A potential impact of SARS-CoV-2 on pituitary glands and pituitary neuroendocrine tumors

Abstract

Introduction Angiotensin-converting enzyme 2 (ACE2) is the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effects of SARS-CoV-2 on normal pituitary glands function or pituitary neuroendocrine tumors (PitNETs) have not yet been elucidated. Thus, the present study aimed to investigate the potential risks of SARS-CoV-2 infection on the impairment of pituitary glands and the development of PitNETs. Methods PitNETs tissues were obtained from 114 patients, and normal pituitary gland tissues were obtained from the autopsy. The mRNA levels of ACE2 and angiotensin II receptor type 1 (AGTR1) were examined by quantitative real-time PCR. Immunohistochemical staining was performed for ACE2 in 69 PitNETs and 3 normal pituitary glands. The primary tumor cells and pituitary cell lines (MMQ, GH3 and AtT-20/D16v-F2) were treated with diminazene aceturate (DIZE), an ACE2 agonist, with various dose regimens. The pituitary hormones between 43 patients with SARS-CoV-2 infection were compared with 45 healthy controls. Results Pituitary glands and the majority of PitNET tissues showed low/negative ACE2 expression at both the mRNA and protein levels, while AGTR1 showed high expression in normal pituitary and corticotroph adenomas. ACE2 agonist increased the secretion of ACTH in AtT-20/D16v-F2 cells through downregulating AGTR1. The level of serum adrenocorticotropic hormone (ACTH) was significantly increased in COVID-19 patients compared to normal controls ( p < 0.001), but was dramatically decreased in critical cases compared to non-critical patients ( p = 0.003). Conclusions This study revealed a potential impact of SARS-CoV-2 infection on corticotroph cells and adenomas.

Assessment of Neuroendocrine Changes and Hypothalamo-Pituitary Autoimmunity in Patients with COVID-19

“…showed that ACTH levels were increased in patients with COVID-19 compared with healthy controls. By contrast, ACTH levels were within the normal range in all participants in our study 46 . The basal cortisol levels were also higher in patients with COVID-19 than in controls.…”

Apoplexy in a previously undiagnosed pituitary macroadenoma in the setting of recent COVID-19 infection

“… 10 11 Studies have shown ACE-2 receptor expression in gonadotrophs, lactotrophs, somatotrophs and corticotrophs, although in low levels, as well as TMPRSS2 pituitary expression. 12 13 This supports the possibility of direct COVID-19 infection of the pituitary, and may explain the event of pituitary apoplexy in more moderate COVID-19 illness as described in both this and other published case reports.…”

“… 14 Additionally, ACTH production has been shown to be increased during moderate COVID-19 infection, but significantly decreased in those who were critically unwell, despite no change in GH, TSH or LH/FSH in either group. 12 It is possible that HPA axis dysfunction may contribute to symptoms attributed to ‘Long COVID-19’ syndrome like fatigue and memory loss. 15 Although this consequence of COVID-19 infection is likely more common than acute vascular events, an assumption about the cause of hypocortisolism in these patients may lead to a delay in diagnosis of more serious pathologies, such as apoplexy in our presented case.…”

Coronavirus disease 2019 in patients with neuroendocrine neoplasms: Preliminary results of the INTENSIVE study

“…We searched PubMed on April 05, 2021, using the search terms (“novel coronavirus” OR “SARS-CoV2” OR “COVID-19”) AND (“neuroendocrine tumors” OR “neuroendocrine tumours” OR “neuroendocrine neoplasms” OR “neuroendocrine carcinomas” OR “carcinoids”) for articles in English that documented the COVID-19 in patients with NENs. Sixteen articles appeared, including three case reports, 12 recommendations or consensus statements and one only mini-series of four cases among a large thoracic cancers series 19 , 22 , 23 , 24 17 , 18 , 20 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 .…”