Pilot Findings on SARS-CoV-2 Vaccine-Induced Pituitary Diseases: A Mini Review from Diagnosis to Pathophysiology

Abstract

Since the emergence of the COVID-19 pandemic at the end of 2019, a massive vaccination campaign has been undertaken rapidly and worldwide. Like other vaccines, the COVID-19 vaccine is not devoid of side effects. Typically, the adverse side effects of vaccination include transient headache, fever, and myalgia. Endocrine organs are also affected by adverse effects. The major SARS-CoV-2 vaccine-associated endocrinopathies reported since the beginning of the vaccination campaign are thyroid and pancreas disorders. SARS-CoV-2 vaccine-induced pituitary diseases have become more frequently described in the literature. We searched PubMed/MEDLINE for commentaries, case reports, and case series articles reporting pituitary disorders following SARS-CoV-2 vaccination. The search was reiterated until September 2022, in which eight case reports were found. In all the cases, there were no personal or familial history of pituitary disease described. All the patients described had no previous SARS-CoV-2 infection prior to the vaccination episode. Regarding the type of vaccines administered, 50% of the patients received (BNT162b2; Pfizer-BioNTech) and 50% received (ChAdOx1 nCov-19; AstraZeneca). In five cases, the pituitary disorder developed after the first dose of the corresponding vaccine. Regarding the types of pituitary disorder, five were hypophysitis (variable clinical aspects ranging from pituitary lesion to pituitary stalk thickness) and three were pituitary apoplexy. The time period between vaccination and pituitary disorder ranged from one to seven days. Depending on each case's follow-up time, a complete remission was obtained in all the apoplexy cases but in only three patients with hypophysitis (persistence of the central diabetes insipidus). Both quantity and quality of the published data about pituitary inconveniences after COVID-19 vaccination are limited. Pituitary disorders, unlike thyroid disorders, occur very quickly after COVID-19 vaccination (less than seven days for pituitary disorders versus two months for thyroid disease). This is partially explained by the ease of reaching the pituitary, which is a small gland. Therefore, this gland is rapidly overspread, which explains the speed of onset of pituitary symptoms (especially ADH deficiency which is a rapid onset deficit with evocative symptoms). Accordingly, these pilot findings offer clinicians a future direction to be vigilant for possible pituitary adverse effects of vaccination. This will allow them to accurately orient patients for medical assistance when they present with remarkable symptoms, such as asthenia, polyuro-polydipsia, or severe headache, following a COVID-19 vaccination.

Keywords: ASIA syndrome; COVID-19; SARS-CoV-2; VITT; apoplexy; hypophysitis; pituitary; vaccine; vaccine-induced thrombotic thrombocytopenia.

Figure 1

Mechanism of action of adjuvants and initial triggers explaining the pathophysiology of the ASIA syndrome following COVID-19 vaccination.

Figure 2

Physiology of pituitary cell protein’s expression and vaccine-induced hypophysitis pathophysiology. Following adjuvant internalization and mRNA release, the viral signal peptide drives antigen production in the endoplasmic reticulum (ER). After sorting in the Golgi network, S protein acquires its final position in the human cell membrane, where S1 is exposed to the extracellular space. Antigen sorting and trafficking may also induce the release of S protein-containing exosomes. Also shown are dendritic cells (professional antigen-presenting cells) engulfing circulating antigens, and antibody-mediated binding of B cells to cell-anchored antigens. All the above mentioned mechanisms potentiate the inflammatory mechanisms. All the Endocrine consequences after hypophysitis are mainly hypogonadism, hypothyroidism, hypoadrenalism and diabetes insipidus.

Figure 3

Proposed figure showing the cascade of pathogenic events that could favor the onset of vaccine-induced immune thrombotic thrombocytopenia in individuals vaccinated with anti-COVID-19 vaccines. After the administration of the vaccine, the recipient’s cells produce harmless COVID-19 proteins and the immune system responds by producing protective antibodies. In some cases, the vaccine’s adjuvants and spike proteins trigger a type I interferon response and the production of VITT antibodies. VITT is caused by antibodies that recognize PF4 bound to platelets. These antibodies are IgGs that activate platelets via low-affinity platelet FcγRIIa receptors (receptors on the platelet surface that bind the Fc portion of IgG). Anti-PF4 antibodies cause cellular activation that, besides activating platelets and coagulation reactions, activates monocytes, neutrophils, and endothelial cells (leading to tissue factor expression). Activation of these other cell types further contributes to the high thrombosis risk accelerated by other factors, such as VWF and procoagulant MP. All of these mechanisms will lead to pituitary apoplexy. (PF4: platelet factor 4; IgG: immunoglobulin G; VITT: vaccine-induced immune thrombotic thrombocytopenia; VWF: Van Willebrand Factor; MP: microparticles).