Effects of laparoscopic sleeve gastrectomy on thyroid hormones and relationship between metabolic parameters and long-term total weight loss.

BACKGROUND: Bariatric surgery has significant effects on metabolic parameters and hormone levels. However, the specific impact of laparoscopic sleeve gastrectomy (LSG) on thyroid hormones and other metabolic parameters remains unclear. This study aimed to investigate the short and long-term effects of LSG on thyroid hormone levels, HbA1c, and other metabolic parameters. METHODS: A total of 619 euthyroid patients without a history of thyroid disease or thyroid hormone replacement therapy were included in the study. Patients with diabetes were excluded from the study. Preoperative, 1-year postoperative, and 5-year postoperative levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), HbA1c, and other metabolic parameters were recorded and analyzed. RESULTS: LSG resulted in significant weight loss and improvements in metabolic parameters. At 1 year postoperatively, there were significant reductions in BMI, HbA1c, TSH, fT3, and triglyceride levels, while fT4 levels increased. A statistically significant negative correlation was found between preoperative HbA1c level and percentage of total weight loss (%TWL) value at the fifth postoperative year. Additionally, a statistically significant negative correlation was found between the 5-year change in TSH and %TWL. CONCLUSION: Being the first study to predict long-term total weight loss based on preoperative HbA1c, it is significant. This finding has important implications for personalized patient management and could aid clinicians in identifying individuals who may benefit most from sleeve gastrectomy as a treatment modality. This is valuable in that it emphasizes multidisciplinary work, including the endocrinologist and dietician.

Investigation of the effect of weight loss after laparoscopic sleeve gastrectomy on cobb angle, waist and back pain: a prospective study.

BACKGROUND: In many studies, it has been stated that obesity causes severe increases in the risks of disc degeneration, vertebral fracture, low back, and back pain. One of the most effective treatment options for obesity is bariatric surgery. OBJECTIVES: In this study, the effect of weight loss on these parameters was investigated by evaluating the Cobb angle, low back, and back pain. SETTING: University Hospital METHODS: A total of 89 patients were included in the study. Laparoscopic sleeve gastrectomy (SG) was performed on all patients. In addition, Cobb angle, height, weight, and body mass index (BMI) measurements were recorded at each visit. Investigating the quality and quantity of low back pain and the loss of function caused by the patients; visual analog scale (VAS), Oswestry Low Back Pain Disability Questionnaire (OLBPDQ), Roland-Morris Disability Questionnaire (RMDQ), and SF-36 Quality of Life Questionnaire (SF36) were administered. RESULTS: According to the preoperative Cobb angles, the decrease in the 6th month (P = .029) and 12th month (P = .007) measurements after the operation was found to be statistically significant (P < .05), but it was found to be clinically insignificant. When the changes in RMDQ, OLBPDQ, VAS, and SF-36 scores were examined, the decrease in the 6th month (P = .001) and 12th month (P = .001) scores after the operation was found to be significant compared to the preoperative scores (P < .01). CONCLUSIONS: In this study, weight loss after SG improved for patients with chronic low back and back pain and significantly improved their quality of life.

Effects of Sleeve Gastrectomy on Pelvic Floor Disorders in Female Patients with Severe Obesity: a Prospective Study.

INTRODUCTION: Obesity is associated with pelvic floor disorders (PFD). Sleeve gastrectomy (SG) is one of the most effective weight loss methods. Although SG has been found to improve urinary incontinence (UI) and overactive bladder (OAB), its impact on fecal incontinence (FI) remains controversial. MATERIALS AND METHODS: This prospective, randomized study involved 60 female patients with severe obesity who were randomly assigned to two groups: the SG group and the diet group. The SG group underwent SG, while the diet group received a low-calorie, low-lipid diet for 6 months. The patients' condition was assessed before and after the study using three questionnaires: the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS), the Overactive Bladder 8-Question Awareness Tool (OAB-V8), and the Wexner Score (CCIS). RESULTS: After 6 months, the SG group had a significantly higher percentage of total weight loss (%TWL) compared to the diet group (p<0.01). Both groups showed a decrease in the ICIQ-FLUTS, OAB-V8, and CCIS scores (p<0.05). UI, OAB, and FI improved significantly in the SG group (p<0.05), but no improvement was observed in the diet group (p>0.05). The correlation between %TWL and PFD was statistically significant but weak, with the strongest correlation between %TWL and ICIQ-FLUTS score and the weakest correlation between %TWL and CCIS score (p<0.05). CONCLUSIONS: We recommend bariatric surgery for the treatment of PFD. However, given the weak correlation between %TWL and PFD after SG, further research should explore factors other than %TWL that are effective in recovery, particularly in relation to FI.

