An Analytical Study to Determine Dose-Volume Threshold for Radiation Induced Hypothyroidism.

Objective: To determine radiation dose volume threshold in predicting the development of hypothyroidism in cancer patients following neck irradiation. Methods: This is a cross sectional follow up study for patients who had been previously irradiated, prior to enrolment in the study. We have done thyroid dose-volumetric analysis on 120 histologically proven cancer patients in the age group of 18-75 years who received neck irradiation as a part of their definitive or adjuvant radiotherapy with three-dimensional conformal or intensity-modulated radiotherapy technique (3D -CRT or IMRT) and completed at least six months post-radiotherapy. Primary tumor sites included carcinoma or lymphoma of the head and neck, breast, cervical, and upper thoracic esophagus, requiring neck irradiation. Results: The proportion of patients who tested positive for Radiation induced hypothyroidism (RIHT) was found to be 40%, with clinical hypothyroidism and subclinical hypothyroidism being 25.8% and 14.2%, respectively. Time to develop hypothyroidism peaks around two years. Mean thyroid gland dose (Dmean) >28 Gy, thyroid gland volume receiving 40 Gy dose (i.e. V40) >49% and age <50 years were found to be significant risk factors for the development of RIHT on binary logistic regression. RT dose >50 Gy and thyroid gland volume spared from 40 Gy (i.e. VS40) < 2.12cm3 were statistically significant predictors for RIHT on chi-square and (Receiver operating characteristic) ROC curve analysis respectively but not on regression analysis. Conclusion: Dose-volume threshold for the thyroid gland as Dmean <28 Gy and V40 <49% may prevent the development of RIHT.

Hypothalamic-Pituitary Adrenal Axis Status 3 Months After Recovery From COVID-19 Infection.

CONTEXT: Coronavirus disease 2019 (COVID-19) predominantly involves the lungs, albeit many other organ systems, including the hypothalamic-pituitary-adrenal (HPA) axis, can be affected due to the expression of the angiotensin-converting enzyme 2 (ACE2) binding receptor. Few studies have reported the involvement of adrenal gland and the HPA axis during the acute phase of COVID-19; however, the data on the long-term effect of COVID-19 on the HPA axis after acute infection is scarce. OBJECTIVE: To assess and compare the changes in HPA axis in mild, moderate and severe COVID-19 categories at ≥ 3 months after acute infection. METHODS: A prospective, observational study was conducted to assess the HPA axis status among COVID-19 subjects at least 3 months after recovery from acute infection. The study was conducted from June 2021 to May 2022. Subjects visited the hospital in the fasting state (8.00-9.00am), serum cortisol levels were measured at baseline, 30 and 60 minutes after a 1-µg short Synacthen test (SST). RESULTS: A total of 66 subjects ≥ 18 years of age were included in the study. The mean age (SD) was 49.13 ± 11.9 years, 45(68.18%) were male and 21 (31.81%) were female subjects. The mean BMI in the study was 25.91 ± 4.26 kg/m2. Seventeen (25.8%) subjects had mild, twelve (18.2%) had moderate and thirty-seven (56.1%) subjects had severe COVID-19 infection. Out of the sixty-six subjects with COVID-19, nine subjects (9/66, 13.63%) had peak serum cortisol < 496.62 nmol/L suggestive of adrenal insufficiency (AI). SST peak serum cortisol levels did not differ significantly across the disease severity [Mild, (628.50 ± 214.65 nmol/L) vs moderate, [603.39 ± 161.95 nmol/L) vs severe, (597.59 ± 163.05 nmol/L), P = 0.617]. Six subjects with AI came for follow-up at 12 months, and all had normal HPA axis. CONCLUSION: HPA axis is affected in 13.63% (9/66) of subjects at least 3 months after recovery from COVID-19 infection. AI in COVID-19 might be transient and would recover spontaneously. These findings have important implications for the clinical care and long-term follow-up of subjects after COVID-19 infection.

Serum Irisin Levels and its Association with Blood Glucose and Insulin Indices in Diagnosing Insulin Resistance in Adolescents with Polycystic Ovarian Syndrome.

