Isolated ACTH deficiency following immunization with the BNT162b2 SARS-CoV-2 vaccine: a case report

Abstract

Background The global COVID-19 pandemic requires urgent development of new vaccines. Endocrinological adverse effects following the new mRNA vaccine against COVID-19 have been reported in several cases. Specific to the involvement of pituitary function; however, only a single case with hypophysis has been reported. This is the first case of isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) following mRNA vaccination against COVID-19. Case presentation A healthy 31-year-old man received the BNT162b2 SARS-CoV-2 mRNA vaccine. The first injection was uneventful. One day after the second injection, he noticed general fatigue and fever. In the following several days, he additionally developed headaches, nausea, and diarrhea. Four days after the vaccine injection, he visited a hospital with worsening of these symptoms. Physical examination revealed slight disorientation but no other deficits. Laboratory tests revealed hyponatremia, hypoglycemia, and extremely low plasma ACTH and serum cortisol levels (ACTH < 1.5 pg/ml, cortisol 1.6 μg/dl). He was diagnosed with adrenal crisis and was emergently treated with hydrocortisone. The symptoms responded well and he recovered within a few days. Magnetic resonance images after the replacement with hydrocortisone revealed an atrophic pituitary gland. The patient was referred to our tertiary hospital for further endocrinological examination. Pituitary endocrine load tests revealed isolated adrenocortical response deficiency. After other clinical assessments, he was diagnosed as having isolated ACTH deficiency. After initiation of hydrocortisone replacement, there has been no recurrence of symptoms related to adrenocortical insufficiency nor involvement of other pituitary functions. Conclusion This is the first reported case of IAD potentially associated with COVID-19 immunization. Recent reports have emphasized the importance of adjuvants in the mRNA vaccine that induce the endocrinological adverse effects through disturbance of the autoimmune system, but details are still unclear. Given the broad and rapid spread of vaccinations against COVID-19, it is clinically important to consider that there could be cases with a rare but emergent adrenal crisis even among those who present common symptoms of adverse effects following inactive SARS-CoV-2 mRNA vaccination.

Hypophysitis after COVID-19 vaccination in a patient with Rathke’s cleft cyst: A case report

“… 9 Morita S reported the case of isolated adrenocorticotropic hormone deficiency and noted that rare but urgent adrenal crises might occur in patients with symptoms of common side effects after the new vaccine and pointed that endocrine adverse reactions might be induced even after injecting inactivated SARS-CoV-2 mRNA vaccine because of the disruption of the autoimmune system by adjuvants in the mRNA vaccine. 17 Especially，the risk of post-vaccination pituitary damage increased in patients with previous pituitary adenomas or previous asymptomatic COVID-19 infection. 18 , 19 …”

Diagnostic strategies in adrenal insufficiency

“…Environmental factors, such as viral infections have all along been implicated as triggering factors in autoimmune diseases. Lately, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection or immunization have been linked with PAI manifestation is some case reports [7,8,9 ▪ ,10 ▪ ]; adrenal lesions in deceased patients with coronavirus disease 2019 (COVID-19) have also been described in autopsy reports [11] including bilateral adrenal infarction [12].…”

Long Covid: Hormone Imbalances and/or Rather Complex Immune Dysregulations?

“…Interestingly, a healthy 31-year-old man who received the BNT162b2 SARS-CoV-2 mRNA vaccine was reported to have developed central adrenal insufficiency with undetectable adrenocorticotropin (ACTH) levels and a serum cortisol of 1.6 µg/dL after the second vaccine injection, hypothesizing that adjuvants in the mRNA vaccine could have been the trigger [ 3 ].…”