Trabecular bone score and bone mineral density as indices of skeletal fragility in endogenous Cushing's syndrome.

OBJECTIVE: Endogenous Cushing's syndrome (CS) is a known cause of secondary osteoporosis. Vertebral fractures (VFs) in endogenous CS may occur despite normal bone mineral density (BMD). Trabecular bone score (TBS) is a relatively new, non-invasive technique to assess bone microarchitecture. The objective of our study was to analyse the BMD and bone microarchitecture using TBS in endogenous CS and compare it with a group of age and sex-matched healthy controls, and also analyse the factors predicting BMD and TBS. DESIGN: Cross-sectional study of cases and controls. PATIENTS AND MEASUREMENTS: We included 40 female patients with overt endogenous CS, out of which 32 were adrenocorticotropic hormone (ACTH)-dependent CS and 8 were ACTH-independent. We also included 40 healthy, female controls. Both patients and controls were subjected to an assessment of biochemical parameters and BMD and TBS. RESULTS: Patients with endogenous CS had significantly lower BMD at the lumbar spine, femoral neck, and total hip and significantly lower TBS than healthy controls (all p < .001), while no significant difference was noted in the distal radius BMD (p = .055). In endogenous CS, a large proportion of patients, n = 13 (32.5%) had normal BMD for age (BMD Z-score ≥ -2.0) with low TBS (L1 -L4 TBS ≤ 1.34). TBS correlated negatively with HbA1c (p = .006), and positively with serum T4 (p = .027). CONCLUSION: TBS should be considered an important complementary tool in addition to BMD for the routine assessment of skeletal health in CS.

A Curious Case of Afebrile Dengue.

A 50-year-old male presented to us with features of diabetic ketoacidosis which was managed with adequate hydration and insulin therapy. His routine laboratory investigation revealed transaminitis, acute kidney injury and pancytopenia. Further evaluation for hematological and biochemical derangements uncovered positive dengue test (NS1 antigen and polymerase chain reaction assay). Patient distinctively reported no history of fever and remained afebrile during the course of illness. We report this case to highlight the possibility of afebrile dengue in endemic areas.

Index-TB guidelines: Guidelines on extrapulmonary tuberculosis for India.

Extrapulmonary tuberculosis (EPTB) is frequently a diagnostic and therapeutic challenge. It is a common opportunistic infection in people living with HIV/AIDS and other immunocompromised states such as diabetes mellitus and malnutrition. There is a paucity of data from clinical trials in EPTB and most of the information regarding diagnosis and management is extrapolated from pulmonary TB. Further, there are no formal national or international guidelines on EPTB. To address these concerns, Indian EPTB guidelines were developed under the auspices of Central TB Division and Directorate of Health Services, Ministry of Health and Family Welfare, Government of India. The objective was to provide guidance on uniform, evidence-informed practices for suspecting, diagnosing and managing EPTB at all levels of healthcare delivery. The guidelines describe agreed principles relevant to 10 key areas of EPTB which are complementary to the existing country standards of TB care and technical operational guidelines for pulmonary TB. These guidelines provide recommendations on three priority areas for EPTB: (i) use of Xpert MTB/RIF in diagnosis, (ii) use of adjunct corticosteroids in treatment, and (iii) duration of treatment. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, which were evidence based, and due consideration was given to various healthcare settings across India. Further, for those forms of EPTB in which evidence regarding best practice was lacking, clinical practice points were developed by consensus on accumulated knowledge and experience of specialists who participated in the working groups. This would also reflect the needs of healthcare providers and develop a platform for future research.

Laryngeal Leishmaniasis with Extra-pulmonary Tuberculosis.

Clinical presentations of Leishmania infection include visceral (most common form), cutaneous, mucocutaneous, mucosal and post-kala-azar dermal leishmaniasis. Mucosal form of leishmaniasis mostly involves oral and nasal mucosa. Rarely, laryngeal and pharyngeal mucosa may also be involved. Its concomitant presence with tuberculosis (TB), a disease rampant in India, is uncommon. Here we are reporting a case of isolated laryngeal leishmaniasis associated with extra-pulmonary tuberculosis (EPTB), with approach to diagnosis and treatment in a tropical resource-limited setting.

