Abstract Background The occurrences of pituitary apoplexy following COVID-19 vaccination had only been reported twice. We present the case of a 24-year-old female who developed pituitary apoplexy following the second dose of an AstraZeneca COVID-19 vaccine. Clinical Case A 24-year-old female presented with sudden onset of severe frontal headache, a day after receiving her second AstraZeneca vaccine dose. She denied other symptoms including blurring of vision, eye pain and diplopia. On admission, her blood pressure was 120/80 mmHg, with no evidence of postural hypotension. She was overweight with a BMI of 29kg/m2. Confrontational visual field assessment was normal with no evidence of bitemporal hemianopia. An MRI of the pituitary showed a heterogenous enhancement of the pituitary gland, extending to the suprasellar region, measuring approximately 1.1cm×1.6×1.9cm (AP×W x CC) with features suggestive of pituitary apoplexy with mass effect to the optic chiasm and cavernous portion of the left ICA. Pituitary hormonal tests results showed normal anterior pituitary hormone levels, with the exception of insulin-like growth factor-1 (IGF-1) at a level of 417 ng/ml. Overnight dexamethasone test was performed and showed suppressed cortisol level of 48.4 nmol/L. Growth hormone suppression test resulted in suppressed GH level of <0.1ng/ml in the presence of hyperglycemia. Pituitary hypophysitis was considered because of the more likely age group and the typical presentation of severe headache. In the context that the headache had started shortly after the administration of the second dose of COVID-19 vaccine, this potentially could have been the trigger for the occurrence of pituitary apoplexy She was treated with high dose steroids and the headache improved. A follow up pituitary MRI showed a significant 50% reduction in the size of the pituitary mass. To date, this report would be the third linking COVID-19 vaccination and pituitary apoplexy. The first one occurred in a 44-year-old man, who presented with sudden onset of blurring of vision 3 days following the second dose of COVID-19 vaccine. His MRI showed a suprasellar mass with optic chiasm. His endoscopic transsphenoidal resection of the pituitary tumor showed focal hemorrhage and necrosis of pituitary adenoma cells. The second case occurred in 37 years old lady 5 days following the dose of Astra Zeneca vaccine. MRI finding showed consistent with pituitary apoplexy . Conclusion This report highlights a rare complication of the COVID-19 vaccine that could cause pituitary apoplexy. Possible explanation could be due to vascular dysfunction secondary to the overwhelming immunological response. Reference Jaggi, S. and S. Jabbour, Abstract #1001394: A Rare Endocrine Complication of the COVID-19 Vaccine. Endocrine Practice, 2021. 27(6): p. S116-S117 Piñar-Gutiérrez, A., P. Remón-Ruiz, and A. Soto-Moreno, CASE REPORT: Pituitary apoplexy after COVID-19 vaccination. Medicina clinica, 2021. Presentation: No date and time listed