Muscle function, exercise capacity, physical activity level and cardiovascular disease risk factor knowledge in patients with prolactinoma.

OBJECTIVE: Prolactinoma can increase the risk of cardiovascular diseases (CVDs), such as arterial stiffness, atherosclerosis, dysrhythmia and heart failure. This study aimed to evaluate and compare muscle function, exercise capacity, physical activity (PA) level, CVD risk factor knowledge level, sleep quality, fatigue and quality of life between prolactinoma patients and healthy controls. METHODS: Nineteen female patients with prolactinomas and 19 healthy women were included in this study. Quadriceps muscle strength (QMS) was measured using a hand dynamometer, and muscular endurance was evaluated via the squat test. The 6-minute walking test (6MWT) distance was also measured. CVD risk factor knowledge levels were evaluated with the Cardiovascular Diseases Risk Factors Knowledge Level Scale (CARRF-KL), PA levels were assessed with the International Physical Activity Questionnaire-short form (IPAQ), sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), fatigue was assessed with the Multidimensional Fatigue Rating Scale (MAF), and quality of life was assessed with the Short Form-36 questionnaire (SF-36). RESULTS: Patients with prolactinomas had significantly lower 6MWT distances; CARRF-KL total scores; SF-36 general health and physical limitation scores; and higher IPAQ-sitting scores than did healthy controls (p < 0.05). Moreover, there were no significant differences between the groups in terms of QMS score; number of squats; severity of IPAQ score; severity, moderate, or total walking score; total PSQI score; or total MAF score (p > 0.05). CONCLUSIONS: Exercise capacity and quality of life are adversely affected, and sedentary behavior is observed in prolactinomas. Patients with prolactinomas have less knowledge about CVD risk factors than healthy individuals. CVD incidence and knowledge and functional capacity should be improved in patients with prolactinomas by the use of a multidisciplinary team for cardiac rehabilitation. CLINICAL TRIAL REGISTRATION: This study is part of a larger clinical trial registered on ClinicalTrials.gov prior to participant enrollment (NCT05236829).

Dietary Total Polyphenol, Flavonoid, and Lignan Intakes Are Associated with Obesity and Diabetes-Related Traits: A Case-Control Study.

Purpose: Dietary phytochemicals have been under examination as adjuvants for the prevention and treatment of obesity and diabetes. This study aimed at examining the potential associations of dietary "Phytochemical Index" (PI) and polyphenol intake with obesity and diabetes-related parameters. Materials and Methods: The case-control study involved 331 participants (156 overweight/obese and 175 normal weight), aged 18-50 years. Dietary intake was assessed using the 24-hr dietary recall method, and the PI score was calculated as the percentage of energy intake provided by phytochemical-rich foods. Polyphenol intakes were calculated using Phenol-Explorer and U.S. Department of Agriculture databases. Anthropometrical measurements were taken, serum glucose, insulin, and lipid profiles were analyzed, homeostatic model assessment for insulin resistance (HOMA-IR) was calculated, and blood pressure was measured. Linear regression analyses were used to examine the potential associations. Results: Participants with higher PI scores had higher total and some sub-classes polyphenol intakes compared with lower ones (P < 0.05, for each). Dietary PI score was not associated with any of the anthropometrical measurements; however, total polyphenol and flavonoids intakes were inversely associated with body mass index (ß = -0.269, P = 0.049; ß = -0.262, P = 0.048; respectively), waist circumference (ß = -0.127, P = 0.021; ß = -0.130, P = 0.016; respectively), and waist-to-hip ratio (ß = -20.724, P = 0.032; ß = -22.199, P = 0.018; respectively) after adjusting for potential confounders. Either dietary PI score or total and sub-class polyphenol intakes were not associated with a better metabolic profile, except for the lignan intake, which was inversely associated with HOMA-IR (ß = -0.048, P = 0.011). Conclusions: Higher dietary polyphenol intake may have potential in the prevention of obesity and diabetes, and validated practical tools are essential for the assessment of polyphenol intake in clinical practice.

Evaluation of the relation between subclinical systolic dysfunction defined by four-dimensional speckle-tracking echocardiography and growth differentiation factor-15 levels in patients with acromegaly.