The Effects of Laparoscopic Sleeve Gastrectomy (LSG) on Obesity-Related Type 2 Diabetes Mellitus: a Prospective Observational Study from a Single Center.

PURPOSE: The objective of the study is to evaluate the effects of laparoscopic sleeve gastrectomy (LSG) on mid- to long-term regulation of blood glucose in patients with obesity and type 2 diabetes mellitus (T2DM) MATERIALS AND METHODS : In this prospective and observational single-center study, a total of 234 patients with obesity and a diagnosis of T2DM who underwent LSG between 2015 and 2020 were evaluated. The demographics and laboratory data, consisting of body mass index (BMI), glycosylated hemoglobin (HbA1c%), and fasting plasma glucose (FPG) and total weight loss (TWL%), were compared preoperative and postoperative at 12th and 18th months and annual follow-up for seven consecutive years. RESULTS: The mean age of 234 patients (female(n)/male(n):191/43) included in the study was 44.69±9.72 years, while the preoperative mean BMI, FPG, and HbA1c values were 47.9±6.82, 132.09±42.84 mg/dl, and 7.02±1.35% respectively. The mean rate of weight loss (TWL%), which was 34.7 in the 18 months, decreased to 23.15 in the 7th year. While the HbA1c % value was 7.02±1.35 in the preoperative, it was found 5.71 ± 0.75 (p<0.001) and 6.30 ± 1.77 (p<0.05) at the 18th month and 7th year after the operation, respectively. While the DM remission rate was 71.1% at the postoperative 18th month, it was 45.4% at the 7th year, despite the patients regaining weight in the follow-ups. CONCLUSIONS: Our study revealed that LSG resulted in high remission rates that continued for 7 years after the surgery, although sustained improvement or remission of diabetes despite some weight regain after the first 18 months.

Insulinoma Misdiagnosed as Post-bariatric Hypoglycemia: A Case Report and Review of the Literature.

Hypoglycemia is seen with increasing frequency after bariatric surgery. After the diagnosis of hypoglycemia has been clarified, malnutrition, drugs, hormone deficiencies, insulinoma, extra-islet tumors, post-bariatric hypoglycemia (PBH), early or late dumping syndrome, and nesidioblastosis should be considered in the differential diagnosis. A few case reports of insulinomas presenting after bariatric surgery have been reported in the literature. The coexistence of insulinoma and type 2 diabetes mellitus (T2D) is very rare. We herein report a clinical case of insulinoma presenting with severe hypoglycemia in a patient with a history of gastric transit bipartition. A patient with type 2 diabetes mellitus underwent gastric transit bipartition surgery due to the inability of medical therapy to provide adequate hyperglycemia control. After the operation, hypoglycemic symptoms appeared, and a reversal operation was performed, considering the diagnosis as PBH. After the reverse operation, the patient's hypoglycemia symptoms did not regress. The patient was admitted to our endocrinology clinic due to the persistence of hypoglycemia and symptoms such as fatigue, palpitation, and syncope. The patient's detailed anamnesis was examined, additional tests were performed, and the patient was diagnosed with insulinoma. The symptoms of hypoglycemia and the need for treatment for diabetes mellitus disappeared after the Whipple operation. This is the first case of insulinoma after gastric transit bipartition and subsequent reversal operations. In addition, the patient's diagnosis of diabetes mellitus makes this case unique. Although this is a very rare case, clinicians must be aware of it, especially if the patient has hypoglycemic symptoms during the fasting state.

