Incidence and risk factors for dysglycaemia in Asian-Indians: a 10-year population-based prospective cohort study.

BACKGROUND: Diabetes prevalence estimates suggest an increasing trend in South-East Asia region, but studies on its incidence are limited. The current study aims to estimate the incidence of type 2 diabetes and pre-diabetes in a population-based cohort from India. METHODS: A subset of Chandigarh Urban Diabetes Study cohort (n=1878) with normoglycaemia or pre-diabetes at baseline was prospectively followed after a median of 11 (0.5-11) years. Diabetes and pre-diabetes were diagnosed as per WHO guidelines. The incidence with 95% CI was calculated in 1000 person-years and Cox proportional hazard model was used to find the association between the risk factors and progression to pre-diabetes and diabetes. RESULTS: The incidence of diabetes, pre-diabetes and dysglycaemia (either pre-diabetes or diabetes) was 21.6 (17.8-26.1), 18.8 (14.8-23.4) and 31.7 (26.5-37.6) per 1000 person-years, respectively. Age (HR 1.02, 95% CI 1.01 to 1.04), family history of diabetes (HR 1.56, 95% CI 1.09 to 2.25) and sedentary lifestyle (HR 1.51, 95% CI 1.05 to 2.17) predicted conversion from normoglycaemia to dysglycaemia, while obesity (HR 2.43, 95% CI 1.21 to 4.89) predicted conversion from pre-diabetes to diabetes. CONCLUSION: A high incidence of diabetes and pre-diabetes in Asian-Indians suggests a faster conversion rate to dysglycaemia, which is partly explained by sedentary lifestyle and consequent obesity in these individuals. The high incidence rates call for a pressing need for public health interventions targeting modifiable risk factors.

Autonomous growth hormone secretion due to McCune Albright syndrome in paediatric age group: an ominous triad.

PURPOSE: The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to elucidate challenges and intricacies in its diagnosis and management. METHODS: It was a single centre study carried out in individuals with MAS and autonomous GH secretion (AGHS). In addition, a systematic search of literature across three databases (PubMed, Scopus and EMBASE) was performed from inception until May 31, 2021 to identify cases of MAS with AGHS in the pediatric age group (<18 years). RESULTS: Three cases from authors centre and 42 cases identified from systematic literature review were analysed. Precocious puberty was the most common presenting endocrinopathy seen in 56.8% (25/44) cases, followed by hyperthyroidism (10/45), hypophosphatemia (4/45), and hypercortisolism (2/45). Cranio-facial fibrous dysplasia (CFFD) was seen in all while polyostotic fibrous dysplasia and Café au lait macule was seen in 40/45 (88.9%) and 35/45 (77.8%), respectively. Pituitary adenoma (58.3% microadenoma) was localized in 53.3% (24/45) cases on pituitary imaging. Biochemical and clinical remission of AGHS was achieved in 61.5% (24/45) cases with medical therapy. CONCLUSION: Diagnosing AGHS in MAS is challenging because of concomitant presence of CFFD, non-GH endocrinopathies associated height spurt and elevated serum IGF-1. GH-GTT should be performed in presence of elevated growth velocity and serum IGF-1 (>1 X ULN) despite adequate control of non-GH endocrinopathies. Medical management can lead to disease control in substantial number of cases and often entails use of multiple agents.

Incidence and predictors of metabolic syndrome in Asian-Indians: a 10-year population-based prospective cohort study.

Background: Metabolic syndrome represents aggregation of risk factors associated with an increased risk of developing type 2 diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). Assessing its incidence is an effective way for estimating the future burden of DM and ASCVD and understanding their secular trends and effect of public health measures on halting the evolution of risk factors. The present study aimed to estimate the incidence of metabolic syndrome and its predictors using a population-based cohort. Methods: A subset of Chandigarh Urban Diabetes Study cohort (n = 1023) without diabetes or metabolic syndrome was prospectively evaluated after a mean of 10.7 years. Metabolic syndrome was defined as per International Diabetes Federation criteria and diabetes as per American Diabetes Association standards. The incidence was calculated in 1000 person years, and multivariate logistic regression was used to estimate the strength of association between incident metabolic syndrome and risk factors. Results: In the followed-up individuals (n = 303), incidence of metabolic syndrome was 32.1 per 1000 person years (95% CI 26.3-38.7 per 1000 person years). Amongst those developing metabolic syndrome, ≥4 components were present in 52% individuals, with low HDL-C being the most common abnormality. Those with metabolic syndrome had a five-time higher risk of diabetes (OR: 4.94; 95% CI: 2.27-9.96; p < 0.001) and a threefold higher risk of hypertension (OR: 2.67; 95% CI: 1.30-5.48; p = 0.006). Conclusion: Asian-Indians have a high incidence rate of metabolic syndrome, which is associated with sedentary lifestyle and consequent central obesity.

