Search Results
Search for other papers by Rimesh Pal in
Google Scholar
PubMed
Search for other papers by Sanjay Kumar Bhadada in
Google Scholar
PubMed
Search for other papers by Awesh Singhare in
Google Scholar
PubMed
Search for other papers by Anil Bhansali in
Google Scholar
PubMed
Search for other papers by Sadishkumar Kamalanathan in
Google Scholar
PubMed
Search for other papers by Manoj Chadha in
Google Scholar
PubMed
Search for other papers by Phulrenu Chauhan in
Google Scholar
PubMed
Search for other papers by Ashwani Sood in
Google Scholar
PubMed
Search for other papers by Vandana Dhiman in
Google Scholar
PubMed
Search for other papers by Dinesh Chandra Sharma in
Google Scholar
PubMed
Search for other papers by Uma Nahar Saikia in
Google Scholar
PubMed
Search for other papers by Debajyoti Chatterjee in
Google Scholar
PubMed
Search for other papers by Vikas Agashe in
Google Scholar
PubMed
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by recalcitrant hypophosphatemia. Reports from the Indian subcontinent are scarce, with most being single center experiences involving few patients. Herein, we conducted a retrospective analysis of 30 patients of TIO diagnosed at three tertiary care hospitals in India. Patients with persistent hypophosphatemia (despite correction of hypovitaminosis D), normocalcemia, elevated alkaline phosphatase, low TmP/GFR and elevated or ‘inappropriately normal’ FGF23 levels were labeled as having TIO. They were sequentially subjected to functional followed by anatomical imaging. Patients with a well-localized tumor underwent excision; others were put on phosphorous and calcitriol supplementation. The mean age at presentation was 39.6 years with female:male ratio of 3:2. Bone pain (83.3%) and proximal myopathy (70%) were the chief complaints; 40% of cases had fractures. The mean delay in diagnosis was 3.8 years. Tumors were clinically detectable in four patients (13.3%). The mean serum phosphate was 0.50 mmol/L with a median serum FGF23 level of 518 RU/mL. Somatostatin receptor-based scintigraphy was found to be superior to FDG-PET in tumor localization. Lower extremities were the most common site of the tumor (72%). Tumor size was positively correlated with serum FGF23 levels. Twenty-two patients underwent tumor resection and 16 of them had phosphaturic mesenchymal tumors. Surgical excision led to cure in 72.7% of patients whereas disease persistence and disease recurrence were seen in 18.2% and 9.1% of cases, respectively. At the last follow-up, serum phosphate in the surgically treated group was significantly higher than in the medically managed group.
Search for other papers by Eeva M Ryhänen in
Google Scholar
PubMed
Search for other papers by Ilkka Heiskanen in
Google Scholar
PubMed
Search for other papers by Harri Sintonen in
Google Scholar
PubMed
Search for other papers by Matti J Välimäki in
Google Scholar
PubMed
Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland
Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland
Search for other papers by Risto P Roine in
Google Scholar
PubMed
Search for other papers by Camilla Schalin-Jäntti in
Google Scholar
PubMed
Health-related quality of life (HRQoL) is frequently impaired in primary hyperparathyroidism (PHPT) but it is unclear if surgery is beneficial. The objective was to prospectively assess HRQoL in PHPT (n=124) with the 15D instrument before and after surgery, to compare it with that of a comparable sample of the general population (n=4295), and search for predictors of HRQoL and its change. HRQoL, and clinical and laboratory parameters were measured before and at 6 and 12 months after surgery. Regression techniques were used to search for predictors of HRQoL and gains from treatment. Before surgery, PHPT patients had significantly lower mean 15D score compared to controls (0.813 vs 0.904, P<0.001). Excretion, mental function, discomfort and symptoms, distress, depression, vitality, and sexual activity were most impaired (all P<0.001). Number of medications (P=0.001) and subjective symptoms (P<0.05) but not calcium or parathyroid hormone (PTH) predicted impaired HRQoL. Serum 25-hydroxyvitamin D (25OHD) was of borderline significance (P=0.051). Compared to baseline, mean 15D score improved significantly 6 months after surgery (0.813 vs 0.865, P<0.001) and the effect sustained at 1 year (0.878, P<0.001). The improvement was clinically important in 77.4% of patients (P<0.001). Educational level independently predicted improvement (P<0.005). HRQoL is severely impaired in PHPT but improves significantly after surgery. The 15D is a sensitive tool for assessing HRQoL and recognizing patients likely to benefit from surgery.
