Identification of Autoimmune Polyendocrine Syndrome Type 1 in Patients with Isolated Hypoparathyroidism

SummaryObjectiveThe 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.Design, patients and measurementsIn 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.ResultsThree (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.ConclusionEight 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.