Bilateral inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome: A reappraisal.

Cushing's syndrome (CS) is a rare disorder, once exogenous causes have been excluded. However, when diagnosed, the majority of cases are adrenocorticotropic hormone (ACTH)-dependent, of which a substantial minority are due to a source outside of the pituitary, ectopic ACTH syndrome (EAS). Differentiating among pituitary-dependent CS, Cushing's disease (CD) and an ectopic source can be problematic. Because non-invasive tests in the evaluation of CS patients often lack adequate sensitivity and specificity, bilateral inferior petrosal sinus sampling (BIPSS), a minimally invasive procedure performed during the investigation of ACTH-dependent CS, can be extremely helpful. BIPSS is considered to be the gold standard for differentiating CD from the EAS. Furthermore, although such differentiation may indeed be challenging, BIPSS is itself a complex investigation, especially in recent times due to the widespread withdrawal of corticotrophin-releasing hormone and its replacement by desmopressin. We review current published data on this investigation and, in the light of this and our own experience, discuss its appropriate use in diagnostic algorithms.

Comprehensive evaluation of body composition in a wide age range of Iranian adults using bioelectrical impedance analysis: Tehran Lipid and Glucose Study.

OBJECTIVE: To evaluate sex- and age-stratified body composition (BC) parameters in subjects with wide age range of 20-79 years. DESIGN: Cross-sectional. SETTING: Participants of Tehran Lipid and Glucose Study (TLGS). PARTICIPANTS: Two thousand nine hundred seventy participants met our inclusion criteria. They were divided into five age groups, and BC parameters were analysed based on sex and age using a bioelectrical impedance analyser (BIA). RESULT: The mean age of the participants was 42·1 ± 12·5 years, and 54 % of them were males. The mean BMI was 26·7 ± 3·7 kg/m2. Obesity indices were significantly higher in females (P < 0·001); however, skeletal muscle mass (SMM) and fat-free mass (FFM) were significantly higher in males (P < 0·001). Both SMM and FFM decreased significantly after the age of 50 years. Obesity indices significantly increased from the age group of 20-29 to 30-39 years in males and the age groups of 30-39 to 40-49 years and 40-49 to 50-59 years in females. The fat mass ratio (fat mass/SMM) showed two peaks in both sexes (after the ages of 30 and 50 years in males and 40 and 50 years in females). A strong correlation was found between BMI and percentage of body fat (r = 0·823 in females v. r = 0·768 in males). CONCLUSION: This is the first community-based study in the MENA region identifying sex- and age-stratified BC values using BIA. Our findings can be used as a reference for comparison in appropriate settings.

The effect of obesity phenotype changes on cardiovascular outcomes in adults older than 40 years in the prospective cohort of the Tehran lipids and glucose study (TLGS): joint model of longitudinal and time-to-event data.

