L. Aliberti*a (Dr), I. Gagliardia (Dr), R. Rizzob (Prof), D. Bortolottib (Dr), G. Schiumab (Dr), P. Franceschettic (Dr), MC. Zatellia (Prof), MR. Ambrosioa (Prof)

a Departement of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Ferrara, ITALY ; b Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, ITALY ; c Endocrine Unit, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, ITALY

* lbrlvc@unife.it

A 50-year-old man was admitted to our hospital for vomit, nausea, diplopia and headache resistant to analgesic drugs. Symptoms started the day after his third COVID-19 mRNA vaccine (Moderna) whereas SARS-CoV-2 nasal swab was negative. Pituitary MRI showed recent pituitary apoplexy in macroadenoma. Biochemistry showed secondary hypogonadism and hypothyroidism and a stress dose dexamethasone was started due to the risk of adrenal insufficiency and to reduce oedema. Inflammatory markers were elevated as well as white blood cells count, fibrinogen and D-dimer. Pituitary tumour transsphenoidal resection was performed and pathology report was consistent with pituitary adenoma with focal haemorrhage and necrosis; we found immunohistochemical evidence for SARS-CoV-2 nearby pituitary vessels, in the presence of an evident lymphocyte infiltrate

There are few reports of pituitary apoplexy after COVID-19 vaccination and infection. The cross-reaction between SARS-CoV-2 proteins and tissue antigens could lead to pituitary autoimmunity. SARS-CoV-2 can bind to ACE2 receptors in the brain barrier endothelium and migrate into the central nervous system (CNS) or may be transported through axons to the CNS. COVID-19-associated coagulopathy includes activation of the coagulation system, inhibition of fibrinolysis and release of prothrombotic mediators, causing microemboli that might lead to infarction of the pituitary adenoma. Similarly, pituitary stimulation and cytokine storm occurring in the infectious state may lead to acute increased pituitary blood demand precipitating apoplexy. Finally, the development of anti-PF4/heparin antibodies after vaccine administration may occur, determining induction of both coagulopathy, thrombocytopenia and bleeding. Ours is the first case of SARS-CoV-2 evidence in pituitary tissue, suggesting that endothelial infection of pituitary vessels might be present before vaccination, supporting the hypothesis that the patient have experienced an asymptomatic SARS-CoV-2 infection that persisted at CNS level, possibly implicated in the apoplexy onset. Our case underlines that SARS-CoV-2 can associate with apoplexy by penetrating into CNS, even in cases of negative nasal swab. Patients with underlying diagnosed or undiagnosed pituitary tumours may be exposed to COVID-19 and may be at increased risk of pituitary apoplexy, therefore clinicians should be conscious of this risk, investigating pituitary hormones

The author has declared no conflict of interest.