CONTEXT: Irisin, a new myokine, has been found to be a biological marker of insulin resistance (IR). There is conflicting evidence on serum irisin level in adult women with polycystic ovarian syndrome (PCOS), and data are lacking in adolescents with PCOS. AIMS: We aimed to evaluate serum Irisin levels and study its association with indices using blood glucose and insulin levels in adolescents with PCOS. SETTINGS AND DESIGN: This case-control study was conducted in the gynecology outpatient department. MATERIALS AND METHODS: This study was carried out from August 2015 to June 2017. Eighty-two adolescent girls aged 15-19 years were included in the study. Fasting irisin, insulin,blood glucose; 2nd-h insulin (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) for all participants with addition of 2nd-h blood glucose for cases. STATISTICAL ANALYSIS: A correlation between serum irisin level and various biochemical parameters was done using Pearson's correlation. RESULTS: Fasting serum irisin was significantly higher among PCOS cases (8.43 [5.84, 13.11]) when compared to controls 4.90 (2.37, 9.09), median (interquartile range) (P = 0.002). Serum irisin was found to have a significant moderate positive correlation with 2nd-h blood glucose, fasting/2nd-h insulin, and HOMA2-IR. A significant moderate negative correlation was observed between irisin and QUICKI. CONCLUSIONS: Serum irisin levels were significantly elevated in adolescents with PCOS when compared to the controls. A significant correlation of serum irisin with blood glucose and insulin indices indicates that serum irisin could serve as a marker of IR and may help in its diagnosis in adolescents with PCOS.

Comparison of criteria of International Association of Diabetes and Pregnancy Study Groups (IADPSG) with National Institute for Health and Care Excellence (NICE) for diagnosis of gestational diabetes mellitus.

BACKGROUND: Different screening procedures and diagnostic criteria are being followed in the same as well as in different countries with no single standard criteria established for diagnosis of GDM. So far, there are no studies in the Indian population comparing IADPSG with NICE criteria. OBJECTIVE: To compare International Association of Pregnancy and Study Groups (IADPSG) criteria with the National Institute for Health and Care Excellence (NICE) for diagnosis of gestational diabetes mellitus and its influence on maternal and perinatal outcomes. METHOD: This prospective observational study was conducted in the Department of Obstetrics and Gynaecology of a tertiary care institute in South India from March 2017 to October 2018. Six-hundred and eighty women with or without risk factors for GDM were recruited in the study and screened for GDM based on IADPSG and NICE criteria. Women with preexisting diabetes mellitus or with fasting plasma glucose ≥ 126 mg/dl were excluded. RESULTS: The overall prevalence of GDM in our study was 27.2% by either IADPSG/NICE criteria. In this study, 25.1% women and 11.6% women were diagnosed as GDM using IADPSG and NICE criteria, respectively. The level of agreement between the two diagnostic criteria was found to be poor in our study and was statistically significant (kappa = 0.429, p < 0.001). Women testing IADPSG-positive NICE-negative had a higher risk of GHTN, abortions, PROM, preterm delivery, caesarean section and congenital anomalies, meconium-stained liquor, and low Apgar scores at 1 min when compared to non GDM group. In addition, except for preterm delivery, women diagnosed as GDM by both IADPSG and NICE criteria had adverse outcomes such as preeclampsia, urinary tract infection, and polyhydramnios. Women diagnosed as GDM in IADPSG-negative NICE-positive had no significant adverse maternal or perinatal outcomes. CONCLUSIONS: IADPSG criteria appear to be more robust than NICE criteria for diagnosis of GDM. Women with substantial risk of maternal and perinatal outcomes are better identified by IADPSG criteria who would have been missed if NICE criteria was used.

Late Effects of Breast Cancer Treatment and Outcome after Corrective Interventions.

Purpose: To study the late toxicities of treatment and its impact on Breast cancer survivors among Indian patients. Materials and Methods: Our study recruited 152 curatively treated non metastatic carcinoma breast patients. The baseline demographic details, disease related and treatment related information were collected. The late effects included breast cancer related lymphedema, shoulder dysfunction, treatment induced bone loss, hypothyroidism, cardiac dysfunction, and chemotherapy induced cognitive dysfunction and Quality of life. Results: The median age was 47 years (range 27 -72 years). The cumulative frequency of BCRL and shoulder dysfunction was 31.57% and 34.86% respectively. The improvement in BCRL with corrective intervention was not statistically significant. The BCRL was significantly associated with shoulder dysfunction. The frequency of loss of bone mineral density was 38.15%. There was statistically significant improvement in bone mineral density with interventions. The cumulative rate of hypothyroidism and cardiac dysfunction was 14.47 % and 2.17% respectively which improved after corrective therapy. We did not find any delayed cognitive dysfunction. There was improvement in global health, physical function, role function, fatigue, Nausea, vomiting, pain scores, insomnia, Loss of appetite, diarrhea and arm symptoms over time with intervention. Conclusion: Our study has shown that nearly half of the survivors were suffering from at least one of the late effects. The intervention helped in improving the loss of bone mineral density, hypothyroidism, cardiac dysfunction and quality of life in Breast cancer survivors.

