Primary Adrenal Insufficiency Due to Bilateral Adrenal Infarction in COVID-19

Abstract

Context Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated. Case report A 46-year-old woman presented with abdominal pain, hypotension, skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol <1.0 ug/dL, ACTH of 807 pg/mL and aldosterone <3 ng/dL. Computed tomography (CT) findings of adrenal enlargement with no parenchymal and minimal peripheral capsular enhancement after contrast were consistent with bilateral adrenal infarction. The patient had autoimmune hepatitis and positive antiphospholipid antibodies, but no previous thrombotic events. The patient was treated with intravenous hydrocortisone, followed by oral hydrocortisone and fludrocortisone. Discussion Among 115 articles, we identified nine articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in five cases, but ACTH levels were measured in only three cases (high in one case and normal/low in other two cases). Bilateral adrenal non- or hemorrhagic infarction was identified in five reports (two had adrenal insufficiency, two had normal cortisol levels and one case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19. Conclusions Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.

Is there a role for the adrenal glands in long COVID?

“…There are at least 12 case studies and nine prospective case series in the literature describing adrenal insufficiency related to COVID-19. These studies reported that adrenal haemorrhages and infarctions might not only occur in severe cases of COVID-19, but also in mild ones 7 . Furthermore, pre-existing adrenal disease or Addison disease can be exacerbated by SARS-CoV-2 infection.…”

The Relationship between COVID-19 and Hypothalamic–Pituitary–Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess—The CAPISCO International Expert Panel

“…Incidental adrenal computed tomography findings compatible with adrenal infarction have been reported in 23% of patients with severe COVID-19 [42], the vast majority with bilateral involvement. However, the clinically relevant cases are less frequently reported [43]. Of note, two out of nine clinically relevant cases had positive antiphospholipid antibodies prior to COVID-19 diagnosis, suggesting a previously described link between the antiphospholipid syndrome and the risk of bilateral adrenal infarction in non-COVID-19 patients as a potential mechanism [43][44][45][46].…”

“…However, the clinically relevant cases are less frequently reported [43]. Of note, two out of nine clinically relevant cases had positive antiphospholipid antibodies prior to COVID-19 diagnosis, suggesting a previously described link between the antiphospholipid syndrome and the risk of bilateral adrenal infarction in non-COVID-19 patients as a potential mechanism [43][44][45][46].…”

Pituitary–Adrenal Responses and Glucocorticoid Receptor Expression in Critically Ill Patients with COVID-19

“…COVID-19 is associated with an increased rate of pulmonary or extrapulmonary thrombotic complications [ 29 ], and adrenal injury may also occur through bilateral adrenal non-hemorrhagic or hemorrhagic infarction. Although incidental computed tomography (CT) findings compatible with adrenal infarction have been reported in 23% of patients with severe COVID-19 [ 30 ], the vast majority with bilateral involvement, clinically relevant cases are sparse with only nine reported so far [ 31 ]. Of note, two of these cases had positive antiphospholipid antibodies prior to COVID-19 diagnosis, suggesting a link between the presence of antiphospholipid syndrome and the risk of bilateral adrenal infarction [ 31 ].…”