Mediators of energy homeostasis in hyperthyroidism

ABSTRACT Objective: The aim of this study was to assess the effect of hyperthyroidism and its treatment on body weight and composition, insulin resistance, and mediators of appetite and energy homeostasis, namely ghrelin, leptin, adiponectin, and fibroblast growth factor 21 (FGF21). Subjects and methods: Thirty-five adult patients (27 female and 8 male, aged 39.63 ± 9.70 years) with overt hyperthyroidism were evaluated for leptin, ghrelin, adiponectin, and FGF21 levels; insulin resistance; and body composition using DEXA both at baseline and a minimum of two months following normalization of serum thyroxin on carbimazole treatment. Comparison of means between the baseline and post treatment values was performed by the paired t test for normally distributed parameters and by the Wilcoxon signed-rank test for non-normally distributed data. Results: Hyperthyroidism correction resulted in an increase in weight from 51.15 ± 8.50 kg to 55.74 ± 8.74 kg (P < 0.001), paradoxically accompanied by a decrease in insulin resistance as measured by HOMA-IR from 1.35 (1.02-1.72) to 0.73 (0.52-0.93) ( P < 0.001). Correction of hyperthyroidism was also associated with a decrease in FGF21 from 58 (55-64) to 52 (47-58) pg/mL ( P < 0.001) and in leptin levels from 17 (7-36) to 11 (4.6-28) ng/mL ( P = 0.03). Conclusion: Despite lower body weight, thyrotoxicosis is associated with insulin resistance. High levels of thermogenic hormones, leptin, and FGF21 were observed in thyrotoxicosis and may be partly responsible for the excessive heat production typical of this condition.

Attenuation of Oxidative Stress, Interleukin-6, High-Sensitivity C-Reactive Protein, Plasminogen Activator Inhibitor-1, and Fibrinogen with Oral Vitamin D Supplementation in Patients with T2DM having Vitamin D Deficiency.

Objectives Type 2 diabetes mellitus (T2DM) associated with oxidative stress and inflammation causes endothelial dysfunction, which promotes cardiovascular risk. Vitamin D with its pleiotropic effect is said to protect against cardiovascular risk. However, with vitamin D deficiency being more prevalent in T2DM, the cardiovascular risk may get compounded. Materials and Methods An interventional study was conducted on 100 patients with T2DM having vitamin D deficiency (vitamin D < 20 ng/mL), who were given oral supplementation of 2,000 IU/day of vitamin D for a period of 6 months. Serum vitamin D, biomarkers of oxidative stress, malondialdehyde (MDA), oxidized LDL (OxLDL), ferric reducing ability of plasma (FRAP), biomarkers of inflammation, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), and fibrinogen were measured at baseline and at the end of the third and sixth month of vitamin D supplementation. Statistical Analysis Repeated measures analysis of variance (ANOVA) was applied for comparison between baseline and third- and sixth-month data after vitamin D supplementation. Linear regression by generalized estimating equations (GEE), which grouped repeated measures for each subject and accounted for correlations that may occur from multiple observations within subjects, was applied. Results Serum vitamin D levels reached normal levels with a significant decrease in OxLDL, hsCRP, IL-6, PAI-1, and fibrinogen levels, with a significant increase in FRAP ( p = 0.001) levels at the end of 6 months of vitamin D supplementation. These changes were observed even after correction with glycemic control (HbA1c). However, a significant decrease in MDA was observed only at the end of the sixth month of vitamin D supplementation. Vitamin D levels showed a significant negative association with Ox-LDL, Hs-CRP, IL-6, PAI-1, and fibrinogen, even after adjusting for BMI and statin use ( p = 0.001). Conclusion Supplementation of vitamin D for a period of 6 months in patients with T2DM having vitamin D deficiency is beneficial in the attenuation of oxidative stress and inflammation.

Mediators of energy homeostasis in hyperthyroidism.