Clinical Impact of Glucagon-Like Peptide-1 Receptor Analogs on the Complications of Obesity.

BACKGROUND: Obesity is a chronic disease associated with increased morbidity and mortality due to its complications. The aims of obesity treatment are primarily to accomplish weight loss, and prevention or treatment of its complications. Lifestyle changes along with behavioral therapy constitute the first-line treatment of obesity followed by pharmacotherapy. Glucagon-like peptide receptor analogs (GLP-1 RAs) are among the approved pharmacotherapy options. Their central effect on suppressing appetite results in considerable weight loss. However, their effect on the complications of obesity has not been very well recognized. This review aims to analyze the effects of GLP-1 RAs on the complications of obesity, as diabetes mellitus, hypertension, nonalcoholic steatohepatitis (NASH), cardiovascular diseases, polycystic ovary syndrome, infertility, obstructive sleep apnea (OSA), osteoarthritis, cancer and central nervous system problems. SUMMARY: Data from preclinical studies and clinical trials have been thoroughly evaluated. Effects regarding the complications as far as the scope of this review have covered can be summarized as blood glucose lowering, blood pressure lowering, resolution of NASH, improving major cardiovascular events, improving fertility and sex hormone levels, and improvement in OSA symptoms and in cognitive scores. Although the mechanisms are not fully elucidated, it is clear that the effects are not solely due to weight loss, but some pleiotropic effects like decreased inflammation, oxidative stress, and fibrosis also play a role in some of the complications. KEY MESSAGES: Treating obesity is not only enabling weight loss but ameliorating complications related to obesity. Thus, any antiobesity medication has to have some favorable effects on the complications. As far as the GLP-RA's analogs are concerned, there seems to be an improvement in many of the complications regardless of the weight loss effect of these medications.

Interobserver and Intraobserver Reliability in Sonoelastographic Assessment of Thyroid Nodules.

BACKGROUND: Thyroid ultrasonography is the first and perhaps most fundamental step for the radiological distinction of benign and malignant nodules. In this study, 2 radiologists reviewed the sonoelastographic and Doppler images of thyroid nodules and evaluated for the intraobserver and interobserver reliability. PURPOSE: We aimed to determine confusing nodule identifiers and sonographic features differently defined by observers. METHODS: A total of 157 nodules in 91 patients (male/female, 72:19) with ages ranging from 18 to 72 years old were included in the study. Ultrasonographic images and video clips of the nodules were obtained and presented to 2 reviewers unaware of the cytopathology results. Two observers defined the characteristics of the nodules based on previously determined criteria. Then, intraobserver and interobserver correlation coefficients were calculated for each subcategory. RESULTS: In the grayscale ultrasonographic examination, varying degrees from low to high interobserver correlation coefficients were obtained for different subcategories (between κ = 0.359 and κ = 0.821). In color Doppler examination, we obtained medium correlation coefficients ( κ = 0.493 and κ = 0.553). On the other hand, there was a high correlation coefficient in tissue compression elastography ( κ = 0.617 and κ = 0.638).According to our study results, elastographic pattern, shape of the nodule, presence of echogenic foci, and pathological lymph nodes are better predictors to determine the malignant potential of thyroid nodule with higher interobserver correlation. Therefore, these criteria may be used primarily for the evaluation of thyroid nodules. The intraobserver correlation coefficient was higher in the practitioner with longer experience, suggesting the importance of professional practice period on the decision-making process.

Vitamin D receptor and estrogen receptor gene polymorphisms in men with type 2 diabetes: Effects on Bone Metabolism.

