Anil Bhansali

In India, the increasing prevalence of diabetes and obesity poses a significant threat towards a surge in the incidence of metabolic dysfunction‐associated steatotic liver disease (MASLD), formerly known as non‐alcoholic fatty liver disease (NAFLD). Concomitant with the evolving guidelines, there is a need to direct and spread awareness among practicing diabetologists to identify and screen high‐risk individuals for MASLD for timely management. Its asymptomatic nature and the evolving guidelines on diagnosis have hindered the precise estimates of MASLD in the high‐risk group of individuals in a clinical setting. Therefore, an expert panel of diabetologists from India convened to review, discuss and document the approach towards screening, diagnosis and management of MASLD. Serum biomarkers, simple non‐invasive tools and imaging techniques could direct the risk stratification of the patients. Early lifestyle interventions including weight loss and exercise are beneficial. The pharmacological landscape of drugs directed to insulin resistance, lipid metabolism, oxidative stress, inflammation, apoptosis and fibrogenesis pathways for the management of MASLD is expanding. In summary, the consensus statements are expected to serve as a useful guide in the screening and management of MASLD in the region and to direct a well‐planned study design that could enhance the scientific value of these statements.

Background: Cancer progression can be promoted by chronic inflammation. Local immune response may be associated with favourable or unfavourable prognosis of Papillary Thyroid Carcinoma (PTC). Regulatory T (Treg) cells and T helper 17 (Th17) cells exert opposing function and their balance may have a vital role in promotion of tumor growth. Treg cells in tumor microenvironment (TME) may promote tumor progression and reduced survival of patients. Whereas, Th17 cells can promote or inhibit tumor progression depending on phenotypic characteristics of tumor. In this study, we aimed to analyse the kind of immune response developed and its prognostic impact in future therapeutics. Methods: Cytometric Bead Array (CBA) analysis of pro and anti-inflammatory cytokines (IFN-gamma, IL-2, IL-6, IL-17 A, TNF-alpha and IL-4, IL-10) was done in 15 PTC irrespective of Lymphocytic Thyroiditis (LT) and 16 Hashimoto’s Thyroiditis (HT) cases. Immunohistochemical expression of FoxP3 and IL-17 A was studied in 27 cases of PTC with LT. Whereas, quantitative gene expression of both was analysed in 10 cases. Results: All the pro-inflammatory cytokines showed mild elevation in PTC with LT. On IHC, IL-17 A expression was observed in 74% PTC with LT. Whereas, FoxP3 was present in only 40% cases. Also, IL-17 A expression was significantly associated with age group (> 45 years), tumor size ≤ 1 cm and disease progression. Conclusions: Increased expression of cytokines suggested correlation between inflammatory factors and progression of thyroid tumors. Along with this, the balance between IL-17 A and FoxP3 may play an important role in PTC development, prognosis and future management.

Introduction: Aggressive pituitary adenomas (APAs) are, by definition, resistant to optimal multimodality therapy. The challenge lies in their early recognition and timely management. Temozolomide is increasingly being used in patients with APAs, but evidence supporting a favorable response with early initiation is lacking.Methods: This was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150–200 mg/m²). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O⁶-methylguanine-DNA methyltransferase (MGMT), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2) was performed, and h-scores (product of the number of positive cells and staining intensity) were calculated. Response was assessed in terms of radiological response using the RECIST criteria. Patients with controlled disease (≥30% reduction in tumor volume) were classified as responders.Results: The study comprised 35 patients (48.6% acromegaly, 37.1% prolactinomas, and 14.3% non-functioning pituitary adenomas). The median number of temozolomide (TMZ) cycles was 9 (IQR 6–14). Responders constituted 68.6% of the cohort and were more likely to have functional tumors, a lower percentage of MGMT-positive staining cells, and lower MGMT h-scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 vs. 15 months, p = 0.01). ROC-derived cutoffs of 31 months for the duration between diagnosis and TMZ initiation, low-to-intermediate MGMT positivity (40% tumor cells), and MGMT h-score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response.Conclusion: Early initiation of TMZ therapy, functional tumors, and low MGMT h-score predict a favorable response to TMZ in APAs.