Metabolic syndrome and life style factors among diabetes patients attending in a teaching hospital, Chitwan.

BACKGROUND: Metabolic syndrome (MetS) is associated with an increased incidence of chronic complications and mortality of diabetes patients. Prevention and treatment of MetS is important means of lowering the risk of cardiovascular diseases and mortality. OBJECTIVE: This study aimed to find out metabolic syndrome and life style factors among diabetes patients. METHODS: A cross-sectional survey was carried out among 296 patients with type 2 diabetes mellitus attending Chitwan Medical College Teaching Hospital. Consecutive sampling technique was used to select sample. Data were collected from 15th December 2021 to 15th March, 2022 using Interview Schedule, bio-physiological measurement and record review. Obtained data were analysed in SPSS version 20 for window using descriptive and inferential statistics. Chi-square test was applied to measure the association between the variables. Logistic regression analysis was performed to identify the factors associated with metabolic syndrome. RESULT: Findings revealed that the prevalence of MetS was 66.2% and 58.4% in patients according to International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria respectively. The most common MetS parameters were raised fasting plasma glucose (94.6%) and abnormal waist circumference (78.4% in IDF criteria) while the least prevalent parameter was reduced HDL level (43.2%). Majorities of the patients were non-vegetarian (85.5%), had poor dietary compliance (poor-46.3%, very poor-32.1%), overweight/obese (65.5%), and suffered from moderate stress (90.1%). Bivariate analysis showed that MetS as per NCEP ATP criteria was significantly associated with gender (p = 0.006), occupation (p = 0.007), presence of other co-morbid condition (<0.001) and sleep problem (p = <0.001). However, MetS as per IDF criteria was significantly associated with age (p = <0.028), duration of diabetes (p = <0.001), follow-up visit (p = <0.030), blood sugar monitoring (p = <0.009) and physical activity of diabetes patients (p = <0.001). Further logistic regression analysis revealed that sleep problem (AOR = 21.812;95%CI = 8.512,55.894) and presence of other comorbidities (AOR = 4.024;95%CI = 2.220,7.295) were the significant factors of metabolic syndrome. CONCLUSION AND RECOMMENDATION: Metabolic syndrome is high in patients with type 2 diabetes mellitus. Therefore, treating physicians and other health workers need to monitor MetS parameters regularly to reduce the risk of cardiovascular diseases, stroke and premature death.

Complete form of pachydermoperiostosis with good initial response to etoricoxib: A case report.

Key Clinical Message: Pachydermoperiostosis is a rare genetic disorder that closely resembles acromegaly. Diagnosis is usually based on distinct clinical and radiological features. Oral etoricoxib therapy showed a good initial response in our patient. Abstract: Pachydermoperiostosis (PDP) is a rare genetic disorder with unclear etiopathogenesis. We report a case of a 38-year-old male who presented with classic features of PDP. Our patient showed a good initial response to etoricoxib therapy but the safety and efficacy over long-term use are yet to be determined in further studies.

Prevalence and Predictors of Osteoporosis/BMD Below Expected Range for Age in Pheochromocytoma/Paraganglioma and BMD, TBS Change Post-Operatively: A Prospective Cohort Study.

