Health related quality of life in pediatric onset Type 1 diabetes mellitus in Kerala, India.

BACKGROUND: To study the health-related quality of life (HRQoL) in pediatric onset Type 1 diabetes mellitus (TIDM) in the state of Kerala in India. METHODS: Diabetes specific HRQoL was determined in 107 subjects with onset of T1DM less than 21 years using the Pediatric Quality of Life Inventory (PedsQL) 3.2 questionnaire of which 69 also completed the PedsQL 4.0 generic questionnaire. The parents of these patients completed the proxy scoring questionnaire. The generic HRQoL of T1DM was compared with control population without diabetes. RESULTS: Mean age of onset of T1DM was 8.2 ± 4.6 years and mean duration was 8.2 ± 5.6 years. The median HbA1c was 8.7% (72 mmol/mol). Microvascular complications were present in 14.9% of the patients. The generic HRQoL was lower in patients with T1DM compared to peers without diabetes (77.43 vs. 87.45; p < 0.001). Parents reported lower scores in diabetes management, treatment barriers, physical functioning and generic scales compared to patients. Parents reported greater worry about the disease with lesser age of onset of diabetes and with presence of complications. Those using insulin vials and on splitmix regimen had lower HRQoL compared to those using insulin pens. The patients belonging to lower socioeconomic status (SES) reported lower diabetes scores (73.7 vs. 58.7; p = 0.015). CONCLUSIONS: The generic HRQoL was lower in children with T1DM compared to peers without diabetes. Parents and children had different perception about HRQoL in many aspects. The diabetes specific scores were lower in those belonging to lower SES.

Monogenic diabetes: A single center experience from South India.

Monogenic forms of diabetes in children are frequently misclassified as either type 1 diabetes or young-onset type 2 diabetes. There is a paucity of literature regarding pediatric monogenic diabetes in the Indian population. A retrospective analysis of case records of 37 children with monogenic diabetes who were diagnosed between 2008 and 2019 in a South Indian tertiary care center was performed. The write-up describes the clinical, biochemical, and genetic characterization of these patients with the diagnoses of neonatal diabetes mellitus (15 patients), MODY (five patients), and various forms of syndromic diabetes (13 with Wolfram syndrome, two with H syndrome, one with mitochondrial diabetes, and one with thiamine responsive megaloblastic anemia).

Utility of Gallium-68 DOTANOC PET/CT in the localization of Tumour-induced osteomalacia.

BACKGROUND: Tumour-induced osteomalacia (TIO) is a rare disorder characterized by hypophosphataemic osteomalacia caused by small mesenchymal tumours secreting fibroblast growth factor 23 (FGF 23). The most difficult part in the management of these patients is the localization of tumours causing TIO. OBJECTIVE: We describe the utility of Gallium (Ga)-68 DOTANOC PET/CT in the localization of tumours causing TIO. PATIENTS AND METHODS: The study was conducted in a single tertiary referral university teaching hospital in India. Ten patients with TIO who underwent Ga-68 DOTANOC PET/CT from the time period 2009 to 2014 were included in this study. Their detailed clinical history, biochemical parameters, imaging modalities, surgical interventions, histopathology and outcomes were reviewed. RESULTS: Ga-68 DOTANOC PET/CT could correctly localize the tumours in TIO in 9 of the 10 cases in which it was performed. Complete resection of the tumour led to full clinical recovery in six of the ten patients; two patients who had partial resection and one patient who underwent radiofrequency ablation showed partial remission. One patient in whom Ga-68 DOTANOC PET/CT was positive in vertebral body with a low standardized uptake value (SUV) did not show up the tumour on surgery. CONCLUSIONS: We conclude that Ga-68 DOTANOC PET/CT can be used as the first imaging modality in patients diagnosed with TIO. The extremely good outcome following the resection of these small otherwise undiagnosed tumours far outweighs its cost even in resource limited settings.

Cost-effective genotyping for classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) in resource-poor settings: multiplex ligation probe amplification (MLPA) with/without sequential next-generation sequencing (NGS).

