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Aim: This study was designed to enumerate regulatory T‑cells (Tregs) and estimate transforming growth factor‑β1 (TGF‑β1) levels in type 1 diabetic (T1D) patients with respect to disease duration and associated autoimmune diseases. Methods: One hundred and fifty patients and twenty healthy controls were recruited in the study. The patients were subcategorized into eight categories on the basis of disease duration (new onset [NO] and long standing [LS]) and associated diseases, i.e., celiac disease (CD) and autoimmune thyroid disease (AiTD). Treg cells were assessed as CD4+ CD25hi+, FOXP3+ cells and serum TGF‑β1 levels were assessed by ELISA. Results: The frequency of Tregs and levels of TGF‑β1 were significantly increased in the patients compared to the healthy controls. Among the different categories of the patients, no significant differences were seen for TGF- β1 levels, but for Tregs in patients with T1D and AiTD (P = 0.035). A significant correlation was also found between percentage count of Tregs and TGF‑β1 levels in NO cases in all disease subcategories, but not in LS patients. Conclusion: Thus, there was an increased percentage of Tregs and serum levels of TGF‑β1 in T1D patients, irrespective of the disease duration and associated autoimmune diseases. The significant correlation in these two parameters at the onset of the disease, but not in LS disease, indicates that the immunological milieu in LS autoimmune diseases is more complicated with disease‑associated conditions such as prolonged hyperglycemia, insulin therapy, and/or continued gluten in diet. Treatment and modulation of these long‑term complications for improving immunological parameters require further research. [ABSTRACT FROM AUTHOR]

Background: The geographical difference in presentation of primary hyperparathyroidism (PHPT) is known. However, there is sparse literature on the influence of age and gender on presentation of PHPT. Aim: To analyze the effect of age and gender on presentation of symptomatic primary hyperparathyroidism. Setting and Design: This is a retrospective analysis of data from the primary hyperparathyroidism registry of a north Indian tertiary care teaching institute. Materials and Methods: Analysis of 184 histopathologically proven PHPT patients registered between March 1990 and March 2010 from a single centre of north India. PHPT patients were divided into three different age groups i.e. children and adolescents less than 25 years, adults 25-49 years, and ≥ 50 years. Clinical presentations, biochemical parameters and parathyroid weight were compared between different age groups and gender using appropriate statistical methods. Results: Mean age of patients was 38.5±13.8 years with female: male ratio of 7:3. Rickets as presenting manifestations were seen in one child and adolescent each. Prevalence of renal stones (P=0.03) and gall stones (P=0.02) was higher in the adult groups compared to the younger and older. There was no difference in bone pain (P=0.7), fracture (P=0.3), osteitis fibrosa cystica (P=0.2), fatigue (P=0.6) and other symptoms among different age groups. There was no difference in serum calcium, phosphate, parathyroid hormone (PTH) and 25 (OH) D levels among different age groups, however, as expected alkaline phosphatase was higher in adolescents compared to adults (P=0.03). Bone pain and muscle aches (P<0.001), fracture (P=0.04), osteitis fibrosa cystica (P=0.01), and gall stones (P=0.03) were more common among women while renal stones (P=0.05) and pancreatitis (P=0.02) were common in men. Serum calcium and phosphate levels were similar in either sex but parathyroid hormone (iPTH) level was higher among women (P=0.02). Parathyroid adenoma weight was higher in older compared to young but did not reach to a level of statistical significance. Conclusion: Age and gender have substantial influence on presentation of PHPT. Bone pain and rickets were common in children and adolescents while renal stones in adults. Women have more severe disease as musculoskeletal manifestations are common and iPTH levels are also higher compared to men. [ABSTRACT FROM AUTHOR]

Background: Pituitary metastasis as a presenting manifestation of silent systemic malignancy is rare. We describe four such cases. Materials and Methods: Four patients (0.7%) of malignancy with pituitary metastasis out of 540 patients of sellar mass within a period of 10 years were analyzed for clinical, hormonal and radiological findings. Result: The age range of these patients was 39-60 years with lag time ranging from 2to 5 months. Pituitary pathology was presenting manifestation in all 4 patients including diabetes insipidus, ophthalmoplegia and variable anterior pituitary hormone deficiency. 2 patients had bronchogenic carcinoma and one each had squamous cell and adenocarcinoma with unknown primary. Diagnosis of pituitary metastasis was confirmed in three on pituitary mass histopathology and in one it was based on rapidly appearing mass in a short time. Conclusion: Rapidly appearing mass in the sellar region, short lag time, sudden onset of ophthalmoplegia, -symptoms and signs disproportionate to the size of mass, presence of diabetes insipidus and destroyed but normal sized sella should invoke the suspicion of pituitary metastasis. [ABSTRACT FROM AUTHOR]