Three-monthly bolus vitamin D supplements (1000 vs 400 IU/day) for prevention of bone loss in children with difficult-to-treat nephrotic syndrome: a randomised clinical trial.

BACKGROUND: Nephrotic syndrome (NS) in children is one of the most common chronic diseases with a remitting and relapsing course. Glucocorticoids (prednisolone) are considered to be the treatment of choice but are associated with osteoporosis. There are no uniform consensus guidelines regarding the optimum dose of calcium and vitamin D for osteoprotection. Some authorities suggest a daily dose of 1000 IU vitamin D for children for osteoprotection, while others suggest a daily dose of 400 IU. OBJECTIVES: To compare the efficacy of three-monthly bolus vitamin D supplementation (1000 vs 400 IU/day) to prevent bone loss in children with difficult-to-treat NS (DTNS). METHODS: In this parallel-group, open-label, randomised clinical trial, 60 children aged 1-18 years with DTNS [37 with frequently relapsing NS (FRNS), 13 steroid-dependent NS (SDNS) and 10 steroid-resistant NS (SRNS)] were enrolled and block randomised in a 1:1 allocation ratio to receive 1000 IU/day vitamin D (Group A, n = 30) or 400 IU/day (Group B, n = 30), administered as three-monthly bolus supplemental doses. In Group A, vitamin D (cholecalciferol, Calcirol®sachet) was administered as a stat dose of 90,000 IU every three months (calculated for a period of three months at 1000 IU/day). In Group B, vitamin D (cholecalciferol) was administered as a stat dose of 36,000 IU every three months (calculated for a period of three months at 400 IU/day). The proportionate change in bone mineral content (BMC) was studied by dual energy X-ray absorptiometry (DEXA) scan in both groups after vitamin D supplementation by analysing the values of BMC obtained 12 months apart (baseline vs. after 12 months). RESULTS: Sixty children were randomised to receive vitamin D at a dose of either 1000 IU/day (Group A) or 400 IU/day (Group B). The two groups were comparable in their baseline clinical and laboratory parameters (including BMC and bone mineral density (BMD)). The distribution of the three types of NS (FRNS, SDNS and SRNS) was also comparable in both groups. In Group A, there were 19, 6 and 5 children with FRNS, SDNS and SRNS, respectively, and in Group B there were 18, 7 and 5 children with FRNS, SDNS and SRNS, respectively. The proportionate change in BMC was not significantly different between the two groups (median proportionate change in BMC in Group A 13.36% vs 11.59% in Group B, p = 0.22). Overall, BMC increased in both groups (96.7% in each). Only one (3.3%) patient in each group exhibited bone loss. None of the patients had a urinary calcium:creatinine ratio >0.2 at the end of the study. CONCLUSION: Three-monthly bolus vitamin D dosing regimens administered either as 1000 or 400 IU/day prevent bone loss in children with DTNS who require long-term steroids. Overall, three-monthly bolus supplemental prophylactic vitamin D, either 1000 or 400 IU/day, would seem to be an effective strategy for preventing bone loss in children with DTNS, as evidenced by the extremely low rates of bone loss (3.3% in each group), and is useful for delivering optimal care to children with DTNS. However, since this study was designed as an equivalence trial and not a superiority trial, further studies are required to demonstrate the superiority of the former regimen over the latter. ABBREVIATIONS: BMC, bone mineral content; BMD, bone mineral density; DEXA, dual energy X-ray absorptiometry; DTNS, difficult-to-treat nephrotic syndrome; FRNS, frequently relapsing nephrotic syndrome; IFRNS, infrequently relapsing nephrotic syndrome; iPTH, intact parathyroid hormone; NS, nephrotic syndrome; SDNS, steroid-dependent nephrotic syndrome; SRNS steroid-resistant nephrotic syndrome.

Effect of two prophylactic bolus vitamin D dosing regimens (1000 IU/day vs. 400 IU/day) on bone mineral content in new-onset and infrequently-relapsing nephrotic syndrome: a randomised clinical trial.

