The Experts below are selected from a list of 534 Experts worldwide ranked by ideXlab platform
Ravinder Goswami - One of the best experts on this subject based on the ideXlab platform.
-
pulmonary alveolar proteinosis pap in Idiopathic Hypoparathyroidism
Case Reports, 2019Co-Authors: Soma Saha, Karan Madan, Deepali Jain, Ravinder GoswamiAbstract:Idiopathic Hypoparathyroidism (IH) and autoimmune pulmonary alveolar proteinosis (PAP) are rare disorders. A patient with IH and optimal calcaemic control on calcium and alfacalcidol was detected to have PAP after 8 years of follow-up. Patient had no respiratory complaints. Routine abdominal imaging for renal calcification showed patchy ground glass opacities in the lower lung fields leading to incidental diagnosis of PAP. Pulmonary function tests showed impaired diffusion capacity of the lung. Anti-granulocyte macrophage-colony stimulating factor autoantibodies were positive. Patient regularly attended the pulmonary clinic and showed progressive improvement in diffusion capacity of the lung during 2 years of follow-up. The calcaemic control in IH remained stable despite its presence with PAP. The autoimmune PAP in the presented case suggests a possible autoimmune basis of IH.
-
auditing the efficacy and safety of alfacalcidol and calcium therapy in Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2019Co-Authors: Soma Saha, Ravinder GoswamiAbstract:Context Patients with Hypoparathyroidism are treated with vitamin D and calcium. PTH is an emerging option because of its physiological action. It is important to assess the efficacy and shortcomings of conventional therapy. Objective We assessed the efficacy and safety of alfacalcidol in a large cohort of patients with Idiopathic Hypoparathyroidism (IH) and identified a subset who could be treated without oral calcium. Design and setting Observational study at tertiary care center. Subjects and methods We assessed 92 patients with IH who were receiving alfacalcidol and oral calcium to maintain an optimal serum total calcium level of 8.0 to 8.5 mg/dL during routine follow-up. Patients with suboptimal control were provided free medicines and followed up frequently. Oral calcium and alfacalcidol doses were titrated sequentially to determine the minimum doses for optimal calcium control. Serum phosphate level, 1,25-dihydroxyvitamin D, fractional excretion of phosphorus (FEPh), and hypercalciuria (urine calcium-to-creatinine ratio, >0.2) were assessed at each step of titration. Results Only 38% of patients had optimal calcium control during routine follow-up. With good compliance, all achieved optimal serum calcium and 1,25-dihydroxyvitamin D levels and 43% of patients could stop taking oral calcium. Hyperphosphatemia, hypercalciuria, and low FEPh persisted at all stages of therapy. Serum phosphorus levels normalized when the serum calcium level increased to 9.9 mg/dL, but this level of serum total calcium was associated with hypercalciuria in 90% of patients. Conclusion Alfacalcidol is effective in achieving calcemic control in IH. Calcemic control without oral calcium was achieved in 43% of patients receiving alfacalcidol. However, optimal calcium control was associated with hyperphosphatemia and hypercalciuria in most patients.
-
central immune tolerance of t and b cells in patients with Idiopathic Hypoparathyroidism t1d and autoimmune thyroiditis
Journal of the Endocrine Society, 2019Co-Authors: Samrina Mahtab, Soma Saha, Vishnubhatla Sreenivas, Parmita Kar, Alessandra Sottini, Luisa Imberti, Ravinder GoswamiAbstract:Context Pathogenesis of Idiopathic Hypoparathyroidism (IH) is under investigation. Abnormalities in central immune tolerance have yet not been investigated in this condition. T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs), formed during receptor gene rearrangements, are tools to assess central T- and B-cell output. Objective We assessed the number of circulating TRECs and KRECs in patients with IH, autoimmune type 1 diabetes (T1D), and autoimmune thyroiditis (ATs) and healthy controls (HCs). Design Comparative case-control at tertiary care center. Subjects and methods Absolute and relative TRECs and KRECs were measured in DNA extracted from whole blood of patients with IH (n = 181, 22 of whom were reassessed after a decade of follow-up) and T1D (n = 133), AT (n = 53), and HC (n = 135) using a quantitative real-time PCR/TaqMan® probe technique. Results Absolute and relative means of TRECs and KRECs in IH were comparable to HCs, and no differences were found between IH with and without calcium-sensing receptor antibodies or class I HLA-A*26:01 association. TRECs and KRECs did not change after a decade of follow-up. T1D had significantly higher absolute TRECs than IH, AT, and HCs, whereas AT patients showed lower TRECs and the highest KRECs; these levels showed no noteworthy correlation with thyroid dysfunctions. Conclusion Patients with IH showed TRECs and KRECs comparable to HCs, indicating an intact mechanism of T- and B-cell central immune tolerance. Interestingly, absolute TRECs were significantly higher in T1D than HCs, suggesting impaired central immune tolerance in T1D.
-
Central immune tolerance of T and B cells in patients with Idiopathic Hypoparathyroidism, T1D and autoimmune thyroiditis.