Objective: The aim of this study was to assess the effect of hyperthyroidism and its treatment on body weight and composition, insulin resistance, and mediators of appetite and energy homeostasis, namely ghrelin, leptin, adiponectin, and fibroblast growth factor 21 (FGF21). Subjects and methods: Thirty-five adult patients (27 female and 8 male, aged 39.63 ± 9.70 years) with overt hyperthyroidism were evaluated for leptin, ghrelin, adiponectin, and FGF21 levels; insulin resistance; and body composition using DEXA both at baseline and a minimum of two months following normalization of serum thyroxin on carbimazole treatment. Comparison of means between the baseline and post treatment values was performed by the paired t test for normally distributed parameters and by the Wilcoxon signed-rank test for non-normally distributed data. Results: Hyperthyroidism correction resulted in an increase in weight from 51.15 ± 8.50 kg to 55.74 ± 8.74 kg (P < 0.001), paradoxically accompanied by a decrease in insulin resistance as measured by HOMA-IR from 1.35 (1.02-1.72) to 0.73 (0.52-0.93) (P < 0.001). Correction of hyperthyroidism was also associated with a decrease in FGF21 from 58 (55-64) to 52 (47-58) pg/mL (P < 0.001) and in leptin levels from 17 (7-36) to 11 (4.6-28) ng/mL (P = 0.03). Conclusion: Despite lower body weight, thyrotoxicosis is associated with insulin resistance. High levels of thermogenic hormones, leptin, and FGF21 were observed in thyrotoxicosis and may be partly responsible for the excessive heat production typical of this condition.

Assessment of Gastric Dysmotility Using Standardized Tc-99m Sulfur Colloid-Labeled Rice Cakes in Diabetic Patients.

Background: Diabetes mellitus is a common lifestyle disease where patients suffer from gastric dysmotility, which is usually underdiagnosed. The aim of this study was to evaluate the utility of Tc-99m sulfur colloid-labeled meal gastric emptying scintigraphy in Type 2 diabetic patients. Methods: A total of 43 patients and 30 controls, satisfying the inclusion criteria from March 2019 to August 2020, were included. Serial planar images were acquired in both anterior and posterior projections for an iso-time of 1 min at 1 min, 60 min (1 h), 120 min (2 h), and 240 min (4 h) after consumption of Tc-99m SC-labeled idly (rice cakes). The gastric emptying was considered delayed if there was <10% emptying at 1 h, <70% emptying at 2 h, and <94% emptying at 4 h. Results: The mean T1/2 was similar among cases (44.11 ± 10.52 min) and controls (49.56 ± 13.44 min, P = 0.056) while the mean gastric emptying at 1 h was slower in cases compared to controls, P = < 0.01. Two cases (4.6%) had delayed gastric emptying while none of the controls had delayed gastric emptying. T1/2 showed no association with duration of diabetes or HbA1c levels (P = 0.76, 0.45) and a weak correlation with fasting blood sugar (FBS) on the day of scan (R value = 0.18). Conclusion: In comparison to controls, diabetic patients had faster gastric emptying with no association with duration of diabetes or HbA1c levels and a weak correlation with FBS on the day of scan.

Effect of Correction of Hyperthyroidism with Anti-thyroid Drugs on the Glycated Hemoglobin in Non-diabetic Patients with Primary Hyperthyroidism.

BACKGROUND: Glycated hemoglobin (HbA1c) levels are dependent not only on the average blood glucose levels over the preceding 2 - 3 months but also on the turnover of erythrocytes. Hyperthyroidism is known to be associated with an increase in erythrocyte turnover that may falsely lower the HbA1c in relation to the level of glycemia. OBJECTIVES: To assess the impact of medical correction of hyperthyroidism on HbA1c, independent of changes in the fasting plasma glucose and 2-hour post-oral glucose tolerance test plasma glucose. METHODS: Adult patients with overt hyperthyroidism (n = 36) were tested for their hemoglobin, reticulocyte percentage, HbA1c and fasting and post-oral glucose tolerance test (OGTT) 2-hour plasma glucose, both at baseline and following at least three months of near normalization of serum thyroxin on Carbimazole treatment. RESULTS: Correction of hyperthyroidism in 36 patients was associated with an increase in the hemoglobin (P = 0.004) and a rise in HbA1c (P = 0.025), even though no significant change was observed in both the fasting (P = 0.28) and post OGTT two-hour plasma glucose (P = 0.54). Also, the proportion of patients with HbA1c ≥ 5.7% rose from 3/36 to 10/36; P = 0.016, while the proportion of patients with either abnormal fasting or abnormal post OGTT 2-hour plasma glucose or both did not show any significant change (P = 0.5). The sensitivity of HbA1c to diagnose prediabetes increased from 20% to 50% post- treatment. CONCLUSIONS: Glycated hemoglobin is falsely low in relation to glycemia in patients with untreated hyperthyroidism.

