key: cord-0762138-giwunoql authors: Cosentini, Deborah; Grisanti, Salvatore; Laganà, Marta; Ferrari, Vittorio Domenico; Volta, Alberto Dalla; Sigala, Sandra; Terzolo, Massimo; Berruti, Alfredo title: Frequency and outcome of SARS-CoV-2 infection in patients with adrenocortical carcinoma followed at a reference center in Italy date: 2021-01-05 journal: Endocrine DOI: 10.1007/s12020-020-02569-x sha: 954d3f5d39bba3681fb8c1b221aaecb1ef3878c5 doc_id: 762138 cord_uid: giwunoql nan Two patients were hospitalized for acute interstitial pneumonia and one of them died in the intensive care unit, due to acute respiratory distress syndrome (ARDS). This patient was the youngest in the studied group, she had multiple metastatic lesions in lung and liver and was receiving mitotane plus temozolomide therapy as second line approach after disease progression to EDP. The last blood count, performed 5 days before hospital admission due to SARS-CoV2 related respiratory impairment, revealed neutropenia G1 and lymphopenia G2, according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). The proportion of COVID-19 related death in our small series of ACC patients was 1 out of 6 (17.0%). From this small series some considerations could be drawn. Firstly, ACC patients seemed to be at higher risk of symptomatic infection in comparison with both the general population and cancer patients bearing other malignancies. Secondly, SARS-CoV-2 infected ACC patients did not appear to be at increased risk of death than cancer patients with other histologies who contracted the virus. Thirdly, symptomatic SARS-CoV-2 infection occurred only in ACC patients under mitotane, regardless of the stage of the disease. Mitotane causes hypoadrenalism and requires a replacement therapy, which is tapered empirically on clinical basis and is therefore imprecise. Thus, steroid replacement may result in either hypo-or hypercortisolism and both these conditions could predispose to SARS-CoV-2 infection [10, 11] . In a recently published retrospective study on 121 patients with Addison's disease under steroid supplementation, only 1 of them (0.8%) developed COVD19 [12] . It seems therefore that hypoadrenalism associated with ACC under treatment with mitotane could be associated with a higher frequency of COVID 19 than hypoadrenalism resulting from non-neoplastic diseases. On the contrary, ACC patients seemed to share the same risk factors of death that other cancer patients. All these data however need confirmation, due to the small number of ACC patients considered. Noteworthy, mitotane serum levels was within the therapeutic range in only one out of six ACC patients developing COVID19. These data suggest mitotane per se may have not contributed to the onset of symptoms. Indeed, the patient who died, due to extensive pneumonia and ARDS, had a metastatic disease with a heavy tumor load and was receiving temozolomide in association with mitotane and steroids. Temozolomide frequently induces lymphopenia [7] and this condition has been shown to be associated with poor prognosis in patients undergoing SARS-CoV2 infection [13] . Both the advanced stage and the documented drug induced lymphopenia could have contributed to the poor outcome of SARS-CoV-2 infection in this patient. Moreover, symptomatic SARS-CoV-2 was mainly confined among patients who were resident in Lombardy, this observation suggests the adoption of strict preventive measures by ACC patients, who are more vulnerable since they are frequently on steroid supplementation, in areas at high incidence SARS-CoV-2 infection. Telemedicine, which uses telecommunications technology to deliver health care at patient home, represents undoubtedly an indispensable tool in the management of cancer patients in the SARS-CoV-2 pandemic, including endocrine cancers [14] , since it has demonstrated to be equivalent to in-person care [15] . More generally, the approach to the patient with ACC should change in the COVID era and every therapeutic choice, such as the decision to start adjuvant mitotane in radically operated patients, or EDP-M in case of advanced disease, should be adopted taking into account the infectious risk and relevant complications in the cost / benefit assessment. Our patient series is small, retrospective, and was not systematically screened for SARS-CoV-2. These are major limitations of this study. We cannot exclude that a number of subjects could have been infected while remaining asymptomatic or mildly symptomatic [16] . Based on these preliminary data, a European Network for the Study of Adrenal Tumors (ENS@T) study, aiming to assess the frequency and outcome of SARS-CoV-2 infection in ACC patients managed at different reference centers worldwide, is currently under way. Author contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Deborah Cosentini, Salvatore Grisanti, Marta Laganà, Vittorio Domenico Ferrari, Alberto Dalla Volta. The first draft of the manuscript was written by Deborah Cosentini, Salvatore Grisanti and Marta Laganà. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Funding The authors received no financial support for the research and authorship. Conflict of interest The authors declare that they have no conflict of interest. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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