2019Co-Authors: Samrina Mahtab, Soma Saha, Parmita Kar, Alessandra Sottini, Luisa Imberti, Vishnubhatala Sreenivas, Ravinder GoswamiAbstract:Abstract Context: Pathogenesis of Idiopathic Hypoparathyroidism is under investigation. Abnormalities in central immune tolerance have yet not been investigated in them. T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs), formed during receptor gene rearrangements, is novel tools to assess central T- and B -cell output. Objective: We assessed the number of circulating TRECs and KRECs in patients with IH, autoimmune type-1 diabetes (T1D), and thyroiditis (AT) and healthy controls (HC). Design: Comparative case-control at tertiary care center. Subjects and methods: Absolute and relative TRECs and KRECs were measured in DNA extracted from whole blood of IH patients (n = 181, 22 of whom were reassessed after a decade of follow-up), T1D (n = 133), AT (n = 53), and HC (n = 135) using quantitative RT-PCR/TaqMan probe® technique. Results: Absolute and relative means of TRECs and KRECs in IH were comparable to HC and no differences were found between IH with and without CaSRAb or class I HLA-A*26:01 association. TRECs and KRECs did not change after a decade of follow-up. T1D had significantly higher absolute TRECs than IH, AT and HC, while AT patients showed lower TRECs and the highest KRECs; these levels showed no significant correlation with thyroid dysfunctions. Conclusion: Patients with IH showed TRECs and KRECs comparable to HC indicating an intact mechanism of T- and B-cell central immune tolerance. Interestingly, absolute TRECs were significantly higher in T1D than HC, suggesting impaired central immune tolerance in T1D.
-
long term outcome of cataract surgery in patients with Idiopathic Hypoparathyroidism and its relationship with their calcemic status
Journal of Bone and Mineral Metabolism, 2017Co-Authors: Soma Saha, Vishnubhatla Sreenivas, Sameer Aggarwal, Shiva Prasad Gantyala, Radhika Tandon, Ravinder GoswamiAbstract:Cataract is a cardinal manifestation of Hypoparathyroidism. Although patients with Hypoparathyroidism require cataract surgery at a younger age than individuals without Hypoparathyroidism, there is limited information on the outcome of this surgery. We assessed long-term complications of cataract surgery in patients with Idiopathic Hypoparathyroidism (IH) and its relationship with their clinical and biochemical parameters. Twenty-seven patients with IH and 25 nonhypoparathyroid controls with a minimum follow-up of 2 years after cataract surgery were assessed for visual acuity, intraocular pressure, lens centricity, Nd:YAG laser capsulotomy, and the severity of posterior capsular opacification (PCO) and anterior capsular opacification. High-resolution optical slit-lamp images were analyzed by an ophthalmologist. Patients with IH had cataract surgery at a younger age than controls (34.0 ± 16.4 years vs 58.0 ± 11.2 years, P < 0.001). A higher proportion of IH patients had dense white PCO (75.0 % vs 39.4 %, P = 0.004), Nd:YAG laser capsulotomy (44.2 % vs 10.0 %, P = 0.001), anterior capsular opacification (97.7 % vs 84.2 %, P = 0.03), and a decentric lens (28.3% vs 2.6 %, P = 0.001) at a comparable time after surgery (8.6 ± 6.1 years vs 8.7 ± 6.8 years, P = 0.85). On regression analysis, the severity of PCO in IH correlated only with male sex and not with other factors, including serum total calcium and inorganic phosphorus levels at the baseline and during follow-up. To conclude, patients with IH are likelier than individuals without IH to develop PCO and to require Nd:YAG laser capsulotomy after cataract surgery. Proper precautions should be taken during surgery to minimize this complication in IH.
Nandita Gupta - One of the best experts on this subject based on the ideXlab platform.
-
calcium sensing receptor autoantibodies and Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2013Co-Authors: Neeraj Tomar, Nandita Gupta, Ravinder GoswamiAbstract:Context: Data on calcium-sensing receptor autoantibodies (CaSRAbs) in Hypoparathyroidism are variable. Objective: We assessed the prevalence and significance of CaSRAbs in Idiopathic Hypoparathyroidism. Design: This was a case-control study. Subjects: One hundred forty-seven patients with Idiopathic Hypoparathyroidism treated during 1998–2011 in a tertiary care setting and 348 controls [healthy, n = 199; type 1 diabetes mellitus (T1DM), n = 99; and chronic lymphocytic thyroiditis (CLT), n = 50] participated in the study. Methods: CaSRAb assays included Western blot with CaSR protein expressed in Escherichia coli or human embryonic kidney (HEK)-293 cells, immunoprecipitation (IP) using in vitro-transcribed/translated protein, and indirect immunofluorescence on HEK293-CaSR. Functional significance was assessed by ERK1/2 phosphorylation. PTH and CaSR genes were sequenced for mutations. Results: E coli-Western blot assay revealed 16.3% CaSRAb positivity in Idiopathic Hypoparathyroidism, which was comparable w...