PURPOSE: In patients with acromegaly, the long-term presence of elevated GH and IGF-1 levels is associated with an unfavorable cardiovascular risk profile. We aimed to assess the relationship of four-dimensional speckle tracking echocardiographic (4DSTE) measurements with growth differentiation factor-15 (GDF-15) levels and the Framingham Cardiovascular Risk Score (FRS) in patients with acromegaly. METHODS: A single-center, cross-sectional study was conducted. The study included 40 acromegaly and 32 age- and gender-matched controls. Anthropometric, biochemical, and echocardiographic assessments were performed. GDF-15 levels were measured using ELISA. RESULTS: In the controlled acromegaly group, global longitudinal (GLS), circumferential (GCS), area (GAS), and radial (GRS) strain measurements identified by 4DSTE were lower than those of the controls (p < 0.05). Moreover, strain parameters were lower in active acromegaly patients than in controls, but the difference was not statistically significant. The GLS was negatively correlated with age, the estimated disease duration, and FRS. Serum GDF-15 levels showed no significant difference between the acromegaly and control groups. In patients with acromegaly, serum GDF-15 levels were positively correlated with age, waist-to-hip ratio, systolic and diastolic blood pressure, FRS, fasting plasma glucose, and HbA1c, but not with strain parameters. The multiple regression analysis revealed that FRS was an independent factor associated with serum GDF-15 levels in patients with acromegaly and the overall cohort (p < 0.001). CONCLUSION: Our study demonstrates that while LVEF was within normal limits, global strain parameters (GLS, GCS, GAS, and GRS) measured by using a novel imaging technique, 4DSTE, were lower in patients with acromegaly, suggesting the presence of subclinical systolic dysfunction in patients with acromegaly. GDF-15 can be a potential predictor of cardiovascular risk in patients with acromegaly.

Nonalcoholic Fatty Liver Disease, Bone and Muscle Quality in Prolactinoma: A Pilot Study.

OBJECTIVE: Hyperprolactinemia has negative impacts on metabolism and musculoskeletal health. In this study, individuals with active prolactinoma were evaluated for nonalcoholic fatty liver disease (NAFLD) and musculoskeletal health, which are underemphasized in the literature. METHODS: Twelve active prolactinoma patients and twelve healthy controls matched by age, gender, and BMI were included. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was used to evaluate hepatic steatosis and magnetic resonance elastography (MRE) to evaluate liver stiffness measurement (LSM). Abdominal muscle mass, and vertebral MRI-PDFF was also evaluated with MRI. Body compositions were evaluated by dual energy X-ray absorptiometry (DXA). The skeletal muscle quality (SMQ) was classified as normal, low and weak by using "handgrip strength/appendicular skeletal muscle mass (HGS/ASM)" ratio based on the cut-off values previously stated in the literature. RESULTS: Prolactin, HbA1c and CRP levels were higher in prolactinoma patients (p<0.001, p=0.033 and p=0.035, respectively). The median MRI-PDFF and MRE-LSM were 3.0% (2.01-15.20) and 2.22 kPa (2.0-2.5) in the prolactinoma group and 2.5% (1.65-10.00) and 2.19 kPa (1.92-2.54) in the control group, respectively and similiar between groups. In prolactinoma patients, liver MRI-PDFF showed a positive and strong correlation with the duration of disease and traditional risk factors for NAFLD. Total, vertebral and pelvic bone mineral density was similar between groups, while vertebral MRI-PDFF tended to be higher in prolactinoma patients (p=0.075). Muscle mass and strength parameters were similar between groups, but HGS/ASM tended to be higher in prolactinoma patients (p=0.057). Muscle mass was low in 33.3% of prolactinoma patients and 66.6 of controls. According to SMQ, all prolactinoma patients had normal SMQ, whereas 66.6% of the controls had normal SMQ. CONCLUSION: Prolactinoma patients demonstrated similar liver MRI-PDFF and MRE-LSM to controls despite their impaired metabolic profile and lower gonadal hormone levels. Hyperprolactinemia may improve muscle quality in prolactinoma patients despite hypogonadism.

Evaluation of Microvascular Complications in Kidney Recipients with Post-Transplant Diabetes Mellitus.