Search for other papers by Sara Lomelino Pinheiro in
Google Scholar
PubMed
Search for other papers by Ana Saramago in
Google Scholar
PubMed
Search for other papers by Branca Maria Cavaco in
Google Scholar
PubMed
Search for other papers by Carmo Martins in
Google Scholar
PubMed
Search for other papers by Valeriano Leite in
Google Scholar
PubMed
Search for other papers by Tiago Nunes da Silva in
Google Scholar
PubMed
Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which 11 carry an inactivating germline mutation in the MEN1 gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery. Serum calcium and parathyroid hormone levels were 15.0 mg/dL (8.4–10.2) and 472 pg/mL (12–65), respectively. The patient underwent parathyroid surgery, and histological findings were consistent with parathyroid carcinoma. Analysis of the MEN1 gene by next-generation sequencing (NGS) identified a novel germline heterozygous nonsense pathogenic variant (c.978C>A; p.(Tyr326*)), predicted to encode a truncated protein. Genetic analysis of the parathyroid carcinoma revealed a c.307del, p.(Leu103Cysfs*16) frameshift truncating somatic MEN1 variant in the MEN1 gene, which is consistent with MEN1 tumor-suppressor role, confirming its involvement in parathyroid carcinoma etiology. Genetic analysis of CDC73, GCM2, TP53, RB1, AKT1, MTOR, PIK3CA and CCND1 genes in the parathyroid carcinoma DNA did not detect any somatic mutations. To our knowledge, this is the first report of a PC case presenting both germline (first-hit) and somatic (second-hit) inactivation of the MEN1 gene.
Search for other papers by Mengting Yin in
Google Scholar
PubMed
Search for other papers by Qianhui Liu in
Google Scholar
PubMed
Search for other papers by Qingzhong Wang in
Google Scholar
PubMed
Search for other papers by Yong He in
Google Scholar
PubMed
Search for other papers by Haolan Song in
Google Scholar
PubMed
Search for other papers by Xin Nie in
Google Scholar
PubMed
Search for other papers by Guixing Li in
Google Scholar
PubMed
Background
The diagnosis of primary hyperparathyroidism (PHPT) remains a challenge because of increased asymptomatic PHPT or patients with normocalcaemic PHPT (NPHPT). In addition, some primary hospitals in China have no equipment to measure parathyroid hormone (PTH) levels. Therefore, an additional, simple, and inexpensive laboratory biochemical marker is urgently needed. The calcium/phosphate (Ca/P) ratio and chloride/phosphate (Cl/P) ratio have been proposed as suitable tools to diagnose PHPT in Europe; however, the Ca/P ratio has never been tested in China. We aimed to conduct a confirmatory study to explore the diagnostic performance of the Ca/P ratio for PHPT in China.
Methods
From January 2015 to December 2020, a total of 155 patients who underwent parathyroidectomy (143 PHPT patients and 12 NPHPT patients) and 153 controls were enrolled in this single-center , retrospective study. Serum calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin vitamin D (25(OH) vitamin D), chloride, alanine transaminase (ALT), aspartate aminotransaminase (AST), estimated glomerular filtration rate (eGFR), and creatinine levels were recorded for all the study participants. Pairwise comparisons were made between groups, and the diagnostic performance of the Ca/P ratio was determined using receiver-operating characteristic (ROC) analysis.
Results
Patients with PHPT had a higher Ca/P ratio than controls (P < 0.001). A Ca/P ratio above 2.94 with a sensitivity of 95.5% and specificity of 98.7% can distinguish PHPT patients from healthy individuals. This index was positively correlated with the PTH level (r = 0.875, P < 0.001).