Insulin resistance in nondiabetic chronic kidney disease patients.

Chronic kidney disease (CKD) is accompanied by numerous metabolic derangements due to risk factors such as oxidative stress, chronic inflammation, and endothelial dysfunction. Insulin resistance (IR) has been reported as an independent risk factor for cardiovascular morbidity and mortality in patients with CKD. As reported from previous studies, it has been shown that IR is also seen in mild-to-moderate stages of CKD. Hence, the present study aimed to study IR in nondiabetic CKD patients and correlated with different stages of CKD. A two-year cross-sectional study was conducted in 175 patients among whom 25 healthy controls and 150 nondiabetic CKD patients in different stages are included. In the present study, fasting insulin and homeostatic model assessment for IR (HOMA-IR) levels were found to be higher in all nondiabetic CKD patients when compared to controls which was found to be statistically significant (P <0.05). In the present study, IR, as evidenced by HOMA-IR, is noted in patients on predialysis, continuous ambulatory peritoneal dialysis (CAPD), and postrenal transplant patients. Hence, periodic monitoring of IR by HOMA-IR might be prudent in CKD patients on predialysis, CAPD and in postrenal transplant patients. Interventions targeting IR in this patient population can also decrease cardiovascular morbidity and mortality.

Efficacy of oral rosuvastatin intervention on HDL and its associated proteins in men with type 2 diabetes mellitus.

PURPOSE: High-density lipoprotein (HDL) undergoes structural and functional modification in patients with type 2 diabetes mellitus (T2DM). There are limited data on effect of rosuvastatin on HDL-associated proteins and the antiatherogenic effects of rosuvastatin. The present study intended to study the efficacy of rosuvastatin intervention on HDL-associated proteins and its other antiatherogenic effects in men with T2DM. METHODS: Men with T2DM on oral antidiabetic treatment, with LDL-C levels > 75 mg/dL and willing for rosuvastatin intervention (20 mg/day orally for a period of 12 weeks), were included. Fasting glucose, lipid profile were measured using standard methods. Oxidized low-density lipoprotein (oxLDL), oxidized HDL (oxHDL), paraoxonase-1 (PON-1), tumour necrosis factor-α (TNF-α) and lecithin:cholesterol acyltransferase (LCAT) in serum were measured by ELISA; serum myeloperoxidase (MPO) by spectrophotometric method and cholesterol efflux by fluorometric assay. Carotid intima-media thickness (cIMT) measurement to assess vascular health status was done using doppler. RESULTS: Rosuvastatin produced a significant decrease (p < 0.05) in lipids (total cholesterol, triglycerides, LDL-C); oxidative stress (oxLDL, oxHDL, MPO); inflammation (TNF-α); LCAT concentration; cIMT; significant increase in antiatherogenic HDL and cholesterol efflux (p < 0.05) and no change in apoA-I levels from baseline to 12 weeks of follow-up. A decrease in MPO activity was found to be independently associated with an increase in cholesterol efflux. CONCLUSIONS: Post intervention there is a quantitative and qualitative improvement in HDL, which helps in its reverse cholesterol transport (RCT) and antioxidant functions. Improvement in HDL functions and suppression of inflammation by rosuvastatin lead to regression in cIMT, which is beneficial in decreasing the progression of cardiovascular disease (CVD) in men with diabetes.

Correction to: Efficacy of oral rosuvastatin intervention on HDL and its associated proteins in men with type 2 diabetes mellitus.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Utility of Short-Acting Intravenous Insulin Therapy in Preparation of F-18 Fluorodeoxyglucose Positron Emission Tomography Computed Tomography Scan in Cancer Patients Incidentally Detected with High Blood Glucose Levels on the Day of Test.

