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.

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.

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.

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.

A rare RET mutation in an Indian pedigree with familial medullary thyroid carcinoma.

Familial medullary thyroid carcinoma (FMTC) is a variant of multiple endocrine neoplasia type 2 (MEN2) associated with the RET gene mutation. We report a rare RET mutation of c.2671T>G; p.Ser891Ala in Exon 15 of the RET gene in an Indian pedigree where seven family members out of 14 screened were found to be positive for the same. RET genetic analysis should be considered as an early approach in the diagnosis of medullary thyroid carcinoma (MTC) since it improves the prognosis and permits surveillance of other family members.

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).

Clinicopathological features and outcome of thyroglobulin elevation and negative iodine scintigraphy (TENIS) patients with negative neck ultrasound: Experience from a thyroid carcinoma clinic in India.

Management of differentiated thyroid carcinoma (DTC) patients with thyroglobulin (Tg) elevation and negative iodine scintigraphy (TENIS) and negative neck ultrasound scan causes considerable diagnostic and therapeutic dilemma, especially in resource-poor settings. The aim of this study was to evaluate clinicopathological features and outcome of TENIS patients with negative neck US attending a thyroid cancer clinic in India. From a DTC database of 722 containing 193 TENIS patients, subjects with negative neck US and negative Tg antibody (TgAb) were selected retrospectively and analyzed using appropriate statistical methods. The study group included 64 patients (male - 17, female - 47, mean age - 44.7 ± 12.8 years) with 54 papillary and 10 follicular thyroid carcinomas, American Thyroid Association (ATA) recurrence risk categorization (2009) - low - 16, intermediate - 28, and high - 2 0. Most of the patients became TENIS within 1 year of diagnosis with median Tg level of 6.5 ng/mL (1.2-996 ng/mL) and mean follow-up of 7.8 years. On follow-up, Tg dropped spontaneously in 27 patients, more among the low and intermediate-risk categories. For those with high or increasing Tg level, further imaging (fluorodeoxyglucose positron emission tomography/computed tomography) was done and 14 out of 18 were positive. Treatment included empiric radioactive iodine therapy-16, external beam radiation therapy (EBRT)-7, and lymph node dissection (LND)-10. A favorable outcome was seen in 36 patients and unfavorable in 28. Distant metastases were associated with unfavorable outcome and poor survival. Progression-free survival was significantly better in the Tg group of <10 at the time of TENIS (111 months) compared to the Tg group >10 (72 months). Tg level dropped spontaneously in nearly half the patients, especially if levels were <10 and more so among the low-risk category. Distant metastasis was predictive of unfavorable outcomes. Along with Tg level, the ATA risk category might help to predict clinical course and reduce unnecessary expensive imaging in resource-poor settings.

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.

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.

Incidence of New-Onset Diabetes and PostTransplant Metabolic Syndrome after Liver Transplantation - A Prospective Study from South India.

BACKGROUND AND AIMS: Liver transplantation has become an effective therapy for patients with end-stage liver disease. The risk of new-onset diabetes after transplantation (NODAT) and posttransplant metabolic syndrome (PTMS) is high among patients after liver transplantation. These are thought to be associated with increased risks of graft rejection, infection, cardiovascular disease, and death. Our study aimed to document the incidence of NODAT and PTMS and analyze pre and posttransplant predictive factors for their development in patients undergoing a liver transplant. METHODS: This was a prospective comparative study on 51 patients who underwent live donor liver transplantation. They were evaluated at baseline, 3 and 6 months after transplantation with fasting glucose, lipids, serum insulin levels, C-peptide, and HbA1C. They were followed up at 5 years to document any cardiovascular events or rejection. RESULTS: The incidence of preoperative diabetes mellitus (DM) in the study group was 25/51 (49%). The incidence of NODAT was 38.5% (10/26 patients) and PTMS 29% (10/35), respectively. Age (47.7 ± 5.4 vs 41.5 ± 12.7 years), HOMA2 - IR (2.3 ± 1.8 vs 2.1 ± 1.6), serum insulin (16.1 ± 12.0 vs 17.9 ± 14.5), and C-peptide (4.6 ± 0.5 vs 4.8 ± 0.7) were similar at baseline in the NODAT group compared to those who did not develop it. Mean tacrolimus levels were higher in PTMS group (6.8 ± 2.9 vs 5.0. ± 2.0 P value = 0.042). By the end of 5 years, 7 patients expired; 6 due to rejection and one due to cardiovascular disease. Moreover, 2 of these patients had preexisting DM and 2 had NODAT. CONCLUSIONS: None of the baseline metabolic factors in patients undergoing liver transplant were predictive of the development of NODAT or PTMS. Mean tacrolimus levels were significantly higher in the PTMS group. A 5-year follow-up showed no excess risk of cardiovascular events or rejection in those with preexisting DM or in those who developed NODAT.