CONTEXT: Limited data on microvascular complications in patients with post-transplant diabetes (PTDM) is an obstacle to developing follow-up algorithms. OBJECTIVES: To evaluate diabetic microvascular complications in patients with long-standing PTDM. METHODS: This study included patients with at least a five-year history of PTDM and age-matched renal transplant recipients without PTDM (NDM). Diabetic peripheral neuropathy (PN) was evaluated using the Michigan Neuropathy Screening Instrument (MNSI), the CASE IV device, and in vivo corneal confocal microscopy (CCM). Cardiac autonomic neuropathy (CAN) tests were performed using the heart rate variability. Nephropathy (DN) screening was assessed using spot urine albumin/creatinine ratio and eGFR calculation. Diabetic retinopathy (DR) was evaluated by fundus examination and photography, and optical coherence tomography. RESULTS: This study included 41 patients with PTDM and 45 patients in the NDM group. The median follow-up was 107.5 months in the PTDM group. PN was significantly higher in the PTDM group than in the NDM group (p = 0.02). In the PTDM patients with PN, the corneal nerve fiber density examined by CCM was significantly lower than in the PTDM patients without neuropathy (p = 0.001). Parasympathetic involvement was observed in 58.5% of the PTDM group and 22% of the NDM group (p = 0.001). Sympathetic involvement was present in 65.9% of the PTDM group and 29.3% of the NDM group (p = 0.001). Retinopathy was observed in 19.5% of patients in the PTDM group, while none were in NDM patients (p < 0.001). Renal functions were similar between the study groups. CONCLUSIONS: CAN and DR can affect patients with PTDM at a high rate. DR was found to be a threat to the vision of PTDM patients. Diabetic PN can be detected early in PTDM patients by CCM.

Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Utility of Noninvasive Scores in Patients With Acromegaly.

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is a metabolical disorder and can lead to liver fibrosis. Because it is commonly seen, several noninvasive scores (NS) have been validated to identify high-risk patients. Patients with NAFLD have been shown to have higher serum angiopoietin-like protein-8 (ANGPTL-8) levels. OBJECTIVE: The risk of NAFLD is known insufficiently in acromegaly. Moreover, the utility of the NS and the link between NAFLD and ANGPTL-8 in acromegaly is unknown. METHODS: Thirty-two patients with acromegaly (n = 15, active [AA] and n = 17, controlled acromegaly [CA]) and 19 healthy controls were included. Magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) was used to evaluate hepatic steatosis, and magnetic resonance elastography to evaluate liver stiffness measurement. ANGPTL-8 levels were measured with ELISA. RESULTS: Median liver MRI-PDFF and NAFLD prevalence in AA were lower than in CA (P = .026 and P < .001, respectively). Median magnetic resonance elastography-liver stiffness measurement were similar across groups. Of the NS, visceral adiposity index, fatty liver index, hepatic steatosis index, and triglyceride-glucose index (TyG) all showed positive correlation with the liver MRI-PDFF in the control group. However, only TyG significantly correlated with liver fat in the AA and CA groups. There was no correlation between traditional NAFLD risk factors (body mass index, waist circumference, C-reactive protein, homeostasis model assessment for insulin resistance, visceral adipose tissue) and liver MRI-PDFF in the AA and CA. Patients with acromegaly with NAFLD had lower GH, IGF-1, and ANGPTL-8 levels than in those without NAFLD (P = .025, P = .011, and P = .036, respectively). CONCLUSION: Active acromegaly may protect from NAFLD because of high GH. In patients with acromegaly, NAFLD risk cannot be explained with classical risk factors; hence, additional risk factors must be identified. TyG is the best score to evaluate NAFLD risk. Lower ANGPTL-8 in patients with acromegaly and NAFLD implies this hormone may be raised because of insulin resistance rather than being a cause for NAFLD.

The Triglycerides-Glucose Index Shows a Stronger Correlation with Serum Adiponectin Levels than Homeostasis Model Assessment of Insulin Resistance and Quantitative Insulin Sensitivity Check Index.