-
calcium sensing receptor autoantibodies and Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2013Co-Authors: Neeraj Tomar, Nandita Gupta, Ravinder GoswamiAbstract:Context: Data on calcium-sensing receptor autoantibodies (CaSRAbs) in Hypoparathyroidism are variable. Objective: We assessed the prevalence and significance of CaSRAbs in Idiopathic Hypoparathyroidism. Design: This was a case-control study. Subjects: One hundred forty-seven patients with Idiopathic Hypoparathyroidism treated during 1998–2011 in a tertiary care setting and 348 controls [healthy, n = 199; type 1 diabetes mellitus (T1DM), n = 99; and chronic lymphocytic thyroiditis (CLT), n = 50] participated in the study. Methods: CaSRAb assays included Western blot with CaSR protein expressed in Escherichia coli or human embryonic kidney (HEK)-293 cells, immunoprecipitation (IP) using in vitro-transcribed/translated protein, and indirect immunofluorescence on HEK293-CaSR. Functional significance was assessed by ERK1/2 phosphorylation. PTH and CaSR genes were sequenced for mutations. Results: E coli-Western blot assay revealed 16.3% CaSRAb positivity in Idiopathic Hypoparathyroidism, which was comparable w...
-
neuropsychological dysfunction in Idiopathic Hypoparathyroidism and its relationship with intracranial calcification and serum total calcium
European Journal of Endocrinology, 2013Co-Authors: Sameer Aggarwal, Nandita Gupta, Raju Sharma, Vishnubhatla Sreenivas, Suparna Kailash, Rajesh Sagar, Manjari Tripathi, Ravinder GoswamiAbstract:Background: There is limited information on neuropsychological and neurological dysfunctions in patients with Idiopathic Hypoparathyroidism (IH). Objective: To assess neuropsychological and neurological dysfunctions in IH and its associated factors in a cross-sectional design. Method: Neuropsychological functions were assessed in 62 patients with IH and 70 controls using a battery of cognitive tests. Neurological assessment included extrapyramidal and cerebellar signs. Assessment of intracranial calcification and volume of basal ganglia calcification (BGC) were made on computed tomography and of calcium control by averaging serum total calcium values available during the follow-up. Results: A significantly higher proportion of patients with IH showed neuropsychological dysfunctions than controls (32.3 (95% CI: 20.9‐45.3) vs 5.7% (95% CI: 1.6‐14.0), P!0.001). Neurological signs were present in 35.5% patients (extrapyramidal: 16.1%; cerebellar: 20.9%). Volume of BGC and number of sites with intracranial calcifications including cerebellum/dentate were comparable in patients with and without neuropsychological, extrapyramidal or cerebellar dysfunctions. Cognitive dysfunction score was lower by 1.7 points in males than in females (PZ0.02) and increased by 0.21 and 5.5 for each year increase in the duration of illness (PZ0.001) and one unit increase in serum calcium‐phosphorus product (PZ0.01) respectively. The scores improved by 0.27 for every mg% increase in serum calcium (PZ0.001). Conclusion: Neuropsychological dysfunctions are present in up to one-third of patients with IH and correlate with duration of illness, female gender, serum calcium and calcium‐phosphorus product during follow-up but not with intracranial calcification. These dysfunctions may affect their daily functions, safety and drug compliance.
-
presence of strong association of the major histocompatibility complex mhc class i allele hla a 26 01 with Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2012Co-Authors: Nandita Gupta, Ravinder Goswami, Archana Singh, Rajni RaniAbstract:Context: The pathogenesis of isolated Hypoparathyroidism, also referred to as Idiopathic Hypoparathyroidism (IH), is not clear. There is a paucity of information related to the immunogenetic basis of the disease due to its rarity. A recurrent theme of several autoimmune disorders is aberrant antigen presentation. Objective: We investigated for the association of alleles of the human leukocyte antigen (HLA) class I and II loci with IH. Patients and Controls: A total of 134 patients with IH and 902 healthy controls from the same ethnic background participated in the study. Results: There was a significant increase of HLA class I alleles HLA-A*26:01 [P < 1.71 × 10−34; odds ratio (OR) = 9.29; 95% confidence interval (CI) = 6.08–14.16] and HLA-B*08:01 (P < 8.19 × 10−6; OR = 2.59; 95% CI = 1.63–4.04) in patients with IH compared to healthy controls. However, the association of A*26:01 was primary because B*08:01 was in linkage disequilibrium with A*26:01. Although the major histocompatibility complex (MHC) is v...
-
prevalence and significance of nalp5 autoantibodies in patients with Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2012Co-Authors: Neeraj Tomar, Nandita Gupta, Esha Kaushal, Madhuchhanda Das, Corrado Betterle, Ravinder GoswamiAbstract:Context: Role of parathyroid autoimmunity in Idiopathic Hypoparathyroidism (IH) is not clear. Recently, parathyroid-specific NACHT leucine-rich-repeat protein 5 (NALP5) autoantibodies (Ab) have been reported in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. Objective: Our objective was to assess prevalence and significance of NALP5 Ab in patients with IH. Design and Setting: This was a case-control study at a tertiary care hospital. Subjects: Subjects included 145 patients with IH recruited from 1998–2011 and 152 healthy controls. Methods: Immunoprecipitation (IP) and Western blot (WB) assays were performed using 35S-labeled NALP5 protein produced by in vitro transcription-translation and recombinant NALP5 protein in Escherichia coli, respectively. AIRE gene sequencing was performed in NALP5 Ab-positive patients. Results: One of 145 patients (0.69%) and none of the 152 controls had NALP5 Ab on IP assay. Nine of 147 patients (6.12%) and four of 152 controls (2.63%) had NALP5 Ab on...
Neeraj Tomar - One of the best experts on this subject based on the ideXlab platform.
