Autoimmune-mediated Primary Adrenal Insufficiency After Covid-19

Isolated cases of autoimmune-mediated primary adrenal insufficiency (PAI) after COVID-19 have been reported. However, the association has not been well characterized. The objective of this study is to determine the association and clinical characteristics of autoimmune-mediated PAI in patients following COVID-19.

We identified patients with autoimmune-mediated PAI following recent COVID-19 illness from a large database and performed a retrospective chart review to analyze their clinical and biochemical presentation. Prior reported cases were reviewed. Inclusion criteria were biochemical confirmation and clinical features of PAI occurring within 12 months after COVID-19 illness, and evidence of autoimmune etiology. We identified 6 novel autoimmune-mediated PAI cases associated with COVID-19, out of 138 052 cases of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction. Eleven cases from the literature were added for a total of 17 patients (58.8% male and 41.2% female). Twelve (70.6%) were <30 years old. Five (29.4%) had a family history of autoimmune conditions. Five (29.4%) had prior autoimmune disease. The median time to PAI diagnosis was 21(9-151) days after SARS-CoV-2 infection. Median serum morning cortisol level was 1.0 (0.5-2.56) μg/dL. Mean serum adrenocorticotropin was 1212.6 ± 599.8 pg/mL, 19.7 ± 11.3 × upper limit of normal. Adrenal atrophy was present in 64%; 21-hydroxylase antibodies were positive in 100% (n = 16) of patients tested.

This is the largest original case series of autoimmune-mediated PAI associated with COVID-19 to date. Severe illness and/or SARS-CoV-2 viral infection may precipitate autoimmune-mediated PAI in susceptible patients.

Awareness of autoimmune-mediated PAI occurring after COVID-19 is critical for the prevention of adrenal crisis in this context.