Endocrine Abstracts

Background : The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of an unprecedented scale, with an ever-growing impact on healthcare systems. The clinical presentation of coronavirus disease 2019 (COVID-19) is diverse, ranging from asymptomatic illness to respiratory failure requiring admission to the intensive care unit (ICU). Risk factors for severe presentation include old age, male gender, underlying comorbidities such as metabolic syndrome, chronic lung diseases, heart-, liver- and kidney diseases, malignancy, immunodeficiency, and pregnancy (1). Little is known about the risk of COVID-19 in patients with rare endocrine malignancies, such as pituitary carcinoma.

Case presentation: We describe the case of a 43-year-old man with ACTH-secreting pituitary carcinoma (with cerebellar and cervical drop metastases) who experienced a severe COVID-19 pneumopathy. He had previously received multiple lines of treatment including surgery, radiotherapy, ketoconazole, pasireotide, cabergoline, bilateral (subtotal) adrenalectomy, and temozolomide chemotherapy, as described elsewhere (2). His most recent therapy was a combination of immune checkpoint inhibitors with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) (anti-CTLA-4 and anti-PD-1, respectively) every 3 weeks for 4 cycles, after which maintenance therapy with nivolumab (240 mg) every 2 weeks was continued. Residual endogenous cortisol production was suppressed with ketoconazole 800mg daily. He had disease stabilisation with a decrease in 08:00h plasma ACTH, urinary free cortisol, and stable radiographic findings. Surgical resection of the left adrenal remnant was planned, but could not proceed due to the development of COVID-19 infection. In March 2021, he consulted our emergency department with respiratory exhaustion due to SARS-CoV-2 infection requiring urgent endotracheal intubation. He was commenced on high dose dexamethasone for 10 days together with broad-spectrum antibiotics for positive sputum cultures containing Serratia, methicillin-susceptible S. aureus and H. Influenzae. He developed multiple organ involvement, including metabolic acidosis, acute renal failure requiring continuous veno-venous hemofiltration, acute coronary syndrome type 2, septic thrombophlebitis of the right jugular vein, and critical illness polyneuropathy. He was readmitted twice to the ICU, for ventilator-associated pneumonia and central line-associated bloodstream infection respectively. He was eventually discharged from the hospital and able to continue his rehabilitation. Regarding his endocrine treatment, a "block-replace" regimen was adopted with the continuation of ketoconazole (restarted on day 11), and the supplementation of hydrocortisone at a dose depending on the current level of stress. The consecutive daily dose of hydrocortisone and ketoconazole is demonstrated in Figure 1.

Discussion: The learning points of this case are twofold. Firstly, this case illustrates the presence of many of the comorbidities for COVID-19 mortality in patients with Cushing’s disease, such as the cardiovascular risk factors of obesity, arterial hypertension, impaired glucose metabolism, as well as increased thromboembolic risk and increased susceptibility to bacterial infections. Patients with endogenous glucocorticoid excess may therefore be particularly susceptible to severe COVID-19. Secondly, a « block-replace » therapy might be preferred in this patient population, to avoid adrenal insufficiency and reduce the need for biochemical monitoring (as suggested by Newell-Price et al.) (3).

References: 1. Gao Y dong, Ding M, Dong X, Zhang J jin, Kursat Azkur D, et al. Risk factors for severe and critically ill COVID-19 patients : A review. Allergy : European Journal of Allergy and Clinical Immunology. 2021.

2. Sol B, de Filette JMK, Awada G, Raeymaeckers S, Aspeslagh S, Andreescu CE, et al. Immune checkpoint inhibitor therapy for ACTH-secreting pituitary carcinoma : A new emerging treatment ? Eur J Endocrinol.2021.

3. Newell-Price J, Nieman LK, Reincke M, Tabarin A. ENDOCRINOLOGY in the TIME of COVID-19 : Management of Cushing’s syndrome. Eur J Endocrinol.2020;