Conclusion
The Ca/P ratio is an ideal and inexpensive indicator for diagnosing PHPT in China when using a cut-off value of 2.94.
Search for other papers by Shu-Meng Hu in
Google Scholar
PubMed
Search for other papers by Yang-Juan Bai in
Google Scholar
PubMed
Search for other papers by Ya-Mei Li in
Google Scholar
PubMed
Search for other papers by Ye Tao in
Google Scholar
PubMed
Search for other papers by Xian-Ding Wang in
Google Scholar
PubMed
Search for other papers by Tao Lin in
Google Scholar
PubMed
Search for other papers by Lan-Lan Wang in
Google Scholar
PubMed
Search for other papers by Yun-Ying Shi in
Google Scholar
PubMed
Introduction
Tertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decreased graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-alpha Klotho (KLA) axis and cardiovascular complications after transplantation.
Materials and methods
Two hundred nine kidney transplant recipients were included and further divided into treated and untreated groups depending on whether they received vitamin D supplementation. We tracked the state of THPT, bone metabolism and FGF23–KLA axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, KLA levels, THPT and cardiovascular complications in recipients.
Results
Vitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in the treated group compared to the untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for intact FGF23 and KLA levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12.
Conclusion
Vitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.
Search for other papers by Maria Stelmachowska-Banaś in
Google Scholar
PubMed
Search for other papers by Izabella Czajka-Oraniec in
Google Scholar
PubMed
Immune checkpoint inhibitors (ICIs) belong to a new group of anticancer drugs targeting T-cell proteins involved in the activation of immune response toward malignancies. Their introduction into clinical practice was a milestone in modern cancer treatment. However, the significant advantage of ICIs over conventional chemotherapy in terms of therapeutic efficacy is accompanied by new challenges related to specific side effects. ICI-induced immune system activation could lead to the loss of self-tolerance, presenting as autoimmune inflammation and dysfunction of various tissues and organs. Thus, the typical side effects of ICIs include immune-related adverse events (irAEs), among which endocrine irAEs, affecting numerous endocrine glands, have been commonly recognized. This review aimed to outline the current knowledge regarding ICI-induced endocrine disorders from a clinical perspective. We present updated information on the incidence and clinical development of ICI-induced endocrinopathies, including the most frequent thyroiditis and hypophysitis, the rarely observed insulin-dependent diabetes mellitus and primary adrenal insufficiency, and the recently described cases of hypoparathyroidism and lipodystrophy. Practical guidelines for monitoring, diagnosis, and treatment of ICI-related endocrine toxicities are also offered. Rising awareness of endocrine irAEs among oncologists, endocrinologists, and other health professionals caring for patients receiving ICIs could contribute to better safety and efficacy. As immunotherapy becomes widespread and approved for new types of malignancies, increased incidences of endocrine irAEs are expected in the future.
Search for other papers by Bekir Cakir in
Google Scholar
PubMed
Search for other papers by F Neslihan Cuhaci Seyrek in
Google Scholar
PubMed
Search for other papers by Oya Topaloglu in
Google Scholar
PubMed
Search for other papers by Didem Ozdemir in
Google Scholar
PubMed
Search for other papers by Ahmet Dirikoc in
Google Scholar
PubMed
Search for other papers by Cevdet Aydin in
Google Scholar
PubMed
Search for other papers by Sefika Burcak Polat in
Google Scholar
PubMed
Search for other papers by Berna Evranos Ogmen in
Google Scholar
PubMed
Search for other papers by Ali Abbas Tam in
Google Scholar
PubMed
Search for other papers by Husniye Baser in
Google Scholar
PubMed
Search for other papers by Aylin Kilic Yazgan in
Google Scholar
PubMed
Search for other papers by Mehmet Kilic in
Google Scholar
PubMed
Search for other papers by Afra Alkan in
Google Scholar
PubMed
Search for other papers by Reyhan Ersoy in
Google Scholar
PubMed
Background
Despite significant improvement in imaging quality and advanced scientific knowledge, it may still sometimes be difficult to distinguish different parathyroid lesions. The aims of this prospective study were to evaluate parathyroid lesions with ultrasound elastography and to determine whether strain index can help to differentiate parathyroid lesions.
