Role of Genetic Testing in the Management of Indeterminate Thyroid Nodules in the Indian Setting.

The increased detection of thyroid nodules in the human population has led to an increase in the number of thyroid surgeries without an improvement in survival outcomes. Though the choice for surgery is straightforward in malignant thyroid nodules, the decision is far more complex in those nodules that get categorized into indeterminate thyroid nodules (ITN) by fine needle aspiration. Therefore, there is a pressing need to develop a tool that will aid in decision-making among the ITN. In this context, the development of various molecular testing (MT) panels has helped to confirm or rule out malignancy, reducing unnecessary surgeries and potentially guiding the extent of surgery as well. Currently, such tests are widely used among the Western population but these MT panels are not used by the South Asian population because of non-availability of validated panels and the high cost involved. There is a need to develop a suitable panel which is population-specific and validate the same. In this review, we would focus on current trends in the management of ITN among the South Asian population and how to develop a novel MT panel which is cost-effective, with high diagnostic accuracy obviating the need for expensive panels that already exist.

Do Bone Mineral Density, Trabecular Bone Score, and Hip Structural Analysis Differ in Indian Men with Parkinson's Disease? A Case-Control Pilot Study from a Tertiary Center in Southern India.

Objective: Parkinson's disease (PD) is a neurodegenerative condition that is characterized by bradykinesia, rigidity, and gait instability. Inherent to this condition is an increased predisposition to falls and fractures. Bone health in Parkinson's disease in India has not been studied thus far. This study aimed to assess the bone mineral density (BMD), trabecular bone score (TBS), and hip structural analysis (HSA) in Indian men with PD and compare them with matched controls. Methodology: A case-control study done at a tertiary care center from southern India. Bone biochemistry, BMD, TBS, and HSA were assessed. Results: Among 40 cases and 40 age, gender, and body mass index (BMI)-matched controls, there was no significant difference in BMD between both groups. The mean (SD) TBS at the lumbar spine [1.349 (0.090)] was significantly (P = 0.019) lower in men with PD as compared to matched controls [1.401 (0.089)]. Among the parameters of HSA, the buckling ratios were significantly higher at the femoral neck [11.8 (2.2) vs 9.4 (2.2); P = 0.001] and inter-trochanteric region [9.4 (2.1) vs 7.8 (1.4); P = 0.002] among cases as compared to matched controls. Vitamin D deficiency was significantly higher in this cohort of patients as was bone turnover marker indicating bone loss and a high bone turnover state. Conclusion: A comprehensive bone health assessment comprising BMD, TBS, and HSA may be required to capture all aspects of bone strength in Indian men with PD as BMD assessment as a stand-alone tool may not suffice to obtain all information pertaining to fracture risk in these individuals.

Caring for the Bone Health Among Liver Transplant Recipients.

Liver transplant outcomes have improved over the years, and currently, the quality of life and long-term well-being of these patients needs to be improved. Improving bone health goes a long way toward achieving this objective. Poor bone health (osteopenia and osteoporosis) although prevalent, is often overlooked owing to its asymptomatic nature. It can be complicated by debilitating fracture affecting quality of life. It is recommended to assess and optimize bone health prior to liver transplant. Multiple factors contribute to poor bone health in a liver transplant recipient and it is vital to understand and ameliorate these. A careful and targeted approach with inputs from multidisciplinary team involving transplant physician, endocrinologist, occupational therapist, nutritionist, and nursing personnel may often be required. In this review, we aim to concisely discuss the various aspects related to prevalence, pathophysiology, evaluation, treatment, and follow-up of bone disease among liver transplant recipients.

Bone Mineral Density and Serum Bone Turnover Markers among Post-Menarchal Girls from Rural South India.