PURPOSE: Genotyping of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is becoming increasingly significant beyond prenatal counseling in the current era of emerging gene therapy/editing technologies. While the knowledge of common variants helps in designing cost-effective genotyping strategies, limited data are currently available from the Indian subcontinent, especially South India, mainly due to financial constraints. The aim of this study is to assess the genotype of individuals with classic CAH from a South Indian cohort in a cost-effective manner. METHODS: The genotypes of 46 unrelated subjects with classic CAH were studied through initial multiplex ligation-dependent probe amplification (MLPA) using the SALSA MLPA Probe-mix P050 CAH (MRC Holland). Next-generation sequencing (NGS) was done in 10 subjects, as their MLPA was either negative or showed heterozygous variants. RESULTS: The common variants observed in our study population of 46 subjects were large deletions (35.8%), intron 2 variant [c.293-13A/C > G] (35.8%), 8 bp del [c.332_339del p.(Gly111Valfs*21)] (7.7%), and R356W [c.1069 C > T p.(Arg357Trp)] (6.6%). MLPA alone detected pathogenic variants in 78.2% of the initial study samples (36/46). Sequential NGS resulted in a 100% detection rate in our study population. CONCLUSION: MLPA appears to be an effective first genotyping modality for this South Indian cohort due to the high prevalence of large deletions and common variants. MLPA as a first initial screening genotyping test with sequential NGS when required may be a cost-effective and highly sensitive approach to CYP21A2 genotyping in our part of the world and in resource-poor settings.

Etiological Profile, Targeted Levothyroxine Dosing and Impact of Partial Newborn Screening in Congenital Hypothyroidism-A Single Centre Experience.

Background: Congenital hypothyroidism (CH) is the most common cause of preventable intellectual disability. Newborn screening (NBS) for CH has been in vogue in many parts of the world since 1970, but despite its well-known benefits, many developing countries including India have not been able to establish universal NBS for CH till date. Objective: The aim of this study was to review the clinical aspects of congenital hypothyroidism in a tertiary care university referral teaching hospital, focusing on aetiology of CH, predictors of permanence, optimal targeted dose strategies based on aetiology and the effect of newborn screening on the time to diagnosis. Material and Methods: The electronic medical records of 233 children with CH referred to our centre between January 2009 and December 2019 were analysed. A partial NBS was established in the state in 2012. Results: Dyshormonogenesis (57.5%) was the most common aetiology of CH. The incidence of transient CH in children with a gland in situ (GIS) was 35%. Levothyroxine (LT-4) dose of >2.75 µg/kg/day (sensitivity 76.5, specificity 72), >2.15 µg/kg/day (sensitivity 82.4, specificity 61.9) and >1.85 µg/kg/day (sensitivity 76.5, specificity 61.9) at years 1, 2 and 3, respectively, were predictors of permanent CH. An initial LT-4 dose ≥8 µg/kg was sufficient and very seldom led to undertreatment in children with dyshormonogenesis. On the contrary, even doses ≥13 mcg/kg/day led to frequent undertreatment in children with thyroid dysgenesis. After the introduction of newborn screening, the median age at diagnosis came down from 45 days (IQR 14-180 days) to ten days (IQR 3-12 days). Conclusion: Targeted dosing based on aetiology of CH may be more appropriate to optimise outcomes. The time to diagnosis of CH reduced significantly after the adoption of even a partial NBS program highlighting the urgent need for implementation of the same in resource poor settings.

Hypercalcemia with renal failure.

We report a cse of nephrocalcinosis with renal failure which on evaluation was found to have hypercalcemia. Further investigations showed an inappropriately normal intact parathormone (iPTH) and 1,25 dihydroxy-vitamin D level in the setting of renal failure. Probing for a cause of non-PTH mediated hypercalcemia led to the diagnosis of sarcoidosis. Treatment with glucocorticoids could partially reverse the renal failure and control the hypercalcemia. This case illustrates the importance of careful interpretation of laboratory parameters especially levels of iPTH and vitamin D metabolites in renal failure.

