Pituitary Disorders and COVID-19, Reimagining Care: The Pandemic A Year and Counting

Abstract

It has been more than a year since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) “eruption” on the world scene and the coronavirus disease 2019 (COVID-19) pandemic engulfed all lives on all continents. And quite the year, was 2020! Physicians from all specialties have been affected, both personally and professionally; from screening for and treating patients with COVID-19, which did not fall in their area of expertise, or from delaying care of patients with acute and chronic disorders with other pathologies. Moreover, COVID-19 created new pathologies and several patients with chronic conditions are at higher risk. Further complicating the picture; most non-acute care has been moved on and off from in-person clinic visits to remote telemedicine visits, while elective surgeries have been also on hold during several “pause” waves. Pituitary diseases and several disease components, such as acute visual loss, tumor mass effects, or chronic conditions such as adrenal insufficiency (AI), hypopituitarism, Cushing’s disease (CD) or growth hormone (GH) excess (acromegaly) have had tremendous interplay with COVID-19. Several recommendations from international experts published by the Pituitary Society (1) or the European Journal of Endocrinology, affiliated with European Society of Endocrinology (2–5) were published early in the course of the pandemic; notably, a re-evaluation every few months in light of emerging data, was suggested (1, 6). Unfortunately, at this time, despite an ongoing unprecedented vaccination campaign, the risk of viral infection load in many countries is the highest it has been and local rules for “lockdown” have been intensified rather than relaxed overall. Furthermore, many patients without a history of pituitary disorders who have had severe SARS-CoV-2 are being treated with high dose glucocorticoids (GC). This is based on data suggesting that abnormal immune reactivity could cause additional lung damage and progression to severe respiratory failure rather than uncontrolled viral replication. Notably, dexamethasone was shown to reduce intermediate (28-day) mortality among patients on either invasive mechanical ventilation or oxygen alone in the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial (7). However, administration of anti-retroviral drugs and high dose GC use could trigger drug–drug interactions and enhance exposure to drugs that are metabolized through the CYP450/CYP3A pathway, impacting the hypothalamic-pituitary-adrenal HPA axis (8) and highlighting a need for HPA axis monitoring at discharge from the hospital. Another interplay between COVID-19 and pituitary disorders is linked to the suggestion that many patients with fractures should start, in addition to calcium and vitamin D supplementation, early bone-targeted treatment, even while in hospital (9). This can prove complicated due to limited resources that prompt early discharge during the COVID-19 pandemic. As such, a communication plan regarding the importance of anti-osteoporosis treatment post-discharge is essential (10). Many patients with pituitary disorders who are at higher risk of fractures such as CD, acromegaly, hypopituitarism (11–14), and central AI could thus possibly need anti-resorptive treatments (15). Here, we focus on updates on the risks associated with COVID-19 in patients with pituitary disorders. We also discuss management of patients with either new or long-standing pituitary disorders in the setting of limited healthcare delivery due to the pandemic. Patients with CD can experience many comorbidities, which can in turn increase complication(s) risk if patients with CD become infected with COVID-19 (1, 5). It has been recognized that the severity of COVID-19 is higher in patients with diabetes mellitus (DM) and hypertension (16) Moreover, COVID-19 might increase the risk of hyperglycemia, which can modulate immune and inflammatory responses, thus worsening the risk of severe disease (17). Complicating the picture even more, many medications used for COVID-19 treatment can affect glucose metabolism, particularly with preexisting DM; thus, both glucose monitoring and individualized management are usually needed for patients with DM and/or hypertension (16). Patients with cardiovascular or kidney disease have been also shown to have a poorer prognosis than those without these diseases and COVID-19 (18, 19). Obesity reduces respiratory system compliance, expiratory reserve volume, and functional capacity. Sleep apnea is more frequent and further impairment of pulmonary function is noted with reduced excursion of diaphragm. Several other comorbidities, including thrombosis, also have a great impact in COVID-19 infected patients’ outcomes (18). However, currently, there are no studies that answer an essential question; are these comorbidities in patients with pituitary disorders having a different impact on outcomes when compared with patients without pituitary function abnormalities (either excess or deficiency)? One could extrapolate that a high burden of cardiovascular, metabolic and respiratory comorbidities would increase overall disease severity in patients with pituitary disorders if they become infected with COVID-19. For patients with active CD who develop COVID-19, risk of severe thromboembolism on already heightened hypercoagulability due to CS could be compounded (20), thus anticoagulation treatment per se, not just preventive doses should be recommended in all hospitalized patients with CS, which can decrease mortality overall (21). Presently, there is limited data on treating patients with CS and COVID-19. Yuno et al., described a 27-year-old female with CD who was awaiting pituitary surgery when she developed COVID-19 pneumonia (22). She was treated with a “block-and-replace” regimen using a steroidogenesis inhibitors combination (high dose...