Premature Ovarian Failure in Patients with Autoimmune Addison's Disease: Clinical, Genetic, and Immunological Evaluation
Abstract
DESIGN: The design of the study was to investigate the prevalence of the following: 1) premature ovarian failure (POF) in patients with autoimmune Addison's disease (AD); 2) steroid-producing cell antibodies (StCA) and steroidogenic enzymes (17α-hydroxylase autoantibodies and P450 side-chain cleavage enzyme autoantibodies) in patients with or without POF; and 3) the value of these autoantibodies to predict POF. PATIENTS: The study included 258 women: 163 with autoimmune polyendocrine syndrome type 2 (APS-2), 49 with APS-1, 18 with APS-4, and 28 with isolated AD. METHODS: StCA were measured by an immunofluorescence technique and 17α-hydroxylase autoantibodies and P450 side-chain cleavage enzyme autoantibodies by immunoprecipitation assays. RESULTS: Fifty-two of 258 women with AD (20.2%) had POF. POF was diagnosed in 20 of 49 (40.8%) with APS-1, six of 18 (33.3%) with APS-4, 26 of 163 (16%) with APS-2, and none of 28 with isolated AD. In patients with APS-1 and APS-4, POF developed after AD, whereas it preceded AD in patients with APS-2. StCA were detected in 31 of 43 with POF (72%) and 51 of 198 without POF (25.7%). StCA were present in 22 of 38 with APS-1 (57.9%) (11 of 13 with POF); in five of 13 with APS-4 (38.5%) (three of four with POF); in 53 of 162 with APS-2 (32.7%) (17 of 26 with POF), and in one of 28 isolated AD patients (3.6%). Twelve of 13 patients with POF with a duration less than 5 yr (92.3%) and 18 of 25 with duration longer than 5 yr (72%) were StCA positive. Twenty-eight of 31 with POF (90.3%) were positive for at least one steroidogenic antibody. Forty-one women with AD less than 40 yr were followed up for a mean period of 9 yr. Eight of 21 women (38%) positive or seroconverted for steroidogenic autoantibodies developed POF at a mean age of 23 yr (six with APS-1, one with APS-2, and one with APS-4), and none of the 20 patients negative for steroidogenic autoantibodies developed POF. CONCLUSIONS: This study indicates that AD is frequently associated with POF and that steroidogenic antibodies are markers of patients with POF. Steroidogenic autoantibodies are predictive markers of POF in patients with AD.
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In the Italian cohort, none of 28 women with isolated primary adrenal insufficiency had premature ovarian insufficiency.
“In an Italian cohort of 258 women with PAI, 20.2% had premature ovarian insufficiency; premature ovarian insufficiency was diagnosed in 20 of 49 (40.8%) with APS-1, six of 18 (33.3%)with APS-4, 26 of 163 (16%) with APS-2, but none of 28 with isolated PAI (159).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [159]
In an Italian cohort of 258 women with primary adrenal insufficiency, 20.2% had premature ovarian insufficiency.
“In an Italian cohort of 258 women with PAI, 20.2% had premature ovarian insufficiency; premature ovarian insufficiency was diagnosed in 20 of 49 (40.8%) with APS-1, six of 18 (33.3%)with APS-4, 26 of 163 (16%) with APS-2, but none of 28 with isolated PAI (159).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [159]
In the Italian cohort, premature ovarian insufficiency was diagnosed in 16% (26/163) of women with APS-2.
“In an Italian cohort of 258 women with PAI, 20.2% had premature ovarian insufficiency; premature ovarian insufficiency was diagnosed in 20 of 49 (40.8%) with APS-1, six of 18 (33.3%)with APS-4, 26 of 163 (16%) with APS-2, but none of 28 with isolated PAI (159).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [159]
In the Italian cohort, premature ovarian insufficiency was diagnosed in 33.3% (6/18) of women with APS-4.
“In an Italian cohort of 258 women with PAI, 20.2% had premature ovarian insufficiency; premature ovarian insufficiency was diagnosed in 20 of 49 (40.8%) with APS-1, six of 18 (33.3%)with APS-4, 26 of 163 (16%) with APS-2, but none of 28 with isolated PAI (159).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [159]
In Reato et al., three of 13 seropositive patients developed premature ovarian insufficiency during a mean observation period of 8 years.
“Using the less sensitive immunofluorescence assay of steroid-cell autoantibodies, Reato et al (159) found that three of 13 seropositive patients developed premature ovarian insufficiency during a mean observation period of 8 years, indicating that the predictive value is not that high.”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [159]
In the Italian cohort, premature ovarian insufficiency was diagnosed in 40.8% (20/49) of women with APS-1.
“In an Italian cohort of 258 women with PAI, 20.2% had premature ovarian insufficiency; premature ovarian insufficiency was diagnosed in 20 of 49 (40.8%) with APS-1, six of 18 (33.3%)with APS-4, 26 of 163 (16%) with APS-2, but none of 28 with isolated PAI (159).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [159]
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References 20 · Cited by 118
Research works printed but not linked: 7
- Husebye ES, Løvås K 2009 Immunology of Addison's disease and premature ovarian failure. Endocrinol Metab Clin North Am 38: 389 -405, ix
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- Authors
- Reato, G., Morlin, L., Chen, S., Furmaniak, J., Smith, B. R., Masiero, S., Albergoni, M. P., Cervato, S., Zanchetta, R., & Betterle, C.
- Affiliations
- University of Padua (IT)
- Azienda Ospedale - Università Padova (IT)
- Corresponding author
- Betterle, C.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2011-08
- Volume
- 96
- Issue
- 8
- Pages
- E1255-E1261
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2096865817
- Cited by
- 118
- References
- 20
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 14 · 2023: 10 · 2022: 4 · 2021: 9 · 2020: 4 · 2019: 13 · 2018: 7 · 2017: 6 · 2016: 7 · 2015: 4 · 2014: 5 · 2013: 12 · 2012: 4
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- premature ovarian failure, autoimmune Addison's disease, autoimmune polyendocrine syndrome type 2, autoimmune ovarian failure, adrenal insufficiency, women's reproductive health
- MeSH terms
- Addison Disease, Adolescent, Adult, Autoantibodies, Child, Child, Preschool, Cholesterol Side-Chain Cleavage Enzyme, Female, Follow-Up Studies, HLA-DR Antigens, Humans, Middle Aged, Predictive Value of Tests, Steroid 17-alpha-Hydroxylase, Prevalence, Primary Ovarian Insufficiency, Polyendocrinopathies, Autoimmune, Young Adult, HLA-DRB1 Chains
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