BACKGROUND: Obesity is a worldwide health concern with serious clinical effects, including myocardial infarction (MI), stroke, cardiovascular diseases (CVDs), and all-cause mortality. The present study aimed to assess the association of obesity phenotypes and different CVDs and mortality in males and females by simultaneously considering the longitudinal and survival time data. METHODS: In the Tehran Lipid and Glucose Study (TLGS), participants older than three years were selected by a multi-stage random cluster sampling method and followed for about 19 years. In the current study, individuals aged over 40 years without a medical history of CVD, stroke, MI, and coronary heart disease were included. Exclusions comprised those undergoing treatment for CVD and those with more than 30% missing information or incomplete data. Joint modeling of longitudinal binary outcome and survival time data was applied to assess the dependency and the association between the changes in obesity phenotypes and time to occurrence of CVD, MI, stroke, and CVD mortality. To account for any potential sex-related confounding effect on the association between the obesity phenotypes and CVD outcomes, sex-specific analysis was carried out. The analysis was performed using packages (JMbayes2) of R software (version 4.2.1). RESULTS: Overall, 6350 adults above 40 years were included. In the joint modeling of CVD outcome among males, literates and participants with a family history of diabetes were at lower risk of CVD compared to illiterates and those with no family history of diabetes in the Bayesian Cox model. Current smokers were at higher risk of CVD compared to non-smokers. In a logistic mixed effects model, odds of obesity phenotype was higher among participants with low physical activity, family history of diabetes and older age compared to males with high physical activity, no family history of diabetes and younger age. In females, based on the results of the Bayesian Cox model, participants with family history of diabetes, family history of CVD, abnormal obesity phenotype and past smokers had a higher risk of CVD compared to those with no history of diabetes, CVD and nonsmokers. In the obesity varying model, odds of obesity phenotype was higher among females with history of diabetes and older age compared to those with no history of diabetes and who were younger. There was no significant variable associated with MI among males in the Bayesian Cox model. Odds of obesity phenotype was higher in males with low physical activity compared to those with high physical activity in the obesity varying model, whereas current smokers were at lower odds of obesity phenotype than nonsmokers. In females, risk of MI was higher among those with family history of diabetes compared to those with no history of diabetes in the Bayesian Cox model. In the logistic mixed effects model, a direct and significant association was found between age and obesity phenotype. In males, participants with history of diabetes, abnormal obesity phenotype and older age were at higher risk of stroke in the Bayesian Cox model compared to males with no history of diabetes, normal obesity phenotype and younger persons. In the obesity varying model, odds of obesity phenotype was higher in males with low physical activity, family history of diabetes and older age compared to those with high physical activity, no family history of diabetes and who were younger. Smokers had a lower odds of obesity phenotype than nonsmokers. In females, past smokers and those with family history of diabetes were at higher risk of stroke compared to nonsmokers and females with no history of diabetes in the Bayesian Cox model. In the obesity varying model, females with family history of diabetes and older ages had a higher odds of obesity phenotype compared to those with no family history of diabetes and who were younger. Among males, risk of CVD mortality was lower in past smokers compared to nonsmokers in the survival model. A direct and significant association was found between age and CVD mortality. Odds of obesity phenotype was higher in males with a history of diabetes than in those with no family history of diabetes in the logistic mixed effects model. CONCLUSIONS: It seems that modifications to metabolic disorders may have an impact on the heightened incidence of CVDs. Based on this, males with obesity and any type of metabolic disorder had a higher risk of CVD, stroke and CVD mortality (excluding MI) compared to those with a normal body mass index (BMI) and no metabolic disorders. Females with obesity and any type of metabolic disorder were at higher risk of CVD(, MI and stroke compared to those with a normal BMI and no metabolic disorders suggesting that obesity and metabolic disorders are related. Due to its synergistic effect on high blood pressure, metabolic disorders raise the risk of CVD.

Dietary determinants of healthy/unhealthy metabolic phenotype in individuals with normal weight or overweight/obesity: a systematic review.

Objectives: Nutritional factors are amongst the major determinants in the onset and development of obesity and metabolic complications. Nevertheless, the dietary determinants of metabolic health are not completely elucidated. The aim of this systematic review is to investigate nutritional and dietary factors that may contribute to metabolic heterogeneity in individuals with obesity or normal weight. Methods: A literature search was performed in PubMed, Scopus, EMBASE, and google scholar databases until August 2021, to locate studies that examined metabolic health and its association with intakes of specific foods or food groups, nutrient intakes or status, as well as adherence to certain dietary patterns. Two researchers had independently screened titles and abstracts, examined full-text studies, conducted data extraction, and evaluated their quality using the Newcastle-Ottawa Scale. Results: Twenty-seven studies, with a total of 39518 subjects, were included. Of these studies, 11 articles evaluated the association between different dietary patterns and metabolic phenotypes, while 15 had investigated the association of single food/nutrients intakes or nutrient status with metabolic phenotype, and one paper evaluated the association of dietary inflammatory index with metabolic health. The findings of these studies propose that healthy dietary patterns such as the Mediterranean pattern, Dietary Approaches to Stop Hypertension, and population-derived patterns (such as the "Healthy" and "Fruit and vegetable" patterns) were associated with higher odds of the metabolically healthy phenotype. Higher intakes of fruits, vegetables, dairy products, coffee/tea, vitamin D, magnesium, and flavonoids, were suggested to lower the risk of developing metabolically unhealthy phenotype, while, higher consumption of saturated fat, carbohydrate and sugar-sweetened beverages, fast foods, organ meats, and a pro-inflammatory diet increased the risk. Conclusion: Results from published studies, which were mostly cross-sectional, suggest that higher adherence to unhealthier dietary patterns, characterized by the consumption of refined and processed foods, was associated with a lower likelihood of having a healthy metabolic phenotype, while the opposite was observed for healthier dietary patterns. Findings may be used in developing nutritional strategies aimed at improving metabolic health in the population.

Cohort profile update: Tehran cardiometabolic genetic study.

