (CI: 0.884 [0.821-0.951], p = 0.001) and MET categories (CI: 0.408 [0.222-0.748], p = 0.004). One hundred seventy patients had DM. Considering glycemic control, only 12 (8.4%) had fasting blood glucose <100 mg/dL and 36 (25.2%) had postprandial BG <160 mg/dL. When patients with and without DM were compared in terms of dietary compliance, MET category, weight loss status, PHQ-9 scores, and GAD-7 scores, only MET categories were different; 29 (11.7%) of patients in the nondiabetic group were in the highly active group compared with 5 (2.9%) in the diabetic group. CONCLUSION: The COVID-19 lockdown resulted in weight gain in about half of our patients, which was related to changes in physical activity and eating habits. Patients with DM who had moderate glycemic control were similar to the general population in terms of weight loss but were less active.

Acromegaly is associated with a distinct oral and gut microbiota.

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.