Purpose: There is an increased fracture risk in type 2 diabetes mellitus [DM] patients independent of bone mineral density [BMD], both in men and women. Estrogen receptor [ER]-alpha and vitamin D receptor [VDR] gene polymorphisms may predispose patients to increased osteoporosis and fracture risk. This study aims to analyze the relationship of the ER-alpha gene and VDR gene polymorphisms with indicators of bone turnover and BMD in male type 2 diabetic patients. Methods: Type 2 diabetic men diagnosed with diabetes for at least one year and healthy controls were included in this cross-sectional study. BMD was measured by dual X ray absorptiometry. Gene polymorphisms were evaluated with polymerase chain reaction-restriction length polymorphism. Serum iPTH, calcium, beta-CrossLaps (cTx), osteocalcin, and free testosterone levels were also evaluated. Results: Participants were 141 type 2 diabetic men [55 ± 8 years] and 100 healthy controls [53 ± 7 years]. BMD measurements were not statistically different between the groups. While iPTH [p < 0.05] and serum calcium levels [p = 0.03] were higher in men with type 2 DM; beta-CrossLaps [p = 0.0001], osteocalcin [p = 0.005], and free testosterone [p = 0.04] were lower than controls. The differences in terms of the frequencies of VDR Apa, Taq, Bsm, Fok and ER-alpha polymorphisms were not statistically significant between the groups. No relationship was observed between polymorphisms and BMD in both groups. Conclusions: VDR and ER-alpha gene polymorphisms seem to have no effect on BMD and bone turnover in men with DM.

Impact of Gestational Weight Gain on Maternal and Perinatal Outcomes After Laparoscopic Sleeve Gastrectomy.

PURPOSE: This study aimed to evaluate the impact of gestational weight gain (GWG) after laparoscopic sleeve gastrectomy (LSG) on maternal and perinatal outcomes according to the Institute of Medicine (IOM) recommendations. MATERIALS AND METHODS: A retrospective, multicenter, observational study of pregnant women who had undergone LSG between 2012 and 2021 was conducted. According to the IOM criteria, GWG was grouped as insufficient, appropriate, and excessive. RESULTS: A total of 119 pregnancies were included in this study. GWG was appropriate in 28 (23.5%), insufficient in 32 (26.9%), and excessive in 59 (49.6%) of the cases. The time from operation to conception was significantly longer in the excessive group than in the insufficient (P = 0.000) and appropriate groups (P = 0.01). The mean GWG was significantly higher in the excessive group than in the appropriate (P = 0.000) and insufficient groups (P = 0.000). When the groups were evaluated according to the IOM recommendations, no statistically significant difference were found between the groups regarding birthweight, gestational age (GA), preterm birth, and whether their child was small or large for their gestational age. Furthermore, there were no differences in terms of anemia and ferritin deficiency level at early pregnancy and predelivery between the groups. CONCLUSION: The GWG after LSG did not impact maternal and perinatal outcomes.

Development of a SERS based cancer diagnosis approach employing cryosectioned thyroid tissue samples on PDMS.

An efficient SERS based novel analytical approach named Cryosectioned-PDMS was developed systematically and evaluated applying on 64 thyroid biopsy samples. To utilize thyroid biopsy samples, a 20-µl volume of h-AgNPs suspension was dropped on a 5-µm thick cryosectioned biopsy specimen placed on the PDMS coated glass slide. The SERS spectra from a 10 × 10 points array acquired by mapping 22.5 µm × 22.5 µm sized area from suspended dried droplets placed on the tissue surface. The probability of correctly predicted performance for diagnosis of malignant, benign and healthy tissues was resulted in the accuracy of 100 % for the spectral bands at 667, 724, 920, 960, 1052, 1096, 1315 and 1457 cm-1 using PCA-fed LDA machine learning. The Cryosectioned-PDMS biophotonic approach with PCA-LDA predictive model demonstrated that the vibrational signatures can accurately recognize the fingerprint of cancer pathology from a healthy one with a simple and fast sample preparation methodology.

Normalisation of serum TSH doesn't represent true euthyroidism for patients on levothyroxine treatment.