BACKGROUND: In diabetic (DM) patients, hyperglycemia degrades image quality in F-18 FDG PET CT by altering bio-distribution of FDG in the body and augmenting soft tissue and muscular uptake. We intend to evaluate the use of short acting I.V insulin in minimising the rescheduling of patients detected with FBG>160 mg/dL on the day of scan. AIM AND OBJECTIVES: To show the utility of short acting IV insulin therapy in preparation of cancer patients incidentally detected with high blood glucose levels for F-18 FDG PET CT scan, (>160mg/dL) and to compare the obtained image quality with patients detected with fasting blood glucose level (FBG) <100mg/dL and <160 mg/dL, using visual and semi quantitative methods. MATERIAL AND METHODS: 613 cancer patients referred for PET CT were divided into 3 groups, Group I (n=30): known diabetics (DM) or incidentally diagnosed with FBG >160 mg/dL, Group II (n=349): DM patients with FBG <160 mg/dL (100-160mg/dL), Group III (n=234): Non DM patients FBG <100mg/dL. In Group I short acting insulin was given intravenously using a sliding scale, post insulin after 90 minutes F-18 FDG (radiotracer) injection was given and PETCT scan was obtained 60 mins post radiotracer injection. Qualitative image analysis was done using biodistribution score and quantitative analysis was done by chi square test, ANOVA (analysis of variance) and paired t-test. RESULTS: In group I patients post insulin there was significant decrease in FBG levels (216±22.2 to 136±13.4mg/dL) and acceptable image quality. Comparison of quantitative parameters (mean and maximum SUV calculated by drawing ROI around brain, heart, liver, muscle, subcutaneous fat) among the 3 groups showed significant intergroup difference with p value <0.05. CONCLUSION: This short acting I.V insulin protocol is safe and can be used to obtain optimal quality F-18 FDG PET CT scan images by alleviating the need for rescheduling patients though they present with high glucose levels.

Association of single nucleotide polymorphisms of adiponectin and leptin genes with breast cancer.

Single nucleotide polymorphisms (SNPs) in adiponectin gene [rs1501299 (+276G/T) and rs266729 (-11377C/G)] and one SNP of leptin gene [rs7799039 (-2548G/A)] are known to influence plasma levels of adiponectin and leptin respectively. Literature is scarce on the association of adiponectin gene polymorphism rs266729 with breast cancer. The present study was taken up to study these polymorphisms and their association with breast cancer. Ninety-three patients diagnosed with malignant breast cancer were included as cases along with 186 age matched healthy controls. Adiponectin +276G/T, -11377C/G and leptin -2548G/A polymorphism were studied using polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Adipokine levels in blood were measured using enzyme linked immunosorbent assay. Adiponectin +276G/T and leptin -2548G/A showed a significant increased risk for breast cancer even after adjusting for confounding variables like present age, age at menarche, age at first child birth and age at menopause. In the subset analysis, based on menopausal state, stronger association was observed between SNP in adiponectin gene +276G/T with the breast cancer in post-menopausal women after adjusting for all other variables. No association was found with adiponectin -11377C/G. No association of the gene polymorphisms with adipokine levels was observed. Also, no significant association was seen for the effect of gene-environment interaction i.e. presence of polymorphism with obesity and menopausal state for any of the SNPs studied. Adiponectin +276G/T is strongly associated with breast cancer in postmenopausal women while leptin -2548G/A polymorphisms is significantly associated with breast cancer irrespective of the menopausal state in south Indian subjects.

Effect of Adequate Thyroid Hormone Replacement on the Hypothalamo-Pituitary-Gonadal Axis in Premenopausal Women with Primary Hypothyroidism.

BACKGROUND: While the effects of thyroxine (T4) replacement on improving gonadal function in hypothyroid men has been well documented, the same has not been adequately studied in hypothyroid premenopausal women. METHODOLOGY: Premenopausal women with overt hypothyroidism (thyroid-stimulating hormone [TSH] > 15 IU/L) were tested in the early follicular phase of their natural menstrual cycles or after a progesterone challenge for gonadotropins, estradiol (E2), and prolactin (PRL). They were then treated adequately with T4 replacement and retested under similar circumstances for the same parameters ≥2 months after the restoration of euthyroidism. RESULTS: Forty premenopausal hypothyroid women were evaluated at baseline and ≥2 months after adequate T4 replacement. At baseline, there was an inverse correlation of the gonadotropins (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and TSH, prolactin (PRL) and free T4 (fT4), and E2 and PRL. After normalization of the thyroid function, there was a significant fall in PRL (p < 0.001) accompanied by a rise in serum E2 (p < 0.001). There were no changes in the levels of the gonadotropins LH and FSH. The proportion of patients with hyperprolactinemia fell 5-fold, from 5/40 to 1/40. While there were 5 patients with low estrogen prior to treatment, there were none with hypoestrogenemia after treatment. CONCLUSION: Hypothyroidism is associated with a reversible partial suppression of the hypothalamo-pituitary-gonadal axis in premenopausal women, demonstrated by lower E2 along with a mild elevation of PRL. Treatment of hypothyroidism improves the level of estrogen and lowers the level of PRL.