Context: Pheochromocytomas/paragangliomas (PPGLs) have recently been shown to be associated with lower bone mineral density (BMD) and trabecular bone score as compared to healthy controls suggesting low bone mineral concentration and disrupted bone microarchitecture. There is paucity of data on prevalence and clinical predictors of low BMD/osteoporosis in PPGL from India and the extent of change in BMD post-operatively. Aims: This study aimed to find prevalence of low BMD/osteoporosis and trabecular bone score (TBS)-adjusted FRAX score in subjects with PPGL and to see the post-operative change in BMD and TBS at follow-up. Material and Methods: 32 consecutively diagnosed adult cases with PPGL were enrolled. Although the provisional diagnosis of PPGL was made based on imaging consistent with PPGL supported by biochemical evidence of catecholamine excess, its confirmation was made histopathologically before final analysis. Results: We found significantly low average BMD T-score/Z-score at spine, hip or wrist. Osteoporosis was evident in 87.5% of subjects (nine of 11 post-menopausal women or men >50 years of age) and BMD below the expected range for age in 42.9% of subjects (nine of 21 pre-menopausal women or men <50 years of age) by International Society for Clinical Densitometry criteria. Conclusions: 87% of older subjects with PPGL had osteoporosis while 43% of younger subjects had BMD below expected range for age (Z-score ≤-2.0), more at lumbar spine than at hip. Decreased body weight was associated with osteoporosis in older or Z-score ≤-2.0 in younger subjects. There was no significant change in BMD and TBS scores at a median of four months post-operatively.

Bone microarchitecture and bone mineral density in Graves' disease.

Objectives: Graves' disease (GD) is the most common cause of thyrotoxicosis. There are many studies that have evaluated bone mineral density (BMD) in Graves' disease. However, the strength of a bone also depends on its microarchitecture which can be assessed by various techniques. Trabecular bone score (TBS) is a new method for assessing bone microarchitecture that is non-invasive and easily performed. Methods: The present study was a cross-sectional study that involved 50 patients with active GD and 50 healthy controls. Both groups were subjected to an assessment of biochemical parameters followed by measurement of BMD and TBS on the same dual energy X-ray absorptiometry (DXA) machine. Results: The mean age of patients with active GD (N = 50) was 31.9 ± 10.9 years while that of controls was 31.2 ± 4.9 years (P = 0.640). The female: male ratio was the same for both groups (F = 31, M = 19). The mean lumbar spine BMD, femoral neck BMD, total hip BMD, and distal radius BMD were significantly reduced in GD when compared to that in controls. The mean absolute lumbar spine TBS in GD was 1.263 ± 0.101 while that in controls was 1.368 ± 0.073 (P < 0.001). On multivariate regression analysis, the factors that predicted TBS were serum thyroxine (T4) and L1-L4 BMD. Conclusions: Patients with Graves' disease had reduced bone density at all sites and degraded microarchitecture. Long-term studies are required to understand the pattern of recovery of bone microarchitecture after the restoration of euthyroidism.

Diabetic Retinopathy among Diabetic Patients at a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

Introduction: The alarming rise in the prevalence of diabetes mellitus is a global public health and economic problem. Diabetic retinopathy is the most common ocular morbidity in the diabetic population and is the leading cause of blindness among the working-age group. This study was aimed to find out the prevalence of diabetic retinopathy in diabetic patients attending to the department of ophthalmology of a tertiary care hospital. Methods: A descriptive cross-sectional study was conducted in the Department of Ophthalmology of a tertiary care hospital from 15th August to 30th November 2021. Ethical clearance was taken from the Institutional Review Committee (Reference number: CMC-IRC/078/079-021). Convenience sampling was done. Basic demographic data, risk factors, clinical characteristics, and prevalence of diabetic retinopathy were noted. Data entry was done using Statistical Package for the Social Sciences version 26.0. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data. Results: Among 540 participants, 146 (27.04%) (23.29-30.79 at 95% Confidence Interval) study subjects had diabetic retinopathy changes in at least one eye. Smoking in 88 (60.27%), type 2 diabetes mellitus in 139 (95.21%), hypertension in 85 (58.22%), raised glycated hemoglobin levels in 120 (82.19%) were the major factors observed in the study subjects. Conclusions: The prevalence of diabetic retinopathy was higher in our study when compared to national studies. Keywords: biomarkers; body mass index; diabetes mellitus; diabetic retinopathy; visual acuity.