OBJECTIVES: To examine the efficacy of two vitamin D dosages (1000 vs. 400 IU/day) for osteoprotection in children with new-onset and infrequently-relapsing nephrotic syndrome (IFRNS) receiving corticosteroids. METHODS: This parallel-group, open label, randomised clinical trial enrolled 92 children with new-onset nephrotic syndrome (NS) (n = 28) or IFRNS (n = 64) to receive 1000 IU/day (Group A, n = 46) or 400 IU/day (Group B, n = 46) vitamin D (administered as a single bolus initial supplemental dose) by block randomisation in a 1:1 allocation ratio. In Group A, vitamin D (cholecalciferol in a Calcirol® sachet) was administered in a single stat dose of 84,000 IU on Day 1 of steroid therapy (for new-onset NS), calculated for a period of 12 weeks@1000 IU/day) and 42,000 IU on Day 1 of steroid therapy (for IFRNS, calculated for a period of 6 weeks@1000 IU/day). In Group B, vitamin D (cholecalciferol in a Calcirol® sachet) was administered as a single stat dose of 33,600 IU on Day 1 of steroid therapy (for new-onset NS, calculated for a period of 12 weeks@400 IU/day) and 16,800 IU on Day 1 of steroid therapy (for IFRNS, calculated for a period of 6 weeks@400 IU/day). The proportionate change in bone mineral content (BMC) was analysed in both groups after vitamin D supplementation. RESULTS: Of the 92 children enrolled, 84 (n = 42 new onset, n = 42 IFRNS) completed the study and were included in the final analysis. Baseline characteristics including initial BMC, bone mineral density, cumulative prednisolone dosage and serum 25-hydroxycholecalciferol levels were comparable in the two groups. There was a greater median proportionate change in BMC in the children who received 1000 IU/day vitamin D (3.25%, IQR -1.2 to 12.4) than in those who received 400 IU/day vitamin D (1.2%, IQR -2.5 to 3.8, p = 0.048). The difference in proportionate change in BMC was only statistically significant in the combined new-onset and IFRNS, but not for IFRNS alone. There was a greater median proportionate change in serum 25-hydroxycholecalciferol, in the children who received 1000 IU/day vitamin D (20.6%, IQR 14.9-36.75) than in those who received 400 IU/day vitamin D (7.7%, IQR 3.5-18.5, p < 0.01). There was a greater median proportionate change in serum calcium in the children who received 1000 IU/day vitamin D (20%, IQR 13.1-29.0) than in those who received 400 IU/day vitamin D (11.3%, IQR 2.8-25.0, p = 0.03). Despite vitamin D therapy, BMC decreased from the baseline in 15 (32.6%) children receiving 1000 IU/day vitamin D and in 17 (36.9%) children receiving 400 IU/day vitamin D. There were no adverse effects attributable to vitamin D. CONCLUSION: The 1000 IU/day dose is marginally more effective than 400 IU/day and it is likely than an even larger dose is required. Further research is required to assess the efficacy and safety of vitamin D doses higher than 1000 IU/day.

Systematic Review on Vitamin D Level in Apparently Healthy Indian Population and Analysis of Its Associated Factors.

BACKGROUND: Vitamin D which is involved in the maintenance of bone mineral homeostasis has been found to portray various pleiotropic effects. Although it has been widely accepted that serum 25-hydroxy Vitamin D level above 30 ng/ml is considered optimal for the biological actions of Vitamin D, there is a need to explore the levels of Vitamin D reported among Indians from various regions of the country. Hence, this systematic review aims to appraise the status of Vitamin D levels reported from apparently healthy Indians across various parts of India. METHODOLOGY: A comprehensive literature search was carried out to identify the range of Vitamin D levels among apparently healthy individuals from various parts of India, with the search term "Vitamin D and India" in the search portals of PubMed, Google Scholar, Indmed, and ScienceDirect. A total of 2998 articles were retrieved by the above search strategy, of which only forty studies fulfilled the criteria to be included in the systematic review. Studies done in various states were compiled under the respective zones based on the classification of Indian zones as specified in Zonal maps of India. RESULTS: The level of Vitamin D from all the forty included studies ranged from 3.15 ± 1.4 to 52.9 ± 33.7 ng/ml. The effect size of Vitamin D level was higher in the South Zone compared to other zones. CONCLUSION: The present study shows that Vitamin D deficiency is prevalent among apparently healthy Indians living in different regions of India, irrespective of their exposure to sunlight.

