Previous, simultaneous, or subsequent occurrence of malignant tumours in patients with primary hyperparathyroidism: a closer look at the single-tertiary-centre cases.

INTRODUCTION: Our aims were to explore the relationship between primary hyperparathyroidism (pHPT) and malignant tumour development, to determine the frequency and the time of occurrence of malignant tumours in patients with pHPT, and to evaluate the characteristics of pHPT in these patients. MATERIAL AND METHODS: This retrospective cohort study included consecutive individuals who were diagnosed with pHPT aged 18 years or older in a university hospital during a 7-year period. A total of 198 patients with pHPT were reviewed retrospectively. Demographic, clinical, biochemical, radiologic findings, and histopathological diagnosis were collected from the electronic medical records of the hospital system. RESULTS: The mean age of the study population was 58 ± 13 years and was predominantly female (female/male: 162/36). There were 42 (21.2%) patients with malignant tumours. Five (12%) out of 42 patients had metachronous double malignancies. The most common 2 concurrent malignancies were breast (36.1%) and thyroid (17.0%). Sixty-eight per cent of the malignant tumours occurred before the diagnosis of pHPT. A higher percentage (87.5%) of simultaneous tumours was seen in the thyroid gland. No statistically significant differences were observed between patients with and without malignant tumours in terms of demographic, clinical, biochemical, radiological, and histopathological features. The median follow-up duration was 24 months after parathyroid surgery. CONCLUSION: The results of this study revealed that pHPT was associated with various tumour types. The frequency of malignant tumours was 21.2%. Breast and thyroid cancers were the most common 2 cancers coexisting with pHPT. A large percentage of malignant tumours occurred before the diagnosis of pHPT. A higher percentage of simultaneous tumours was seen in the thyroid gland. pHPT patients with and without malignant tumours seemed to have similar characteristics.

Early Post-operative Stimulated Serum Thyroglobulin: Role in Preventing Unnecessary Radioactive Iodine Treatment in Low to Intermediate Risk Papillary Thyroid Cancer.

AIM: The aims of the study are to evaluate the predictive value of early post-operative stimulated thyroglobulin (sTg) analysis on the recurrence risk, and to define a cut-off value that is related to recurrence risk in low to intermediate risk papillary thyroid cancer (PTC). METHODS: This retrospective cohort study included individuals who were diagnosed with PTC aged 18 years or older and had been operated by experienced surgeons of a tertiary university hospital between the years 2011 and 2021. The American Thyroid Association thyroid cancer guidelines version 2015 was used as the risk stratification system. Early sTg measurement obtained at 3-4 weeks after surgery when TSH >30 µIU/mL. Data was collected from the hospital database. A total of 328 patients who had post-operative early sTg values with negative anti-Tg antibodies were included. RESULTS: The median age was 44 years. Of the 328 patients, 223 (68%) were women. The median tumor diameter was 11 mm. One hundred ninety-one patients (58.2%) had low risk and 137 (41.8%) had intermediate risk for recurrent disease. Of the 328 patients, 4.0% had recurrent disease. In multivariate Cox regression, post-operative early sTg value [OR: 1.070 (1.038-1.116), P = .000], and the pre-operative malign cytology [OR: 1.483 (1.080-2.245), P = .042] were independent risk factors for recurrence. On the ROC curve analysis, the cut-off value of early sTg was 4.1 ng/mL for those with recurrent disease. CONCLUSION: This study demonstrated that early sTg could predict recurrent disease in patients with low to intermediate risk PTC. A cut-off of 4.1 ng/mL was identified with a high negative predictive value.

Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.

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

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.

Is obesity paradox valid for critically-ill COVID-19 patients with respiratory failure?