-
calcium sensing receptor autoantibodies and Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2013Co-Authors: Neeraj Tomar, Nandita Gupta, Ravinder GoswamiAbstract:Context: Data on calcium-sensing receptor autoantibodies (CaSRAbs) in Hypoparathyroidism are variable. Objective: We assessed the prevalence and significance of CaSRAbs in Idiopathic Hypoparathyroidism. Design: This was a case-control study. Subjects: One hundred forty-seven patients with Idiopathic Hypoparathyroidism treated during 1998–2011 in a tertiary care setting and 348 controls [healthy, n = 199; type 1 diabetes mellitus (T1DM), n = 99; and chronic lymphocytic thyroiditis (CLT), n = 50] participated in the study. Methods: CaSRAb assays included Western blot with CaSR protein expressed in Escherichia coli or human embryonic kidney (HEK)-293 cells, immunoprecipitation (IP) using in vitro-transcribed/translated protein, and indirect immunofluorescence on HEK293-CaSR. Functional significance was assessed by ERK1/2 phosphorylation. PTH and CaSR genes were sequenced for mutations. Results: E coli-Western blot assay revealed 16.3% CaSRAb positivity in Idiopathic Hypoparathyroidism, which was comparable w...
-
calcium sensing receptor autoantibodies and Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2013Co-Authors: Neeraj Tomar, Nandita Gupta, Ravinder GoswamiAbstract:Context: Data on calcium-sensing receptor autoantibodies (CaSRAbs) in Hypoparathyroidism are variable. Objective: We assessed the prevalence and significance of CaSRAbs in Idiopathic Hypoparathyroidism. Design: This was a case-control study. Subjects: One hundred forty-seven patients with Idiopathic Hypoparathyroidism treated during 1998–2011 in a tertiary care setting and 348 controls [healthy, n = 199; type 1 diabetes mellitus (T1DM), n = 99; and chronic lymphocytic thyroiditis (CLT), n = 50] participated in the study. Methods: CaSRAb assays included Western blot with CaSR protein expressed in Escherichia coli or human embryonic kidney (HEK)-293 cells, immunoprecipitation (IP) using in vitro-transcribed/translated protein, and indirect immunofluorescence on HEK293-CaSR. Functional significance was assessed by ERK1/2 phosphorylation. PTH and CaSR genes were sequenced for mutations. Results: E coli-Western blot assay revealed 16.3% CaSRAb positivity in Idiopathic Hypoparathyroidism, which was comparable w...
-
prevalence and significance of nalp5 autoantibodies in patients with Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2012Co-Authors: Neeraj Tomar, Nandita Gupta, Esha Kaushal, Madhuchhanda Das, Corrado Betterle, Ravinder GoswamiAbstract:Context: Role of parathyroid autoimmunity in Idiopathic Hypoparathyroidism (IH) is not clear. Recently, parathyroid-specific NACHT leucine-rich-repeat protein 5 (NALP5) autoantibodies (Ab) have been reported in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. Objective: Our objective was to assess prevalence and significance of NALP5 Ab in patients with IH. Design and Setting: This was a case-control study at a tertiary care hospital. Subjects: Subjects included 145 patients with IH recruited from 1998–2011 and 152 healthy controls. Methods: Immunoprecipitation (IP) and Western blot (WB) assays were performed using 35S-labeled NALP5 protein produced by in vitro transcription-translation and recombinant NALP5 protein in Escherichia coli, respectively. AIRE gene sequencing was performed in NALP5 Ab-positive patients. Results: One of 145 patients (0.69%) and none of the 152 controls had NALP5 Ab on IP assay. Nine of 147 patients (6.12%) and four of 152 controls (2.63%) had NALP5 Ab on...
-
prevalence of clinical remission in patients with sporadic Idiopathic Hypoparathyroidism
Clinical Endocrinology, 2010Co-Authors: Ravinder Goswami, Neeraj Tomar, Nandita Gupta, Siya Goel, Vanshika Lumb, Yagya D SharmaAbstract:Summary Background Remission of disease activity is a characteristic feature of autoimmune endocrine disorders such as Graves’ disease, Addison’s disease and occasionally in patients with premature ovarian failure. Autoimmunity is also implicated in sporadic Idiopathic Hypoparathyroidism (SIH) with clinical remission of disease reported in three cases. Objective To assess the rate of remission in patients with sporadic Idiopathic Hypoparathyroidism and review the cases reported so far. Subjects and methods Subjects included 53 patients (M:F, 24:29) with SIH who had been symptomatic for at least 1 year (range 1–31 years). They were treated with calcium and 1-α-(OH)D3/cholecalciferol therapy and had a mean duration of follow up of 5·0 ± 3·2 years. Treatment was withdrawn in two stages in the patients who maintained normal levels of serum total calcium during the preceding year of treatment. In stage-1, the dose of therapy was reduced to half and subsequently all treatment was stopped (stage 2) in those patients who maintained normal serum total calcium levels on the reduced dose. Remission of SIH was defined as maintenance of normal serum total (≥2·12 mmol/l) and ionized calcium, inorganic phosphorus and serum intact parathyroid hormone (iPTH) for at least 3 months after withdrawal of calcium and 1-α-(OH)D3/cholecalciferol therapy. Calcium sensing receptor autoantibodies (CaSRAb) were determined by Western blot. Results Two of the 53 patients (3·8%) with SIH stayed in remission for 1 year after complete withdrawal of therapy. CaSRAb was absent in both the cases. The clinical features, age at onset and duration of hypocalcaemic symptoms in cases with remission were comparable to those who did no show remission. Conclusion Sporadic Idiopathic Hypoparathyroidism is not irreversible as is widely believed and spontaneous remission of disease may occur in 3·8% of patients.