Purpose: To evaluate the association between diverse surrogate markers of insulin resistance and adiponectin concentrations. Methods: Four hundred healthy participants were included. Two different cohorts were formed according to the body mass index (BMI) values. Group 1 (n = 200) consisted of individuals with normal BMI values (18.50-24.99 kg/m2), whereas in Group 2 (n = 200) there were overweight or obese individuals (BMI ≥25.00 kg/m2). Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and triglycerides-glucose index (TyG) were calculated. Serum adiponectin levels were measured by ELISA. A correlation analysis was performed to assess the association between serum adiponectin and HOMA-IR, QUICKI, and TyG. Results: Participants in Group 2 were older (age in years: Group 1, 33.3 ± 6.8 vs. Group 2, 36.4 ± 7.0, P < 0.001). There was no gender difference between groups. Overweight or obese participants had higher BMI, waist circumference, fat mass, fat ratio, fasting plasma glucose, fasting plasma insulin, triglycerides, total cholesterol, and low-density lipoprotein cholesterol values, whereas high-density lipoprotein cholesterol was higher in participants with normal BMI measures. Overweight or obese subjects were more insulin resistant (higher TyG index and HOMA-IR) and less insulin sensitive (lower QUICKI), P < 0.001 for all. Serum adiponectin levels were lower in Group 2 (serum adiponectin in ng/mL: Group 1, 11,880 ± 6838 vs. Group 2, 9115 ± 5766, P < 0.001). The correlation between TyG index and adiponectin was stronger than the correlation between QUICKI and adiponectin, and HOMA-IR and adiponectin (r for TyG and adiponectin -0.408, r for QUICKI and adiponectin 0.394, r for HOMA-IR and adiponectin -0.268, respectively, P < 0.001 for all correlations). Conclusions: TyG has a stronger association with adiponectin than HOMA-IR and QUICKI.

Follow, consider, and catch: second primary tumors in acromegaly patients.

BACKGROUND AND AIM: The risk of second primary tumors is increased in general cancer population, however, there is no data on acromegalic cancer patients in this regard. The aim of this study is to determine the prevalence of patients with two primary tumors among acromegalic cancer patients and to evaluate if patients with two primaries have distinct clinical characteristics or risk factors compared to those with one. METHODS: This is a single-center retrospective cohort study. The study included 63 patients with at least one malignant tumor out of a total number of 394 acromegaly patients. Patients with multiple primary neoplasms were evaluated in detail. RESULTS: This study revealed a 16% cancer prevalence in acromegaly patients, with 14% (9/63) having two primary neoplasms. Papillary thyroid carcinoma was the most prevalent tumor in the entire cancer cohort (41%, 26/63), and in the group of patients with two primaries (44%, 4/9). Patients with two primary tumors were older than those with one when diagnosed with acromegaly (48.3 ± 16.6 vs. 43.3 ± 10.7 years), which might be attributed to a longer diagnostic delay (median of 4.5 vs. 2 years). The period between the onset of acromegaly symptoms and diagnosis was not associated with earlier cancer diagnosis. No relationship between circulating GH or IGF-I levels and the number of neoplasms was found. CONCLUSION: The development of second primary tumors in acromegalic patients with cancer diagnosis is not rare. Acromegalic cancer patients should be closely monitored for new symptoms or signs that could be associated with second primary tumors.

Giant growth hormone-secreting pituitary adenomas from the endocrinologist's perspective.

OBJECTIVES: Since giant (≥40 mm) GH-secreting pituitary adenomas are rarely encountered, data on their characteristics and treatment outcomes are limited. We aimed to investigate the characteristics of giant GH-secreting pituitary adenomas and to compare their clinical, biochemical, imaging and histopathological features with non-giant macroadenomas. MATERIALS AND METHODS: We have evaluated 15 (six female/nine male) and 57 (29 female/28 male) patients with acromegaly in giant and <40 mm adenoma groups, respectively. Patients with <40 mm adenoma were further divided into subgroups with adenoma size 20-29 mm and 30-39 mm. RESULTS: In giant adenoma group, median (IQR) preoperative maximal diameter of adenoma was 40 mm (5 mm), median preoperative GH level was 40 (153.4) ng/mL and median baseline IGF-1 level was 2.19 (1.88) × ULN for age and sex. The number of surgeries was significantly higher in giant adenoma group (median 2, IQR 2) in which 66.7% of patients underwent repeated surgeries (p = 0.014). Residual tumor was detected after last operation in all patients with giant adenoma. Total number of treatment modalities administered postoperatively increased as adenoma size increased (p = 0.043). After a median follow-up duration of 10 years (IQR 10), hormonal remission was achieved in six patients (40%) of giant adenoma group, while the rate of hormonal remission in non-giant adenoma group was 37%. Although preoperative GH and IGF-1 levels and Ki-67 index tended to be higher with increasing adenoma size, there was no statistically significant difference between groups in terms of these variables, as well as age, sex and invasion status. CONCLUSION: Hormonal remission rates of acromegaly patients with ≥20 mm pituitary macroadenoma were comparable. However, giant GH-secreting pituitary adenomas require an aggressive multimodal treatment approach.

Serum growth differentiation factor-15 levels are associated with the severity of diabetic foot ulcer.

