A 45-year-old male was referred to our hospital with the chief complaints of bitemporal hemianopsia and vision loss (visual acuity, left: 0.04, right: 0.03) (Supplementary Figure S1). Brain magnetic resonance imaging (MRI) revealed a giant pituitary tumor which was compressing to optic apparatus and bilateral basal ganglia (Supplementary Figure S2), while endocrine findings obtained at that time showed no evidence of a functional pituitary neuroendocrine tumor (Supplementary Table S1). Moreover, the level of cortisol was very low, suggesting hypoadrenalism, although thyroid function was still within the reference range (Supplementary Table S1). The levels of testosterone, growth hormone (GH) and insulin like growth factor 1 (IGF-1) were also low, suggesting hypogonadism and GH deficiency (Supplementary Table S1). On the other hand, the level of prolactin (PRL) was elevated, suggesting stalk effect by a giant pituitary tumor (Supplementary Table S1).
A surgical procedure was planned as soon as possible, however, at this point, due to the COVID-19 outbreak in Japan, a second Pfizer/BioNTech vaccine was already scheduled and administered 1 month after a first visit to our department while awaiting the operation. As a result, the operation was planned 2-3 weeks after the second COVID-19 vaccination.
Three days after the second COVID-19 vaccine injection, the patient was presented to our emergency department because of a progressively worsening headache and vomiting. Emergency computed tomography (CT) results showed a hyperdense suprasellar mass lesion in the upper part of the known pituitary tumor (Figure 1). Furthermore, vision was decreased to finger counting at 30 cm. Because of partial hypopituitarism as shown on Supplementary Table S1, we assumed that the patient with pituitary apoplexy had adrenal insufficiency. Hydrocortisone (dose with 100 mg), therefore, was administered intravenously on admission, and then, 200 mg of hydrocortisone per day was continued to infuse during and after the surgery to prevent from adrenal crisis as replacement therapy.
Although laboratory data on the coagulation system showed that prothrombin time (PT) was slightly prolonged, there was no apparent evidence of vaccine-induced thrombotic thrombocytopenia (Supplementary Table S2).
An emergency endoscopic endonasal transsphenoidal surgical procedure was performed after confirming negative COVID-19 polymerase chain reaction (PCR) test results. Intraoperative findings revealed an intrasellar mass lesion that formed a relatively soft tumor similar to an ordinary pituitary neuroendocrine tumor (Figure 2A). Following resection of the intrasellar mass, the arachnoid membrane on the left side of the diaphragm was exposed (Figure 2B), which revealed compression of the pituitary gland on the superior left side (Figure 2C). Furthermore, on the superior right side a hemorrhagic necrotic hard tumor was observed. The hard tumor was intentionally left, as removal was considered to be dangerous and could potentially cause damage to the neurovascular structure (Figure 2D). Based on histopathology results, the diagnosis was pituitary neuroendocrine tumor (Figure 3). The findings showed tumor cells with eosinophilic cytoplasm (white arrow) invaded by lymphocytes (white arrowhead) and red blood cells suggesting pituitary apoplexy (Figure 3).
Following surgery, the headache was improved and improvement of visual acuity in the left eye to 0.7 was noted. However, as compared to visual function status findings before apoplexy development, visual acuity and visual field impairment in the right eye had worsened (visual acuity, right: 0.01) (Supplementary Figure S3). The patient developed diabetes insipidus (DI) with thirst and hypotonic polyuria during the immediate postoperative period, which was controlled with oral desmopressin. Postoperative CT findings showed the residual tumor with hematoma in the suprasellar region (Figure 4). Dynamic endocrine test results after discharge indicated panhypopituitarism, thus various hormone replacements were administered. Five months later, brain MRI results showed tumor shrinkage because of natural hematoma absorption and decompression of the optic apparatus (Supplementary Figure S4). Eye examinations are continuing as part of the clinical course, with no additional radiation therapy performed at the time of writing.