Background: The data on the bone mineral density (BMD) and bone turnover markers (BTMs) in Indian adolescents are limited. Objectives: To assess BMD at lumbar spine (LS, L1-L4) and femoral neck (FN) in South Indian post-menarchal girls and correlate it with dietary calcium intake (mg/day), physical activity score and post-menarchal years. The study also assessed serum BTMs and their correlation with chronological age in the study population. Methods: This cross-sectional study included apparently healthy post-menarchal adolescent girls aged 12-16 years randomly selected from the community. Participants with vitamin D deficiency were excluded. The data on calcium intake and physical activity were obtained using validated questionnaires. All participants were evaluated with serum calcium, 25-hydroxy vitamin D, parathyroid hormone, N-terminal propeptide of type 1 collagen (P1NP) and Beta-CrossLaps (CTx) and BMD at LS and FN using dual X-ray absorptiometry (DXA). Statistical Analysis: EpiData version 3.1 was used for the data entry. The data analysis was done using Statistical Package for Social Sciences (SPSS) version 21. Continuous variables were expressed as mean ± SD. Pearson's correlation coefficient (r) was calculated, and two-tailed Kendall's tau-b test was used for assessing correlation of all nonparametric measures. Results: A total of 103 participants were screened, and data from 77 were analysed. There was a significant positive correlation of BMD at LS with chronological age (r: +0.235, P = 0.036), but not at FN. Positive correlation of BMD with increase in post-menarchal years was also noted at LS (r: +0.276, P = 0.015). There was no significant association of BMD with calcium intake and physical activity scores at both sites. There was a significant negative correlation of serum BTMs with age CTx (r: -0.596, P = 0.0001) and P1NP (r: -0.505, P = 0.0001). Conclusion: This study provides insight into the reference BMD range at LS spine and FN in South Indian rural post-menarchal adolescent girls. BMD positively correlated, whereas BTMs negatively correlated with age. The study also provides the first Indian reference range for serum BTMs in this age group.

Bone health in ambulatory male patients with chronic obstructive airway disease - A case control study from India.

Objective: Chronic obstructive airway disease (COPD) is characterized by airflow limitation due to airway and/or alveolar abnormalities with significant extra-pulmonary manifestations. Bone health impairment is an extra-pulmonary complication of COPD which is less well studied in India. Moreover, it can contribute to significant morbidity and mortality. Hence, we aim to estimate the prevalence of osteoporosis and metabolic parameters of adverse bone health in patients with COPD. Methods: In this case control study, male subjects aged 40-70 years with COPD attending the respiratory outpatient clinic in a tertiary care hospital were recruited over a period of 2 years and the control population were derived from the historical cohort who were apparently healthy with no obvious diseases. Metabolic parameters of bone health measured from fasting blood samples were calcium, albumin, alkaline phosphatase, phosphorous, parathormone, creatinine, 25-hydroxy vitamin D, and testosterone. Bone mineral density (BMD) was estimated using DXA scan and the World Health Organization (WHO) criteria was used to categorize into osteoporosis, osteopenia, and normal BMD based on the T-score at femoral neck, lumbar spine and distal forearm. Pulmonary function tests and 6 minute walk test were performed if they had not been done in the previous 3 months. The associations of COPD with osteoporosis were analyzed using linear regression analysis and effect size are presented as beta with 95% confidence interval. Results: Of the 67 participants with COPD enrolled in the study, osteoporosis was present in 61% (41/67) and osteopenia in an additional 33% (22/67) of the cases, which was higher when compared to the control population (osteoporosis 20% [50/252] and osteopenia 58% [146/252]). In regression modeling, there was a trend toward adverse bone health with advanced age, low body mass index, low forced expiratory volume in 1 second and testosterone deficiency in COPD. Conclusion: Individuals with COPD have a substantially higher prevalence of osteoporosis and osteopenia, up to almost twice that of the general population, with a significant number demonstrating at least one parameter of adverse metabolic bone health on assessment. Hence, bone health assessment should be a part of comprehensive COPD care to prevent adverse consequences due to poor bone health.

Tenofovir-induced hypophosphatemic osteomalacia: how do bone mineral density, trabecular bone score and proximal hip geometry change with treatment?