Factors Determining Risk Categories in Differentiated Thyroid Carcinoma: Study of an Indian Cohort.

Introduction: Differentiated thyroid carcinoma/cancer (DTC) burden in developing countries could be different from that of the developed nations. Aims and Objectives: To describe the clinicopathological characteristics in a cohort of DTC patients in a south Indian state of Kerala and to compare with the data from other centres. Materials and Methods: A retrospective analysis of the data collected on DTC patients, from January 2010 to August 2018, attending thyroid cancer clinic at a tertiary care centre. Results: mong the 944 patients (male 262; female 682; mean age 43.8 years; standard deviation, SD 13.8), types of tumour were as follows: classical papillary thyroid carcinoma (cPTC) 48.3%, follicular variants of PTC (FVPTC) 28.8%, follicular and hurthle cell carcinoma (FTC&HCC) 10.1%. Mean size of the tumour was 2.7 cm (SD 1.8) papillary thyroid micro carcinomas (PTMC) were seen in 113 patients (12%), which were detected incidentally. Metastases were present at diagnosis in 40.2% cases, most common site being cervical lymph nodes. Distant metastases were seen in 113 patients (14.5%) and commonest site was bone. The American Thyroid Association (ATA) risk stratification was possible only in 684 subjects and showed 31.3% low risk, 41.8% intermediate risk and 26.9% at high-risk category. Lymph node metastasis and distant metastasis were the commonest determining factors for intermediate and high-risk category, respectively. High-risk category was significantly higher in patients >55 years, tumour size >4 cm, FTC/HCC tumour type and extranodal extension (ENE) of lymph node metastasis. Radio active iodine ablation was given to 85.2% subjects. Conclusion: In our DTC population, FVPTC formed the second most common type and PTMC were all incidentalomas. Metastasis at diagnosis was higher suggesting delayed presentation. Old age, FTC/HCC, large size of the tumour, ENE were significantly higher in high-risk patients. Rest of the features of these cohort was comparable with the United States cohort of DTC patients.

Oral Levothyroxine is an Effective Option for Myxedema Coma: A Single-Centre Experience.

INTRODUCTION: Myxedema coma is an endocrine emergency with a very high mortality rate. As per the American Thyroid Association, initial thyroid hormone replacement for myxedema coma should be intravenous levothyroxine (LT4). However, in India, the availability of intravenous LT4 is limited. Often, crushed LT4 tablets are given through the enteral route when parenteral therapy is unavailable. No data or protocol is available for the administration of oral LT4 in myxedema coma. The aim of this study was to assess the effectiveness of oral LT4 in patients diagnosed with myxedema coma and to formulate a protocol for oral LT4 that can be used to guide the treatment of patients when intravenous LT4 is unavailable. METHODS: This retrospective observational study included patients diagnosed with myxedema coma between January 2010 and December 2019. The diagnosis of myxedema coma was based on the diagnostic scoring system for myxedema coma proposed by Popoveniuc et al. [Endocr Pract. 2014 Aug;20(8):808-17]. Dosing of oral LT4 was decided as per our institutional protocol. RESULTS: Fourteen patients (11 males and 3 females) with a median age of 67.5 years (range 11-82) with myxedema coma were included. All patients had central nervous system manifestations, and sepsis was the most common precipitating factor. The median myxedema score was 72.5 (normal ≤25), and the median length of hospital stay was 12 days (range 3-18). The oral LT4 regimen consisted of a loading dose of 300-500 µg, followed by taper over the next 3-5 days. With this regimen, 13 patients survived, and only 1 patient died. CONCLUSION: Oral LT4 is an effective treatment option for myxedema coma when intravenous LT4 is unavailable.

FRAX-based osteoporosis treatment guidelines for resource-poor settings in India.