OBJECTIVE: We aimed to analyze the association between body mass index and mortality in patients with coronavirus disease 2019 induced acute respiratory distress syndrome. MATERIAL AND METHODS: In this retrospective cohort study, we analyzed 108 consecutive patients admitted in the intensive care unit for coronavirus disease 2019-induced lung disease in a single center between March 2020 and February 2021. Coronavirus disease 2019 infection was confirmed by real-time reverse transcription-polymerase chain reaction assay of nasal swabs or lower respiratory tract samples. Acute respiratory distress syndrome was defined using Berlin criteria. Acute respiratory distress syndrome severity was assessed with partial pressure of arterial oxygen/fraction of inspired oxygen ratio. We categorized patients according to the body mass index as underweight, <18.5 kg/m2; normal weight, from 18.5 kg/m2 to <25 kg/m2; overweight, from 25 kg/m2 to <30 kg/m2; obese, ≥30 kg/m2. Clinical characteristics and mortality were compared among groups. Demographic and clinical data were collected from electronic medical records of the hospital system. RESULTS: The mean age was 67.3 ± 13.3 years. Study participants were predominantly males (66.7%). The mean BMI was 28.2 ± 5.6 kg/m2. There were 2 patients (2%), 28 (26%), 42 (39%), and 36 patients (33%) in the underweight, normal-weight, overweight, and obese groups, respectively. The hospital mortality was 40.7%. There was no association between body mass index and mortality (P = .09). In multivariate analysis, mortality was associated with the presence of cancer [odds ratio = 7.338 (1.636-32.914), P = .009], and time between diagnosis and intubation [odds ratio = 1.318 (1.150-1.509), P ≤ .001]. CONCLUSION: Neither acute respiratory distress syndrome severity nor mortality was higher in patients with higher body mass index compared to the ones with normal body mass index.

The frequency of acceptance of oral glucose tolerance test in Turkish pregnant women: A single tertiary center results.

Objective: It is thought that there is not enough data about the frequency of acceptance of oral glucose tolerance test (OGTT) in Turkish pregnant women. The aim of this study was to investigate the frequency of acceptance of OGTT among participants in our single tertiary center. Methods: The data of non-diabetic 344 pregnant women seen at the Obstetrics Clinic of our hospital between September 2016 and September 2017 were obtained from the hospital records. Women who did not have regular follow-up during pregnancy were excluded. One of the two or one-step approaches was used in the diagnosis of gestational diabetes mellitus (GDM) depending on the choice of the physician following the patient. Results: There were 223 subjects eligible for the study. One hundred seventy-seven pregnant women (79.4%) accepted to do OGTT. We determined that 46 women (20.6%) did not complete at least one OGTT, of whom 74% (n=34) never completed the recommended screening test in this cohort. The overall frequency of GDM was approximately 15.2% (n=34). OGTT acceptability was higher among pregnant women with university graduates (p=0.02). Adverse pregnancy outcomes were similar between the accepted and rejected groups. Among the reasons for OGTT rejection, the media had a significant influence (n=35). Conclusion: Our results show that a significant percentage of patients refused to do OGTT. Therefore the actual frequency of pregnant women with GDM could not be determined. One way to increase compliance may be recommending only the one-step test for pregnant women in countries with a high rejection rate of OGTT.

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.

The Role of Obesity in Predicting the Clinical Outcomes of COVID-19.

INTRODUCTION: The aim of this was to describe the predictors of mortality related to COVID-19 infection and to evaluate the association between overweight, obesity, and clinical outcomes of COVID-19. METHODS: We included the patients >18 years of age, with at least one positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction. Patients were grouped according to body mass index values as normal weight <25 kg/m2 (Group A), overweight from 25 to <30 kg/m2 (Group B), Class I obesity 30 to <35 kg/m2 (Group C), and ≥35 kg/m2 (Group D). Mortality, clinical outcomes, laboratory parameters, and comorbidities were compared among 4 groups. RESULTS: There was no significant difference among study groups in terms of mortality. Noninvasive mechanical ventilation requirement was higher in group B and D than group A, while it was higher in Group D than Group C (Group B vs. Group A [p = 0.017], Group D vs. Group A [p = 0.001], and Group D vs. Group C [p = 0.016]). Lung involvement was less common in Group A, and presence of hypoxia was more common in Group D (Group B vs. Group A [p = 0.025], Group D vs. Group A [p < 0.001], Group D vs. Group B [p = 0.006], and Group D vs. Group C [p = 0.014]). The hospitalization rate was lower in Group A than in the other groups; in addition, patients in Group D have the highest rate of hospitalization (Group B vs. Group A [p < 0.001], Group C vs. Group A [p < 0.001], Group D vs. Group A [p < 0.001], Group D vs. Group B [p < 0.001], and Group D vs. Group C [p = 0.010]). CONCLUSION: COVID-19 patients with overweight and obesity presented with more severe clinical findings. Health-care providers should take into account that people living with overweight and obesity are at higher risk for COVID-19 and its complications.