-
prevalence of thyroid autoimmunity in sporadic Idiopathic Hypoparathyroidism in comparison to type 1 diabetes and premature ovarian failure
The Journal of Clinical Endocrinology and Metabolism, 2006Co-Authors: Ravinder Goswami, Neeraj Tomar, Nandita Gupta, Raman K Marwaha, Deepti Goswami, Debarti Ray, Satveer SinghAbstract:Context: Thyroid autoimmunity is the most common coexistent endocrinopathy in type 1 diabetes (T1D), Addison’s disease, and premature ovarian failure (POF). Although the role of autoimmunity is being investigated in patients with sporadic Idiopathic Hypoparathyroidism (SIH), there is little information on coexistent thyroid autoimmunity. Objective: Our objective was to assess the prevalence of thyroid peroxidase autoantibodies (TPOAb) and thyroid dysfunction in patients with SIH and its comparison with that in T1D, POF, and Hashimoto’s thyroiditis (HT) and age- and sex-matched healthy controls (for SIH). Design and Setting: We conducted a case control study in a tertiary care setting. Patients and Methods: Subjects were consecutive patients with SIH (n = 87), T1D (n = 100), POF (n = 58), and HT (n = 47) and healthy controls (100 females and 64 males). Serum free T3, free T4, TSH, and TPOAb (normal ≤ 34 IU/ml) were measured by electrochemiluminescence assay. Subjects with 1) serum TSH at least 5 μU/ml alon...
Soma Saha - One of the best experts on this subject based on the ideXlab platform.
-
pulmonary alveolar proteinosis pap in Idiopathic Hypoparathyroidism
Case Reports, 2019Co-Authors: Soma Saha, Karan Madan, Deepali Jain, Ravinder GoswamiAbstract:Idiopathic Hypoparathyroidism (IH) and autoimmune pulmonary alveolar proteinosis (PAP) are rare disorders. A patient with IH and optimal calcaemic control on calcium and alfacalcidol was detected to have PAP after 8 years of follow-up. Patient had no respiratory complaints. Routine abdominal imaging for renal calcification showed patchy ground glass opacities in the lower lung fields leading to incidental diagnosis of PAP. Pulmonary function tests showed impaired diffusion capacity of the lung. Anti-granulocyte macrophage-colony stimulating factor autoantibodies were positive. Patient regularly attended the pulmonary clinic and showed progressive improvement in diffusion capacity of the lung during 2 years of follow-up. The calcaemic control in IH remained stable despite its presence with PAP. The autoimmune PAP in the presented case suggests a possible autoimmune basis of IH.
-
auditing the efficacy and safety of alfacalcidol and calcium therapy in Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2019Co-Authors: Soma Saha, Ravinder GoswamiAbstract:Context Patients with Hypoparathyroidism are treated with vitamin D and calcium. PTH is an emerging option because of its physiological action. It is important to assess the efficacy and shortcomings of conventional therapy. Objective We assessed the efficacy and safety of alfacalcidol in a large cohort of patients with Idiopathic Hypoparathyroidism (IH) and identified a subset who could be treated without oral calcium. Design and setting Observational study at tertiary care center. Subjects and methods We assessed 92 patients with IH who were receiving alfacalcidol and oral calcium to maintain an optimal serum total calcium level of 8.0 to 8.5 mg/dL during routine follow-up. Patients with suboptimal control were provided free medicines and followed up frequently. Oral calcium and alfacalcidol doses were titrated sequentially to determine the minimum doses for optimal calcium control. Serum phosphate level, 1,25-dihydroxyvitamin D, fractional excretion of phosphorus (FEPh), and hypercalciuria (urine calcium-to-creatinine ratio, >0.2) were assessed at each step of titration. Results Only 38% of patients had optimal calcium control during routine follow-up. With good compliance, all achieved optimal serum calcium and 1,25-dihydroxyvitamin D levels and 43% of patients could stop taking oral calcium. Hyperphosphatemia, hypercalciuria, and low FEPh persisted at all stages of therapy. Serum phosphorus levels normalized when the serum calcium level increased to 9.9 mg/dL, but this level of serum total calcium was associated with hypercalciuria in 90% of patients. Conclusion Alfacalcidol is effective in achieving calcemic control in IH. Calcemic control without oral calcium was achieved in 43% of patients receiving alfacalcidol. However, optimal calcium control was associated with hyperphosphatemia and hypercalciuria in most patients.