Using the FRAX® model for India, thresholds for osteoporosis evaluation and treatment without bone mineral density measurement were derived and were validated in a cohort of 300 patients. We suggest the use of this newer age and ethnic-specific FRAX®-derived thresholds for management of osteoporosis in India. PURPOSE: Our study aimed to formulate population-specific intervention thresholds for treatment of osteoporosis in India which can be used even without dual X-ray absorptiometry (DXA). METHODS: Using the FRAX® model for India, thresholds for different age groups for men and women were calculated without bone mineral density (BMD) measurement. The lower assessment threshold (LAT) was based on the 10-year probability of a major osteoporosis fracture (MOF) or hip fracture (HF) equivalent to patients without clinical risk factors. The intervention threshold (IT) was based on the 10-year probability equivalent to patients with fracture. The upper assessment threshold (UAT) was set at 1.2 times the IT. Probability-based thresholds for no intervention (LAT), treatment initiation (UAT) and BMD assessment (between LAT and UAT) were derived. The thresholds were validated in a cohort of 300 patients who were referred for BMD testing. RESULTS: Graphs for age, gender, BMI and ethnic-specific LAT, IT and UAT for MOF and HF are derived. In the validation cohort, BMD testing to initiate/defer treatment was required in only 32.3% patients. The intervention thresholds derived without BMD testing were valid in 98.7% patients. Use of National Osteoporosis Foundation (NOF) guidelines would have resulted in overtreatment in 56/300 (18.6%) patients. CONCLUSION: We suggest the use of this newer age and ethnic-specific FRAX®-derived thresholds for management of osteoporosis. Adopting these cut-offs will ensure that those requiring osteoporosis treatment will not be denied of it just because of lack of a DXA machine and will also help avoid overtreatment.

Clinical Profile of Medullary Thyroid Carcinoma: Audit from a Tertiary Care Center in South India.

CONTEXT: Medullary thyroid carcinoma (MTC), being an aggressive disease, requires meticulous follow-up and multidisciplinary management. The clinical presentation, management, outcome of MTC varies among different populations. AIMS: An audit was conducted to evaluate the demography, clinical presentation, management, and outcome of MTC in a tertiary care center in South India. SETTINGS AND DESIGN: A retrospective analysis was conducted of data from hospital records of patients with MTC treated at our center from 2004 to 2019. STATISTICAL ANALYSIS: All analyses were performed with SPSS software (version 16). RESULTS: Among the 82 patients (M 42, F 40), mean age was 42.07 years (SD 14.5), 46 were operated at our center and 36, outside. Follow-up data were not available for all patients. Median duration of the disease was 36 months and median follow-up was 28 months. Lymphnode dissection was more common (37/46) in patients operated at our center than outside operated patients (17/36) (P < 0.01). At presentation, more than half of the patients had stage IV disease and 8 had distant metastases. Bone, lung, and liver were the common sites of metastases. Persistent hypercalcitoninemia >50 pg/mL was seen in 49.9%. Salvage surgeries of the neck were necessary in 29 patients (38.2%). Mean survival was 66 months and 10-year survival was 35%. Male gender (P = 0.008) and Stage IV disease at presentation (P = 0.038) were associated with poorer survival. CONCLUSION: MTC, in our population, presented at an advanced stage. Male gender and stage IV at presentation had poor survival. Early diagnosis, aggressive initial neck clearance, close follow-up with tumor markers, appropriate imaging, along with prompt surgical intervention will help to improve outcome.

Prospective Study of Bethesda Categories III and IV Thyroid Nodules: Outcomes and Predictive Value of BRAFV600E Mutation.

