From the Journals

Cushing’s and COVID-19: Nontraditional symptoms keys to assessment, treatments



Do not rely on more traditional signs and symptoms of COVID-19 like fever and dyspnea when assessing patients with Cushing’s syndrome for the novel coronavirus, Rosario Pivonello, MD, PhD, and colleagues urged.

Physicians evaluating patients with Cushing’s syndrome for COVID-19 “should be suspicious of any change in health status of their patients with Cushing’s syndrome, rather than relying on fever and [dyspnea] as typical features,” Dr. Pivonello, an endocrinologist with the University of Naples (Italy) Federico II, and colleagues wrote in a commentary published in The Lancet Diabetes & Endocrinology.

COVID-19 symptoms are a unique concern among patients with Cushing’s syndrome because many of the cardiometabolic and immune impairments that place someone at higher risk of more severe disease or mortality for the novel coronavirus – such as obesity, hypertension, diabetes, and immunodeficiency syndromes – are also shared with Cushing’s syndrome.

Increased cardiovascular risk factors and susceptibility to severe infection are “two leading causes of death” for patients with Cushing’s syndrome, Dr. Pivonello and colleagues noted.

The immunocompromised state of patients with Cushing’s syndrome may make detection of COVID-19 infection difficult, the authors say. For example, fever is a common symptom of patients with COVID-19, but in patients with active Cushing’s syndrome, “low-grade chronic inflammation and the poor immune response might limit febrile response in the early phase of infection,” Dr. Pivonello and colleagues wrote.

In other cases, because Cushing’s syndrome and COVID-19 have overlapping symptoms, it may be difficult to attribute a particular symptom to either disease. Dyspnea is a common symptom of COVID-19, but may present in Cushing’s syndrome because of “cardiac insufficiency or weakness of respiratory muscles,” the authors wrote. Instead, physicians should look to other COVID-19 symptoms, such as cough, dysgeusia, anosmia, and diarrhea, for signs of the disease.

Patients with Cushing’s syndrome may also be predisposed to a more severe course of COVID-19 because of the prevalence of obesity, hypertension, or diabetes in these patients, which have been identified as comorbidities that increase the likelihood of severe COVID-19 and progression to acute respiratory distress syndrome (ARDS). “However, a key element in the development of ARDS during COVID-19 is the exaggerated cellular response induced by the cytokine increase, leading to massive alveolar–capillary wall damage and a decline in gas exchange,” Dr. Pivonello and colleagues wrote. “Because patients with Cushing’s syndrome might not mount a normal cytokine response, these patients might [paradoxically] be less prone to develop severe ARDS with COVID-19.”

As both Cushing’s syndrome and COVID-19 are associated with hypercoagulability, the authors “strongly advise” using low-molecular-weight heparin in hospitalized patients with active Cushing’s syndrome who develop COVID-19. In both diseases, there is also a risk of longer duration of viral infections and opportunistic infections such as atypical bacterial and invasive fungal infections. For this reason, the authors also recommended patients with Cushing’s syndrome who have COVID-19 be placed on prolonged antiviral and broad-spectrum antibiotic treatment as a prophylactic measure.

During the pandemic, avoiding surgery for Cushing’s syndrome should be considered to reduce the likelihood of acquiring COVID-19 in a hospital setting, the authors wrote. Medical therapy can be temporarily used where appropriate, such as using ketoconazole, metyrapone, osilodrostat, and etomidate to lower cortisol levels. They acknowledge that some cases of malignant Cushing’s syndrome may require “expeditious definitive diagnosis and proper surgical resolution.”

After remission, while infection risk should be significantly lowered, other comorbidities like obesity, hypertension, diabetes, and thromboembolic diathesis may remain. “Because these are features associated with an increased death risk in patients with COVID-19, patients with Cushing’s syndrome in remission should be considered a high-risk population and consequently adopt adequate self-protection strategies to [minimize] contagion risk,” the authors wrote.

Dr. Pivonello reported relationships with Novartis, Strongbridge Biopharma, HRA Pharma, Ipsen, Shire, and Pfizer, Corcept Therapeutics, IBSA Farmaceutici, Ferring, and Italfarmaco in the form of receiving grants and/or personal fees. One coauthor reported receiving grants and/or nonfinancial support from Takeda, Ipsen, Shire, Pfizer, and Corcept Therapeutics. One coauthor reported receiving grants and personal fees from Novartis and Strongbridge, and grants from Millendo Therapeutics. Another coauthor reported receiving grants and/or personal fees from Novartis, Ipsen, Shire, Pfizer, Italfarmaco, Lilly, Merck, and Novo Nordisk. The other authors reported no relevant conflicts of interest.

SOURCE: Pivonello R et al. Lancet Diabetes Endocrinol. 2020 Jun 9. doi: 10.1016/S2213-8587(20)30215-1.

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