OBJECTIVE: To evaluate whether normalisation of serum thyroid-stimulating hormonelevels with levothyroxine is related with metabolic parameters and psychologic wellbeing. METHODS: The observational, case-control study was conducted from to May to July 2019 in the outpatient thyroid clinics of Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey, and comprised of hypothyroid patients in the euthyroid state with levothyroxine treatment and euthyroid controls. Psychological wellbeing was assessed using the General Health Questionnaire-12, and metabolic parameters with lipid levels and body composition were analysed for both the groups. Data was analysed using SPSS 25. RESULTS: Of the 159 subjects, 110(69%) were cases with a mean age of 50.1±11.7 years, and 49(31%) were controls with a mean age of 47.3±15.2 years. There was no significant difference related to thyroid-stimulating hormone levels between the groups (p=0.191). Free throxine levels were significantly higher in the cases, while free triiodothyroinine levels were higher in the controls (p<0.001). Total cholesterol and triglycerides levels were significantly higher in the cases than the controls (p<0.05). The cases had lower basal metabolic rate and fat free mass than the controls, but the difference was not significant (p>0.05). The cases scored higher in terms of wellbeing than the controls, but the difference was not significant (p>0.05). CONCLUSIONS: Thyroid hormone replacement needs to be adjusted to provide a satisfactory treatment for hypothyroid patients with normal thyroid-stimulating hormone levels who remain clinically and biochemically asymptomatic. In symptomatic patients, peripheral parameters of hypothyroidism, such as lipid levels, physiological symptoms and quality of life, might be useful in determining the levothyroxine dose and bringing the thyroid-stimulating hormone level within the normal range.

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.

Effect of Exenatide Use on Cognitive and Affective Functioning in Obese Patients With Type 2 Diabetes Mellitus: Exenatide Use Mediates Depressive Scores Through Increased Perceived Stress Levels.

PURPOSE/BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a molecule used to treat type 2 diabetes mellitus (T2DM). Given their widespread expression in the nervous system, GLP-1 receptors also play a role in regulating mood and cognitive function. Here, we aimed to compare obese patients with T2DM, with or without exenatide (a GLP-1R agonist) use on cognitive and affective functioning. METHODS/PROCEDURES: A total of 43 patients with T2DM (23 on exenatide and 20 without exenatide) were evaluated with the Snaith-Hamilton Pleasure Scale, Cognitive Failures Questionnaire, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7, Childhood Trauma Questionnaire, Perceived Stress Scale (PSS), and Chronic Stress Scale, in addition to laboratory-based measures of reward learning (the probabilistic reward task) and working memory (Letter-N-Back task). FINDINGS/RESULTS: Patients on exenatide had higher body mass index (BMI) (37.88 ± 5.44 vs 35.29 ± 6.30; P = 0.015), PHQ-9 (9.70 ± 4.92 vs 6.70 ± 4.66; P = 0.026), and PSS (29.39 ± 6.70 vs 23.35 ± 7.69; P = 0.015) scores. Other stress scales (Childhood Trauma Questionnaire and Chronic Stress Scale), Generalized Anxiety Disorder-7 scores, response bias, or discriminability as assessed by probabilistic reward task and self-report (Cognitive Failures Questionnaire) and laboratory-based (Letter-N-Back) cognitive measures were not significantly different between groups (both Ps > 0.05). Multivariate linear regression analyses adding BMI and PSS as covariates revealed that although BMI had no effect (P = 0.5), PSS significantly predicted PHQ-9 scores (P = 0.004). Mediation analysis showed that exenatide users reported higher PSS, with greater PSS associated with higher PHQ-9 levels (b = 0.236). There was no evidence on exenatide directly influencing PHQ-9 independent of PSS (c' = 1.573; P = 0.305; 95% bootstrap confidence interval, -1.487 to 4.634). IMPLICATIONS/CONCLUSIONS: Based on previous research and our findings, exenatide use might be mediating depression scores through disrupting stress responses.

Effects of Treatment Adherence on Quality of Life in Hypoparathyroid Patients.