INTRODUCTION: Atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has emerged as the most controversial category because of its heterogeneity and inconsistent reporting. There is a definite paucity in data available from the Indian subcontinent about the outcome of nodules carrying Bethesda category III or Bethesda category IV diagnoses. AIMS AND OBJECTIVES: The primary objective of our study was to determine the malignancy rate in Bethesda categories III and IV nodules. The secondary objectives were to determine predictive value of BRAFV600E mutation analysis on indeterminate thyroid nodules, predictive value of Thyroid image reporting and data system (TI-RADS) in malignancy prediction and to study the common histological variants in indeterminate nodules. MATERIALS AND METHODS: This prospective study included 176 consecutive nodules of Bethesda categories III and IV, diagnosed over a period of 2 years from August 2015 to August 2017. A part of the fine needle aspirate was used to perform the BRAFV600E mutation analysis. The malignancy risk associated with these Fine needle aspiration Cytology categories were discussed with the patients. Those with Bethesda category IV diagnosis was advised surgery, whereas those with Bethesda category III were given the options of close follow-up with repeat FNA in 3 months or immediate surgery. RESULTS: In our prospective study, there were 176 consecutive samples of categories III (140/79.5%) and IV (36/20.5%). Seventy-five (53.6%) category III nodules and 29 (80.6%) category IV nodules underwent immediate surgical excision. Fifty-five consecutive indeterminate cytology nodules were subjected for BRAFV600E. One of the samples was found to be positive for BRAF T1799A (V600E) mutation. The second sample harboured a missense mutation at position 1819 (TCC--GCC), wherein the codon 607 (TCC) coding for serine was substituted by alanine (GCC) which is a variant of unknown significance. In our study, the malignancy rate of Bethesda categories III and IV, which were triaged for immediate surgery were 54.6% and 72.4%, respectively. CONCLUSION: Malignancy rate in Category III at our center was much higher than that described by ATA and by other studies published from centers around the world, including the only two studies from India. In view of the strikingly high malignancy rate in these indeterminate nodules, strong consideration to surgery should be given to patients with FNA results suggesting these two categories. BRAFV600E mutation analysis in FNA specimen has limited utility in improving the preoperative diagnostic rate for malignancy.

Outcomes of Bilateral Adrenalectomy in Cushing's Syndrome.

CONTEXT: The literature on outcomes of bilateral adrenalectomy (BADx) in Cushing's syndrome (CS) is scant. AIMS: The aim of this study is to analyze the short- and long-term outcomes of patients who underwent BADx and to compare the outcomes among different etiologies of CS. SETTINGS AND DESIGN: This is a retrospective analysis of patients who underwent BADx for CS at our center between 2005 and 2018. MATERIALS AND METHODS: In all, 33 patients were studied for clinical outcomes, survival rates, and long-term complications. STATISTICAL ANALYSIS: All analyses were performed with SPSS software (version 21.0). RESULTS: The mean age at surgery was 39.33 ± 15.67 years. The primary etiology for CS was Cushing's disease (CD) in 42.42%, ectopic source in 36.36%, primary pigmented nodular adrenocortical disease (PPNAD) in 12.12%, and adrenocorticotrophin hormone-independent macronodular adrenal hyperplasia (AIMAH) in 9.09% of patients. The median follow-up time was 72.77 months. Improvement in hypertension and diabetes status after surgery was seen in 78% and 76.19% of patients, respectively. Proximal myopathy improved in 68% of patients. Nelson's syndrome and adrenal crisis were seen in 21.4% of patients each on long-term follow-up. Total mortality after BADx was 33.3%. Mortality in the first 30 days after surgery was seen in five patients (15.15%). Higher cortisol levels at presentation and age more than 40 years were predictors of mortality. Among the Cushing's subtypes, PPNAD had the best prognosis followed by CD. Perioperative Infections were a major cause of mortality. CONCLUSION: BADx is an effective treatment for CS especially in patients with PPNAD and CD but carries a significant mortality rate too.

Klinefelter Syndrome: Clinical Spectrum Based on 44 Consecutive Cases from a South Indian Tertiary Care Center.