The Tehran cardiometabolic genetic study (TCGS) is a large population-based cohort study that conducts periodic follow-ups. TCGS has created a comprehensive database comprising 20,367 participants born between 1911 and 2015 selected from four main ongoing studies in a family-based longitudinal framework. The study's primary goal is to identify the potential targets for prevention and intervention for non-communicable diseases that may develop in mid-life and late life. TCGS cohort focuses on cardiovascular, endocrine, metabolic abnormalities, cancers, and some inherited diseases. Since 2017, the TCGS cohort has augmented by encoding all health-related complications, including hospitalization outcomes and self-reports according to ICD11 coding, and verifying consanguineous marriage using genetic markers. This research provides an update on the rationale and design of the study, summarizes its findings, and outlines the objectives for precision medicine.

Comparing Effects of Bariatric Surgery on Body Composition Changes in Metabolically Healthy and Metabolically Unhealthy Severely Obese Patients: Tehran Obesity Treatment Study (TOTS).

BACKGROUND: Among two popular obesity phenotypes, metabolically healthy severely obese (MHSO) and metabolically unhealthy severely obese (MUSO), it is important to clarify whether or not those with MHSO phenotype would benefit from bariatric surgery in terms of an improvement in body composition parameters. METHODS: A prospective cohort was conducted on a total of 4028 participants (1404 MHSO and 2624 MUSO) who underwent bariatric surgery; MHSO was defined as having abnormalities in none or one of these four parameters: systolic blood pressure and/or diastolic blood pressure, triglycerides, fasting plasma glucose, and high-density lipoprotein. Otherwise, the definition of MUSO was met. Body composition analysis was performed at the baseline and 6-, 12-, 24-, and 36-month post-surgery using bioelectrical impedance analyzer. RESULTS: Both phenotypes showed a significant decrease in fat mass (FM) and fat-free mass (FFM) and a significant increase in EWL% and TWL% (Ptrend < 0.05). FFM, FM%, and excess weight loss (EWL%) were significantly different between the two phenotypes (Pbetween < 0.05) during the follow-up. Multivariate linear regression demonstrated that compared to MUSO patients, MHSO individuals experienced a greater increase in total weight loss (TWL%) and EWL% at 12- and 24-month and in EWL% at 36-month post-surgery and also a lower decrease in the FFML/WL% after 12 months. CONCLUSION: Despite a lower decrease of FFML/WL% and a greater increase in TWL and EWL in MHSO phenotype at some time points, there were no clinically significant differences between the study groups in terms of body composition changes throughout the follow-up period.

A Comparative Analysis of Safety and Efficacy of Bariatric Surgery During the COVID-19 Pandemic and Pre-Pandemic Period: Insights from the Tehran Obesity Treatment Study.

BACKGROUND: The COVID-19 pandemic has raised global health concerns and posed challenges for postoperative follow-up care for patients undergoing bariatric surgery due to social distancing rules. METHODS: This was a cohort study on patients with morbid obesity who underwent bariatric surgery and had been enrolled in Tehran Obesity Treatment Study. Patients who had surgery between March 2020 and March 2021 were classified as those undergoing the procedure amid the COVID-19 pandemic, while those who had surgery between March 2017 and March 2018 were categorized as the pre-pandemic group. RESULTS: The study included 982 patients in the pre-COVID-19 pandemic group and 602 patients in the COVID-19 pandemic group, with mean ages of 39.61 and 39.51 years, respectively. After adjusting for preoperative body mass index (BMI) and surgery type, the patients who underwent surgery during the COVID-19 pandemic demonstrated comparable results to the pre-COVID-19 group in terms of total weight loss %, excess weight loss %, BMI reduction, and fat mass reduction during the 12-month postoperative period. Additionally, the rate of complications with a grade≥III based on the Clavien-Dindo classification was significantly lower in patients who underwent surgery during the COVID-19 pandemic. Notably, there were no deaths reported in either group. CONCLUSION: Despite social isolation and unfavorable lifestyle modifications, bariatric surgery-induced weight loss after one year was the same in patients undergoing the procedure either before or after the implementation of social distancing measures. More research is needed to analyze the influence of the COVID-19 pandemic on the long-term outcomes of bariatric surgery.

Association between BMI trajectories from childhood to early adulthood and the carotid intima-media thickness in early adulthood: Tehran lipid and glucose study.