Background & objectives: Hypophosphataemic rickets/osteomalacia (HRO) is an uncommon metabolic bone disorder which affects all ages and either sex. It is characterized by low concentration of serum phosphate levels leading to impairment of mineralization of bone matrix with variable aetiology. We present clinical profile and treatment outcome of 17 patients of HRO. Methods: Seventeen consecutive patients (8 were < 18 yr of age, with median age of presentation being 27.5 yr) of HRO who came to the department of Endocrinology in a tertiary care hospital in north India from January 2000 to December 2006 were included in the present study. Their aetiology, clinical features, biochemical parameters, radiographic features, treatment and outcome were analyzed. Results: HRO was commoner in females (70.5%) with positive family history observed in 6 (35.3%) patients. Common presenting features were short stature (58.8%), backache (58.8%), bony deformities (58.8%), joint pain (52.9%), fractures (29.4%) and dental abnormalities (23.5%). Radiological abnormalities noted were generalized bony deformities (58.8%), fractures (29.4%), and pseudo fractures (17.6%). Mesenchymal tumours were localized in the pelvis in one patient and in the right jaw in another. The patients were treated with calcium (elemental calcium 1 g/d) and oral phosphate supplements (dose 30 - 50mg/kg/day in divided doses) along with active vitamin D supplements (dose 1-3 µg/day) and followed up for a mean of 2 yr. Two patients also received growth hormone (GH) therapy in the dose of 2U/day for 6 and 18 months respectively. Symptomatic well being was reported by all the patients and improvement was noted in the levels of phosphate (P<0.005) and alkaline phosphatase (P<0.05) after treatment. Interpretation & Conclusions: A diagnosis of HRO should be considered in all patients presenting with short stature, deformities or musculoskeletal pains along with low serum phosphate with normal iPTH and 25 - hydroxy vitamin D. [ABSTRACT FROM AUTHOR]

The article presents information on a study which analyzes the characteristics of primary hyperparathyroidism in adolescents in India. A brief overview is given on the incidence of primary hyperparathyroidism (PHPT) as the third most common endocrine disorder in the country. It summarizes the presenting complaints and associated conditions which include pathological fracture, bone pain, bone deformity, and muscle weakness. It describes the demography and symptoms of PHPT in different studies in children and adolescent.

Context. Giant parathyroid adenoma (GPA) is a rare entity that is rarer with Multiple endocrine neoplasia type 1 (MEN1) syndrome. Objectives. Describe the clinical presentation, diagnostic difficulties, and management strategy for GPA in MEN1 Methods. We searched Pubmed, SCOPUS and EMBASE for GPA in MEN1 for GPA in association with MEN1. Hereby, we describe index case of largest ever reported GPA. Results. We identified 7 cases of GPA reported till date in association with MEN1. The mean adenoma weight was 7.1 gram. The index case is largest-ever reported GPA (weight 97 gram) in MEN1 presenting with compressive symptoms and mediastinal mass. Incidentally, she was found to have hypercalcemia with increased parathyroid hormone, suggesting primary hyperparathyroidism. The possibilities of an ectopic parathyroid tumor and thymic carcinoid were considered. She also had acromegaloid features, and was found to have a sellar tumor. Subsequently, MENIN gene mutation was identified confirming MEN1 syndrome. Patient underwent trans-sternal excision of the mass weighing 97 grams and confirmed as parathyroid adenoma on histopathologic examination. Conclusion. Despite rarity of ectopic mediastinal parathyroid tumors, calcium profile should be considered as part of work-up of considering varied etiologies of anterior mediastinal mass. [ABSTRACT FROM AUTHOR]

A young woman with severe vitamin D deficiency presented with proximal muscle weakness, fragility fracture and pseudoarthrosis. On evaluation, she was found to have hypercalcaemia, a single parathyroid adenoma and an undetectable 25-hydroxyvitamin D level. She received parenteral cholecalciferol and subsequently underwent curative parathyroidectomy. Postoperatively, she had hungry bone syndrome, which she gradually recovered from with calcium and calcitriol replacement. Notably, her calcium levels were in the lower limit of normal range and associated with elevated alkaline phosphatase levels at postoperative Day 14. Follow-up for the next four years showed that the patient had remarkable symptomatic and radiological improvements. In this report, we discuss the pathophysiological interactions between vitamin D deficiency and associated primary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

A response by P. Dutta and colleagues to a letter to the editor about their article "Pituitary Metastasis As a Presenting Manifestation of Silent Systemic Malignancy: A Retrospective Analysis of Four Cases," published in the 2011 issue, is presented.