-
central immune tolerance of t and b cells in patients with Idiopathic Hypoparathyroidism t1d and autoimmune thyroiditis
Journal of the Endocrine Society, 2019Co-Authors: Samrina Mahtab, Soma Saha, Vishnubhatla Sreenivas, Parmita Kar, Alessandra Sottini, Luisa Imberti, Ravinder GoswamiAbstract:Context Pathogenesis of Idiopathic Hypoparathyroidism (IH) is under investigation. Abnormalities in central immune tolerance have yet not been investigated in this condition. T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs), formed during receptor gene rearrangements, are tools to assess central T- and B-cell output. Objective We assessed the number of circulating TRECs and KRECs in patients with IH, autoimmune type 1 diabetes (T1D), and autoimmune thyroiditis (ATs) and healthy controls (HCs). Design Comparative case-control at tertiary care center. Subjects and methods Absolute and relative TRECs and KRECs were measured in DNA extracted from whole blood of patients with IH (n = 181, 22 of whom were reassessed after a decade of follow-up) and T1D (n = 133), AT (n = 53), and HC (n = 135) using a quantitative real-time PCR/TaqMan® probe technique. Results Absolute and relative means of TRECs and KRECs in IH were comparable to HCs, and no differences were found between IH with and without calcium-sensing receptor antibodies or class I HLA-A*26:01 association. TRECs and KRECs did not change after a decade of follow-up. T1D had significantly higher absolute TRECs than IH, AT, and HCs, whereas AT patients showed lower TRECs and the highest KRECs; these levels showed no noteworthy correlation with thyroid dysfunctions. Conclusion Patients with IH showed TRECs and KRECs comparable to HCs, indicating an intact mechanism of T- and B-cell central immune tolerance. Interestingly, absolute TRECs were significantly higher in T1D than HCs, suggesting impaired central immune tolerance in T1D.
-
Central immune tolerance of T and B cells in patients with Idiopathic Hypoparathyroidism, T1D and autoimmune thyroiditis.
2019Co-Authors: Samrina Mahtab, Soma Saha, Parmita Kar, Alessandra Sottini, Luisa Imberti, Vishnubhatala Sreenivas, Ravinder GoswamiAbstract:Abstract Context: Pathogenesis of Idiopathic Hypoparathyroidism is under investigation. Abnormalities in central immune tolerance have yet not been investigated in them. T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs), formed during receptor gene rearrangements, is novel tools to assess central T- and B -cell output. Objective: We assessed the number of circulating TRECs and KRECs in patients with IH, autoimmune type-1 diabetes (T1D), and thyroiditis (AT) and healthy controls (HC). Design: Comparative case-control at tertiary care center. Subjects and methods: Absolute and relative TRECs and KRECs were measured in DNA extracted from whole blood of IH patients (n = 181, 22 of whom were reassessed after a decade of follow-up), T1D (n = 133), AT (n = 53), and HC (n = 135) using quantitative RT-PCR/TaqMan probe® technique. Results: Absolute and relative means of TRECs and KRECs in IH were comparable to HC and no differences were found between IH with and without CaSRAb or class I HLA-A*26:01 association. TRECs and KRECs did not change after a decade of follow-up. T1D had significantly higher absolute TRECs than IH, AT and HC, while AT patients showed lower TRECs and the highest KRECs; these levels showed no significant correlation with thyroid dysfunctions. Conclusion: Patients with IH showed TRECs and KRECs comparable to HC indicating an intact mechanism of T- and B-cell central immune tolerance. Interestingly, absolute TRECs were significantly higher in T1D than HC, suggesting impaired central immune tolerance in T1D.
-
long term outcome of cataract surgery in patients with Idiopathic Hypoparathyroidism and its relationship with their calcemic status
Journal of Bone and Mineral Metabolism, 2017Co-Authors: Soma Saha, Vishnubhatla Sreenivas, Sameer Aggarwal, Shiva Prasad Gantyala, Radhika Tandon, Ravinder GoswamiAbstract:Cataract is a cardinal manifestation of Hypoparathyroidism. Although patients with Hypoparathyroidism require cataract surgery at a younger age than individuals without Hypoparathyroidism, there is limited information on the outcome of this surgery. We assessed long-term complications of cataract surgery in patients with Idiopathic Hypoparathyroidism (IH) and its relationship with their clinical and biochemical parameters. Twenty-seven patients with IH and 25 nonhypoparathyroid controls with a minimum follow-up of 2 years after cataract surgery were assessed for visual acuity, intraocular pressure, lens centricity, Nd:YAG laser capsulotomy, and the severity of posterior capsular opacification (PCO) and anterior capsular opacification. High-resolution optical slit-lamp images were analyzed by an ophthalmologist. Patients with IH had cataract surgery at a younger age than controls (34.0 ± 16.4 years vs 58.0 ± 11.2 years, P < 0.001). A higher proportion of IH patients had dense white PCO (75.0 % vs 39.4 %, P = 0.004), Nd:YAG laser capsulotomy (44.2 % vs 10.0 %, P = 0.001), anterior capsular opacification (97.7 % vs 84.2 %, P = 0.03), and a decentric lens (28.3% vs 2.6 %, P = 0.001) at a comparable time after surgery (8.6 ± 6.1 years vs 8.7 ± 6.8 years, P = 0.85). On regression analysis, the severity of PCO in IH correlated only with male sex and not with other factors, including serum total calcium and inorganic phosphorus levels at the baseline and during follow-up. To conclude, patients with IH are likelier than individuals without IH to develop PCO and to require Nd:YAG laser capsulotomy after cataract surgery. Proper precautions should be taken during surgery to minimize this complication in IH.