Summary: Tenofovir-induced osteomalacia secondary to proximal renal tubular dysfunction is not an uncommon complication known to occur. A 46-year-old woman was referred for the evaluation of osteoporosis which was diagnosed elsewhere. She had polyarthralgia, bony pains and proximal muscle weakness of 1 year duration. She was diagnosed to have HIV infection and was on antiretroviral therapy that consisted of tenofovir, lamivudine and efavirenz for the past 12 years. She had attained menopause 5 years back. On examination, she had bone tenderness, proximal myopathy and painful restriction of movement of her lower limbs. Investigations showed features of renal tubular acidosis, hypophosphatemia and raised alkaline phosphatase that were suggestive of osteomalacia. X-ray of the pelvis showed diffuse osteopenia and an MRI of the pelvis done showed multiple insufficiency fractures involving the head of femur on both sides. Following this, her tenofovir-based regimen was changed to abacavir, efavirenz and lamivudine with addition of neutral phosphate supplements and calcitriol. On follow-up after 6 months, she had significant improvement in her symptoms as well as in the bone mineral density at the lumbar spine (33.2%), femoral neck (27.6%), trabecular bone score (13.2%) and reduction in the buckling ratio at the narrow neck (6.3%), inter-trochanteric region (34%) and femoral shaft (28.8%). Tenofovir-induced osteomalacia is encountered in individuals on prolonged treatment with tenofovir. Treatment consists of changing to a non-tenofovir-based regimen, as well as supplementation of phosphate and calcitriol. Treatment results in remarkable improvement in symptoms and most densitometric indices. Learning points: Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) and is a major drug in the treatment of retroviral and hepatitis B infections. Tenofovir-related hypophosphatemic osteomalacia is related to proximal tubulopathy and is not an uncommon occurrence. Treatment mandates changing to a non-tenofovir-based regimen with supplementation of neutral phosphate and calcitriol. Treatment results in a significant improvement in bone mineral density, trabecular bone score and hip geometric parameters.

Chronic Alcohol Consumption and its Impact on Bone and Metabolic Health - A Narrative Review.

Chronic consumption of a large quantity of alcohol often results in the disruption of the communication between the nervous, endocrine and immune systems leading to profound and serious consequences at the physiological and behavioral levels. The overall impact of excessive alcohol consumption on bone health, metabolic profile and body composition, especially at moderate levels, is not well understood. Chronic excessive alcohol consumption adversely affects bone health through multiple mechanisms leading to low bone mass. It may also be significantly associated with various components on the metabolic syndrome. This review summarizes the findings from published studies that provide consistent evidence on the various effects of alcohol abuse on the bone health and metabolism.

A Pilot Study of Electrocardiographic Features in Patients with Obesity from a Tertiary Care Centre in Southern India (Electron).

Background: Obesity is associated with increased all-cause mortality and cardiovascular disease (CVD). An electrocardiogram (ECG) may be used to screen for subtle signs of CVD or altered cardiac morphology in the obese. Methodology: This observational cross-sectional analysed ECG changes in patients with obesity at a tertiary care centre in southern India. Results: One hundred and fifty adult patients with a mean (SD) BMI of 39.9 (6.7) kg/m2 were recruited in the study after excluding those with comorbidities (diabetes mellitus, systemic hypertension) or on chronic medications (ACE inhibitors). The cohort showed a female predominance (69.3%), with a mean (SD) age of 45.4 (11.2) years. Most patients exhibited a sinus rhythm (78%), with one patient showing features of first-degree conduction block. Sinus tachycardia was seen in 32 (21.3%) patients. We observed left and right ventricular hypertrophy in five (3.3%) and three (2%) patients, respectively. Observed ECG patterns included a prolonged QTc in 16 (10.7%) patients, inverted T-waves (mostly in the inferior leads) in 39 (26%) patients and ST-segment depression (predominantly in the lateral leads) in 14 (9.3%) patients. A greater prevalence was noted for morbid obesity. No deaths were reported in our cohort. Conclusions: The predominant ECG variations in this cohort included tachycardia, atrial enlargement, ventricular hypertrophy, conduction defects, LAD, features of ischemia or old infarction and repolarization abnormalities, with a greater prevalence in morbid obesity. Further studies are needed to assess the impact of weight reducing measures on reversibility of these changes and determine the association with outcomes in obese patients.

OSTA as a screening tool to predict osteoporosis in Indian postmenopausal women - a nationwide study.