BACKGROUND: Klinefelter syndrome (KFS) is the commonest chromosomal abnormality, yet remains largely underdiagnosed due to its varied clinical presentation. This study was done to understand the clinical spectrum in our population. AIM: We intended to study the clinical characteristics of children and adults with KFS in our population. We also desired to identify any special features of Klinefelter variants. METHODS: Forty-four patients with karyotype diagnosis of KFS during the time period 2007-2015 were included in this retrospective study. Clinical details and hormonal profile were obtained from hospital information system. RESULTS: Our study population consisted of 17 (38.6%) participants in pediatric age group (age <18 years) and 27 (61.4%) adults. Clinical presentation prompting evaluation in the former group included cardiac anomalies (29.4%), dysmorphism (23.5%), hypogonadism (17.6%), developmental delay (11.8%), tall stature (11.8%), and cryptorchidism (5.9%). Among adults, 16 (59.2%) presented with hypogonadism and 9 (20.4%) had primary infertility. Six children (35.3%) had micropenis and four (three children, one adult) had unilateral undescended testis. Behavioral problems were detected in 19 (43.2%) subjects. Mean follicle stimulating hormone (FSH) and luteinizing hormone (LH) values were 38 IU/mL and 18 IU/mL, respectively. The classical 47 XXY karyotype was detected in 38 (86.4%) subjects and 6 (13.6%) had karyotype consistent with Klinefelter variants. CONCLUSION: KFS was diagnosed only after 18 years of age in two-thirds of patients. Developmental delay, cardiac anomalies, behavioral abnormalities, and intellectual disabilities were the common presentations in pediatric subjects. Adults predominantly presented with hypogonadism. Individuals with Klinefelter variant karyotype sought medical attention predominantly for non-gonadal concerns.

Novel mutations and spectrum of the disease of NR0B1 (DAX1)-related adrenal insufficiency in Indian children.

Background X-linked adrenal hypoplasia congenita (AHC), due to mutations in the nuclear receptor superfamily 0, group B, member 1 (NR0B1)/dosage-sensitive sex reversal, AHC, critical region on the X chromosome, gene 1 (DAX1) gene, usually presents with a salt-wasting adrenal crisis in infancy and hypogonadotropic hypogonadism (HH) in adolescents. Genetic reports in the literature from patients of diverse ethnicity are limited. We describe the atypical clinical characteristics and molecular genetic results in six Indian patients. Methods Both exons and flanking intronic sequences of the NR0B1 gene were amplified and sequenced in five patients. In the sixth patient, suspected to have a large deletion, multiplex ligation-dependent probe amplification (MLPA) and chromosomal microarray analysis were performed. Results Sequencing revealed three novel mutations: a nonsense mutation (c.776C > A), a deletion (c.298del), both causing loss of domains which are highly conserved among nuclear receptor families, and a missense mutation (c.1112T > C). In-silico analysis by structure-based protein modeling predicted a de-stabilizing effect of the novel missense mutation. Two previously reported mutations were seen in patients with atypical manifestations such as late-onset adrenal insufficiency and precocious puberty. One patient had a 7.15-Mb contiguous deletion involving the NR0B1, Duchenne muscular dystrophy (DMD), glycerol kinase (GK) and melanoma antigen, family B, 16 (MAGEB16) genes. Conclusions Our report emphasizes the wide clinical spectrum of AHC, including rare manifestations, and enumerates unique mutations in the NR0B1 gene.

Metabolic profile, cardiovascular risk factors and health-related quality of life in children, adolescents and young adults with congenital adrenal hyperplasia.

Background The present study was designed to evaluate the metabolic profile, cardiovascular risk factors and quality of life in children with congenital adrenal hyperplasia (CAH) and compare it with age- and sex-matched controls. Methods Fifty-two patients aged 3-21 years with classic CAH due to 21-hydroxylase deficiency were included in the study. Metabolic profiling was done for 36 cases and compared with 28 healthy age- and sex-matched controls. Quality of life was assessed in all 52 children and their parents using a validated Pediatric Quality of Life Inventory (PedsQL) questionnaire and was compared with normative data from the same population. Results The median age was 12 years with 14 (27%) males and 38 (73%) females. Out of the total 52 patients, 35 (67%) had salt wasting and 17 (33%) had simple virilising CAH. The median height standard deviation score (SDS) of cases was similar to that of controls (-0.72 vs. -0.64, p = 0.57) and 81% of females had normal pubertal status indicating a good control of the disease. Weight SDS, body mass index (BMI) SDS, mean diastolic blood pressure and insulin resistance were significantly higher in cases when compared to controls (0.31 vs. -0.3; 0.96 vs. 0.17; 67.8 ± 10.49 vs. 61 ± 8.49 and 2.1 vs. 0.95, respectively). The quality of life was significantly reduced in all domains as per parents' perspective, whereas the children reported reduced quality of social and school functioning. There was no significant correlation between quality of life and metabolic parameters. Conclusions Children with CAH despite a reasonably good control of the disease have a higher cardiovascular risk and reduced quality of life when compared to healthy controls.