Paediatric Pituitary Adenomas: Clinical Presentation, Biochemical Profile and Long-Term Prognosis.

Context: Paediatric pituitary adenomas (PPAs) are uncommon, with evidence confined to small cohorts. Aim: We aimed to elucidate the baseline profile and outcomes of PPAs in a large, contemporary, monocentric cohort. Settings, Design: Pituitary clinic at PGIMER over 8 years (2010-2018). Subjects and Methods: PPAs in patients (≤20 years at diagnosis) were included. A retrospective review of their baseline clinico-biochemical and radiological profiles and outcomes post pituitary surgery/medical management was performed. Results: There were a total of 74 patients, of which 42 were female. The median age was 15 (IQR 13-18) years. Corticotropinomas (32.4%) and somatotropinomas (25.7%) were common, with 1 case of TSHoma and pituitary blastoma. The most common presentation was headache (57%) overall and menstrual irregularities (64.2%) in girls. Most (78%) had macroadenomas. Prolactinomas showed an excellent response to primary medical therapy (83.3%). Transsphenoidal surgery was performed in 81% of patients. Diabetes insipidus (30%) and hyponatremia (26.7%) emerged as common postoperative complications. Adjuvant medical management was required in 25%, and radiotherapy in 18%. Remission rates in Cushing's and acromegaly were 62.5% and 57.8%, respectively, with long-term hormone deficits noted in one-third of patients. Conclusion: PPAs have unique features and management challenges, including effects on growth and puberty. Functional tumours and macroadenomas are common. Remission can be achieved in more than half of the patients, with endocrine deficits persisting in about a third of cases, needing long-term surveillance.

Abdominal obesity and incident cardio-metabolic disorders in Asian-Indians: A 10-years prospective cohort study.

BACKGROUND AND AIMS: To estimate the strength of association between abdominal obesity and incident cardio-metabolic diseases. METHODS: A subset of Chandigarh Urban Diabetes study cohort (n = 543) was followed after a mean of 10.7 years for development of diabetes, prediabetes, dysglycaemia (either prediabetes or diabetes), hypertension and atherosclerotic cardiovascular disease (ASCVD). Diabetes and prediabetes were defined as per American Diabetes Association consulting group criteria, hypertension as blood pressure of ≥140/90 mmHg and ASCVD after review of medical records. Abdominal obesity was defined as waist circumference of ≥80 cm and ≥90 cm in females and males, respectively. RESULTS: As compared to non-obese (n = 209), abdominally obese individuals (n = 334) had a higher risk of diabetes [RR:1.82(1.28-2.57)], prediabetes [RR:1.40(1.05-1.85)], dysglycaemia [ RR:1.38(1.07-1.78)], hypertension [RR: 1.84(1.30-2.59)] and ASCVD [RR:2.12(1.02-4.4)]. The optimal cut-off of waist circumference for detecting incident diabetes, hypertension and ASCVD in females was 88 cm, 85 cm and 91 cm, respectively; while in males it was 90 cm, 87 cm and 94 cm, respectively. CONCLUSION: In Asian-Indians, abdominal obesity as defined by waist circumference of ≥90 cm and ≥80 cm in males and females, respectively is associated with a twofold higher risk of diabetes, hypertension and ASCVD. In addition, the current-cut-offs of waist circumference to define abdominal obesity need reconsideration to optimally identify individuals at a higher risk of cardio-metabolic diseases. However, a high attrition rate represents a major limitation.

Spectrum of Endocrine Dysfunction and Association With Disease Severity in Patients With COVID-19: Insights From a Cross-Sectional, Observational Study.

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% on room air or those with comorbidities) (n= 35) and group II (mild disease, with 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.

Endonasal endoscopic versus microscopic transsphenoidal surgery in pituitary tumors among the young: A comparative study & meta-analysis.