Rajni Rani - One of the best experts on this subject based on the ideXlab platform.
-
presence of auto reactive mhc class i restricted calcium sensing receptor casr specific cd8 t cells in Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2016Co-Authors: Samrina Mahtab, Soma Saha, Ravinder Goswami, Utpreksha Vaish, Archana Singh, Rajni RaniAbstract:Context:Autoimmunity to Calcium sensing receptor (CaSR) has been implicated in aetiopathogenesis of Idiopathic Hypoparathyroidism (IH). While humoral immune responses have been shown, cell mediated auto-immune responses have not been demonstrated.Objective:To study CaSR specific cytotoxic T cell responses in PBMCs of IH patients.Design:Twenty four peptides of CaSR (RH1-RH24) were evaluated for their ex-vivo potential to stimulate PBMCs from IH patients and controls in IFN-γ ELISPOT assays.Setting:Tertiary patients care Centre and National Institute of Immunology, New Delhi, India.Patients or Other Participants:45 patients with IH attending endocrine clinic of All India Institute of Medical Sciences and 22 healthy controls.Main Outcome Measures:We hypothesized that MHC class-I restricted, CaSR specific cytotoxic CD8+ T cell may have a role in aetiopathogenesis of the diseases since we have earlier shown that MHC class-I allele HLA-A*26:01 and HLA Supertype A01 (STA01) were significantly increased in IH. Th...
-
CLINICAL STUDY Prevalence of calcium sensing receptor autoantibodies in patients with sporadic Idiopathic Hypoparathyroidism
2015Co-Authors: Ravinder Goswami, Rajni Rani, Edward M Brown, Narayana Kochupillai, Olga Kifor, Ita Gupta, Naibedya ChattopadhyayAbstract:Objective: The pathogenesis of sporadic Idiopathic Hypoparathyroidism is unclear. The calcium sensing receptor (CaSR) plays a pivotal role in extracellular calcium homeostasis and is the candidate auto-antigen in Hypoparathyroidism associated with autoimmune polyglandular endocrinopathy syn-drome. We therefore looked for antibodies (Ab) against the CaSR in patients with sporadic Idiopathic Hypoparathyroidism and their association, if any, with the major histocompatibility com-plex (MHC) class II human leukocyte antigen (HLA)-DR haplotypes. Methods: The subjects included 51 patients with sporadic Idiopathic Hypoparathyroidism and 45 healthy controls. Investigations included computerised tomography, serum calcium, phosphorus, thyroxine, TSH, cortisol, intact parathyroid hormone (iPTH), ACTH and thyroid peroxidase (TPO) and adrenal antibodies. The CaSRAb were assayed in patients ’ sera by Western blot. Genotyping of the HLA-DR locus was performed using PCR and sequence-specific oligonucleotide probes. Results: Intracranial calcification and cataract were present in 76.5 % and 41.1 % of the patients respectively and 62.7 % had convulsions. Autoantibodies against the 168 kDa CaSR protein were demonstrated in the serum of 49.0 % of the patients and in 13.3 % of the controls (P, 0.001)
-
presence of strong association of the major histocompatibility complex mhc class i allele hla a 26 01 with Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2012Co-Authors: Nandita Gupta, Ravinder Goswami, Archana Singh, Rajni RaniAbstract:Context: The pathogenesis of isolated Hypoparathyroidism, also referred to as Idiopathic Hypoparathyroidism (IH), is not clear. There is a paucity of information related to the immunogenetic basis of the disease due to its rarity. A recurrent theme of several autoimmune disorders is aberrant antigen presentation. Objective: We investigated for the association of alleles of the human leukocyte antigen (HLA) class I and II loci with IH. Patients and Controls: A total of 134 patients with IH and 902 healthy controls from the same ethnic background participated in the study. Results: There was a significant increase of HLA class I alleles HLA-A*26:01 [P < 1.71 × 10−34; odds ratio (OR) = 9.29; 95% confidence interval (CI) = 6.08–14.16] and HLA-B*08:01 (P < 8.19 × 10−6; OR = 2.59; 95% CI = 1.63–4.04) in patients with IH compared to healthy controls. However, the association of A*26:01 was primary because B*08:01 was in linkage disequilibrium with A*26:01. Although the major histocompatibility complex (MHC) is v...