Role of Procalcitonin as a Predictor of Clinical Outcome in Acute Diabetic Foot Infections: A Prospective Study.

BACKGROUND: Prediction of outcome in diabetic foot infection (DFI) remains difficult due to lack of active signs of infection, and apparently normal white blood cell (WBC) count. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have been studied previously in this regard and were not useful. Hence, we evaluated procalcitonin (PCT) as a prognostic marker in this study. OBJECTIVES: We aimed to study the role of PCT, CRP, and ESR levels in predicting clinical outcome of acute DFI. MATERIALS AND METHODS: A total of 250 subjects (197 men, 53 women) with acute DFI were enrolled. WBC count, ESR, CRP, and PCT were done for all subjects at admission after obtaining informed consent. Subjects were managed according to hospital protocol and followed up for 1 month. Clinical outcome was assessed based on mobility and morbidity status of the subject. RESULTS: Old age, anemia, hyponatremia, hypoalbuminemia, and elevated serum creatinine were risk factors for poor outcome. Presence of cardiac failure, diabetic retinopathy, peripheral vascular disease, previous amputations, and positive bone culture had negative influence on clinical outcome. Elevated WBC count, ESR, CRP, and serum PCT were significantly associated with bad outcome. Elevated PCT (>2 ng/ml) [odds ratio (OR) (95% confidence interval (CI)), 2.03 (1.13-5.19), P < 0.001], gangrene [OR (95% CI), 2.2 (1.02-4.73), P = 0.04], and sepsis [OR (95% CI), 10.101 (4.34-23.25), P < 0.001] were good predictors of clinical outcome in acute DFI. CONCLUSION: PCT proved to be a reliable marker of acute DFI and good predictor of clinical outcome than existing markers WBC count, ESR, and CRP. Hence it should be useful for clinicians while managing acute DFI.

Insulin Autoantibody Syndrome: Varying Clinical Presentations and Response Patterns of an Underrecognized Entity.

CONTEXT: Insulin autoantibody syndrome (IAAS) is considered to be a rare cause of hyperinsulinaemic hypoglycaemia. Lack of familiarity with the varied clinical manifestations leads to underdiagnosis. Localization techniques aimed at insulin-secreting neoplasms and nesidioblastosis, which are expensive often are ordered when the correct diagnosis is not made. AIMS: We describe the myriad of clinical manifestations associated with IAAS based on single centre experience. SETTINGS AND DESIGN: Retrospective analysis of patients who got admitted with symptoms suggestive of hypoglycaemia and underwent mixed meal test and prolonged hypoglycaemic test from 2016 to 2019. SUBJECTS AND METHODS: Retrospective data of 12 patients with IAAS who were diagnosed in the threeyear time period between 2016 and 2019 are included in this analysis. Clinical details, biochemical parameters and imaging modalities were analysed. STATISTICAL ANALYSIS: All analyses were performed with SPSS software (version 17). RESULTS: Total of twelve patients 12 (5 male and 7 females) were identified as IAAS. Median age of presentation was 57 years. Median insulin levels and median C-peptide levels were 300 miu/ml and 18.5 ng/ml respectively. Only 3 (25%) patients had spontaneous resolution. Steroid induced remission occurred by 3 months in the remaining patients. Intermittent hyperglycaemia was seen in 9 (75%) patients. Implicatable drug use preceding the occurrence of the clinical symptoms was observed in five patients. CONCLUSION: IAAS is not uncommon in India. The diagnosis should be pursued in patients with hyperinsulinaemic hypoglycaemia especially when insulin levels are very high or when there is intermittent hyperglycaemia.