Primary Ovarian Insufficiency in Women With Addison’s Disease

Abstract

Context Primary ovarian insufficiency (POI) is defined by menopause before 40 years of age. POI prevalence is higher among women with autoimmune Addison’s disease (AAD) than in the general population, but their clinical characteristics are insufficiently studied. Objective To assess the prevalence of POI in a large cohort of AAD women and describe clinical, immunological, and genetic characteristics. Design and settings An observational population-based cohort study of The Norwegian National Addison Registry. The Norwegian Prescription Database (NorPD) was used to assess prescription of menopausal hormone replacement therapy (HRT). Patients A total of 458 women with AAD were studied. Main outcome measures The primary outcome was prevalence of POI. Secondary outcomes were clinical characteristics, autoantibodies, and genome-wide single nucleotide polymorphism (SNP) variation. Results The prevalence of POI was 10.2% (47/458) and one third developed POI before 30 years of age. POI preceded or coincided with AAD diagnosis in more than half of the women. The prevalence of concomitant autoimmune diseases was 72%, and AAD women with POI had more autoantibodies than AAD women without (≥2 autoantibodies in 78% vs 25%). Autoantibodies against side-chain cleavage enzyme (SCC) had the highest accuracy with a negative predictive value for POI of 96%. HRT use was high compared to the age adjusted normal population (11.3 % vs 0.7%). Conclusion One in ten AAD women have POI. Autoantibodies against SCC are the most specific marker for autoimmune POI. We recommend testing AAD women < 40 years with menstrual disturbances or fertility concerns for autoantibodies against SCC.

Autoimmune Thyroid Disorders in Autoimmune Addison Disease

“…This emphasizes the importance of patient information about symptoms of hyperglycemia and annual screening with glucose and glycated hemoglobin A 1c . Furthermore, we confirm recent observations that the risk of having premature gonadal insufficiency among women with AAD is high, found in 9% of women with hypothyroidism and AAD ( 27 ). In comparison, Betterle and colleagues ( 4 ) report a prevalence of 14% in their APS-2 patients, but included also those with so-called subclinical ovarian autoimmunity.…”

A review of autoimmunity and immune profiles in patients with primary ovarian insufficiency

“…Autoimmune oophoritis was first described in the cases of Addison’s disease, [ 3 ] and approximately 10% women with Addison’s disease have POI. [ 45 ] These findings were potent support for the hypothesis of autoimmune etiology of POI. Interestingly, POI frequently precedes Addison’s disease, sometimes even 8 to 14 years earlier, [ 3 , 46 ] which implied that the occurrence of autoimmune oophoritis, POI, and Addison’s disease might be regulated by the same factors.…”

Successful live birth following a short course of glucocorticoid suppression in a patient with autoimmune polyglandular syndrome type 2 and premature ovarian insufficiency: A case report

“…Our patient met the criteria for APS‐2 given her dual diagnoses of Addison's disease and Hashimoto's thyroiditis. Up to 20% of women with Addison's disease will develop POI before the age of 40 years 5 . Although 21‐hydroxylase (21OH) is not involved in ovarian steroidogenesis, 21OHAb is the best single immune marker to classify autoimmune POI, a diagnosis which no longer requires histological confirmation 1 .…”