PURPOSE: The transsphenoidal approach presents unique challenges in young, with scanty literature. This study compares the outcome of pituitary tumors among young in our center between endoscopic(EES) and microscopic(MTS) transsphenoidal surgery, with a meta-analysis. METHODS: Patients within 20 years were studied for their surgical approach to a favorable outcome of endocrine remission (ER) (functioning) or Gross/Near-Total resection (nonfunctioning), besides the need for retreatment. Relevant studies were pooled and analyzed according to PRISMA guidelines. RESULTS: Out of 64 young patients with pituitary tumors, 48 underwent transsphenoidal surgery using MTS(33) or EES(15). Of these, 21, 14, 5, and 8 had Cushing's, somatotropinomas, prolactinomas, and non-secreting tumors, respectively. Mean symptom duration was 28months, with weight gain(50 %) and visual complaints(29 %) most prevalent. Hypogonadism(21 %) was the most frequent endocrinopathy. The mean tumor volume was 3.8 cm3. Over mean follow-up of 4.4years, favorable outcome was significantly higher after EES than MTS(78.6 % vs. 46.7 %)(odds ratio 4.18, p = 0.05). EES's better outcome was homogeneous across subgroups of age and tumor type, with no significant subgroup difference. Symptom duration was significantly higher among those who required retreatment(p = 0.05), while ER had a non-significant association with tumor volume(p = 0.07). Overall, 40 %, 27 %, 17 %, and 8% were on hydrocortisone, thyroxine, sex hormone, and desmopressin, respectively, at follow-up with no significant difference between EES and MTS. In pooled analysis of literature, both favorable outcome(74 % vs. 48 %,p = 0.02) and retreatment rate(8% vs. 37 %,p = 0.004) were significantly better with EES than MTS. CONCLUSION: Among young patients with pituitary tumors, the favorable outcome and retreatment rates are better with endonasal endoscopy and associated with symptom duration and tumor volume.

Incidence and risk factors for dysglycaemia in Asian-Indians: a 10-year population-based prospective cohort study.

BACKGROUND: Diabetes prevalence estimates suggest an increasing trend in South-East Asia region, but studies on its incidence are limited. The current study aims to estimate the incidence of type 2 diabetes and pre-diabetes in a population-based cohort from India. METHODS: A subset of Chandigarh Urban Diabetes Study cohort (n=1878) with normoglycaemia or pre-diabetes at baseline was prospectively followed after a median of 11 (0.5-11) years. Diabetes and pre-diabetes were diagnosed as per WHO guidelines. The incidence with 95% CI was calculated in 1000 person-years and Cox proportional hazard model was used to find the association between the risk factors and progression to pre-diabetes and diabetes. RESULTS: The incidence of diabetes, pre-diabetes and dysglycaemia (either pre-diabetes or diabetes) was 21.6 (17.8-26.1), 18.8 (14.8-23.4) and 31.7 (26.5-37.6) per 1000 person-years, respectively. Age (HR 1.02, 95% CI 1.01 to 1.04), family history of diabetes (HR 1.56, 95% CI 1.09 to 2.25) and sedentary lifestyle (HR 1.51, 95% CI 1.05 to 2.17) predicted conversion from normoglycaemia to dysglycaemia, while obesity (HR 2.43, 95% CI 1.21 to 4.89) predicted conversion from pre-diabetes to diabetes. CONCLUSION: A high incidence of diabetes and pre-diabetes in Asian-Indians suggests a faster conversion rate to dysglycaemia, which is partly explained by sedentary lifestyle and consequent obesity in these individuals. The high incidence rates call for a pressing need for public health interventions targeting modifiable risk factors.

Triple A (Allgrove) syndrome due to AAAS gene mutation with a rare association of amyotrophy.

INTRODUCTION: Triple A (Allgrove) syndrome is a rare autosomal recessive disorder characterized by cardinal features of primary adrenal insufficiency (AI) due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrima. It is frequently associated with neurological manifestations such as autonomic dysfunction, cognitive dysfunction, cranial nerve, or motor involvement. Amyotrophy/motor neuron disease is a rare association. CASE PRESENTATION: We herein report a 19-year-old boy diagnosed with triple A syndrome (TAS), with the classic triad of ACTH-resistant adrenal insufficiency, achalasia, and alacrima. Additionally, he had distal spinal muscle amyotrophy. Alacrima was the earliest feature evident in early childhood, followed by achalasia at 12 years of age. He was diagnosed with AI at the age of 19 years, with involvement of the mineralocorticoid axis. Further evaluation showed a neurogenic pattern on electromyography, consistent with a diagnosis of motor neuron disease. A nerve conduction study revealed no significant neuropathy. Genetic analysis confirmed a pathogenic homozygous mutation in the AAAS gene c.43C>A, p.Gln15Lys. He improved with glucocorticoid and mineralocorticoid supplements for AI, and nifedipine for achalasia and artificial tears. He is planned for esophagomyotomy. CONCLUSION: In any young patient with AI not due to congenital adrenal hyperplasia, Allgrove syndrome should be ruled out. Though mineralocorticoid sparing pattern is classical, it can rarely be involved, as seen in the index case. Various components of the syndrome, as well as amyotrophy and other neurologic features, may present in a metachronous fashion. Hence, a high index of clinical suspicion can aid in early diagnosis and management.