AIMS: To assess serum growth differentiation factor-15 (GDF-15) levels in patients with diabetic foot ulcer and to reveal whether any association exists between GDF-15 and the severity of diabetic foot ulcer. DESIGN: A cross-sectional study including three age- and sex-matched cohorts comprising 17 patients (7 F, mean age: 52 ± 7 years) with diabetic foot ulcer (DMf), 17 patients with type 2 diabetes (6 F, mean age: 51 ± 6 years) with no foot complication (DM), and 20 healthy controls (8 F, mean age: 50 ± 8 years) (C) was conducted. RESULTS: DMf had higher GDF-15 levels, followed by DM and C (GDF-15, median ± IQR (pg/mL), DMf: 1039 (884-1566), DM: 649 (375-1148), and C: 296 (212-534), p < 0.001). The severity of diabetic foot disease was positively associated with serum GDF-15 (GDF-15, median ± IQR (pg/mL), Wagner grade 1: 893 (698-1039), Wagner grade 3: 1705 (1348-2197), and Wagner grade 4: 3075 (1974-4176), p for trend = 0.006). In multivariate regression model, only Wagner grade (ß = 0.55, 95% CI (87-753), p = 0.02) was found to be an independent factor affecting serum GDF-15 concentration. CONCLUSIONS: Serum GDF-15 levels are high in patients with diabetic foot ulcer. The level is higher in more advanced lesions. GDF-15 measurement can have clinical utility in the management of diabetic foot ulcers.

Reduced irisin levels in patients with acromegaly.

OBJECTIVES: Several metabolic disturbances are seen in acromegaly however, data regarding the contribution of irisin to these disturbances is currently insufficient. In a cohort of patients with acromegaly, we measured serum irisin levels in active and controlled cases and determined independent factors that effect serum irisin including fibronectin type III domain-containing protein 5 (FNDC5) genotyping. METHODS: A cross-sectional case-control study including 46 patients with acromegaly (28 F/18 M, age: 50.3 ± 12.1 year, BMI: 30.7 ± 5.1 kg/m2) and 81 age-, gender-, body mass index- and body composition-matched healthy controls was conducted. 15 acromegalic patients (33%) had active disease. Irisin levels were measured by enzyme-linked immunosorbent assay. Three different regions (rs3480, rs1746661, and rs16835198) of FNDC5 were subjected to polymorphism analyses. RESULTS: Both groups were overweight and had similar body composition. Irisin levels were lower in patients with acromegaly than controls (median [IQR]: 44.8 [41.7-46.7] ng/mL vs. 51.7 [45.5-60.1] ng/mL, p≤0.001, respectively). Active and controlled patients had similar irisin levels. Irisin was not correlated with growth hormone (GH), insulin-like growth factor 1 (IGF-1), and IGF-1 index. In multiple linear regression model, somatostatin receptor ligand use (ß=-20.30, 95% CI [-34]-[-6], p=0.006) was determined as the only independent factor that affect serum irisin. CONCLUSIONS: Serum irisin levels are low in patients with acromegaly who are on somatostatin receptor ligand therapy. Single nucleotide polymorphisms (SNPs) of FNDC5 have no independent effects on circulating irisin levels under somatostatin ligand action. Endocrine muscle functions also seem to be regulated by somatostatin action, which requires further studies.

Association of Human Leukocyte Antigen Genotypes with Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine-Induced Subacute Thyroiditis.

Background: Despite mass vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) is rarely seen as a complication. The reason why some individuals are susceptible to developing vaccine-induced SAT is not known. SAT develops in genetically predisposed individuals who carry specific human leukocyte antigen (HLA) haplotypes. It is unknown whether specific HLA alleles are associated with SARS-CoV-2 vaccine-induced SAT. Objective: This study compared the HLA profiles of patients with SARS-CoV-2 vaccine-induced SAT to controls, to assess whether there is an association between specific HLA genotypes and development of SAT. The relationship between HLA genotypes and the clinical course of SARS-CoV-2 vaccine-induced SAT was also evaluated. Methods: A case-control study was conducted in a Turkish tertiary care center. Fourteen patients with SARS-CoV-2 vaccine-induced SAT and 100 healthy controls were included. HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 frequencies were analyzed by next-generation sequencing. Results: The frequencies of HLA-B*35 and HLA-C*04 alleles were significantly higher in SARS-CoV-2 vaccine-induced SAT cohort when compared with controls (HLA-B*35: 13 [93%] vs. 40 [40%], p < 0.001; HLA-C*04: 13 [93%] vs. 43 [43%], p < 0.001, respectively). More severe thyrotoxicosis was seen in patients having HLA-B*35 and HLA-C*04 homozygous alleles (free thyroxine: 4.47 ng/dL [3.77-5.18] vs. 1.41 ng/dL [1.22-2.63], p = 0.048). Inflammation tended to be more severe in homozygous patients (C-reactive protein: 28.2 mg/dL [13.6-42.9] vs. 4.8 [1.2-10.5], p = 0.07). Conclusions: The frequencies of HLA-B*35 and HLA-C*04 alleles were higher in SARS-CoV-2 vaccine-induced SAT compared with controls. Homozygosity for HLA-B*35 and HLA-C*04 was associated with thyrotoxicosis and a greater inflammatory reaction. Our findings should be confirmed in studies of other populations.