This cross-sectional study done on 5356 postmenopausal women showed that OSTA may be used as a reliable screening tool for osteoporosis across different regions of India, a country known for its ethno-linguistic, cultural, and genetic diversity. BACKGROUND: The gold standard for diagnosing osteoporosis is DXA (dual-energy X-ray absorptiometry) scan, and this is not widely available across India. OSTA (Osteoporosis Self-Assessment Tool for Asians) score predicts risk of osteoporosis and can be used as reference tool for DXA. At a cutoff of ≤ + 1, OSTA predicted femoral neck osteoporosis with a sensitivity of 88% in a previous study among south Indian postmenopausal women. This study was done to validate the OSTA score in postmenopausal women across India. METHODOLOGY: A cross-sectional study in 5356 postmenopausal women from four regions of India namely south, east, north, and west. Bone mineral density (BMD) and trabecular bone score (TBS) were assessed by DXA. The performance of OSTA in predicting BMD and TBS was assessed using ROC curve. RESULTS: The mean (SD) age was 61.6 (7.6) years. The performance of OSTA in predicting osteoporosis was fair (P < 0.001) with an AUC of 0.727 (95% CI 0.705-0.749) in the south, 0.693 (95% CI 0.664-0.723) in east India, 0.730 (95% CI 0.700-0.759) in the north, and 0.703 (95% CI 0.672-0.735) in the western region. At a cut-off below + 1.0, sensitivity was 76-84% and specificity was 45-53% in diagnosing osteoporosis at any site. In predicting degraded microarchitecture, the AUC was 0.500-0.600. CONCLUSION: OSTA may be reliably used as a screening tool for women at high risk of osteoporosis across India and may circumvent the limited availability of DXA scanners across the country.

Weight Stigma in Patients With Obesity and Its Clinical Correlates: A Perspective From an Indian Bariatric Clinic.

Introduction Obesity being a global epidemic, currently has several adverse health outcomes. Weight stigma is a significant barrier to delivering quality services and also impairs clinical progress. We intended to study the association of stigma with demographic and clinical variables in obese patients to identify the obstacles in treatment-seeking, so stigma could be adequately addressed to improve clinical outcomes. Methods This study was a retrospective chart review in a Bariatric clinic in a tertiary care hospital. The weight self-stigma questionnaire (WSSQ) was routinely used in the clinic. Demographic and clinical data were collected for 146 obese patients.  Results Female patients (73%) had higher stigma scores. The mean total stigma score was 41.6(SD 3.83), the total self-devaluation score was 21.88(SD 2.10), total fear of enacted stigma was 21.26(SD 2.33). Multivariate analysis revealed an association between stigma with multiple dysfunctional eating patterns like bingeing, overeating, and grazing (Adjusted aOR 3.86, 95% CI- 1.66-8.96) and psychiatric diagnosis (adjusted aOR 3.00, CI- 1.25-7.17). Conclusion This study found an association between stigma and certain clinical variables that maintain and worsen obesity and comorbid psychiatric diagnoses. This highlights the importance of an assessment of mental health and stigma in general practice when dealing with patients with obesity. Treating the underlying psychiatric comorbidities and addressing unhealthy eating behaviors can help reduce self-stigma. Stigma is a barrier to treatment-seeking that needs to be addressed in the community.

Impact of teriparatide therapy in Indian postmenopausal women with osteoporosis with regard to DXA-derived parameters.

