Prevalence and severity of coronal and radicular caries among patients with type 2 diabetes mellitus: A cross sectional study.

Background: Studies among type 2 diabetes mellitus patients have reported total caries experience; however the severity and clinical consequences of untreated dental caries are often ignored. Methods: For this study, 150 well (I) and poorly controlled (II) diabetic participants were recruited. The spectrum of caries was evaluated using DMFT (Decayed, Missing and Filled Tooth) index, Dental Caries Severity Classification Scale, PUFA (Pulpal involvement, Ulceration, Fistula and Abscess) index, RCI (Root Caries Index) and the severity of radicular caries by Root Surface Caries Severity Index. Results: The prevalence of coronal and root caries was 90.7% and 23.3%, respectively. There was significant difference among caries experiences for D, M and DMFT. In group II, severity of coronal caries and mean rank of P, F, A and PUFA scores were higher, so were prevalence of root caries and severity of RD2, RD3 and RD4. HbA1c level had positive correlation with DMFT and PUFA scores (r = 0.458 and 0.522), so was the duration of diabetes with coronal caries, DMFT, PUFA score, root caries and RCI score (r = 0.235, 0.320, 0.273, 0.308 and 0.323). Conclusion: This is probably the first study to examine the severity of coronal caries, prevalence of untreated dental caries and severity of radicular caries in diabetic patients. Uncontrolled diabetes causes substantial increase in prevalence and severity of coronal and radicular caries.

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.

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).

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.

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.

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.

A Comparison of Clinicopathological Characteristics and Short-Term Outcome of Papillary Thyroid Carcinoma with Tall Cell Histology and Classic Papillary Thyroid Carcinoma: A Single-Institution Experience.

CONTEXT: Papillary thyroid carcinoma with tall cell histology (PTC-TCH) is an aggressive subtype in terms of clinicopathological features and outcome. Even 10% of tall cells can show aggressive features. AIMS: The aim of this study is to investigate the behavior of PTC-TCH, to compare with classic PTC (cPTC), and evaluate the short-term outcome. SETTINGS AND DESIGN: This is a retrospective analysis of patients with cPTC and those with TCH (PTC-TCH) seen from January 2010 to May 2017 seen in our Thyroid Cancer Clinic. MATERIALS AND METHODS: A total of 40 patients with TCH were compared with 352 cPTC and evaluated for age, gender, tumor size, presence of multifocality, capsular, vascular invasion, extrathyroid extension, and appearance of metastases. Short-term response to therapy was assessed using the 2015 American Thyroid Association guidelines. STATISTICAL ANALYSIS: P < 0.05 was considered statistically significant. All analyses were performed with SPSS software (Version 21.0, Chicago, IL, USA). RESULTS: PTC with TCH presented at a younger age, had larger tumors, and more extrathyroid extension. Seven out of 40 cases developed lung metastases, (17.5% vs. 4.5% in cPTC), within a year of diagnosis. CONCLUSION: PTC-TCH irrespective of percentage of tall cells showed aggressive features and early metastases. They should be recognized early as an aggressive subtype and treated intensively. Close follow-up must be instituted to look for metastases, especially to the lungs.

Radiofrequency Ablation Followed by Percutaneous Ethanol Ablation Leading to Long-Term Remission of Hyperparathyroidism.

A 30-year-old male with cerebral palsy and motor impairment presented with right femur fracture. He had gradually worsening mobility and contractures of all extremities for the preceding 5 years. Evaluation showed multiple vertebral and femoral fractures, severe osteoporosis, a large parathyroid adenoma, and parathormone (PTH) exceeding 2500 pg/mL. Because of poor general health and high anesthetic risk, parathyroidectomy was deemed impractical. Ultrasound-guided radiofrequency ablation (RFA) helped achieve 50% size reduction and PTH levels with better control of hypercalcemia. Later, as calcium and PTH remained elevated, percutaneous ethanol ablation was performed with resultant normalization of PTH and substantial symptomatic improvement. Two years later, he still remains normocalcaemic with normal PTH levels. We propose that RFA and percutaneous ethanol ablation be considered as effective short-term options for surgically difficult cases, which could even help achieve long-term remission. Although not previously reported, our case illustrates that both RFA and percutaneous ethanol ablation could be safely performed successively achieving long-term remission.

Unilateral adrenal mass as the sole initial manifestation of differentiated thyroid cancer.

Unilateral adrenal metastases without disseminated disease has rarely been reported in differentiated thyroid carcinoma (DTC). A 72-year-old female presented with vague abdominal discomfort and loss of appetite of 2 months duration. She had undergone left hemithyroidectomy for a benign thyroid nodule 18 years ago. A contrast CT of the abdomen showed a large left adrenal mass measuring 11×9 cm, suspicious of adrenocortical carcinoma. Hormonal evaluation was in keeping with a non-functional tumour. The patient underwent left adrenalectomy, histopathology of which revealed metastatic well-differentiated thyroid carcinoma. Ultrasound of thyroid done postoperatively showed a subcentimetric hypoechoic lesion with increased vascularity and microcalcifications in the right thyroid bed. Histopathology from a completion thyroidectomy specimen was consistent with follicular variant of papillary thyroid carcinoma. She was treated with high-dose radioiodine ablation therapy and has remained disease-free on follow-up for more than a year.

Technetium uptake predicts remission and relapse in Grave's disease patients on antithyroid drugs for at least 1 year in South Indian subjects.

CONTEXT: Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. AIM: To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. SUBJECTS AND METHODS: Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. STATISTICAL ANALYSIS USED: Mann-Whitney U-test and Chi-square tests were used when appropriate to compare the groups. RESULTS: Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). CONCLUSION: The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease.

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.