BACKGROUND AND AIMS: Childhood and adolescence overweight/obesity is an important predictor of obesity and increased long-term cardiometabolic abnormalities in adulthood. In this study, we aimed to investigate the association of body mass index (BMI) and waist circumference (WC) trajectories among children and adolescents with adulthood carotid intima-media thickness (cIMT) as a determinant of subclinical atherosclerosis. METHODS: In this prospective cohort study, 1265 participants aged 3 to 18 were followed up for 18 years. By using Latent Class Growth Analysis, three groups of BMI and WC trajectory were defined; low stable, moderate-increasing, and high-increasing. Linear and logistic regression analysis were used to investigate the association of each lifetime BMI and WC trajectory group with cIMT. RESULTS: Although the high-increasing BMI trajectory group was significantly associated with higher cIMT (ß=0.0464, P < 0.001), moderate-increase was not (ß=0.0096, P = 0.102); in reference to the low-stable BMI trajectory group. Among WC trajectory groups, both moderate- (ß=0.0177, P = 0.006) and high-increasing (ß=0.0533, P < 0.001), in reference to the low-stable group, were significantly associated with higher cIMT. The results did not change after adjustment for baseline BMI. The ORs of high-increasing BMI, moderate-increasing WC, and high-increasing WC trajectories were 3.24, 1.92, and 3.29, respectively for high cIMT. CONCLUSION: Our study resulted that a high-increasing trajectory of childhood BMI and moderate- and high-increasing trajectories of childhood WC are associated with higher cIMT and higher risk of high-cIMT. Regular monitoring and screening of BMI and WC trajectory from childhood may improve identifying individuals with high risks of cardiovascular disease, more accurately.

BMI category-specific waist circumference thresholds based on cardiovascular disease outcomes and all-cause mortality: Tehran lipid and glucose study (TLGS).

BACKGROUND: Waist circumference (WC), a representative of abdominal visceral fat, is strongly associated with cardiovascular disease (CVD) and its outcomes. We aimed to define body mass index (BMI)-specific WC thresholds as predictors of CVD and all-cause mortality. METHODS: In this prospective cohort study in the context of the Tehran Lipid and Glucose Study (TLGS), a total of 3344 men and 4068 women were followed up for 18 years. Based on BMI, the participants were categorized into three groups: BMI < 25, 25 < BMI < 30, and BMI > 30. In each BMI category, sex-specific WC thresholds were estimated by the maximum value of Youden's index to predict based on incident CVD events and all-cause mortality prediction. RESULTS: Overall 667 and 463 CVD events (the incidence rate of 3.1 to 4.5 in men and 1.1 to 2.6 in women per 1,000 person-years within BMI categories) and 438 and 302 mortalities (the incidence rate of 2.1 to 2.7 in men and 1.2 to 1.4 in women per 1,000 person-years within BMI categories) were recorded in men and women, respectively. WC thresholds in the BMI categories of < 25, 25-30, and BMI > 30 kg/m2 with regard to CVD events were 82, 95, and 103 cm in men and 82, 89, and 100 cm in women, and regarding all-cause mortality, the respective values were 88, 95, and 103 cm in men and 83, 90, and 99 cm among women. CONCLUSION: BMI-specific WC thresholds observed here can help to better identify individuals at high risk of developing CVDs.

Diet quality and anthropometric indices of patients undergone bariatric surgery: the prospective Tehran obesity treatment study.

BACKGROUND: Patients undergone bariatric surgery (BS) has long-term risks including decrease in diet quality, nutritional deficiencies and weight regain. This study focus on assessing dietary quality and food group components in patients one year after BS, the relationship between dietary quality score and anthropometric indices, and also evaluating the trend of body mass index (BMI) of these patients three years after BS. METHODS: A total of 160 obese patients (BMI ≥ 35 kg/m2) were undergone sleeve gastrectomy (SG) (n = 108) or gastric bypass (GB) (n = 52), participated in this study. They were assessed for dietary intakes using three 24-hour dietary recalls one year after surgery. Dietary quality was assessed using food pyramid for post BS patients and healthy eating index (HEI). Anthropometric measurements were taken pre-surgery and 1, 2 and 3 years after operation. RESULTS: The mean age of patients was 39.9 ± 11 years (79% female). The mean ± SD percentage of excess weight loss was 76.6 ± 21.0 one year after surgery. Intake patterns are generally (up to 60%) not consistent with the food pyramid. The mean total HEI score was 64 ± 12 out of 100. More than %60 of participants is exceeding the recommendations for saturated fat and sodium. The HEI score did not show significant relationship with anthropometric indices. The mean of BMI in SG group increased over three years of follow up, while in GB group, there were no significant differences in BMI during three years of follow up. CONCLUSIONS: These findings showed that patients had not healthy pattern intake one year after BS. Diet quality did not show significant relationship with anthropometric indices. The trend of BMI three years after surgery was different based on surgery types.