Effects of combined aerobic-strength training and yoga on quality of life and related parameters in women with pituitary adenoma after surgery: a randomized crossover study.

Objective: The pituitary gland is responsible for hormonal balance in the body, and disruption of hormonal balance in patients with pituitary adenoma (PA) indirectly affects the quality of life. This study aimed to examine the effects of yoga and combined aerobic and strength training (A+ST) on quality of life and related parameters such as sleep, fatigue, emotional state, sexual function, and cognitive status in women with PA. Design: Ten women with PA were included in this randomized crossover study. Group 1 (n = 5, mean age: 52 ± 13.5 years) received A+ST for the first 6 weeks, a 2-week washout period, and yoga for the second 6 weeks. Group 2 (n = 5, mean age: 41.8 ± 14 years) received the yoga program first, followed by the A+ST program. Methods: Participants were assessed using the following tools before and after each exercise intervention: Functional Assessment of Cancer Therapy-Brain (FACT-Br) (quality of life), Pittsburg Sleep Quality Index, Fatigue Severity Scale (FSS), Female Sexual Function Index (FSFI), Hospital Anxiety and Depression Scale (HADS), and Montreal Cognitive Assessment Scale (MOCA). Results: FACT-Br scores were higher after the yoga program, HADS anxiety score was lower after the A+ST program, and MOCA scores increased after both exercise programs (P < 0.05). FSS score decreased after both exercise programs, but not significantly. In addition, nonsignificant decreases in HADS anxiety and depression scores and increased FSFI scores were observed after the yoga program. Conclusion: A+ST and yoga have positive effects on the quality of life in PA. We recommend yoga and A+ST as a supportive therapy for this population that may face comorbidities after surgical and medical treatment. Our results indicate these patients may benefit from physiotherapist-guided exercise programs.

Discrimination between non-functioning pituitary adenomas and hypophysitis using machine learning methods based on magnetic resonance imaging­derived texture features.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Interaction between Dietary Fat Intake and Metabolic Genetic Risk Score on 25-Hydroxyvitamin D Concentrations in a Turkish Adult Population.

Previous studies have pointed out a link between vitamin D status and metabolic traits, however, consistent evidence has not been provided yet. This cross-sectional study has used a nutrigenetic approach to investigate the interaction between metabolic-genetic risk score (GRS) and dietary intake on serum 25-hydroxyvitamin D [25(OH)D] concentrations in 396 unrelated Turkish adults, aged 24-50 years. Serum 25(OH)D concentration was significantly lower in those with a metabolic-GRS ≥ 1 risk allele than those with a metabolic-GRS < 1 risk allele (p = 0.020). A significant interaction between metabolic-GRS and dietary fat intake (energy%) on serum 25(OH)D levels was identified (Pinteraction = 0.040). Participants carrying a metabolic-GRS ≥ 1 risk allele and consuming a high fat diet (≥38% of energy = 122.3 ± 52.51 g/day) had significantly lower serum 25(OH)D concentration (p = 0.006) in comparison to those consuming a low-fat diet (<38% of energy = 82.5 ± 37.36 g/d). In conclusion, our study suggests a novel interaction between metabolic-GRS and dietary fat intake on serum 25(OH)D level, which emphasises that following the current dietary fat intake recommendation (<35% total fat) could be important in reducing the prevalence of vitamin D deficiency in this Turkish population. Nevertheless, further larger studies are needed to verify this interaction, before implementing personalized dietary recommendations for the maintenance of optimal vitamin D status.