Concomittant occurence of well-differentiated thyroid carcinoma metastasis and chronic lymphocytic leukemia in the same lymph node along with internal jugular vein thrombus: a case report.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common adult leukemia. The coexistence of CLL and papillary thyroid carcinoma (PTC) is extremely rare. PTC sometimes shows microscopic vascular invasion but rarely cause a tumor thrombus in the internal jugular vein (IJV). It is also rare to find both differentiated and poorly differentiated types of thyroid cancer in the same metastatic location. We report a case of 63-year-old Turkish man with history of CLL who had CLL/SLL involvement and PTC metastasis in the same lymph node. Additionally, there was macroscopic metastasis to the IJV with poorly differentiated areas in the removed tumor thrombus. Patient was treated with total thyroidectomy, left radical neck dissection, resection of the left IJV segment that contained the tumor thrombus and radioactive iodine (RAI) therapy. Furthermore, metastatic lesions were found in the brain, lung and bone. Radiotherapy and chemotherapy were performed. However, our patient died approximately 12 months after thyroidectomy. To our knowledge, our present report is the first description with its current features.

The relationship between glycemic variability and blood pressure variability in normoglycemic normotensive individuals.

BACKGROUND AND AIM: Glycemic fluctuations around a mean glucose level, referred as glycemic variability and blood pressure variability (BPV) are considered as independent risk factors for cardiovascular diseases, all-cause mortality, and cardiovascular disease-mortality. With this background in mind, we aimed to investigate the association between glycemic variability and BPV and their association in normoglycemic and normotensive individuals. MATERIALS AND METHOD: Twenty-seven normotensive normoglycemic individuals were recruited. Twenty-four hour Holter devices were utilized to measure ambulatory blood pressure (BP) while continuous glucose monitoring (CGM) devices were applied to measure glycemic variability simultaneously to the subjects. These devices were kept on for 48 h. For BP recordings, daytime, nighttime, and 24-h BP determinations, their mean and SD were calculated. From CGM measurements, mean blood glucose (MBG), SD of blood glucose, the mean amplitude of glycemic excursions (MAGE), the mean of daily differences (MODD), coefficient of variation (correction of variability for the MBG), and daytime and nighttime blood glucose were determined. RESULTS: The mean age of the subjects was 23.8 ± 2.7 years and 66% were women (18/27). In the correlation analysis between glycemic variability parameters and BPV parameters, SD of 24-h SBP was correlated with the SD of MBG (r = 0.52, P = 0.006), MAGE (r = 0.49, P = 0.009), and MODD (r = 0.46, P = 0.015). SD of daytime SBP was correlated with, MAGE (r = 0.42, P = 0.03) and MODD (r = 0.43, P = 0.02). CONCLUSION: We report correlation between glycemic variability and BPV variables in normoglycemic and normotensive healthy individuals.

Association between BRAFV600E mutation and the clinicopathological features in incidental papillary thyroid microcarcinoma: A single-center study in Turkish patients.

OBJECTIVE: In this study, we evaluated the influences of BRAFV600E mutation on clinicopathological features in incidentally found papillary thyroid microcarcinomas (PTMCs). METHODS: This retrospective cohort study included 72 patients with PTMC who underwent surgery from 2008 to 2012. The mean follow-up of the whole cohort was three years. DNA was isolated using QIAamp DNA formalin-fixed, paraffin-embedded (FFPE) tissue kit. BRAF gene was amplified by the polymerase chain reaction-restriction fragment length (PCR-RFL) polymorphism method with the following primers. The clinicopathologic features (age, gender, histologic subtype, tumor size, presence of tumor capsule, bilaterality, multifocality, extrathyroidal extension (ETE), thyroid capsular invasion, presence of Hashimoto's thyroiditis, lymph node metastasis (LNM) and distant metastasis) were compared between the BRAF (+) and BRAF (-) patient groups. RESULTS: BRAFV600E mutation was detected in 30 of the 72 patients (41.6%). The presence of the mutation was statistically significantly associated with classic variant (p=0.046), invasion of thyroid capsule (p=0.002) and absence of tumor capsule (p=0.003). CONCLUSION: Although incidental PTMCs positive for the BRAFV600E mutation had more invasive behavior, the presence of the mutation was not associated with recurrences within three years of follow-up.

