COVID-19 and Cushing Disease: A Protective or a Deadly Combination?

Background: Manifestations of Cushing disease, including diabetes mellitus, hypertension, and obesity are risk factors for severe novel coronavirus disease 2019 (COVID-19) disease. A potential for severe COVID-19 disease might be hypothesized in Cushing disease patients. We present a finding of asymptomatic COVID-19 positive nasopharyngeal PCR test in an untreated Cushing disease patient. Case: A 19 year old female presented in January 2020 reporting amenorrhea and cushingoid facies. Her last menstrual period was two years ago. Low energy, fatigue, easy bruising and dark stretch marks on her legs, axillae and flanks were reported. Physical exam showed blood pressure 123/83 mmHg, pulse 89 bpm, BMI 20.80 kg/m². She had a cushingoid appearance with fullness in the face, neck and supraclavicular area, mild proptosis, pink cheeks and a few faint lavender striae on the inner thighs and flanks. Test results relevant to or supporting a diagnosis of Cushing disease included the following: 1 mg overnight dexamethasone suppression test: AM cortisol 23.9 ug/dl (6.7-22.6 ug/dl). Random 1019 hrs AM ACTH was 32 pg/ml (<47 pg/ml), cortisol 6.5 ug/dl (4-22ug/dl). Repeat 1 mg overnight dexamethasone suppression test: AM cortisol was 36.5 ug/dl (4-22 ug/dl), Dexamethasone 249.2 ng/dl (140-295 expected post 1 mg DXA the night before). 24 hr urine free cortisol was 391.4 (<=45.0 ug/d). Other endocrine labs were within normal limits. Left sided hypoenhancing lesion (2mmx2mmx2mm) consistent with pituitary microadenoma was seen on pituitary MRI. Inferior petrosal sinus sampling supported the presence of central disease and left pituitary location, concordant with the MRI. The time course from first clinical presentation to surgery was impacted by the COVID 19 pandemic temporarily halting elective surgical treatments and her access to care. At August, 2020 pre-op evaluation, the COVID-19 nasopharyngeal PCR was positive. Surgery was rescheduled. She denied symptoms of COVID-19 but recalled community exposure, including known COVID-19 positive contacts, while working as a waitress. Discussion: Increased susceptibility to and increased severity of COVID-19 manifestations might be feared in Cushing disease patients due to Cushing disease-associated immunosuppression, hyperglycemia, hypertension, obesity and venous thromboembolism. In contrast, randomized control trials have shown glucocorticoids, at doses sufficient to produce iatrogenic Cushing syndrome, may improve mortality in COVID-19 patients. Although asymptomatic COVID-19 infection is known to occur in young adults, the finding of asymptomatic COVID-19 positive test in a young woman with untreated Cushing disease also raises the possibility that endogenous hypercortisolism confers a similar benefit against severe manifestations of COVID-19 infection.