Value of cytokeratin-19, Hector Battifora mesothelial-1 and galectin-3 immunostaining in the diagnosis of thyroid neoplasms.

BACKGROUND: Diagnosis of types and aggressiveness of thyroid cancers is difficult. The "gold standard" in diagnosis is using routine hematoxylin and eosin staining. Several markers have been investigated for differentiating them among which cytokeratin-19 (CK-19), Hector Battifora mesothelial cell (HBME-1), and galectin-3 are found to be most commonly used. Most studies have evaluated the single expression of markers in various thyroid lesions. AIMS AND OBJECTIVES: To know the value of immunohistochemical expression of CK-19, HBME-1, and galectin-3 in diagnosing thyroid neoplasms. To study the expression and compare the results of HBME-1, CK-19, and galectin-3 immunohistochemical markers in histopathologically diagnosed malignant lesions and nonmalignant lesions and demonstrate their usefulness in differentiating them. MATERIALS AND METHODS: A prospective study was carried out on thyroidectomy specimens sent in 10% buffered formalin to Department of Pathology, SVIMS, Tirupati, from May 2013 to August 2014. Sensitivity and specificity for each marker and their combination in diagnosis were calculated. RESULTS: Among 120 cases, nonmalignant lesions were 70 (58.33%) and malignant lesions 50 (41.67%). Among nonmalignant lesions, 65 (93%) were adenomatous goiter and 5 (7%) were follicular adenomas. In malignant lesions, 48 (96%) were papillary carcinoma and 1 (2%) each of follicular carcinoma and anaplastic carcinoma. Among papillary carcinomas, classical were 26 (54.16%) followed by 17 follicular variant (35.41%). Galectin-3 had highest sensitivity of 90% and HBME-1 had highest specificity of 97.14%. CONCLUSIONS: Panel of HBME-1+ galectin-3 or CK-19, HBME-1, and galectin-3 increase the accuracy of diagnosis in histopathologically difficult cases.

Heterogenous origins of hyperandrogenism in the polycystic ovary syndrome in relation to body mass index and insulin resistance.

BACKGROUND: Insulin resistance and obesity are not universal features of polycystic ovary syndrome (PCOS). We planned to assess the differences between patients with nonobese /insulin-sensitive phenotype vs. obese/ insulin-resistant phenotype in terms of the potential mechanisms underlying their hyperandrogenism. MATERIALS AND METHODS: A total of 52 women satisfying Androgen Excess Society (AES) criteria were included. Hormonal and metabolic profile including prolactin, dehydroepiandrosterone sulfate (DHEAS), free testosterone, sex hormone binding globulin (SHBG), fasting plasma glucose and insulin were measured in follicular phase. RESULTS: DHEAS was found to be higher in the nonobese patients as compared to the obese (p = 0.01). There was also a strong trend for a higher DHEAS among patients with lower insulin resistance by homeostatic model assessment (HOMA-IR< 2.3) (p = .06).While the total testosterone (p = .044) and SHBG (p = .007) were found to be lower in the more insulin-resistant group (HOMA-IR ≥ 2.3), the free testosterone levels were similar. However, the percentage of free testosterone was higher in the more insulin-resistant group (p = .005). CONCLUSIONS: The hyperandrogenic state in PCOS appears to have heterogenous origins. Nonobese patients with PCOS have adrenal hyperandrogenism as the underlying mechanism while their obese/ insulin-resistant counterparts have low SHBG and hence an increased fraction of free testosterone.

Impact of Severity of Illness on the Function of the Hypothalamo-pituitary-gonadal Axis in Postmenopausal Women with Acute Severe Illness: Implications for Predicting Disease Outcome.