Patterns of change in obesity indices and other cardiometabolic risk factors before the diagnosis of type 2 diabetes: two decades follow-up of the Tehran lipid and glucose study.

BACKGROUND: Identifying patterns of variation in obesity indices and other cardiometabolic risk factors before the diagnosis of type 2 diabetes could provide insight into the critical period when drastic changes occurred and facilitate targeted interventions for the prevention of diabetes. Therefore, this study sought to explore patterns of change in obesity indices and other cardiometabolic risk factors before diabetes diagnosis. METHODS: We investigated 6305 participants (43.7% men) aged 20-65 from the Tehran Lipid and Glucose Study (TLGS) who were free of diabetes at baseline. First, we jointly estimated developmental multi-trajectories of obesity indices using multivariate latent class growth mixed model, and then patterns of cardiometabolic risk factors within the identified multi-trajectories were assessed using mixed-effects models. RESULTS: Three patterns of change in obesity indices were identified. Most participants belonged to the "progressing" group (83.4%; n = 742), with a slight but steadily rising in obesity indices until diagnosis in both men and women. All multi-trajectory groups showed similar exponential increases in fasting and 2-h plasma glucose concentrations 6 years before diagnosis and linear increases in blood pressure and total and LDL cholesterol throughout follow-up. Patterns of triglyceride and HDL cholesterol accompanied each group's patterns of change in obesity indices. CONCLUSION: Three patterns of the joint progression of obesity indices before diabetes diagnosis were accompanied by similar blood glucose patterns and other cardiometabolic risk factors. These findings suggest the impact of the increasing trend of obesity indices and other metabolic factors on the incidence of diabetes and emphasize the importance of assessing the metabolic risk factors at each visit.

The mediating role of bariatric surgery in the metabolic relationship between parathyroid hormone and 25-hydroxyvitamin D.

Vitamin D metabolism is altered in obese individuals. Our findings indicated that in patients with severe obesity, a relatively low 25(OH)D concentration was required to suppress PTH. The PTH inflection point increased following surgery-induced weight loss, highlighting 25(OH)D different regulation mechanisms in patients with obesity. INTRODUCTION: An optimal and sufficient concentration of 25-hydroxyvitamin D (25(OH)D) has been suggested as the level required to maximally suppress intact parathyroid hormone (iPTH). We evaluated the role of surgery-induced weight loss in determining the threshold(s) of 25(OH)D required to suppress iPTH. METHODS: This study was conducted in the framework of the Tehran Obesity Treatment Study (TOTS). We prospectively analyzed 687 patients with severe obesity who participated in the TOTS and underwent bariatric surgery from March 2013 to March 2019. The patients were followed for 1 year after surgery. Anthropometric parameters and serum levels of iPTH, 25OHD, phosphorous, and calcium were measured. Nonlinear and piecewise linear regression was used to evaluate the relationship between 25(OH)D and iPTH and to determine the 25(OH)D-suppression point at which iPTH was maximally suppressed. RESULTS: Body mass index was 44.6 kg/m2 at the baseline and decreased to 29.7 kg/m2 1 year after surgery (P < 0.05). Before the surgery, iPTH and 25(OH)D showed an exponential relationship; iPTH began to decrease rapidly at 25(OH)D concentration of 12 ng/mL, reaching maximal suppression at 30 ng/mL. However, the relationship between 25(OH)D and iPTH was non-exponential 1 year after surgery. The piecewise linear regression model revealed the 25(OH)D concentration of 21 ng/mL as the inflection point following surgery-induced weight loss. CONCLUSION: In patients with severe obesity, PTH was suppressed at a relatively lower concentration of 25(OH)D; this threshold increased following surgery-induced weight loss. These findings suggest a role for bariatric surgery in regulating 25(OH)D metabolism in patients with obesity.

Diagnostic accuracy of bilateral inferior petrosal sinus sampling using desmopressin or corticotropic- releasing hormone in ACTH-dependent Cushing's syndrome: A systematic review and meta-analysis.

