COVID-19 and the pituitary gland

Coronavirus disease-19 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2). COVID-19 has become a pandemic and has without precedent affected people worldwide in many respects, including individual health, public health, the economy, and individual livelihoods.

COVID-19 is primarily recognized as a respiratory infection; however, it has become evident that it involves multiple organ systems in the body. The angiotensin-converting-enzyme II is the main portal of entry for SAR-CoV-2 to human cells, and this is widely expressed in various tissues, including the pituitary gland.[[1]],[[2]] In addition, SAR-CoV-2 infection can stimulate a dramatic immune response which sometimes causes widespread thrombosis and microangiopathy across various organs.[[3]],[[4]]

It is not surprising, therefore, that the interactions between COVID-19 and pituitary status are complex. The infection may influence the function of the normal pituitary gland, and it may also have effects in those with preexisting pituitary disease. Similarly, preexisting pituitary disorders and their treatments may influence the risk of developing the infection and complicate its course. These interactions are comprehensively reviewed in the current issue of this journal.[[5]]

Pituitary manifestations of COVID-19 infection which have been reported include apoplexy, hypophysitis, and pituitary insufficiency. In most cases, COVID-19 has uncovered undiagnosed preexisting pituitary disease, which is a well-recognized phenomenon in other severe infections. Hypopituitarism resulting directly from viral infection with associated hypophysitis is likely in some cases. SAR-CoV-2 could access the pituitary by hematogenous spread. Alternatively, the infection could result from viral invasion from neighboring structures, in view of the proximity of the pituitary to the nasal passages, the main route for SAR-CoV-2 transmission. Irrespective of the mode of entry, the infection can result in an inflammatory response which, if excessive, can damage the gland.[[6]]

Treatment of severe COVID-19 with high-dose corticosteroids, which is now standard therapy, can further suppress the hypothalamic-pituitary-adrenal axis and result in subsequent adrenocorticotropic hormone deficiency. This is usually self-limiting unless the high-dose corticosteroid treatment is prolonged. Potential long-term adverse effects of COVID-19, and/or its treatment on pituitary function have not yet been fully defined.

As with other kinds of infection, COVID-19 can complicate the course of those with preexisting pituitary disease. It can trigger adrenal crisis in patients with central adrenal insufficiency, as is the case in many people with hypopituitarism. In patients with Cushing's disease treated medically or by surgical adrenalectomy, it can also result in acute adrenal insufficiency unless glucocorticoid replacement dosages are modified appropriately. During infection, a variety of disorders of sodium and water balance have been reported, resulting from insensible water loss due to pyrexia and tachypnea, in conjunction with inadequate drinking and/or vomiting.[[5]] People with diabetes insipidus, with or without anterior pituitary hormone deficiency, are, particularly at risk. Absorption of nasal desmopressin may be limited or variable, due to nasal congestion or for other reasons; oral or systemic administration is recommended during COVID-19 infection.[[7]]

Even in the absence of COVID-19 in the patients themselves, many, perhaps most, patients during the pandemic at its height experienced interruptions in care and/or less direct physical interaction with clinical staff as it was replaced by virtual consultations via some form of telemedicine. These changes in care delivery resulted from concerns about patient safety during visits to clinical environments or were necessary due to the re-allocation of staff and resources away from the care of apparently stable medical conditions to look after those with active infection. Home assessment of biochemical and replacement hormone status using saliva or urine samples has been suggested to replace blood samples, although such assessments will be inevitably incomplete and will bring their own problems such as infection risk in processing and measurement using saliva samples.

As discussed in this issue of the journal,[[5]] some management protocols have been modified to reduce potential exposure of patients to infection with SAR-CoV-2 during hospital and other clinical interactions. In some instances, and where possible, patients have been managed medically rather than surgically in the short or long term. Reduction in the number of people undergoing surgery could, in theory, adversely affect surgeons' experience and skill, although hopefully, this will be a short-term issue. For those in whom surgical intervention was urgently required, modified pre-, intra-, and post-operative measures have been implemented to mitigate the risk of infection to patients and health care personnel.[[5]]

In addition to physical health, the COVID-19 pandemic could psychologically affect patients with pituitary diseases. This may be especially the case in those with prolactinoma who are taking dopamine agonists and who may be at greater than average risk of developing mental health disorders such as depression.[[8]]

Pituitary disorders may also increase the risk of developing COVID-19 infection and aggravate COVID-19-related morbidity and mortality. Patients with uncontrolled Cushing's disease may be at exaggerated risk of contracting SAR-CoV-2 as high glucocorticoid levels can suppress the immune system.[[9]] In addition, active Cushing's disease and acromegaly are in themselves associated with cardiovascular disease, diabetes mellitus, and hypertension, all of which in other situations are factors known to predispose to severe COVID-19 infection and increased mortality. Patients with Cushing's disease may also be at a higher than average risk of thromboembolism. In addition, they may be predisposed to multiorgan failure due to the endothelial dysfunction and microangiopathy associated with COVID-19.[[3]],[[4]] Patients with acromegaly may be at heightened risk of breathing difficulty as a result of soft tissue hypertrophy in the airway passages with COVID-19 pulmonary infection. The hypogonadism associated with pituitary disorders can increase the prevalence of osteoporotic vertebral fractures, which could compromise respiratory function. Inadvertently high desmopressin dosages to control diabetes insipidus can increase fluid retention and worsen pulmonary edema in COVID-19 patients with acute respiratory distress syndrome.[[6]] Medical therapy for functioning pituitary tumors, such as somatostatin analogs and steroidogenesis inhibitors, can interact with the medications used in treating COVID-19, such as hydroxychloroquine azithromycin and ritonavir.[[9]] Finally, endoscopic endonasal surgery for pituitary tumors has been reported to induce acute respiratory and neurological dysfunction in COVID-19 patients who were initially asymptomatic.[[11]]

COVID-19 has negatively affected us individually and globally. It is possible that it will remain a public health emergency of international concern for the unforeseeable future. We, therefore, need to monitor and document the issues likely to affect people with pituitary disease and their optimal management based on solid clinical and experimental evidence. As discussed in the paper in this issue of the journal,[[5]] management strategies will need to be implemented to mitigate the disruption by COVID-19 of clinical care and treatment. As with other specialties, telemedicine has been employed extensively in managing patients with pituitary disorders during the pandemic, and this may find an increased role during the post-COVID-19 era in view of its being accessible and of low cost. All will need to be carefully monitored and evaluated. In COVID-19 survivors, long-term effects on organ systems, including the pituitary, will need to be monitored and documented. Lessons learned during the COVID-19 pandemic should help us prepare for future infectious disease emergencies which are likely to recur.

Conflict of Interest

There are no conflicts of interest.

Financial support and sponsorship

Nil.

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Publication History

Received: 02 September 2021

Accepted: 02 September 2021

Article published online:
06 July 2022