The Growing Understanding of the Pituitary Implication in the Pathogenesis of Long COVID-19 Syndrome: A Narrative Review

Abstract

Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection, is a condition where individuals who have recovered from the acute phase of COVID-19 continue to experience a range of symptoms for weeks or even months afterward. While it was initially thought to primarily affect the respiratory system, it has become clear that Long COVID-19 can involve various organs and systems, including the endocrine system, which includes the pituitary gland. In the context of Long COVID-19, there is a growing understanding of the potential implications for the pituitary gland. The virus can directly affect the pituitary gland, leading to abnormalities in hormone production and regulation. This can result in symptoms such as fatigue, changes in appetite, and mood disturbances. Long COVID-19, the persistent and often debilitating condition following acute COVID-19 infection, may be explained by deficiencies in ACTH and Growth hormone production from the pituitary gland. Corticotropin insufficiency can result in the dysregulation of the body’s stress response and can lead to prolonged feelings of stress, fatigue, and mood disturbances in Long COVID-19 patients. Simultaneously, somatotropin insufficiency can affect growth, muscle function, and energy metabolism, potentially causing symptoms such as muscle weakness, exercise intolerance, and changes in body composition. Recently, some authors have suggested the involvement of the pituitary gland in Post COVID-19 Syndrome. The exact mechanisms of viral action on infected cells remain under discussion, but inflammatory and autoimmune mechanisms are primarily implicated. The aim of our study will be to review the main pituitary complications following COVID-19 infection. Moreover, we will explain the possible involvement of the pituitary gland in the persistence of Post COVID-19 Syndrome.

Sex differences of post-Covid patients undergoing outpatient pulmonary rehabilitation

“…Further, sex differences regarding responses of the hypothalamic-pituitary-adrenal (HPA) axis to acute and chronic stress are well-established and enhanced activity in women was suggested as contributing factor to higher rates of stress-related disorders such as depression [ 25 ]. Direct impairment of the pituitary gland and HPA dysregulation may occur during Covid-19 and cause typical symptoms of PCS such as fatigue in sex-dependent manner [ 26 ].…”

Pituitary Apoplexy: Description of Medical and Surgical Treatment and Clinical, Visual, and Endocrinological Outcomes During the SARS-CoV-2 Pandemic and Over Three Years

“…Some authors have studied the link between pituitary dysfunction and persistent COVID-19 symptoms, involving disturbances in the hypothalamic-pituitary-adrenal (HPA) axis, alterations in hormone production and secretion, or interactions between the immune system and the endocrine system [ 27 , 28 ].…”

Response to Letter to the Editor From Josef Finsterer: “Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis”

“…In a recent meta-analysis, the pooled prevalence of depression and anxiety among patients with long-COVID syndrome was estimated to be 23% [ 3 ]. In this context, it is recognized that chronic stress would exacerbate the cortisol response, potentially leading to a pseudo-Cushing state [ 4 ]. However, it is crucial to emphasize that our study primarily focused on evaluating corticotropic insufficiency.…”

“…The concern regarding the potential central nervous system involvement in causing pituitary insufficiency in the acute stage of SARS-CoV-2 infection is indeed valid. Determining the actual occurrence rate of hypophysitis following COVID-19 proves to be challenging [ 4 ]. There are only some cases that were reported, with 1 case of infundibuloneuro-hypophysitis [ 5 ].…”