The current gold standard diagnostic method for Cushing disease (CD) is bilateral inferior petrosal sinus sampling (BIPSS) after corticotropin-releasing hormone (CRH) stimulation. Due to shortages of CRH, BIPSS has been performed with desmopressin (DDAVP) instead. The objective of this systematic review and meta-analysis was to estimate the diagnostic accuracy of BIPSS using DDAVP or CRH for the differential diagnosis of Cushing's syndrome (CS). A literature review was done in PubMed, Scopus, EMBASE, and google scholar databases to derive summary estimates of the overall diagnostic sensitivity and accuracy of BIPSS using DDAVP or CRH in Cushing's syndrome. Pooled sensitivity, specificity, diagnostic odds ratio and summary receiver operating characteristic curves (SROC) for differential diagnosis of Cushing's syndrome in the random-effects models, were computed. Overall, 11 different studies with a total of 612 participants, were eligible for the analysis. Five articles with data on BIPSS using DDAVP, 5 papers on BIPSS using CRH, and another one evaluated the results of stimulation using DDAVP, with or without CRH, for differential diagnosis of Cushing's syndrome. The pooled (95% CI) sensitivity and specificity of BIPSS using DDAVP, were 96% (91-98%) and 1.00 (0.00-1.00), respectively. The area under the SROC curve was 0.95. The pooled (95% CI) sensitivity and specificity of BIPSS using CRH, were 98% (92-99%) and 1.00 (0.00-1.00), respectively, and the area under the SROC curve was 0.98. The I2 index (95% CI) was 0% (0-100%) for both BIPSS using DDAVP and using CRH. As a result, DDAVP stimulation is a safe, effective, less expensive, valuable and available alternative to CRH in the setting of BIPSS for all age groups of patients with CS. Registration code in PROSPERO: CRD42021292531.

Mental health and quality of life in different obesity phenotypes: a systematic review.

OBJECTIVES: It has been suggested that obesity phenotypes are related to mental health problems and health-related quality of life (HRQoL). However, there is no certain consensus. This systematic review aimed to evaluate the association between different obesity phenotypes with common psychiatric symptoms and HRQoL. METHODS: Electronic databases i.e. PubMed, Scopus, EMBASE, and google scholar were searched until September 2021, to identify studies that investigated associations between the obesity phenotypes with psychiatric symptoms and/or mental and physical HRQoL. Two researchers independently checked titles and abstracts, evaluated full-text studies, extracted data, and appraised their quality using the Newcastle-Ottawa Scale. RESULTS: Eighteen studies, with a total of 3,929,203 participants, were included. Of the studies included in this systematic review, 10 articles evaluated the association between obesity phenotypes and psychiatric symptoms, while six papers investigated the association between HRQoL and obesity phenotypes, and two studies assessed both. As a whole, the findings of these studies suggest that obese individuals with a favorable metabolic profile have a slightly higher risk of mental health problems and poor quality of life, however, the risk becomes larger when obesity is combined with an adverse metabolic profile. So, metabolically healthy obesity may not be a completely benign condition in relation to mental disorders and poor quality of life. CONCLUSION: According to published research, obesity is likely to increase the risk of mental health problems and poor quality of life when metabolic disturbances are present.

MRI-negative Cushing's Disease: Management Strategy and Outcomes in 15 Cases Utilizing a Pure Endoscopic Endonasal Approach.

BACKGROUND: Cushing's disease (CD) is among the most common etiologies of hypercortisolism. Magnetic resonance imaging (MRI) is often utilized in the diagnosis of CD, however, up to 64% of adrenocorticotropic hormone (ACTH)-producing pituitary microadenomas are undetectable on MRI. We report 15 cases of MRI negative CD who underwent surgical resection utilizing a purely endoscopic endonasal approach. METHODS: Endoscopic endonasal transsphenoidal surgery (EETS) was performed on 134 CD cases by a single surgeon. Fifteen cases met inclusion criteria: no conclusive MRI studies and no previous surgical treatment. Data collected included signs/symptoms, pre- and post-operative hormone levels, and complications resulting from surgical or medical management. Data regarding tumor diameter, location, and tumor residue/recurrence was obtained from both pre- and post-operative MRI. Immunohistochemistry was performed to assess for tumor hormone secretion. RESULTS: Aside from a statistically significant difference (P = 0.001) in histopathological results between patients with negative and positive MRI, there were no statistically significant difference between these two groups in any other demographic or clinical data point. Inferior petrosal sinus sampling (IPSS) with desmopressin (DDAVP®) administration was performed on the 15 patients with inconclusive MRIs to identify the origin of ACTH hypersecretion via a central/peripheral (C/P) ratio. IPSS in seven, five and three patients showed right, left, and central side lateralization, respectively. With a mean follow-up of 5.5 years, among MRI-negative patients, 14 (93%) and 12 patients (80%) achieved early and long-term remission, respectively. In the MRI-positive cohort, over a mean follow-up of 4.8 years, 113 patients (94.9%) and 102 patients (85.7%) achieved initial and long-term remission, respectively. CONCLUSIONS: Surgical management of MRI-negative/inconclusive Cushing's disease is challenging scenario requiring a multidisciplinary approach. An experienced neurosurgeon, in collaboration with a dedicated endocrinologist, should identify the most likely location of the adenoma utilizing IPSS findings, followed by careful surgical exploration of the pituitary to identify the adenoma.

