Posterior reversible encephalopathy syndrome and parkinsonism as the first manifestation of primary hyperparathyroidism - a report of two cases.

BACKGROUND/OBJECTIVE: Primary hyperparathyroidism (PHPT) may be asymptomatic or present with renal calculi, secondary osteoporosis, fractures and neuropsychiatric manifestations. Posterior reversible encephalopathy syndrome (PRES) and parkinsonism are atypical manifestations that may be rarely associated with PHPT. We report two patients who presented with the conditions mentioned above. CASE REPORT: The first patient involved a 38-year-old woman who presented with diminution of vision, seizures, altered behavior and hypertension over eight months. An MRI of the brain done had shown vasogenic edema involving the parieto-occipital regions, suggestive of PRES. A metabolic screen revealed PTH-dependent hypercalcemia that was localized to the left inferior parathyroid gland. Following focused parathyroidectomy, there was improvement in sensorium, vision and normalization of blood pressure. The second patient was of a 74-year-old man who presented with progressive extrapyramidal symptoms of gait abnormalities and rigidity since the past eight months. He was initiated on Selegeline and Levodopa for the same purpose, and subsequently reported minimal improvement in symptoms. Investigations revealed PHPT associated with a right inferior parathyroid adenoma. Within two weeks following surgery, there was an improvement in rigidity and gait and he was able to ambulate without support. DISCUSSION: PRES has been reported to occur in the context of preeclampsia, hypertension, infection, sepsis and autoimmune conditions. PRES associated with hypercalcemia is rarely reported. While extra-pyramidally related manifestations are described in hypoparathyroidism, PHPT related parkinsonism is not commonly encountered. Identifying the underlying aetiology and initiation of corrective measures may lead to amelioration of patient symptomatology. CONCLUSION: The occurrence of PRES and parkinsonism is rare in primary hyperparathyroidism; the two patients described above highlight the importance of screening for hypercalcemia in the setting of neurological manifestations.

A Lower Prevalence of Central Nervous System and Higher Prevalence of Cardiac Symptoms Characterises Indian Patients with Thyrotoxic Storm: A Retrospective Analysis.

Introduction: Thyroid storm is an uncommon but life-threatening presentation of thyrotoxicosis with a mortality rate of 10%. Our objective was to study the demographics, clinical and biochemical characteristics, and outcomes of inpatients diagnosed with thyroid storm in the Indian context. Methods: This retrospective study was conducted by analysing the institutional electronic medical records (EMR) of all patients admitted with thyroid storm from 2004 to 2020 with a Burch-Wartofsky score (BWS) of ≥45. Results: Thirty-five patients with a BWS ≥45 were included, of whom 71.4% were women, with a mean age of 44.9 ± 10.2 years. 43% did not have any prior history of thyrotoxicosis. Graves' disease was the most common underlying aetiology (71.4%), followed by toxic multinodular goitre (14.3%). Cardiovascular (94.3%) and gastrointestinal-hepatic dysfunction (88.6%) were the most common clinical manifestations. Features of Central nervous system (CNS) dysfunction were seen in only 42.3% of patients diagnosed with a thyroid storm. The Japanese Thyroid Association (JTA) criteria diagnosed only 26 patients (74.3%) with "definite" thyroid storm. The mortality rate was 8.6%, and all three patients expired within 48 hours of admission. Conclusion: Nearly one in every two patients with thyroid storm had previously undiagnosed thyrotoxicosis. Toxic multinodular goitre is a notable aetiology in Indians. Features of CNS dysfunction, considered relatively specific for thyroid storm, were less prominent in our series. The JTA criteria might alter the classification of some patients diagnosed with a thyroid storm, when compared to the BWS score due to fewer CNS features among Indian patients.

Neuroendocrine challenges and clinical outcomes in men with chronic traumatic brain injury: a cross-sectional study.

BACKGROUND AND OBJECTIVES: Marked changes in the hypothalamic-pituitary axis have been documented in patients with traumatic brain injury (TBI). These enduring endocrine challenges could significantly influence the physical and psychological outcomes thereby impacting overall recovery. This study aimed to determine the prevalence and types of endocrine dysfunction in men with chronic TBI and to determine the association of endocrine dysfunction with clinical outcomes. METHODOLOGY: A cross-sectional study that included male participants of 25-45 years (N = 66) with moderate to severe TBI within 6-24 months of injury. Serum Cortisol, Free T4, TSH, Luteinizing hormone, Testosterone, ACTH, Prolactin and IGF-1 were assessed. Glasgow Outcome Scale Extended (GOS-E) and Modified Barthel Index (MBI) scores were also assessed in them. RESULTS: The study cohort comprised male patients with a mean ± age of 32.8 ± 5.7 years. Low IGF-1 levels were most commonly encountered, followed by hypogonadism. Hypopituitarism was present in 56.1%. The proportion of hypogonadism was significantly higher in the group with moderate-total dependence (13/26) as compared to the functionally independent (8/40) group (50% vs. 20%; P = 0.011). Univariate and multivariate logistic regression analysis was used to determine the factors associated with hypopituitarism, revealing that severity of injury (OR = 2.6;) and GOS-E (OR = 3.1) were significant (P < 0.10) on univariate analysis. CONCLUSIONS: This study emphasizes the need to screen TBI patients for neuroendocrine dysfunction during the chronic phases and to establish screening criteria.

Femoral Neck Osteoporosis Is Associated with a Higher Odds of Coronary Artery Disease in Indian Postmenopausal Women: A Cross-sectional Study from a Teaching Hospital in Southern India.

Purpose: Epidemiological studies have shown an association between coronary artery disease (CAD) and osteoporosis. We studied the prevalence of CAD among postmenopausal women with osteoporosis. Factors that were significantly associated with CAD were also assessed. Methods: This was a cross-sectional study conducted over a period of 2 years. Consecutive postmenopausal women aged ≥50 years were recruited. The details of an underlying CAD were obtained. Bone biochemical parameters, bone mineral density and body composition were assessed. Results: A total of 370 postmenopausal women with mean (standard deviation [SD]) ages of 61.6 (6.2) and 60.1 (6.0) years and a body mass index of 25.3 (14.1) kg/m2 were recruited. Among them, 110 of 370 patients (29.7%) had an underlying CAD and 222 of 370 (60%) had osteoporosis at either the femoral neck or lumbar spine (LS). The odds of CAD among those with osteoporosis were 3.5 (95% confidence interval [CI]: 2.1-5.9). An LS T-score of ≤-2.2 had a sensitivity of 80% and a specificity of 45% in predicting CAD (area under the curve, AUC: 0.736; 95% CI: 0.677-0.795; p<0.001). A femoral neck T-score of ≤-1.9 had a sensitivity of 80% and a specificity of 60% in predicting CAD (AUC: 0.748; 95% CI: 0.696-0.800; p<0.001). On a logistic regression analysis after adjusting for various clinical parameters, femoral neck osteoporosis had the highest odds of CAD. Conclusion: The prevalence of CAD was higher among postmenopausal women with osteoporosis. Femoral neck osteoporosis conferred the highest odds of CAD after adjustment for other clinical factors.

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.

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.

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.

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.

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.

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.