Background: There is paucity of literature on the impact of teriparatide on hip geometry and bone microarchitecture globally and none from the Indian subcontinent. This study examined the outcome of teriparatide therapy on vertebral fractures, bone mineral density (BMD), hip structural analysis (HSA), and trabecular bone score (TBS) in Indian postmenopausal women with severe osteoporosis. Methodology: Ambulatory postmenopausal women above the age of 50 years with either severe osteoporosis or vertebral fractures, or both, were recruited. All patients received cholecalciferol (2000 IU/day), calcium carbonate (elemental calcium 1 g/day), and teriparatide (20 mcg subcutaneously/day) for 24 months. Baseline bone biochemistry, BMD, TBS, and HSA were assessed and repeated after 24 months of therapy. Incident vertebral and nonvertebral fractures were also studied. Results: A total of 51 postmenopausal women with mean (SD) age of 65.7(8.6) years, and mean (SD) body mass index of 22.7 (3.5) kg/m2 were recruited in this study. Vertebral fractures were present in 74.5% (38/51) at baseline. Following teriparatide therapy, significant improvement was observed in the BMD (g/cm2) at both the lumbar spine (0.706-0.758: p < 0.001) and femoral neck (0.551-0.579: p = 0.047) as well as the TBS (1.160-1.271: p < 0.001). Most indices of proximal hip geometry also showed significant improvement following teriparatide therapy at 24 months. Incident vertebral fractures were noted in only 7.8% (4/51) of participants, while 92% (47/51) of participants did not develop any new vertebral fractures on follow-up. Conclusion: In South Indian postmenopausal women with either severe osteoporosis or vertebral fractures, or both, teriparatide was effective in improving the bone mineral parameters and bone quality.

Cathepsin K Mutation-A Subtle Clinical Presentation.

Context: Pyknodysostosis is an uncommon inherited disorder associated with consanguinity, often presenting with sclerotic bone disease, short stature, dysmorphic features, and recurrent fragility fractures at an early age. Case: A 34-year-old woman was evaluated for the cause of recurrent fragility fractures. She was born of a third-degree consanguineous marriage and had a twin brother who was of short stature. The index patient had a height of 141 cm, dysmorphic features including frontoparietal bossing, blue sclera with short stubby fingers and toes. Radiological evaluation revealed diffuse osteosclerosis with acro-osteolysis exclusively in the toes, apart from mid-facial hypoplasia, lack of pneumatization of the paranasal sinuses, dental abnormalities, and scoliosis. Dual-energy x-ray absorptiometry revealed increased bone mineral density. Based on the clinical features, the patient was tested for cathepsin K gene variants using next-generation sequencing and was found to be positive for a novel homozygous c.224T>C, p.Met75Thr likely pathogenic missense variant. Discussion: This patient presented at a later age than expected with recurrent fragility fractures and the diagnosis was not suspected till adulthood, owing to the subtle clinical features. Confirmation with genetic testing helped in establishing the diagnosis. Conclusion: Pyknodysostosis, although uncommon, is one of the differential diagnoses for diffuse osteosclerosis presenting with recurrent fragility fractures. Next-generation sequencing in an appropriate setting may confirm the diagnosis.

Comprehensive evaluation of patterns of hypoglycemia unawareness (HUA) and glycemic variability (GV) in patients with fibrocalculous pancreatic diabetes (FCPD): A cross-sectional study from South India.

OBJECTIVES: Hypoglycemia unawareness (HUA) in patients with FCPD is common with an unclear etiology. We evaluated the prevalence, characteristics of HUA, glycemic variability (GV), its possible association with pancreatic glucagon secretion & cardiac autonomic function in patients with FCPD. METHODS: A two-week ambulatory glucose profile (AGP) and cardiac autonomic function test was done in patients with FCPD (n = 60), and categorized into UNAWARE (n = 44) and AWARE (n = 16) groups based on the Hypoglycemia Unawareness Index (HUI) score. Glycaemic variability was assessed from the AGP data using Easy GV 9.0.2 software. A subset of patients from both the groups (n = 11) underwent a mixed-meal challenge test and were compared with healthy individuals (controls; n = 11). RESULTS: HUA was evidenced in 73% (44/60) of patients with FCPD. Significant hypoglycemia, nocturnal hypoglycemia, duration of hypoglycemia and poor cardiac autonomic functions (p = 0.01) were prominent in the UNAWARE group. The overall GV was greater in the UNAWARE group. In the UNAWARE group, significantly reduced fasting and post prandial glucagon levels negatively correlated with HUI (r = -0.74, p < 0.05) and GV-hypoglycemia indices (p < 0.05) In contrast, significantly higher post prandial glucagon levels in the AWARE group positively correlated with post prandial hyperglycemia (r = 0.61, p < 0.05). CONCLUSION: Heterogeneity in patterns of glucagon secretion were significantly associated with HUA and GV. Reduced glucagon levels contribute to greater risks of HUA, nocturnal hypoglycemia and greater GV, while hyperglucagonemia predisposes to postprandial hyperglycemia and hypoglycemia awareness in patients with FCPD.