OBJECTIVES: This study aimed to evaluate the current situation of hypoparathyroid patients and to investigate the relationship between treatment adherence and quality of life. STUDY DESIGN: Prospective, multicentre study. METHODS: Adult patients presenting with the diagnosis of hypoparathyroidism to 20 different endocrinology clinics were included. They were receiving conventional therapies for hypoparathyroidism, using calcium, active vitamin D, and magnesium. We collected data on demographic features, disease- and treatment-related information, and results of routine laboratory tests, treatment adherence, and presence of complications. Beck Depression Inventory, Beck Anxiety Inventory, and Short Form-36 quality of life assessments were administered. RESULTS: Among the 300 patients studied, 60.7% were adherent to their treatment, and 34.1% had complications. Anxiety and depression scores were significantly higher in non-adherent versus treatment-adherent patients (p<0.001 and p=0.001, respectively). Most of the domains of quality-of-life scores were also significantly lower in non-adherent patients. Both anxiety and depression scores showed significant, negative correlations with serum calcium and magnesium concentrations (r=-0.336, p<0.001 and r=-0.258, p<0.001, respectively). CONCLUSIONS: Nearly 40% of the patients were non-adherent to conventional treatment for hypoparathyroidism, and such patients had higher anxiety and depression scores and poorer quality of life scores. Conventional treatment might not be sufficient to meet the needs of patients with hypoparathyroidism. In addition to seeking new therapeutic options, factors influencing quality of life should also be investigated and strategies to improve treatment adherence should be developed.

Patterns and preferences of antidiabetic drug use in Turkish patients with type 2 diabetes - A nationwide cross-sectional study (TEMD treatment study).

AIMS: The treatment preferences in type 2 diabetes (T2DM) are affected by multiple factors. This survey aims to find out the profiles of the utilization of antidiabetics and their determinants. METHODS: The nationwide, multicenter TEMD survey consecutively enrolled patients with T2DM (n = 4678). Medications including oral antidiabetics (OAD) and injectable regimens were recorded. Multiple injectable regimens with or without OADs were defined as complex treatments. RESULTS: A total of 4678 patients with T2DM (mean age: 58.5 ± 10.4 years, 59% female) were enrolled. More than half of patients (n = 2372; 50.7%) were using injectable regimens with or without OADs, and others (n = 2306, 49.3%) were using only OADs. The most common OADs were metformin (93.5%), secretagogues (40.1%), and DPP-4 inhibitors (37.2%). The rates of the use of basal, basal-bolus and premix insulin were 26.5%, 39.5% and 22.4%, respectively. Patients using OADs achieved better glycemia, blood pressure and weight control (p < 0.001 for all) but poorer LDL-C control (p < 0.001). The independent associates of complex treatments were diabetes duration, obesity, eGFR, glycated haemoglobin, macro and microvascular complications, education level, and self-reported hypoglycemia. CONCLUSION: This study is the first nationwide report to show that almost half of the patients with T2DM are using injectable regimens in Turkey.

Clinical and demographic aspects of Paget disease of bone: A multicentric study from Turkey.

OBJECTIVE: Paget disease of bone (PDB) is a metabolic bone disease that has been rarely reported in the Eastern countries. This study aimed to evaluate the clinical and demographic characteristics of patients with PDB followed up at endocrinology clinics in Turkey. METHODS: An invitation was sent to tertiary endocrinology clinics to complete a survey on the demographic, clinical, radiological, and laboratory parameters, as well as treatment modalities of patients with PDB. This study enrolled clinically and radiologically proven 185 patients with PDB from 18 endocrinology centers based in 10 cities of Turkey. RESULTS: This cohort of PDB had female preponderance (women/men: 105/80) with a mean age, during diagnosis, of 57±10 years. Most of the patients (59.6%) were symptomatic at diagnosis. Bone pain and headache were the predominant clinical symptoms. Polyostotic disease was observed in 67.5% (n=125) of patients. Frequently affected bones were skull (41.6%), pelvis (53.5%), spine (41%), and femur (25.4%). Moreover, 17 patients with skull involvement had hearing loss. Mean serum alkaline phosphatase (ALP) level (552±652 IU/L; range: 280-5762 IU/L) was over the normal reference cutoff with normal serum calcium levels. Intravenous bisphosphonates (zoledronic acid, 5 mg; pamidronate, 60-90 mg) were the most used drugs (75%) for the treatment of PDB. Most of the patients (87.1%) treated with intravenous bisphosphonates responded well, with a decrease in serum ALP level (117±114 IU/L) in the 12th month of therapy. Furthermore, 16 patients relapsed after the second year of therapy; 3 patients did not respond to the initial intravenous bisphosphonate treatment. CONCLUSION: The patients with PDB followed up by endocrinology clinics of Turkey exhibited polyostotic disease with classical clinical, radiological, and biochemical features and women's predominance with good response to intravenous bisphosphonate therapy.

