title: II. Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases: markers of high progression to clinical Addison's disease.
abstract: Adrenal cortex autoantibodies (ACA) were measured by immunofluorescence in 808 children with organ-specific autoimmune diseases without adrenal insufficiency. ACA were found in 14 children (1.7%), mostly in hypoparathyroidism (48%). Ten ACA-positive and 12 ACA-negative children were followed up for a maximum of 10 yr by evaluation of adrenocortical function (ACTH test) and autoantibody status. In all patients steroid-producing cell autoantibodies were assessed by immunofluorescence and autoantibodies to steroid 21-hydroxylase, 17 alpha-hydroxylase, and cytochrome P450 side-chain cleavage enzyme by immunoprecipitation assay. All 10 ACA-positive patients were positive for 21-hydroxylase autoantibodies. Six were positive for steroid-producing cell autoantibodies and 5 also for autoantibodies to 17 alpha-hydroxylase and/or P450 side-chain cleavage enzyme. Overt Addison's disease developed in 9 (90%) ACA/21-OH-antibody-positive children after 3-121 months, and 1 remaining child had subclinical hypoadrenalism. By contrast, all ACA/21-OH antibody-negative children maintained normal adrenal function. Adrenal failure was not related to ACA titres, sex, adrenal function, type of preexisting autoimmune disorder, or human leucocyte antigens D-related status. In conclusion, in children with autoimmune endocrine diseases, ACA/21-hydroxylase autoantibodies are important predictive markers for the development of Addison's disease.
authors.affiliation: Chair of Clinical Immunology and Allergy, University of Padova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Betterle
authors.forename: M
authors.initials: M
authors.lastname: Volpato
authors.forename: B
authors.initials: B
authors.lastname: Rees Smith
authors.forename: J
authors.initials: J
authors.lastname: Furmaniak
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Zanchetta
authors.forename: N A
authors.initials: NA
authors.lastname: Greggio
authors.forename: B
authors.initials: B
authors.lastname: Pedini
authors.forename: M
authors.initials: M
authors.lastname: Boscaro
authors.forename: F
authors.initials: F
authors.lastname: Presotto
mesh_terms: D000224:Addison Disease / Q000209:etiology*; D000302:Adrenal Cortex / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D001327:Autoimmune Diseases / Q000150:complications* / Q000276:immunology*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009928:Organ Specificity; D011446:Prospective Studies; D013255:Steroid 21-Hydroxylase / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D013255:Steroid 21-Hydroxylase