Introduction Primary hyperparathyroidism (PHPT) in India is mostly symptomatic with renal and skeletal complications. Evidence on mortality outcomes following parathyroidectomy from India, where the disease is predominantly symptomatic is limited. Material and methods This was a prospective study to evaluate mortality outcomes in the Indian PHPT registry over the past 25 years (n = 464). Pre- and postoperative parameters and mortality data were obtained from medical records and/or by verbal autopsy, a method validated by WHO for data collection in settings where several deaths are noninstitutional. Patients were divided into survivor (SG) and nonsurvivor groups (NSG) to ascertain differences in presentation and the effect of parathyroidectomy. Results The overall mortality was 8.8% at a median follow-up of 8 years (IQR 1–13) after parathyroidectomy. Chronic kidney disease was the most common background cause of death (43.5%), followed by pancreatitis (28.2%). NSG had significantly more frequent renal dysfunction (91.9% vs 73.9%), anaemia (50 vs 16.6%) and pancreatitis (24.3 vs 6.4%). PTH (61.9 vs 38.3 pmol/l) and baseline creatinine (97.2 vs 70.7 µmol/l) were significantly higher and eGFR lower (66.7 vs 90.7 ml/min/1.73m²) in the NSG than SG. By Cox proportional modelling, renal dysfunction [HR 2.88 (1.42–5.84)], anaemia [HR 2.45 (1.11–5.42)] and pancreatitis [HR 2.65 (1.24–5.66)] on univariate and renal dysfunction [HR 3.33 (1.13–9.77)] on multivariate analysis were significant for mortality. Survival curves demonstrated a significantly higher mortality with lower eGFR values. Conclusions Nonsurvivors in PHPT had greater prevalence and more severe baseline renal dysfunction than survivors. Survival after parathyroidectomy was significantly associated with estimated glomerular filtration rate at baseline.

Introduction: Evidence on new-onset endocrine dysfunction and identifying whether the degree of this dysfunction is associated with the severity of disease in patients with COVID-19 is scarce.Patients and Methods: Consecutive patients enrolled at PGIMER Chandigarh were stratified on the basis of disease severity as group I (moderate-to-severe disease including oxygen saturation 94% and without comorbidities) (n=49). Hypothalamo-pituitary-adrenal, thyroid, gonadal axes, and lactotroph function were evaluated. Inflammatory and cell-injury markers were also analysed.Results: Patients in group I had higher prevalence of hypocortisolism (38.5 vs 6.8%, p=0.012), lower ACTH (16.3 vs 32.1pg/ml, p=0.234) and DHEAS (86.29 vs 117.8µg/dl, p= 0.086) as compared to group II. Low T3 syndrome was a universal finding, irrespective of disease severity. Sick euthyroid syndrome (apart from low T3 syndrome) (80.9 vs 73.1%, p= 0.046) and atypical thyroiditis (low T3, high T4, low or normal TSH) (14.3 vs 2.4%, p= 0.046) were more frequent in group I than group II. Male hypogonadism was also more prevalent in group I (75.6% vs 20.6%, p=0.006) than group II, with higher prevalence of both secondary (56.8 vs 15.3%, p=0.006) and primary (18.8 vs 5.3%, p=0.006) hypogonadism. Hyperprolactinemia was observed in 42.4% of patients without significant difference between both groups.Conclusion: COVID-19 can involve multiple endocrine organs and axes, with a greater prevalence and degree of endocrine dysfunction in those with more severe disease.

Background Clinicians have long been struggling to find an effective tool to predict onset of puberty. Objective To explore stimulability of inhibin B after exogenous FSH and its potential role for prediction of onset of puberty. Design and participants Study subjects were enrolled into “exploratory cohort” (n = 42) and “validation cohort” (n = 19). The exploratory cohort was further divided into group 1 (healthy children with spontaneous puberty [SP], n = 26) and group 2 (patients with hypogonadotropic hypogonadism [HH], n = 16). The validation cohort included children who presented with complaints of delayed puberty. Intervention and outcome Participants were subjected to FSH stimulation test and GnRH analogue stimulation test. Cutoffs derived from the exploratory cohort for basal and FSH stimulated inhibin B (FSH-iB) were applied on the validation cohort. Basal LH, GnRH analogue-stimulated LH, basal inhibin B, and FSH-iB were compared with clinical outcomes on a prospective follow-up for prediction of onset of puberty. Results There was statistically significant increment in inhibin B after exogenous FSH in group 1 (SP) in both male (188.8 pg/mL; P = 0.002) and female (1065 pg/mL; P = 0.023) subjects. The increment was not statistically significant in group 2 (HH) in both sexes. FSH-iB at a cutoff of 116.14 pg/mL in males and 116.50 pg/mL in females had 100% sensitivity and specificity for labelling entry into puberty. On application of these cutoffs on the validation cohort, FSH-iB had 100% positive predictive value, negative predictive value, and diagnostic accuracy for prediction of pubertal onset. Conclusion Inhibin B was stimulable in both male and female subjects. FSH-iB can be considered a novel and promising investigation for prediction of onset of puberty. Future studies are required for further validation.