Methods
Patients with biochemically confirmed hyperparathyroidism and localised parathyroid lesions in ultrasonography were included. All patients underwent B-mode US and USE examination. Ultrasound elastography scores and strain index of lesions were determined. Strain index was defined as the ratio of strain of the thyroid parenchyma to the strain of the parathyroid lesion.
Results
Data of 245 lesions of 230 patients were analysed. Histopathologically, there were 202 (82.45%) parathyroid adenomas, 26 (10.61%) atypical parathyroid adenomas, and 17 (6.94%) cases of parathyroid hyperplasia. Median serum Ca was significantly higher in atypical parathyroid adenoma patients than parathyroid hyperplasia patients (P = 0.019) and median PTH was significantly higher in APA compared to PA patients (P < 0.001). In 221 (90.2%) of the parathyroid lesions, USE score was 1 or 2. The median SI of atypical parathyroid adenomas was significantly higher than parathyroid adenomas and hyperplasia lesions (1.5 (0.56–4.86), 1.01 (0.21–8.43) and 0.91 (0.26–2.02), respectively, P = 0.003).
Conclusion
Our study revealed that SI of parathyroid lesions as well as serum calcium, parathyroid hormone levels, and B-mode US features may help to predict the atypical parathyroid adenoma. Ultrasound elastography can be used to differentiate among parathyroid lesions and guide a surgical approach.
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Search for other papers by Felix Haglund in
Google Scholar
PubMed
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Search for other papers by Gustaf Rosin in
Google Scholar
PubMed
Search for other papers by Inga-Lena Nilsson in
Google Scholar
PubMed
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Search for other papers by C Christofer Juhlin in
Google Scholar
PubMed
Search for other papers by Ylva Pernow in
Google Scholar
PubMed
Search for other papers by Sophie Norenstedt in
Google Scholar
PubMed
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Search for other papers by Andrii Dinets in
Google Scholar
PubMed
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Search for other papers by Catharina Larsson in
Google Scholar
PubMed
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Search for other papers by Johan Hartman in
Google Scholar
PubMed
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Search for other papers by Anders Höög in
Google Scholar
PubMed
Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness.
Search for other papers by Natércia Neves Marques de Queiroz in
Google Scholar
PubMed
Search for other papers by Franciane Trindade Cunha de Melo in
Google Scholar
PubMed
Search for other papers by Fabrício de Souza Resende in
Google Scholar
PubMed
Search for other papers by Luísa Corrêa Janaú in
Google Scholar
PubMed
Search for other papers by Norberto Jorge Kzan de Souza Neto in
Google Scholar
PubMed
Search for other papers by Manuela Nascimento de Lemos in
Google Scholar
PubMed
Search for other papers by Ana Carolina Lobato Virgolino in
Google Scholar
PubMed
Search for other papers by Maria Clara Neres Iunes de Oliveira in
Google Scholar
PubMed
Search for other papers by Angélica Leite de Alcântara in
Google Scholar
PubMed
Search for other papers by Lorena Vilhena de Moraes in
Google Scholar
PubMed
Search for other papers by Tiago Franco David in
Google Scholar
PubMed
Search for other papers by Wanderson Maia da Silva in
Google Scholar
PubMed
Search for other papers by Scarlatt Souza Reis in
Google Scholar
PubMed
Search for other papers by Márcia Costa dos Santos in
Google Scholar
PubMed
Search for other papers by Ana Carolina Contente Braga de Souza in
Google Scholar
PubMed
Search for other papers by Pedro Paulo Freire Piani in
Google Scholar
PubMed
Search for other papers by Neyla Arroyo Lara Mourão in
Google Scholar
PubMed
Search for other papers by Karem Mileo Felício in
Google Scholar
PubMed
Search for other papers by João Felício Abrahão Neto in
Google Scholar
PubMed
Search for other papers by João Soares Felício in
Google Scholar
PubMed
Objective:
Investigate the prevalence of vitamin D deficiency in an equatorial population through a large-sample study.