Effect of Vitamin D Supplementation on Vascular Functions and Oxidative Stress in Type 2 Diabetic Patients with Vitamin D Deficiency.

BACKGROUND: Vitamin D levels are reported to have an inverse liaison with the risk of cardiovascular diseases. Hence, we aimed to evaluate the effect of Vitamin D supplementation on changes in vascular functions and oxidative stress in type 2 diabetic patients with Vitamin D deficiency. SUBJECTS AND METHODS: One hundred and three patients with type 2 diabetes attending endocrinology outpatients department in a tertiary care hospital were screened for Vitamin D deficiency. Patients with serum 25-hydroxy Vitamin D levels <20 ng/ml were considered as deficient and were administered 60,000 IU of oral Vitamin D3 weekly for 8 weeks. In these patients, parameters of vascular functions (carotid-femoral pulse wave velocity, brachial-ankle pulse wave velocity, and arterial stiffness index) and oxidative stress (serum malondialdehyde levels and total antioxidant status) were measured at baseline and after 8 weeks of oral Vitamin D supplementation. RESULTS: Among 103 patients with type 2 diabetes, 75 (72.82%) were found to have Vitamin D deficiency. Amidst these patients, carotid-femoral pulse wave velocity (991.6 ± 161.82 vs. 899.29 ± 151.86, P < 0.001), right brachial-ankle pulse wave velocity (1446.16 ± 204.33 vs. 1350.8 ± 178.39, P < 0.001), and left brachial-ankle pulse wave velocity (1493.81 ± 219.65 vs. 1367.61 ± 220.64, P < 0.001) showed a significant reduction following Vitamin D supplementation. Further, these patients were found to have significant fall in serum malondialdehyde levels with rise in total antioxidant status ensuing Vitamin D supplementation. CONCLUSION: The present study shows that oral Vitamin D supplementation of 60,000 IU/week for 8 weeks significantly improves vascular functions and reduces oxidative stress in type 2 diabetic patients with Vitamin D deficiency.

Body Fat Analysis in Predialysis Chronic Kidney Disease: Multifrequency Bioimpedance Assay and Anthropometry Compared With Dual-Energy X-Ray Absorptiometry.

OBJECTIVES: Body composition analysis is required for accurate assessment of nutritional status in patients with predialysis chronic kidney disease (CKD). The reference method for assessing body fat is dual-energy X-ray absorptiometry (DXA), but it is relatively expensive and often not available for widespread clinical use. There is only limited data on the utility of less expensive and easily available alternatives such as multifrequency bioimpedance assay (BIA) and skinfold thickness (SFT) measurements for assessing body fat in predialysis CKD. The study intends to assess the utility of BIA and SFT in measuring body fat compared to the reference method DXA in subjects with predialysis CKD. METHODS: Body composition analysis was done in 50 subjects with predialysis CKD using multifrequency BIA, SFT, and DXA. The agreement between the body fat percentages measured by reference method DXA and BIA/SFT was assessed by paired t-test, intraclass correlation coefficients (ICCs), regression, and Bland-Altman plots. RESULTS: Percentage of body fat measured by BIA was higher compared to the measurements by DXA, but the difference was not significant (30.44 ± 9.34 vs. 28.62 ± 9.00; P = .071). The ICC between DXA and BIA was 0.822 (confidence interval: 0.688, 0.899; P = .000). The mean values of body fat percentages measured by anthropometry (SFT) was considerably lower when compared to DXA (23.62 ± 8.18 vs. 28.62 ± 9.00; P = .000). The ICC between DXA and SFT was .851 (confidence interval: 0.739, 0.915; P = .000). Bland-Altman plots showed that BIA overestimated body fat by a mean of 1.8% (standard deviation, 6.98), whereas SFT underestimated body fat by 5% (standard deviation, 4.01). Regression plots showed a better agreement between SFT and DXA (R(2) = .79) than BIA (R(2) = .50). Overall, SFT showed better agreement with the DXA. Body mass index (BMI) showed a moderate positive correlation with body fat measured by DXA whereas serum albumin failed to show good correlation. CONCLUSIONS: SFT showed relatively better agreement with the reference method DXA, compared to BIA. SFT can be used as a tool for assessing nutritional status in predialysis patients with CKD.