A Case of Functional Adrenal Insufficiency Secondary to COVID-19 Infection

Since the outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic, over seventy million cases have been reported worldwide. Patients present with various symptoms, including extra-pulmonary manifestations. However, manifestations on adrenal glands have not been reported extensively. Here, we present a case of functional adrenal insufficiency in a COVID-19 patient. A 61-year-old male with a history of hyperlipidemia presented with fatigue, cough, and dyspnea, subsequently tested positive for COVID-19. His blood pressure (BP) on admission was 128/68 mmHg with 86% oxygen saturation on room air. Dexamethasone 6mg daily was started for ten days. Remdesivir was contra-indicated, considering the ALT of 246 and AST of 248. On day seven of hospitalization, he had progressively worsening respiratory symptoms and was transferred to the Intensive Care Unit with BP of 105/63 mmHg. Within 48 hours, he showed positive orthostatic vitals with BP of 85/54 mmHg. Despite intravenous hydration, his BP was consistently low on subsequent days with 88/53 mmHg and 99/66 mmHg. His serum total cortisol level was 9.2 μg/dL, and he showed a positive response to IV Hydrocortisone 50mg as well as oral prednisone 10 mg the following day. We did not obtain a cosyntropin stimulation test because of recent corticosteroid therapy. Midodrine 2.5mg three times daily (TID) was started, then increased to 10 mg to maintain BP and alleviate orthostatic symptoms. However, symptomatic positive orthostatic vitals were persistent. He was discharged on midodrine 7.5 mg TID and Fludrocortisone 0.1 mg daily for suspicion of functional adrenal insufficiency. Additionally, a HDL level of 22 mg/dL was recorded (vs 56 mg/dL six months ago). At three months follow-up, he was off fludrocortisone and midodrine with improved orthostatic symptoms. Hypotension and orthostatic symptoms in COVID-19 could be due to IL-1, IL-6, or tumor necrosis factor-mediated reduction in ACTH secretion. Acute illnesses, including COVID-19, may also increase cortisol demand, causing adrenal insufficiency. Decreased HDL noted in our patient could be another etiology. "Critical Illness-Related Corticosteroid Insufficiency" (CIRCI) is a functional adrenal insufficiency that is not strictly dependent on cortisol level for diagnosis but mostly on the inadequacy of cortisol for inflammation control or supplying the raised metabolic demand. Decreased cortisol complex cleavage, increased activity of an enzyme responsible for cortisol inactivation, and decreased numbers and affinity of cortisol receptors were postulated to play a role. Therefore, adrenal insufficiency as a cause of hypotension following COVID-19 infection should not be overlooked despite normal cortisol levels.