Methods:
Cross-sectional study with 30,224 healthy individuals from the North Region, in Brazil (Amazônia – state of Pará), who had 25-hydroxy-vitamin D (25(OH)D) and intact parathyroid hormone (PTH) serum levels measured by immunoassay method. Those with history of acute or chronic diseases were excluded. Abnormal levels of calcium, creatinine, glycemia and albumin were also exclusion criteria.
Results:
25(OH)D levels were 29.1 ± 8.2 ng/mL and values <12.7 ng/mL were equal to < −2 s.d. below average. Hypovitaminosis D was present in 10% of subjects according to the Institute of Medicine (values <20 ng/mL) and in 59%, in consonance with Endocrine Society (values 20–30 ng/mL as insufficiency and <20 ng/mL as deficiency) criteria. Individuals were divided according to four age brackets: children, adolescents, adults and elderly, and their 25(OH)D levels were: 33 ± 9; 28.5 ± 7.4; 28.3 ± 7.7; 29.3 ± 8.5 ng/mL, respectively. All groups differed in 25(OH)D, except adolescents vs adults. Regression model showed BMI, sex, living zone (urban or rural) and age as independent variables to 25(OH)D levels. Comparing subjects with vitamin D deficiency (<20 ng/mL) to those with vitamin D insufficiency (20–30 ng/mL), a difference between PTH levels in these two groups was observed (95.9 ± 24.7 pg/mL vs 44.2 ± 64.5 pg/mL; P < 0.01). Additionally, the most accurate predictive vitamin D level for subclinical hyperparathyroidism in ROC curve was 26 ng/mL.
Conclusion:
Our equatorial population showed low prevalence of vitamin D hypovitaminosis ranging with age bracket. The insufficient category by Endocrine Society was corroborated by our PTH data.
Search for other papers by Ghazala Zaidi in
Google Scholar
PubMed
Search for other papers by Vijayalakshmi Bhatia in
Google Scholar
PubMed
Search for other papers by Saroj K Sahoo in
Google Scholar
PubMed
Search for other papers by Aditya Narayan Sarangi in
Google Scholar
PubMed
Search for other papers by Niharika Bharti in
Google Scholar
PubMed
Search for other papers by Li Zhang in
Google Scholar
PubMed
Search for other papers by Liping Yu in
Google Scholar
PubMed
Search for other papers by Daniel Eriksson in
Google Scholar
PubMed
Search for other papers by Sophie Bensing in
Google Scholar
PubMed
Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden
Search for other papers by Olle Kämpe in
Google Scholar
PubMed
Search for other papers by Nisha Bharani in
Google Scholar
PubMed
Search for other papers by Surendra Kumar Yachha in
Google Scholar
PubMed
Search for other papers by Anil Bhansali in
Google Scholar
PubMed
Search for other papers by Alok Sachan in
Google Scholar
PubMed
Search for other papers by Vandana Jain in
Google Scholar
PubMed
Search for other papers by Nalini Shah in
Google Scholar
PubMed
Search for other papers by Rakesh Aggarwal in
Google Scholar
PubMed
Search for other papers by Amita Aggarwal in
Google Scholar
PubMed
Search for other papers by Muthuswamy Srinivasan in
Google Scholar
PubMed
Search for other papers by Sarita Agarwal in
Google Scholar
PubMed
Search for other papers by Eesh Bhatia in
Google Scholar
PubMed
Objective
Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients.
Design
Twenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2–19) years.
Methods
Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied.
Results
Patients varied widely in their age of presentation [3.5 (0.1–17) years] and number of clinical manifestations [5 (2–11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3–23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians.
Conclusions
Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.