Empagliflozin-induced ketoacidosis in a patient presenting with new-onset type 2 diabetes mellitus due to indolent pancreatic cancer.

Not required for Clinical Vignette.

Effect of prophylactic central neck dissection on the surgical outcomes in papillary thyroid cancer: experience in a single center.

PURPOSE: Morbidity due to papillary thyroid carcinoma (PTC) is increased mostly due to lymph node (LN) metastases, which lead to reoperations and complications associated with these operations. The aim is to compare the outcomes of PTC having total thyroidectomy and prophylactic central lymph node dissection (TT + PCND) with patients having total thyroidectomy (TT) alone. METHODS: This study is a retrospective cohort analysis of 358 PTC patients that were operated by a single surgeon in a single center. Data about the patients were extracted from the medical records. RESULTS: Of the patient cohort, 258 patients had TT + PCND (42.5 ± 11.3 years) and 100 patients (41.2 ± 11.9 years) had only TT. Total number of LN extracted in the TT + PCND group was 8.1 ± 6.9. The mean number of metastatic LN were 2.2 ± 1.9. Percentage of patients that had RAI were less in the TT + PCND group compared to the TT group. Seven patients (2.7%) in the TT + PCND group and 19 (19.0%) in TT group had recurrent disease (p < 0.0001). Of the complications, only transient hypoparathyroidism was increased in TT + PCND group compared to TT group (26.7% vs 10%, p < 0.0001). CONCLUSION: TT + PCND performed by an experienced surgeon seems to decrease the number of LN recurrences, and the need for reoperations.

The clinicopathologic characteristics of familial and sporadic papillary thyroid carcinoma in Turkish patients

Background/aim: The aim of this study is to investigate clinicopathologic features of familial papillary thyroid carcinoma (fPTC) and compare them with sporadic papillary thyroid carcinoma (sPTC) in Turkish patients. A retrospective analysis of the papillary thyroid carcinoma (PTC) cases, with or without family history with a follow-up around 10 years was performed. Materials and methods: A series of patients with fPTC (82 fPTC families with 146 affected individuals) were compared with patients with sPTC (n = 112). The clinicopathologic features [(age, gender, histologic subtype, tumour size, bilaterality, multifocality, extrathyroidal extension (ETE), lymph node metastasis (LNM)] and treatment procedures (lymph node dissection, radioactive iodine ablation), and the outcomes like recurrences in the neck region, distant metastasis, and the need for reoperation were compared between the groups. Results: When the groups were compared, there was no significant difference in age (P = 0.449), and tumour size (P = 0.898) between familial and sporadic PTC patients. fPTC group had a significantly higher risk of male gender (P=0.001), bilaterality (P = 0.004), multifocality (P = 0.011), LNM (P = 0.013), ETE (P = 0.040), and distant metastasis (P ≤ 0.0001) than the sPTC group. However, recurrence rate was similar between the 2 groups (P = 0.436). Conclusion: The results of this study confirms a more aggressive nature in fPTC patients, in terms of bilaterality, multifocality, ETE, LNM, and distant metastasis, compared to sPTC patients in Turkish population.

Insulin Resistance, Obesity and Lipotoxicity.

Lipotoxicity , originally used to describe the destructive effects of excess fat accumulation on glucose metabolism, causes functional impairments in several metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. Lipotoxicity has roles in insulin resistance and pancreatic beta cell dysfunction. Increased circulating levels of lipids and the metabolic alterations in fatty acid utilization and intracellular signaling, have been related to insulin resistance in muscle and liver. Different pathways, like novel protein kinase c pathways and the JNK-1 pathway are involved as the mechanisms of how lipotoxicity leads to insulin resistance in nonadipose tissue organs, such as liver and muscle. Mitochondrial dysfunction plays a role in the pathogenesis of insulin resistance. Endoplasmic reticulum stress, through mainly increased oxidative stress, also plays important role in the etiology of insulin resistance, especially seen in non-alcoholic fatty liver disease. Visceral adiposity and insulin resistance both increase the cardiometabolic risk and lipotoxicity seems to play a crucial role in the pathophysiology of these associations.