SARS-CoV-2 Vaccine-induced Thyroiditis: Safety of Revaccinations and Clinical Follow-up.

CONTEXT: The number of reported cases with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) and Graves' disease (GD) is growing. However, active debate continues about managing such side effects and the safety of repeat or booster doses of the vaccines in such cases. OBJECTIVES: This study aims to present long-term clinical follow-up of SARS-CoV-2 vaccine-induced SAT or GD cases and provide data regarding the safety of revaccinations. METHODS: Patients diagnosed with SARS-CoV-2 vaccine-induced SAT or GD were included. Data regarding the long-term clinical follow-up of SARS-CoV-2 vaccine-induced SAT and GD cases and outcomes of repeat or booster SARS-CoV-2 vaccinations were documented. The literature, including cases of SARS-CoV-2 vaccine-induced SAT or GD, was reviewed. RESULTS: Fifteen patients with SARS-CoV-2 vaccine-induced SAT and 4 with GD were included. Pfizer/BioNTech COVID-19 vaccine (BNT162b2) was associated with symptoms in a majority of cases with SAT and all with GD. Median time from vaccination to symptom onset was 7 and 11.5 days, respectively, while 7 and 2 patients required medical treatment in SAT and GD groups, respectively. Remission was documented in 10 SAT patients, with a median time to remission of 11.5 weeks. No exacerbation/recurrence of SAT occurred in 7 of 9 patients who received a repeat vaccination dose, while symptoms of SAT worsened following the second vaccination in 2 cases. None of the patients experienced severe side effects that could be associated with revaccinations. CONCLUSIONS: Revaccinations appear to be safe in patients with SARS-CoV-2 vaccine-induced SAT cases, while more evidence is needed regarding SARS-CoV-2 vaccine-induced GD.

Specific FSTL1 polymorphism may determine the risk of cardiomyopathy in patients with acromegaly.

BACKGROUND: We have investigated the role of a cardiomyokine, follistatin-like 1 (FSTL1), and its single nucleotide polymorphism on acromegalic cardiomyopathy. METHODS: The study was performed as a cross-sectional case research in a Tertiary Referral Centre. Forty-six patients with acromegaly (29 F-17 M, mean age: 50.3 ± 12.1 years) were included. FSTL1 levels were measured and the rs1259293 region of the FSTL1 gene was subjected to polymorphism analysis. 1.5 Tesla MRI was used to obtain cardiac images. RESULTS: There were 15 active (6 F-9M) and 31 (22 F-9M) controlled patients. Active patients had a higher left ventricular mass (LVM) and left ventricular mass index (LVMi). GH levels were positively correlated with left ventricular end-diastolic volume index (LVEDVi), stroke volume index (SVi), cardiac index (Ci), LVM and LVMi; r = 0.35, 0.38, 0.34, 0.39 and 0.39, respectively. IGF-1 index was positively correlated with LVEDVi, left ventricular end-systolic volume index (LVESVi), SVi, Ci, LVM and LVMi; r = 0.36, 0.34, 0.32, 0.31, 0.42 and 0.42, respectively. Twenty out of 46 patients with acromegaly (43.5%) had myocardial fibrosis. FSTL1 levels were neither correlated with disease activity nor with any functional and structural cardiac parameter. Multivariate linear regression analysis revealed no association between FSTL1 and any study parameters. The rs1259293 variant genotype CC was significantly associated with low left ventricular mass. CONCLUSIONS: Serum FSTL1 levels are not associated with functional and structural measures of myocardium in patients with acromegaly. However, the risk of left ventricular hypertrophy is reduced in CC genotyped individuals of FSTL1.

Acute and short-term effects of Lactobacillus paracasei subsp. paracasei 431 and inulin intake on appetite control and dietary intake: A two-phases randomized, double blind, placebo-controlled study.