Transition from metabolically healthy to unhealthy overweight/obesity and risk of cardiovascular disease incidence: A systematic review and meta-analysis.

AIMS: Discrepant results have been demonstrated regarding the cardiovascular (CV) risk of populations with metabolically healthy overweight/obesity (MHO) who were transitioned into metabolically unhealthy states. So, the objective of this systematic review and meta-analysis was to estimate the risk of cardiovascular diseases (CVD) incidence in individuals with transitional MHO phenotype. DATA SYNTHESIS: A literature review was done in PubMed, Scopus, EMBASE, and google scholar databases. Pooled HRs for all fatal and nonfatal CV events were computed using random-effect models for transitional MHOs in general as well as for each sex subgroup separately. This systematic review and meta-analysis included a total of 7 prospective observational studies with a total of 7,720,165 participants, published between 2018 and 2020. The mean follow-up duration of participants was 11.7 (5.5) years. Overall, the transitional MHO individuals had a significant risk of CVD incidence [HR = 1.42, 95% CI (1.24-1.60)]. In addition, in both male and female subgroups, unstable MHO phenotype demonstrated a significant CVD risk and HRs for incident CVD in males and females were 1.51 (1.07-1.96) and 1.71 (1.08-2.34), respectively. CONCLUSION: Transition from MHO to unhealthy state throughout follow-up elevated the risk of CVD in both male and female groups. This can explain the association between MHO and incidence of CV events especially with longer follow up period. REGISTRATION CODE IN PROSPERO: CRD42021270225.

Anemia After Sleeve Gastrectomy and One-Anastomosis Gastric Bypass: An Investigation Based on the Tehran Obesity Treatment Study (TOTS).

BACKGROUND: Bariatric surgery has been associated with iron, folate, and vitamin B12 deficiencies, which can lead to anemia. This study compares the incidence of anemia between sleeve gastrectomy (SG) and one-anastomosis gastric bypass (OAGB). METHODS: Patients from a prospectively collected database of patients with morbid obesity undergoing a primary bariatric procedure from April 2013 to September 2018 were included. Statistical analysis was performed using the general estimation equation. Patients were followed for 6, 12, 24, and 36 months post-surgery. RESULTS: The present study included 2618 patients, of whom 72.3% underwent SG and 27.6% underwent OAGB. The majority of the study population were women (75.7%), and the mean age of the participants was 39.5 ± 11.7 years. At the end of the follow-up, the excess weight loss percentage was 66.15 in the SG group and 75.41 in the OAGB group (P < 0.05). The incidence of anemia at 12-, 24-, and 36-month was 16.2, 19.7, and 24.3% in the SG group and 28.4, 37.6, and 56.5% in the OAGB group, showing significantly higher incidence in the OAGB than the SG group ([Formula: see text] < 0.001). However, there was no significant difference between the SG and OAGB groups regarding the incidence of iron and vitamin B12 deficiency. CONCLUSIONS: The patients undergoing bariatric surgery, especially OAGB, should be closely monitored post-surgery regarding the incidence of anemia, and supplementation in developing countries could be continued even after the first year.

Association of childhood obesity phenotypes with early adulthood Carotid Intima-Media Thickness (CIMT): Tehran lipid and glucose study.