The article focuses on a case history of an 8 year old boy suffering from type I diabetes mellitus. He was treated with purified bovine insulin, developed lipohypertrophy at the site of insulin injection. Lipohypertrophy is a relatively more common complication than lipoatrophy with purified insulin treatment. It should be specifically looked for before increasing insulin dose whenever a previously euglycaemic patient presents with uncontrolled blood glucose. Good glycaemic control can be achieved by just rotating the injection site in the uninvolved area.

Background & objectives: Ectopic secretion of adrenocorticotropic hormone (ACTH) is rare, contributing In 10 per cent cases of endogenous Cushing's syndrome. We describe our experience of about two decades of patients with ectopic Cushing's syndrome (ECS) seen at a tertiary care centre from north India. Methods: Records of patients with ECS from 1985 to 2006 were retrospectively reviewed thai included the presenting manifestations, clinical symptoms and signs, biochemical investigations including plasma cortisol, ACTH and high dose dexamethasone suppression test (HDDST), imaging modalities to localize the non pituitary source of ACTH production, management and follow up of these patients. Results: The study group included 12 patients (7 men) with mean (±SD) age at presentation 27.6 ± 9.5 yr (range 13 to 48 yr) and the mean lag period between onset of symptoms and the diagnosis was 18.3 ± 12.9 months with a range of 3 to 48 months. The weight loss (41.7%) followed by hyperpigmentation (25%) and infections (16.7%) were the common presenting manifestations. Cuticular atrophy (100%), hypertension (100%), bruise (92%) and proximal myopathy (83%) were the commonest signs. Plasma cortisol at 0800 h was 1267.3 ± 483.3 nmol/l and at 2200 h was 1214.9 ± 442.6 nmol/l indicating loss of circadian rhythm. The mean plasma ACTH was 221.1 ± 55.9 (range 21.7 to 950 pg/ml). All but 2 patients had non-suppressibility of 0800 h plasma cortisol with HDDST. Five patients had thymic carcinoid, 3 had bronchial and one each had islet, hepatic and gut carcinoid and one had medullary thyroid carcinoma as a cause of ectopic ACTH secretion, The mean duration of follow up of these patients was 42.6 months and only two could sustain cure while remaining had either residual or recurrence. Interpretation & conclusion: Ectopic Cushing's syndrome is a rare disease with varied manifestations and associated with increased morbidity and mortality. It presents with clinical features quite similar to classical Cushing's. Surgery with removal of primary tumour was found to he treatment of choice. [ABSTRACT FROM AUTHOR]

