PMON21 Autoimmune Polyglandular Syndrome, Type 1: A Rare Condition Manifested by Multiple Endocrine and Non-Endocrine Disorders

Abstract

Abstract Introduction Autoimmune Polyglandular Syndrome Type 1 (APS-1) is a rare autoimmune disorder with a prevalence of 1 in 2-3 million births. It is an autosomal recessive disorder caused by loss of function mutation of the Auto- Immune REgulator gene (AIRE gene) on chromosome 21. It leads to formation of autoantibodies to various hormonal, connective tissue, and protein antigens. It is characterized by the presence of two of the following three cardinal features: chronic muco-cutaneous candidiasis, hypoparathyroidism, and Addison's disease (primary adrenal insufficiency). Recently AIRE gene mutations have been seen in patients who have one of the three classic findings, but have other less commonly associated autoimmune disorders. The other auto-immune conditions associated with APS-1 are: type 1 diabetes mellitus, vitiligo, pernicious anemia, primary hypothyroidism, primary hypogonadism, pituitary failure, autoimmune hepatitis, and interstitial nephritis. The diagnosis is based on the history suggestive of endocrine and autoimmune disorders and the biochemical testing for endocrinopathies. The definitive diagnosis is made by genetic testing for AIRE gene mutation. Treatment is identical as for each isolated condition, i.e., hormone replacement, electrolyte correction and antifungals. Case Presentation A 19-year-old patient with a past medical history of congenital single kidney, oral thrush and vaginal candidiasis, hypothyroidism, intellectual disabilities, seizure disorder (onset two years earlier) and depression, was referred to the Endocrinology clinic for the evaluation of hypocalcemia. Her serum calcium was 7.9 mg/dl (normal: 8.5-10.0 mg/dl). She complained of fatigue, and constipation, but denied carpopedal spasms or perioral paresthesia. She has a family history of thyroid dysfunction and diabetes (mother). Initial workup for hypocalcemia revealed low serum calcium with low ionized calcium. Normal magnesium, creatinine, vitamin D-1,25 dihydroxy and 25-hydroxy vitamin D, and TSH (patient on levothyroxine for hypothyroidism). The parathyroid hormone level was low at 6.4 pg/ml (normal 8.0 to 65.0 pg/ml). She was diagnosed with hypoparathyroidism of unknown etiology. She was started on vitamin D and calcium supplementation. The biochemical testing for adrenal insufficiency was negative. The anti-adrenal and thyroid antibody panel was negative. She had a hormone-releasing birth control implant so ovarian function could not be assessed. Given the history of candidiasis and hypothyroidism with the new diagnosis of hypoparathyroidism, she was diagnosed with autoimmune polyglandular syndrome type 1. Conclusion Autoimmune Polyglandular Syndrome, type 1 is a rare autoimmune disorder and needs a high level of suspicion for diagnosis. The syndromic nature of this rare disorder should be recognized to facilitate early detection of other possible auto-immune conditions which can be associated with it. A history of more than one endocrine disorder and the presence of autoimmune conditions should prompt the physician to consider APS-1 as one of the possible diagnoses. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.