Sensitive Sequencing Analysis Suggests Thyrotropin Receptor and Guanine Nucleotide-Binding Protein G Subunit Alpha as Sole Driver Mutations in Hot Thyroid Nodules.

Background: Constitutively activating mutations in the thyrotropin receptor (TSHR) and the guanine nucleotide-binding protein G subunit alpha (GNAS) are the primary cause of hot thyroid nodules (HTNs). The reported prevalence of TSHR and GNAS mutations in HTNs varies. Previous studies show TSHR mutations in 8-82% of HTNs and GNAS mutations in 8-75% of HTNs. With sensitive and comprehensive targeted next-generation sequencing (tNGS), we re-evaluated the prevalence of TSHR and GNAS mutations in HTNs. Methods: Samples from three previous studies found to be TSHR and GNAS mutation negative were selected and re-evaluated using high-resolution melting (HRM) PCR. Remaining mutation negative samples were further reanalyzed by tNGS with a sequencing depth between 3000 × and 10,000 × . Our tNGS panel covered the entire TSHR coding sequence along with mutation hot spots in GNAS. Sequencing reads were aligned to reference and variants were called using Torrent Suite software v5.8. Results: In total, 154 of 182 previously mutation negative HTNs were positive for TSHR or GNAS mutations, resulting in an 85% prevalence of TSHR and GNAS mutations in HTNs, 79% and 6%, respectively. In a subset of 25 HTNs with multiple samples per nodule, and analyzed by tNGS at high sequencing depth, TSHR mutations were detected in 23 (92%) HTNs and 1 GNAS mutation was detected in 1 (4%) HTN, 96% mutation positive HTNs in this subset. Conclusions: Owing to the higher sensitivity of tNGS as compared with denaturing gradient gel electrophoresis and HRM-PCR, TSHR or GNAS mutations could be detected in 85% of HTNs. The detection of TSHR and GNAS mutations occurred in 96% of HTNs in a sample set with multiple samples per nodule analyzed by tNGS. Taken together with the fact that no other driver mutations could be identified by whole exome sequencing, our study strongly supports the hypothesis that TSHR and GNAS mutations are the main somatic mutations leading to HTNs.

Insulin autoimmune syndrome - time to remember.

Not required for Clinical Vignette.

Efficacy and safety of dapagliflozin on diabetic patients receiving high-doses of insulin.

OBJECTIVE: In this study we aimed to investigate the efficacy and safety of dapagliflozin addition to diabetic patients using high dose insulin. METHODS: The current study was carried out in the outpatient diabetic clinics of Fatih Sultan Mehmet Education and Research Hospital. Thirty diabetic patients who were receiving high dose (>0,5U/kg) insulin and oral antidiabetic treatment (other than SGLT 2 inhibitors) were included in this study. Primary end point was the change in HbA1c, insulin doses and serum electrolyte from the addition of dapagliflozin 10 mg to the week 12. RESULTS: At the end of three month BMI were obviously decreased from 33.31 ±4.51 to 32.14 ±4.66 (p: 0.001). There was also an evident decrease of insulin requirement from 76 ±23.15 U/kg to 57.60 ±17.61 U/day (p<0.001). As well as the decrease in insulin doses, there was also a significant decline in HbA1c (Δ 1.6 %) and fasting blood glucose levels (Δ68.6 mg/dl) (p<0.001). Among serum electrolyte levels slight but meaningful increase of blood urea nitrogen (BUN) and sodium (Na) levels were seen (p: 0.044 and p: 0.026). There were no significant changes in serum cholesterol levels with electrolytes such as potassium, calcium, phosphorus magnesium and vitamin D (p> 0.05). CONCLUSION: In diabetic patients with inadequately controlled glucose regulation despite high-dose insulin therapy, dapagliflozin may be an alternative combination choice to decrease the need of insulin dose and obtain an optimal HbA1c, fasting plasma glucose levels and weight without major side effects.