Atypical parathyroid adenoma: Severe manifestations in an adolescent girl.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a disease that is usually diagnosed in an asymptomatic state during routine biochemical screening. It generally manifests as a sporadic disease in post-menopausal women. However, in India and developing countries, we continue to see severe skeletal and renal manifestations of the disease. CASE REPORT: Herein, we describe the case of a 16-year-old adolescent girl who presented with severe manifestations of primary hyperparathyroidism. Biochemically, she had severe parathyroid hormone (PTH)-dependent hypercalcaemia with hypophosphataemia and vitamin D deficiency (serum total Ca - 18.5 mg/dl [8.5-10.5 mg/dl], serum PO4 - 1.9 mg/dl [2.5-4.5 mg/dl], serum ALP - 2015 IU/l [80-240 IU/l], serum 25[OH]D - 19.1 ng/ml [30-100 ng/ml] and serum iPTH > 5000 pg/ml [15-65 pg/ml]). Pre-operatively, she required management with saline diuresis, bisphosphonate, and calcitonin. After surgery, the patient had severe hungry bone syndrome (serum Ca - 4.1 mg/dl, serum PO4 - 2.1 mg/dl, serum ALP > 10,000 IU/l) that required treatment with calcium infusions for almost 3 months. Although the clinical and biochemical picture was suggestive of parathyroid carcinoma, histopathology revealed atypical parathyroid adenoma with low proliferative index. Atypical parathyroid adenoma is a term applied to a neoplasm with 'worrisome' features but not fulfilling the 'absolute histopathological criteria of malignancy'. CONCLUSIONS: Atypical parathyroid adenoma, a rare cause of PHPT, may be associated with severe manifestations. Although malignancy was not discerned in the immediate post-operative period, we plan to continue long-term follow-up of the patient to look for any signs of recurrence or development of parathyroid carcinoma.

The spectrum of manifestations of primary hyperparathyroidism in children and adolescents.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a rare disease in children and adolescents. Early recognition of this disease is important to prevent significant morbidity and mortality. MATERIAL AND METHODS: We included 10 consecutive patients with PHPT aged 14 to 19 years of age and followed-up prospectively upto one year after parathyroidectomy. RESULTS: Our cohort included 6 females and 4 males. The mean age of the patients was 16.7 ±1.8 years. The symptoms at presentation were musculoskeletal pain (90%), bone deformity (50%), fracture (30%), proximal myopathy (40%), renal stones (50%), reflux symptoms (40%), and pancreatitis (30%). The mean serum calcium was 3.1 ±0.5 mmol/l, mean serum inorganic phosphorus was 0.9 ±0.3 mmol/l and median serum alkaline phosphatase (ALP) was 1911.5 IU/l (IQR: 522.7-5702.3). The median serum intact parathyroid hormone was 133.5 pmol/l (IQR: 69.5 -178.7) while serum 25(OH)D was 47.7 nmol/l (IQR: 23.7-72.7). Hypercalciuria was observed in 7 patients. Hungry bone syndrome was observed in 4 (40%) patients after surgery. Typical parathyroid adenoma was found in 9 (90%) patients while one patient had atypical adenoma with high mitotic index. After one year of surgery, all patients had significant improvement in clinical and biochemical parameters with persistence of residual bone deformities. CONCLUSIONS: Our study showed the spectrum of manifestations of PHPT in children and adolescents and outcomes of parathyroidectomy till one year. Long-term follow-up studies with bigger cohorts are required to understand the true nature of the disease in children and adolescents.

Endocrine causes of heart failure: A clinical primer for cardiologists.

Heart failure (HF) may be a presenting manifestation of a few endocrine disorders and should be considered in evaluation of heart failure causes. This clinically oriented review is an attempt to highlight the protean manifestations of heart failure in endocrine diseases which could present either as acute or chronic heart failure. Acute heart failure manifests as hypertensive crisis, Takotsubo syndrome, or as tachy/brady cardiomyopathies. Chronic heart failure could masquerade with features of hyperdynamic heart failure, or hypertrophic, restrictive or dilated cardiomyopathy. Rarely constrictive features or resistant heart failure could be the presenting feature. Isolated presentation as pulmonary hypertension and right heart failure are also documented. Good history-taking and physical examination with targeted investigations will help in the timely management for reversing the pathophysiology to a significant extent by appropriated management.