BACKGROUND: While elevated levels of estradiol were predictive of mortality in critically ill surgical and trauma patients, their ability to predict outcome in nonsurgical patients has not been studied. We aimed to study the determinants of gonadotropin levels in acutely ill postmenopausal women with nonsurgical disease and the impact of changes in the gonadal axis on the outcome of these patients. METHODS: Thirty-five postmenopausal women admitted to medical intensive care with acute severe illness and having a Simplified Acute Physiology Score (SAPS II score) ≥30 (in-hospital mortality rate ≥ 10%) were recruited. On the 5th day of hospitalization, fasting samples were collected at 8.00 am and tested for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, free triiodothyronine, free thyroxine, thyrotropin, cortisol, prolactin, dehydroepiandrosterone, androstenedione, and sex hormone-binding globulin. Multiple linear regression analysis was performed to identify independent determinants if any of LH and FSH. Receiver operating characteristic (ROC) curves were drawn for different cutoffs of LH, FSH, and estradiol to diagnose mortality and prolonged hospitalization. RESULTS: There was an independent negative association between the FSH and the SAPS II score (beta = -0.435; P = 0.014), but not with any of the other tested parameters (estradiol, prolactin, or cortisol). Among components of the SAPS II score, the total leukocyte count (TLC) was negatively associated with serum FSH (beta coefficient = -0.635, P = 0.013). None of these parameters were determinants of LH. On ROC analysis, neither estradiol nor gonadotropins were diagnostic for in-hospital mortality. However, among survivors, low estradiol was diagnostic for prolonged hospital stay (area under the curve = 0.785; P = 0.015). CONCLUSION: FSH, but not LH, is negatively associated with the severity of illness, particularly to its inflammatory component (TLC). Low estradiol in survivors was a predictor of prolonged hospital stay.

Risk Factors for Cardiovascular Disease in Obese Children.

OBJECTIVE: To study the prevalence of cardiovascular risk factors in pediatric obesity. METHODS: 50 obese children (age 5-17y) and 50 apparently healthy non-obese children (body mass index of over 95th percentile and between 5th to 95th percentiles, respectively) using Centre for Disease Control growth charts were included. Fasting blood sugar, lipid profile, insulin, homeostasis model assessment of insulin resistance, uric acid, fibrinogen, lipoprotein (a), homocysteine, malondialdehyde, ferric reducing ability of plasma and nitric oxide were measured. RESULTS: Insulin, insulin resistance, triglycerides, uric acid, fibrinogen, malondialdehyde, ferric reducing ability of plasma and nitric oxide were significantly higher (P <0.001) in obese children. Body mass index showed significant positive correlation with insulin r=0.519, P<0.001; insulin resistance r =0.479, P<0.001; uric acid r= 0.289, P=0.005; fibrinogen r=0.461, P<0.001; and nitric oxide r=0.235, P=0.012. CONCLUSION: Pediatric obesity is associated with dyslipidemia, oxidative stress, insulin resistance and endothelial dysfunction, which are cardiovascular risk factors and components of metabolic syndrome. These children must be targeted for lifestyle and dietary modification.

Atypical Parathyroid Adenoma with Multiple Brown Tumors as Initial Presentation: A Rare Entity.

Brown tumors seen in hyperparathyroidism are rare, non-neoplastic lesions because of abnormal bone metabolism, and they can mimic benign bone tumors or malignancy. Although biopsy is considered as the gold standard for diagnosis, it can be inconclusive. As the diagnosis of brown tumors is often challenging, a high index of suspicion is essential for diagnosis. We present a case of 21-year-old woman who presented with multiple painful bony lesions, which were initially misdiagnosed as fibrous dysplasia. Due to persistent bone pain and deterioration in her physical mobility, she was referred to tertiary care centre. After thorough clinical workup, she underwent Tc-99m methylene diphosphonate bone scintigraphy that raised strong clinical suspicion of hyperparathyroidism and brown tumors. Subsequently, Tc-99m-methoxy isobutyl isonitrile (MIBI) parathyroid scintigraphy revealed a solitary MIBI avid focal lesion, suggestive of left inferior parathyroid adenoma. Later parathyroidectomy was performed and histopathological examination confirmed it as atypical parathyroid adenoma.

Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study.

OBJECTIVE: Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients. DESIGN: Twenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2-19) years. METHODS: Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied. RESULTS: Patients varied widely in their age of presentation [3.5 (0.1-17) years] and number of clinical manifestations [5 (2-11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3-23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians. CONCLUSIONS: Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.

Glycemic management during Jain fasts.

This review describes the various fasts observed by adherents of the Jain religion. It attempts to classify them according to their suitability for people with diabetes and suggests appropriate regime and dose modification for those observing these fasts. The review is an endeavor to encourage rational and evidence-based management in this field of diabetology.