Background: Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is the rarest functioning pituitary adenoma.Methods: A retrospective analysis of eight patients of TSHomas to highlight the presentations, diagnostic challenges, and treatment outcomes.Results: Median age at diagnosis was 42 years, median latency to diagnosis was 2.5 years, and thyrotoxic and compressive symptoms were the most common presenting symptoms. At presentation, three cases were plurihormonal, six cases were on medical treatment including thyroxine, and two cases were incidentally discovered. Imaging revealed macroadenoma in all cases. Seven cases underwent pituitary surgery, after which three achieved remission. Another case entered remission after adjunctive radiotherapy. Thyrotropin (TSH) immunostaining was demonstrated in six out of seven adenomas.Conclusion: TSHoma is a rare functioning pituitary tumor with both silent and symptomatic presentations. Diagnosis can be established with biochemical and imaging features, even without dynamic tests.

Background No validated measures exist for evaluating diabetes self-management in Indian type 1 diabetes (T1D) patients. Objective To cross culturally adapt and evaluate the psychometric properties of Hindi version of Diabetes Self-Management Profile-Self Report (DSMP-SR-Hindi) in Indian T1D patients. Methods Total 160 T1D patients and their parents participated in the study. The mean age of patients was 13.5 +/- 2.5 years and HbA1c was 8.6 +/- 2.2%. Results Exploratory factor analysis employing principle axis factoring with promax rotation was conducted. Monte Carlo parallel analysis identified three sub-scales instead of five sub-scales proposed in original version. Because of underlying ceiling and floor effects and insufficient loadings, five items were eliminated. Consequently, final Hindi version of DSMP-SR contained 19 items from DSMP-SR-24. Internal consistencies were adequate for overall scale (Cronbach's alpha= 0.835), identified sub-scales (Cronbach's alpha= 0.702-0.802) and comparable between genders. DSMP-19 total scores (r= -0.74) and three subscales correlated significantly with HbA1c (SMBG and Corrective Adjustments [r= -0.58], Exercise [r= -0.48], and Conformity to Diet and Insulin Routine [r= -0.64]). For every one SD improvement (11.2 marks) in DSMP-SR-Hindi score, odds of falling into poor glycaemic group (HbA1c > 7.5%) dropped to 0.242 times (95% CI 0.144-0.405;P < .001). Conclusions DSMP-SR-Hindi is a reliable and valid self-report measure of diabetes self-management behavior in Indian T1D patients. The revealed three subscales are reliable to use in isolation and across the genders. It will help in monitoring patient's progress in stepwise manner, ranging from their basic understanding of prescribed regimen to taking advance corrective actions in face of altered needs.

Aim To ascertain the predictors of remission and relapse in patients of Cushing’s disease (CD) undergoing pituitary transsphenoidal surgery (TSS). Methods Patients with CD subjected to TSS over 35 years at a tertiary care center were included. Patients were grouped into remission and persistent disease at 1 year after surgery, and were further followed up for relapse. Demographic, clinical, biochemical, histological, radiological and post-operative follow-up parameters were analyzed. Results Of the 152 patients of CD, 145 underwent TSS. Remission was achieved in 95 (65.5%) patients at 1 year. Patients in remission had shorter duration of symptoms prior to presentation (p = 0.009), more frequent presence of proximal myopathy (p = 0.038) and a tumor size of < 2.05 cm (p = 0.016) in comparison to those with persistent disease. Post-TSS, immediate post-operative 0800-h cortisol (< 159.85 nmol/L; p = 0.001), histological confirmation of tumor (p = 0.045), duration of glucocorticoid replacement (median 90 days; p = 0.001), non-visualization of tumor on MRI (p = 0.003), new-onset hypogonadism (p = 0.001), 3-month 0800-h cortisol (< 384.9 nmol/L; p = 0.001), resolution of diabetes (p = 0.001) and hypertension (p = 0.001), and recovery of hypothalamic–pituitary–adrenal axis (p = 0.018) favored remission. In logistic regression model, requirement of glucocorticoid replacement (p = 0.033), and resolution of hypertension post-TSS (p = 0.003) predicted remission. None of the parameters could predict relapse. Conclusion The study could ascertain the predictors of remission in CD. Apart from the tumor characteristics, surgical aspects and low post-operative 0800-h cortisol, the results suggest that baseline clinical parameters, longer glucocorticoid replacement, and resolution of metabolic complications post-TSS predict remission in CD. Long-term follow-up is essential to look for relapse.