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.

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.

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.

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.

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.

Performance of ATA Risk Stratification Systems, Response to Therapy, and Outcome in an Indian Cohort of Differentiated Thyroid Carcinoma Patients: A Retrospective Study.

INTRODUCTION: For better individualized management of differentiated thyroid carcinoma (DTC), ATA risk stratification systems (RSS) of 2009 and 2015 as well as a response to therapy re-classification (ATA RTR-2015) are used worldwide for assessing risk of recurrence. But there are no validation studies of these systems from the Indian subcontinent. OBJECTIVES: To compare ATA RSS-2009, ATA RSS-2015, and ATA RTR-2015 for their accuracy in predicting outcome in DTC patients. METHODS: This was a retrospective review of 236 adult patients with DTC >1 cm attending the Thyroid Cancer Clinic at our Institute who had undergone total thyroidectomy and radioactive iodine ablation. Initial risk stratification using ATA RSS-2009 and RSS-2015, clinical response at 1 year and outcome at last follow-up measured by clinical end points were collected and analyzed. RESULTS: ATA RSS-2015 could not be applied to this cohort due to lack of histopathology details. While 77.3% of low-risk ATA RSS-2009 had disease-free status (NED, no evidence of disease) on follow-up, 96.1% of patients, in excellent response in ATA RTR-2015, showed NED. Whereas persistent structural disease was predicted by the high-risk group in ATA RSS-2009 (61.9%) and by the incomplete structural response group in ATA RTR-2015 (57.1%) equally well, the best predictor for NED at 1 year in this cohort was ATA RTR-2015 (p < 0.001). CONCLUSION: This study found that both ATA RSS-2009 and ATA RTR-2015 are reliable in predicting outcome in DTC patients after initial treatment. However, the response to initial therapy at 1 year predicted outcome more accurately than the initial risk status.

Treatment outcomes in pediatric differentiated thyroid carcinoma.

Background Until the American Thyroid Association (ATA) guidelines on management of pediatric differentiated thyroid carcinoma (DTC) became available in 2015, all children with DTC were treated like adults. This study aims to investigate the outcome of pediatric DTC and factors predicting the response to therapy in pediatric DTC managed according to adult guidelines. Methods Clinical records of 41 children less than 18 years of age diagnosed with DTC followed from 2007 in a single center were reviewed. According to the new ATA classification for pediatric DTC, five had low-risk, 28 had intermediate-risk and eight had high-risk disease at presentation. Results There was no mortality or recurrence in this cohort of pediatric DTC patients and the cure rate was 46% during a mean follow-up of 44 months when they were managed according to adult guidelines. Neither the new ATA risk classification nor any clinicopathological character was identified which could predict the response to therapy. The new ATA guidelines would have avoided 27% of the radioiodine therapies given. Conclusions This study showed that DTC in children managed according to adult guidelines had a good cure rate. The new ATA guidelines on pediatric DTC might have drastically reduced the number of radioiodine therapies in the affected children. Long term prospective studies are needed to validate the benefits and risks of both these approaches.