PMON317 Rapid Progression of Adrenal insufficiency in Child with Autoimmune Polyendocrine Syndrome Type 1
Authors: Umscheid Jacob , Al Muhaisen Fadi , Mitre Naim 
Published: November 2022

Background

Autoimmune Polyendocrine Syndrome type 1 (APS-1) is an autosomal recessive rare disease resulting from mutations in the autoimmune regulator gene (AIRE) on chromosome 21q22.3. APS-1 was first described as a syndrome in 1946 as a triad of mucocutaneous candidiasis, primary hypoparathyroidism, and adrenal insufficiency. With an AIRE gene mutation, the immune system will have a T-regulatory cell defect, which leads to a loss of immune tolerance. This will increase the risk of autoimmune disease in the body's organs such as the pancreas, thyroid, adrenal gland, liver, intestine, skin, and parathyroid gland.

Clinical case

A 6-year-old male was admitted to the pediatric floor for new-onset seizures and tetany. Initial laboratory assessment was concerning for severe hypocalcemia associated with low parathyroid hormone (PTH) and hyponatremia. Blood workup showed: low serum sodium 130 mmol/L (136-144), potassium 4.1 mmol/L(3.4-4.7), carbon dioxide 16 mmol/L; ionized calcium 0.67 mmol/L (1.19-1.41), phosphorus 7.4mg/dL (4.0-7.0), PTH 9.0pg/mL (12.0-88.0). Calcium replacement and calcitriol were initiated with a resolution of symptoms.

Further investigations were done for the adrenal gland given his low sodium level. He underwent an ACTH stimulation test that he passed, with a cortisol baseline of 39mcg/dl with a peak of 48mcg/dl. ACTH level was high at 120pg/mL (5-27), and a repeat in 4 weeks was normal at 11pg/ml. His renin activity was elevated at 71ng/ml/hr (1.5-3.5). Renin activity was repeated and was elevated again at 34ng/ml/hr, prompting adrenal antibody testing, which revealed an elevated titer 1: 10 (&lt;1: 10). Due to concern for APS-1, genetic testing was obtained and revealed a pathological variant of AIRE of c.892G&gt;A and c.967_979del consistent with APS-1. He was started on 0.1mg Florinef and was later followed routinely at an outpatient endocrinology clinic. Fifteen months after diagnosis, he had a repeat ACTH stimulation test, and his baseline cortisol was 9.1mcg/dl with a peak at 60 minutes of 9.6mcg/dl (&lt;18). ACTH level was elevated at 425pg/ml at this time. He was started on hydrocortisone replacement. Of note, investigation of siblings revealed a 10-month-old sister with abnormal AIRE mutation and a 17-month-old sister with unexplained death.

Conclusion

APS-1 can affect multiple organs, and cases can significantly vary in age and the number of affected organs at presentation. The patient presented with atypical presentation as he had hypocalcemia and hypoparathyroidism as an initial abnormality. Typically, adrenal insufficiency appears in the second decade of life but, the patient has it at the time of diagnosis, and it rapidly progresses. Family history plays an essential role in investigating autoimmune disease and warrants further assessment for autoimmune markers. While typically a disease that progresses insidiously into adulthood, cases like ours demonstrate rapid autoimmune disease progression.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.