Adrenal Hyperplasia as Possible Predictor of Mortality in Patients Admitted for Suspected SARS-Cov-2 Infection: A Prospective Study
Authors: Reimondo Giuseppe , Solitro Federica , Puglisi Soraya , Casale Davide , Tiranti Giorgio Maria , Perini Anna , Cultrera Alessandra , Pia Anna , Terzolo Massimo , Veltri Andrea 
Published: May 2021

Abstract
A large percentage of patients affected by SARS-CoV-2 disease (COVID) have associated comorbidities such as arterial hypertension, obesity, diabetes mellitus and thrombophilia. On the contrary, the prevalence in COVID patients of diseases of the adrenal glands has not been reported. Since the visualization of the adrenal glands is almost always available in chest CT performed in patients with suspected or confirmed SARS-CoV-2 infection, the evaluation of the frequency and characteristics of morphological disorders of the adrenal masses in such patients appears of interest. We carried out a prospective consecutive series of 402 patients (M 222, 55.2%; F 180, 44.8%) with a median age of 76 years (IQR 64–84 years), admitted in the emergency department for suspected SARS-CoV-2 infection. One hundred patients had a PCR-confirmed diagnosis of infection on a naso-pharyngeal swab (24.9%). All patients underwent a chest MDCT study including the adrenal region and clinical assessment of co-morbidities. Compared to subjects without confirmed disease, COVID patients had more frequently close contact with other positive subjects (24% vs 4.6%, p &lt;0.001), typical symptoms (68% vs 28.5%, p &lt;0.001), and suggestive chest CT findings (90% vs 31.1%, p &lt;0.001). We found altered adrenal morphology in 100 patients (24.9%): 62 subjects had adrenal hyperplasia, which was unilateral in 42 of them (67.7%) and bilateral in 20 (32.3%), while 38 patients had discrete adrenal nodules, unilateral in 34 of them (89.4%) and bilateral in 4 (10.6%). The median size of adrenal nodules was 16 mm (10–50 mm) with a median density of 10 HU (-41 - 42 HU). In 17 patients with adrenal hyperplasia, a previous CT was available for comparison: in all cases an increase in thickness was evident at admission (from 1 to 15 mm, with a median of 1.95 mm increase). COVID patients had a higher frequency of adrenal nodules (12% vs 8.6%, p=NS). Sixty-three patients (16%) died. They were older (80 vs 74 years, p = 0.001), had a higher frequency of adrenal hyperplasia (25% vs 14%, p = 0.03), more frequent active cancer disease (37% vs 19%, p = 0.003) and COVID (23% vs 13.2%, p = 0.02). In a multivariate model, adrenal hyperplasia is an independent risk factor for mortality (OR 2.52, 1.15–5.55, p=0.02), as well as age (OR 1.04, 1.01–1.07, p=0.005), active oncological disease (OR 3.06, 1.44–6.49, p=0.004), and COVID (OR 2.88, 1.38–6.01, p=0.005). This is the first study reporting the prevalence of morphological alterations of adrenal glands in suspected COVID patients. The frequency of discrete adrenal nodules (9.5%) is in line with the high prevalence of adrenal incidentalomas in elder subjects. The high frequency of adrenal hyperplasia associated with increased risk of mortality suggests that this may be the consequence of an exaggerated activation of the HPA axis due to a highly stressful condition.