-
parathyroid hormone gene polymorphism and sporadic Idiopathic Hypoparathyroidism
The Journal of Clinical Endocrinology and Metabolism, 2004Co-Authors: Ravinder Goswami, Neeraj Tomar, Nandita Gupta, Trilochan Mohapatra, Rajni Rani, Anupam Dikshit, Ram Kumar SharmaAbstract:The pathogenetic mechanisms involved in the development of sporadic Idiopathic Hypoparathyroidism are currently under investigation. Although autoantibodies against the calciumsensing receptor (CaSR) have been implicated to play a role, these could be demonstrated in only 49% of a group of 51 patients with sporadic Idiopathic Hypoparathyroidism that we previously studied. Therefore, we investigated 49 of these patients further, regardless of their antibody status, and looked for mutations in the section of the PTH gene sequence that coded for prepro-PTH as well as the 3-untranslated region (3-UTR) of the gene, which is believed to be involved in the stability of its mRNA. We also examined the relationship between the clinical manifestations of the disease and the occurrences of two commonly observed single nucleotide polymorphisms (SNPs) in the PTH gene. In 49 of the patients with Idiopathic Hypoparathyroidism and in 55 healthy controls, the SNPs were characterized by restriction analysis using DraII and BstBI enzymes. In a subset of these patients, exons 2 and 3 of the PTH gene (n 37) and its 3-UTR region (n 40) were also sequenced. No mutations were observed in the segment of the PTH gene coding for the signal peptide, prohormone, or the 3-UTR region. However, three well described SNPs were observed: 1) an A3 G substitution in intron 1 in 35.1% of the patients; 2) a G3 A substitution in intron 2, characterized by BstBI, in one or both alleles in 27%; and 3) a C3 A substitution at codon 52 (CGA) of exon 3, characterized by DraII, in one or both alleles in 59.7% of the patients. There was no significant difference in the frequency of occurrence of these SNPs between the patient and the control groups. Furthermore, the mean age at onset of symptoms, body mass index, frequency of cataract, tetany, convulsion, basal ganglia calcification, serum calcium, inorganic phosphorus, and intact PTH were not significantly different between patients with and without the above-described SNPs. Thus, the data from this report demonstrate that in patients with sporadic Idiopathic Hypoparathyroidism, neither the clinical manifestations nor the biochemical indexes of the disease are related to the occurrence of mutations or SNPs in the PTH gene. Because neither patient nor control samples exhibited any variations in the sequence of their 3-UTR regions, it is unlikely that mRNA instability is a factor in the pathogenesis of the disease. Additional studies are required to investigate the role of other genes and autoantigens that may be involved in the genesis of Idiopathic Hypoparathyroidism. (J Clin Endocrinol Metab 89: 4840 – 4845, 2004) T HE FUNDAMENTAL MECHANISMS involved in the development of Idiopathic Hypoparathyroidism still remain unidentified and are currently a subject of investigation. We recently demonstrated autoantibodies against the calcium-sensing receptor (CaSR) in 49% of a group of 51 patients with Idiopathic Hypoparathyroidism (1). The presence of CaSR autoantibodies in association with specific human leukocyte antigen DR haplotypes indicate organspecific autoimmunity; therefore, this subset of patients could be classified as having autoimmune Hypoparathyroidism. However, the remaining half of the patients in whom no CaSR autoantibodies could be detected would still have to be classified as having Idiopathic Hypoparathyroidism. Studies in patients with familial Hypoparathyroidism have revealed point mutations in the signal peptide-coding region of PTH gene in some of them (2, 3). The human PTH gene has been cloned; it is located on chromosome 11 and consists of three exons. Exon 1 is untranslated, exon 2 codes for the 25-amino acid signal peptide and part of the prohormone, and exon 3
-
prevalence of calcium sensing receptor autoantibodies in patients with sporadic Idiopathic Hypoparathyroidism
European Journal of Endocrinology, 2004Co-Authors: Ravinder Goswami, Nandita Gupta, Rajni Rani, Edward M Brown, Narayana Kochupillai, Olga Kifor, Naibedya ChattopadhyayAbstract:Objective: The pathogenesis of sporadic Idiopathic Hypoparathyroidism is unclear. The calcium sensing receptor (CaSR) plays a pivotal role in extracellular calcium homeostasis and is the candidate autoantigen in Hypoparathyroidism associated with autoimmune polyglandular endocrinopathy syndrome. We therefore looked for antibodies (Ab) against the CaSR in patients with sporadic Idiopathic Hypoparathyroidism and their association, if any, with the major histocompatibility complex (MHC) class II human leukocyte antigen (HLA)-DR haplotypes. Methods: The subjects included 51 patients with sporadic Idiopathic Hypoparathyroidism and 45 healthy controls. Investigations included computerised tomography, serum calcium, phosphorus, thyroxine, TSH, cortisol, intact parathyroid hormone (iPTH), ACTH and thyroid peroxidase (TPO) and adrenal antibodies. The CaSRAb were assayed in patients’ sera by Western blot. Genotyping of the HLA-DR locus was performed using PCR and sequence-specific oligonucleotide probes. Results: Intracranial calcification and cataract were present in 76.5% and 41.1% of the patients respectively and 62.7% had convulsions. Autoantibodies against the 168 kDa CaSR protein were demonstrated in the serum of 49.0% of the patients and in 13.3% of the controls (P , 0.001). Pre-incubating serum samples from the CaSRAb-positive patients with parathyroid membrane produced a 90% decrease in the band intensity. HLA-DRB1*01 and DRB1*09 alleles were significantly associated with Idiopathic Hypoparathyroidism (relative risk of 7.8, P ¼ 0.001). The frequency of HLA-DRB1*09 and DRB1*10 alleles tended to be higher in patients positive for the CaSRAb. There was no significant difference in the frequency of occurrence of convulsions, cataract, intracranial calcification, calcium:phosphorus ratio, and iPTH levels between patients with and without CaSRAb. Conclusion: 49.0% of the patients studied had serological evidence of organ-specific autoimmunity against the CaSR protein. The occurrence of CaSRAb and the HLA-DR associations imply an autoimmune component to the disease, but the primary role of the CaSRAb in the pathogenesis of the disease needs to be assessed further.