BACKGROUND AND AIMS: Over the past few years, obesity and metabolic syndrome prevalence among children and adolescence have an increasing trend. This study aims to investigate the association of obesity phenotypes during childhood and adolescence with early adulthood carotid intima-media thickness (CIMT). METHODS AND RESULTS: Participants were divided into four obesity phenotypes: Metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Participants were followed for 18 years. Multivariate-adjusted Risk Ratios (RRs) were calculated for high CIMT (≥95% percentile) incidence. In this cohort study 1220 children and adolescents with the average age of 10.9 ± 4.0 years were included. CIMT values had a significantly increasing trend from MHNW to MUO group (p for trend<0.001). Individuals with normal weight status, even with an unhealthy metabolic profile did not have higher risk of high CIMT. Similarly, Children with obesity but healthy metabolic status was not at higher risk. On the other hand, MUO phenotype during childhood was associated with increased risk of high CIMT in early adulthood (RR = 2.13, 95%CI (1.02-4.48)). This association became insignificant for all obesity phenotypes after adjusting for adulthood BMI. CONCLUSION: Adulthood CIMT has an increasing trend based on childhood and adolescence obesity phenotypes from MHNW to MUO. Children with MUO phenotype was the only ones that had an increased risk of high CIMT incidence in early adulthood.

Association of cumulative excess weight and waist circumference exposure with transition from metabolically healthy obesity to metabolically unhealthy.

BACKGROUND AND AIMS: The association between obesity severity and duration with the transition from metabolically healthy obese/overweight (MHO) phenotype to metabolically unhealthy obese (MUO) phenotype is not well understood. METHODS AND RESULTS: This study includes the Tehran Lipid and Glucose Study participants who were initially classed as MHO. Cumulative excess weight (CEW) and cumulative excess waist circumference (CEWC) scores, which represent the accumulation of body mass index and waist circumference deviations from expected values over time (kg/m2 ∗ y and cm ∗ y, respectively), were calculated until the transition from MHO to MUO or the end of follow-up. The sex-stratified association of CEW and CWEC with the transition from MHO to MUO was investigated by time-dependent Cox models, adjusting for confounders. Out of 2525 participants, 1732 (68.5%) were women. During 15 years of follow-up, 1886 (74.6%) participants transitioned from MHO to MUO. A significant association was found between CEW and CEWC quartiles with the development of MUO among women participants (fully adjusted hazard ratios in the fourth quartile of CEW and CEWC [95% (CI)]:1.65 [1.37-1.98] and [95% CI]: 1.83 [1.53-2.19]). There was no significant association between CEW and CEWC with the MHO transition to MUO among men participants. CONCLUSION: Over 15 years of follow-up in TLGS, general and central obesity accumulation was associated with the increased transition from MHO to MUO among women participants. More research with a larger sample size is needed to confirm and explain why the results are different for men and women.

The association of the age, period, and birth cohort with 15-year changes in body mass index and waist circumference in adults: Tehran lipid and glucose study (TLGS).

OBJECTIVE: To examine the association of age, period, and birth cohort with body mass index (BMI) and waist circumference (WC) changes among the participants of the Tehran Lipid and Glucose Study from 1999 to 2015. METHODS: This prospective cohort study included 4895 participants aged ≥20 years (41.3% men), who were divided into twelve gender stratified groups, having a ten-year age difference between them. Analyses were conducted to explicitly assess the association of age vs. period on BMI and WC changes. In addition, we evaluated BMI and WC changes among different birth cohorts. RESULTS: Upon 15 years of follow-up, the mean BMI of men and women increased from 26.0 ± 3.9 to 27.5 ± 4.3 kg/m2 and from 27.5 ± 4.8 to 29.9 ± 5.4 kg/m2 (P trend < 0.001), and this trend was accompanied by an increase in WC from 88.8 ± 10.9 to 97.8 ± 10.4 cm and from 87.3 ± 12.4 to 95.8 ± 12.1 cm, respectively (P trend < 0.001). Men and women in all age cohorts tended to have a rise in their BMI and WC with aging throughout the follow-up period. For men, this trend was more prominent in younger birth cohorts at phase III for BMI and at phases III and V for WC (indicating a significant negative association with birth cohort). For women, this trend was more prominent in older birth cohorts at both phases III and V for BMI and WC (indicating a significant positive association with the birth cohort). CONCLUSION: The rise in BMI and WC was strongly associated with age in both sexes. The men born in the recent birth cohorts and the women born in earlier birth cohorts had the most alarming BMI and WC trends. More efforts must be spent on obesity prevention policies, especially for younger men.