Vanishing Bone Disease of the Thoracic Cage: Challenges in the Management of a Rare Entity.

Background/Objective: Vanishing bone disease (VBD) is a rare entity, characterized by massive osteolysis and lymphovascular proliferation. Our objective was to report the case of a 22-year-old man who presented with VBD of the ribs and the challenges involved with its management in this location. Case Report: A 22-year-old man presented with left-sided chest and back pain. An x-ray revealed that the fourth to sixth ribs on the left side of the chest were missing. The erythrocyte sedimentation rate was normal (5 mm/h; normal value, <10 mm/h), ruling out overt infectious and inflammatory pathology. A positron emission tomography-computed tomography scan excluded an underlying malignancy. Findings of serum protein electrophoresis did not show an M band. Normal levels of calcium (9.0 mg/dL; normal range, 8.3-10.4 mg/dL) and parathyroid hormone (38 pg/mL; normal range, 8-74 pg/mL) excluded primary hyperparathyroidism as a cause for osteolysis. A computed tomography scan of the chest revealed only lytic destruction and resorption of the fourth to sixth ribs on the left side. A diagnosis of VBD was made. A biopsy was deferred owing to the location of the disease involving the thoracic cage that could cause permanent lymphatic leakage. He was administered parenteral zoledronate 4 mg monthly for 3 months and subsequently once every 3 months for the next 2 years with subcutaneous interferon alfa-2b 6 MIU thrice weekly initially, then twice a week, and subsequently tapered to once every 10 days. On the follow-up at 3 years, he remained stable, with no further osteolysis or radiographic progression of the disease. Discussion/Conclusion: VBD may present diagnostic and therapeutic challenges; the abovementioned patient was diagnosed with VBD after excluding secondary causes of osteolysis. Although a high index of suspicion is required to diagnose VBD, it also mandates close monitoring and follow-up.

Losartan as a Steroid-Sparing Adjunct in a Patient With Features of Refractory Camurati-Engelmann Disease.

Objective: The treatment of Camurati-Engelmann disease (CED) involves the use of glucocorticoids, analgesics, and bisphosphonates; experience with the use of losartan is limited. Our objective was to describe the case of a patient diagnosed with CED whose symptoms remained refractory while on steroids and bisphosphonates and who was successfully treated with losartan. Case Report: A 27-year-old woman presented with bone pain involving her extremities and large joints for 1 year. Clinical examination revealed bone tenderness and proximal myopathy with elevated C-terminal peptide of type 1 collagen (1617 pg/mL; normal range, 137-573 pg/mL) and N-terminal propeptide of type 1 procollagen levels (163 ng/mL; normal range, 5.1-58.3 ng/mL). Calcium (9.4 mg/dL; normal range, 8.3-10.4 mg/dL), phosphate (3.4 mg/dL; normal range, 2.5-4.5 mg/dL), and parathyroid hormone (62 pg/mL; normal range, 8-80 pg/mL) levels were within the normal range. Radiographs showed hyperostosis involving the diaphyseal region of long bones of the lower and upper limbs, and a provisional diagnosis of CED was made. She was treated with prednisolone, 30 mg daily, with which she reported some improvement. As exogenous Cushing syndrome had developed in her because of prednisolone, its dose was tapered. Subsequently, her bone pain worsened. Thereafter, she was initiated on oral alendronate. Due to persistent pain, losartan was added, after which she had marked decrease in bone pain with a reduction in the C-terminal peptide of type 1 collagen (375 pg/mL) and N-terminal propeptide of type 1 procollagen (50 ng/mL) levels. Discussion: Occasionally, CED presents therapeutic challenges, and when its symptoms remain refractory to conventional doses of steroids and bisphosphonates, other options may be needed. The abovementioned patient was initiated on losartan, which acts by downregulation of transforming growth factor ß1, leading to the reduction in pain. Conclusion: Losartan downregulates transforming growth factor ß1 and may be offered as a steroid-sparing option in individuals diagnosed with CED if symptoms remain refractory to conventional treatment.