New onset Primary Adrenal Insufficiency and Autoimmune Hypothyroidism in a Pediatric Patient presenting with MIS-C due to COVID- 19 infection

ABSTRACT

Objectives There is emerging speculation that the inflammatory state associated with SARS-CoV-2 infection may trigger autoimmune conditions, but no causal link is established. There are reports of autoimmune thyroiditis, and one of adrenal insufficiency in adults post-COVID. We describe the first pediatric report of adrenal insufficiency and autoimmune hypothyroidism after COVID- 19. Methods A 14-year-old previously healthy girl, with vitiligo, one week of fever, lethargy, diarrhea, and vomiting, presented in shock. Three weeks prior, she had congestion and fatigue, and a negative COVID test. Father was known to be positive for COVID-19. Results Labs were remarkable for sodium 129mmol/L, K 4.3mmol/L, creatinine 2.9mg/dL, hemoglobin 6.9g/dL and positive COVID-19 PCR and SARS CoV-2 IgG. She was resuscitated with normal saline and required pressor support. EKG showed abnormal repolarization presumed secondary to myocarditis. She met criteria for Multisystem Inflammatory Syndrome in Children (MIS-C), received intravenous immune globulin and IL-1R antagonist, and was admitted for intensive care. Persistent hypotension, despite improved inflammatory markers, and an undetectable cortisol led to initiation of hydrocortisone. She was then able to rapidly wean off pressors and hydrocortisone within 48 hours. A week later, tests undertaken for bradycardia confirmed autoimmune hypothyroidism with TSH 131mcunit/ml, freeT4 0.85ng/dL, and positive thyroid autoantibodies. Basal and stimulated cortisol were undetectable on standard 250mcg cosyntropin stimulation test, with ACTH >1250pg/mL confirming primary adrenal insufficiency. Treatment was initiated with hydrocortisone, levothyroxine, and fludrocortisone. Adrenal sonogram did not reveal any hemorrhage and anti-adrenal antibody titers were positive. The family retrospectively reported oligomenorrhea, increased salt craving in the months prior, and family history of autoimmune thyroiditis. The cytokine panel was notably different from other cases of MIS-C. Conclusions This is the first pediatric report, to our knowledge, of primary adrenal insufficiency and hypothyroidism following COVID-19, leading to a unique presentation of autoimmune polyglandular syndrome type 2. The initial presentation was attributed to MIS-C, but the response to hydrocortisone suggests the possibility of adrenal crisis. It remains unknown if COVID-19 had a causal relationship in triggering the autoimmune adrenal insufficiency and hypothyroidism.