In this meta-analysis, we analyzed 7 observational studies for assessing the fracture risk in patients with hypoparathyroidism (hypoPT). We found that the risk of vertebral fractures is increased by almost 2-fold, especially those with nonsurgical hypoPT., Purpose: Patients with hypoPT have higher bone mineral density than age- and sex-matched controls. This would theoretically translate into a lower risk of fractures, although available clinical evidence is contradictory. Hence, the present systematic review and meta-analysis was undertaken to collate and provide a precise summary of fracture risk in hypoPT., Methods: PubMed, Scopus, and Web of Science databases were systematically searched using appropriate keywords till March 8, 2021, to identify observational studies reporting the rate of occurrence of fractures among hypoPT patients (nonsurgical and/or postsurgical) compared to non-hypoPT subjects (controls). Study quality was assessed using Newcastle-Ottawa Scale. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated. Subgroup analyses of nonsurgical and postsurgical hypoPT patients were also conducted., Results: We identified 7 observational studies of high-quality pooling data retrieved from 1470 patients with hypoPT. When stratified based on the skeletal site, pooled analyses showed that hypoPT patients were at an increased risk of vertebral fractures compared to non-hypoPT controls (OR 2.22, 95% CI: 1.23, 4.03, p = 0.009, I 2 = 49%, random-effects model). The increased risk of vertebral fractures was seen only in patients with nonsurgical hypoPT (OR 2.31, 95% CI: 1.32, 4.03, p = 0.003, I 2 = 3%, random-effects model) but not in those with postsurgical hypoPT. hypoPT patients were not at an increased or decreased risk of any, humerus, or proximal femur/hip fractures than controls., Conclusions: Nonsurgical hypoPT patients are at an almost 2-fold increased risk of vertebral fractures and thus need to be actively screened irrespective of the underlying BMD., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Asia Pacific Consortium on Osteoporosis (APCO) comprises of clinical experts from across the Asia Pacific region, uniting to develop solutions to problems facing osteoporosis management and care. The vision of APCO is to reduce the burden of osteoporosis and fragility fractures in the Asia Pacific region., Introduction: The Asia Pacific (AP) region comprises 71 countries with vastly different healthcare systems. It is predicted that by 2050, more than half the world's hip fractures will occur in this region. The Asia Pacific Consortium on Osteoporosis (APCO) was set up in May 2019 with the vision of reducing the burden of osteoporosis and fragility fractures in the AP region., Methods: APCO has so far brought together 39 clinical experts from countries and regions across the AP to develop solutions to challenges facing osteoporosis management and fracture prevention in this highly populous region of the world. APCO aims to achieve its vision by engaging with relevant stakeholders including healthcare providers, policy makers and the public. The initial APCO project is to develop and implement a Framework of pan-AP minimum clinical standards for the screening, diagnosis and management of osteoporosis., Results and Conclusions: The Framework will serve as a platform upon which new national clinical guidelines can be developed or existing guidelines be revised, in a standardised fashion. The Framework will also facilitate benchmarking for provision of quality of care. It is hoped that the principles underlying the formation and functioning of APCO can be adopted by other regions and that every health care facility and progressively every country in the world can follow our aspirational path and progress towards best practice.

Backgrounds and Objectives: Short-term studies have demonstrated potential therapeutic efficacy of dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors) in patients with poorly controlled T1DM. In this study we evaluated the effect of DPP4 inhibitor, linagliptin, on glycaemic control and variability, and incretinaxis in well controlled T1DM patients to mitigate the effect of glucotoxicity on incretin secreting cells., Methods: Twenty T1DM patients were randomized to receive either linagliptin (10 patients, dose-5 mg/day) or placebo (10 patients), in addition to insulin for 3 months. HbA1C, continuous glucose monitoring (CGM) and mixed meal test (MMT) were performed before and at the end of the study period., Results: HbA1C reduction and change in glycaemic variability and insulin requirement in the linagliptin group did not attain the level of statistical significance. The increase in AUC GLP1 (Area under curve for GLP1) and decrease in AUC glucagon (Area under curve for glucagon) during the MMT in linagliptin group were also statistically insignificant., Interpretations and Conclusions: Linagliptin is not effective in reducing HbA1C and glycaemic variability in relatively well controlled T1DM patients., (© Journal of the Association of Physicians of India 2011.)

Background: Though cardiac involvement is common in acromegaly, overt congestive heart failure is uncommon., Materials and Methods: This is retrospective analysis of hospital record between 1996 and 2007. We analyzed records of 150 consecutive patients with acromegaly. We included the patients with acromegaly those who had overt congestive heart failure either at presentation or during the course of illness for the present analysis. The diagnosis of acromegaly and congestive cardiac failure were based on standard criteria., Results: Out of 150 patients with acromegaly, 6 patients had overt CHF (4.0%), of which 4 presented with the features of CHF and 2 developed during the course of illness. Three patients had hypertension and 1 had diabetes. Baseline echocardiography showed severe biventricular dysfunction and global hypokinesia in all. Angiography showed dilated hypokinetic left ventricle with normal coronaries in 3, it was confirmed at autopsy in 1. Three underwent trans-sphenoidal surgery, 1 received somatostatin analogue as primary treatment modality. Normalization of growth hormone and IGF-1 led to improvement in cardiac function in 1, 1 patient lost to follow up, and 4 died during the course of illness. In 1 patient, autopsy was performed and cardiac specimen revealed normal coronaries, concentric ventricular hypertrophy, and dilatation with myofibrolysis and interfascicular fibrosis., Conclusion: Prevalence of overt CHF is 4% in present series. Overt CHF carries poor prognosis and hence, this complication should be recognized at earliest, and medical management to normalized cardiac function should be given utmost priority.