Renal Tubular Acidosis Manifesting as Severe Metabolic Bone Disease.

Renal tubular acidosis (RTA) is a condition characterized by normal anion gap metabolic acidosis. Type 1 and type 2 RTA are the most common, and are caused by defective secretion of hydrogen ions and impaired absorption of bicarbonate, respectively. Long-standing uncorrected acidosis can lead to metabolic bone disease (MBD). Rickets and osteomalacia remain the commonest manifestations of uncorrected RTA. In addition, there can be a myriad of other skeletal manifestations like fractures, pseudofractures, secondary osteoporosis and even sclerotic bone disease. The postulated mechanism for bone involvement includes acidosis-mediated exaggerated osteoclastic bone resorption. Other contributory factors include abnormal renal handling of phosphate leading to hypophosphataemia in proximal RTA, and impaired vitamin D metabolism and action. In distal RTA, hypercalciuria and secondary hyperparathyroidism may play a key role for bone involvement. Recognizing the disease in its early course is important to prevent permanent sequelae of skeletal involvement. Most of these patients may, in fact, undergo orthopaedic interventions without primary correction of acidosis. We describe five cases who presented with MBD in varied forms. While evaluating the aetiology of MBD, they were diagnosed with RTA. Subsequently, we attempted to analyse the causes of RTA. Although the common causes were ruled out, genetic aetiology could not be ascertained due to resource constraints. RTA remains an important differential diagnosis of MBD. More awareness is required to diagnose the disease early and to treat it adequately. Our case series is an attempt to provide the clinical, biochemical and skeletal spectrum of RTA. In addition, we have attempted to provide algorithms for the approach and evaluation of RTA along with their varied causes.

X-Linked Hypophosphatemic Rickets Manifesting as Sclerotic Bone Disease and Enthesopathy.

X-linked hypophosphatemic (XLH) rickets is a genetic disease caused due to the inactivation of the PHEX gene (phosphate regulating gene with homology to endopeptidase on the X chromosome). The usual presentation is with rickets and osteomalacia, and dental abscesses leading to premature loss of teeth. However, enthesopathy and sclerotic bone disease in XLH have also been reported in a few case reports. In this report, we describe the case of a 23-year-old female patient who presented to us with severe bone deformities, proximal myopathy, truncal weakness, and recent onset of pain and stiffness around the joints. She was diagnosed with XLH and was found to have severe enthesopathy along with heterotopic ossification.

Diabetes mellitus in pheochromocytoma and paraganglioma: Prevalence, dynamics of insulin secretion / sensitivity and predictors of remission.

BACKGROUND AND AIMS: Pheochromocytoma and paraganglioma (PPGL) are associated with dysglycemia and diabetes mellitus (DM) much of which improves post operatively. In this study, we set out to ascertain pre and post-operative prevalence of DM in patients with PPGL based on oral glucose tolerance test (OGTT) and HbA1c and to evaluate effect of insulin secretion and sensitivity indices on DM pre-operatively. METHODS: Clinical and anthropometric data collection, HbA1c, 75 g OGTT with serum insulin estimation were done pre-operatively (n = 34) and at follow-up after successful surgery (n = 24) in patients with PPGL. RESULTS: Pre and post-operative prevalence of DM were 48%(18/37) and 17% (4/24) respectively. Comparison of patients with highest (Q4) and lowest (Q1) quartiles of insulinogenic index (IGI),a parameter of insulin secretion, revealed trends towards higher prevalence of DM in patients with lower IGI (Q4 to Q1: 29% versus 71%,n = 28, p = 0.24)but no association was observed with HOMA-IR (Q4 to Q1:50% versus 57%, n = 28, p = 1.00), an insulin sensitivity index. DM remitted in 77% patients post-operatively, predicted by duration of DM of<3 years. CONCLUSION: There is high prevalence of DM in PPGL, with marked remission post-operatively, especially predicted by shorter duration of DM. Impaired insulin secretion is more strongly associated with pre-operative DM than increased insulin resistance.