title: Identification of autoimmune polyendocrine syndrome type 1 in patients with isolated hypoparathyroidism.
abstract: OBJECTIVE
  The prevalence of autoimmune polyendocrine syndrome type 1 (APS1) among isolated hypoparathyroidism (HP) or primary adrenal insufficiency (PAI) is not well established. We studied the frequency of APS1 in patients with HP or PAI by measuring interferon-α (IFN-α) antibody levels, a highly sensitive and specific marker for APS1.
  
  
  METHODS
  In a single-centre cross-sectional study, 37 Indian patients with isolated HP and 40 patients with PAI were tested for IFN-α antibody using an indirect ELISA. In patients with elevated IFN-α antibody, the autoimmune regulator (AIRE) gene was bidirectionally sequenced.
  
  
  RESULTS
  Three (8·1%) patients with isolated HP had elevated IFN-α antibody levels (range: 367-17382 units; positive titre >56 units). Homozygous or compound heterozygous AIRE mutations were detected in all three patients, including a novel mutation (p.T68P). All three APS1 patients had atypical features. The first patient, diagnosed at 7 years of age, died suddenly 5 months later. The second patient had late-onset HP (at the age of 34 years) and a solitary episode of transient mucocutaneous candidiasis 5 years later. The final patient developed HP at the age of 14 years and premature ovarian insufficiency 14 years later. Interleukin-22 antibodies, as well as most other organ-specific antibodies, were absent in the 3 APS1 patients. All patients with PAI were negative for IFN-α antibody.
  
  
  CONCLUSIONS
  Eight percentage of patients with isolated HP had elevated IFN-α antibody levels and AIRE mutation-positive APS1. All APS1 patients had atypical clinical features. Testing for IFN-α antibody should be considered in patients with idiopathic HP.
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Saroj K
authors.initials: SK
authors.lastname: Sahoo
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Ghazala
authors.initials: G
authors.lastname: Zaidi
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Rajni
authors.initials: R
authors.lastname: Srivastava
authors.affiliation: Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Aditya N
authors.initials: AN
authors.lastname: Sarangi
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Niharika
authors.initials: N
authors.lastname: Bharti
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eriksson
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bensing
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.|Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Amita
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Aggarwal
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. ebhatia@sgpgi.ac.in.
authors.forename: Eesh
authors.initials: E
authors.lastname: Bhatia
mesh_terms: D000224:Addison Disease / Q000150:complications*; D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000032:analysis; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007011:Hypoparathyroidism / Q000150:complications / Q000209:etiology / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis*; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult; D000096927:AIRE Protein
chemical_list: D000906:Antibodies; D016898:Interferon-alpha; D014157:Transcription Factors; D000096927:AIRE Protein