This study aims to examine the acute and short-term effects of prebiotics, probiotics, and their combination on appetite, energy intake and satiety related hormones in two phases. The first phase was a randomized, double blind, placebo controlled crossover study. Prebiotic (16 g inulin), probiotic (Lactobacillus paracasei subsp. paracasei 431 (L. casei 431) (>106 cfu/ml), synbiotic (their combination) and control (16 g maltodextrin) dairy drinks were consumed by 16 healthy men with a standard breakfast on four separate test days, and the following satiety responses and ad libitum food intake at lunch and over 24 h were assessed. In the second phase, the effects of 21 days of synbiotic (n = 10) or control (n = 11) drink consumption on appetite sensation, energy intake, serum glucose, insulin, peptide YY, ghrelin, obestatin and adiponectin concentration were assessed in a randomized double-blind placebo-controlled design. In the first phase, energy intake values during ad libitum lunch were the lowest in the prebiotic drink, followed by probiotic, synbiotic and control drinks, respectively (p = 0.017); also the rest of the day and 24-h dietary energy intake was lower by prebiotic and probiotic drinks compared to the control drink (p < 0.05 for each). For short-term effects, no significant difference in anthropometric measurements, hunger-satiety scores and serum glucose, insulin, PYY, ghrelin, obestatin and adiponectin concentrations were recorded. Despite the potential of prebiotics and probiotics to reduce energy intake, further studies are required for a better understanding of their role in satiety related mechanisms.

Clinical course and management of pembrolizumab-associated isolated adrenocorticotrophic hormone deficiency: a new case and literature review.

Hypophysitis is rarely reported in patients receiving pembrolizumab-only immunotherapies. Since the clinical presentation is usually as isolated adrenocorticotrophic hormone (ACTH) deficiency, patients may be misjudged as having clinical symptoms due to cancer or chemotherapy. A 49-year-old male with laryngeal cancer applied to our clinic just after the tenth cycle of his pembrolizumab treatment, with weakness and nausea/vomiting. Serum morning cortisol and ACTH were 0.47 mcg/dl and 10.1 pg/ml, respectively; the remaining anterior pituitary hormone levels were normal. Pituitary MRI revealed mild glandular enlargement and loss of posterior pituitary bright-spot. All symptoms and signs improved with low-dose prednisolone. This is the second reported case of pembolizumab-associated isolated ACTH deficiency having abnormal pituitary MRI findings as we have reviewed all reported cases in the literature.

Lay abstract Immune check point inhibitors (ICIs) are used in order to enhance antitumoral immune mechanisms in certain cancers. As a result, immune-related side effects have commonly been reported in patients taking ICIs, one of which is hypophysitis. Pembrolizumab is a type of ICI which has rarely been associated with hypophysitis. Since the clinical presentation of pembrolizumab-associated hypophysitis is usually as isolated adrenocorticotrophic hormone deficiency and related cortisol insufficiency, patients may be misjudged as having clinical symptoms due to cancer or chemotherapy, due to shared symptoms such as fatigue, loss of appetite and nausea. Here we have reported a case with pembrolizumab-associated isolated adrenocorticotrophic hormone deficiency and reviewed all other cases available in the literature to improve our understanding of such patients.

Klotho gene G395A and C1818T polymorphisms in acromegaly: Association with clinical presentation and comorbidities.

BACKGROUND: Klotho is a new identified anti-ageing gene with tumour suppressor activities. Current data suggest that there is a tight relationship between Klotho protein and growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. PURPOSE: This study aimed to investigate the possible association of Klotho gene polymorphisms with acromegaly and to assess whether these polymorphisms contribute to clinical characteristics, comorbidities and biochemical variables in these patients. METHODS: The study included 52 patients with acromegaly and 52 unrelated healthy subjects. The Klotho G395A and C1818T polymorphisms were assessed by Sanger sequencing. Serum levels of sKlotho were determined by ELISA method. RESULTS: Subjects carrying GA genotype of Klotho G395A polymorphism had 3.27 times higher risk of developing acromegaly [odds ratio (OR), 3.27; 95% confidence interval (CI): 1.37-7.81; p = .023]. The A allele of G395A was significantly associated with acromegaly risk (OR, 2.27; 95% CI: 1.1-4.72; p = .022). No association was observed between the studied polymorphisms and disease characteristics including age at acromegaly diagnosis, size of adenoma, baseline GH and IGF-1 concentrations, and final outcome. G395A polymorphism was associated with the presence of malignancy (OR, 2.24, 95% CI: 1.63-3.08; p = .019) and colorectal polyps (OR, 1.99; 95% CI: 1.02-3.88; p = .047) in patients with acromegaly. Serum sKlotho levels were significantly higher and correlated with GH and IGF-1 levels among acromegaly patients. There was no association between the studied polymorphisms and sKlotho levels. CONCLUSIONS: Klotho G395A polymorphism is associated with acromegaly susceptibility and increased risk of malignancy and colorectal polyps in these patients.