Pituitary Apoplexy in the Setting of Oral Anticoagulation Therapy With Apixaban

Abstract

Background: Several medical conditions require chronic anticoagulation, but there are potential long-term complications, including intracranial hemorrhages. Pituitary apoplexy (PA), caused by infarction or bleeding into the pituitary gland, is a rare condition that commonly occurs in the setting of a pituitary adenoma. However, several reports have shown an increased risk of PA associated with anticoagulation therapy. Recent case reports have shown that even the newer oral anticoagulants may increase the risk of PA. Typically patients present with an acute headache, visual disturbances and pituitary hormonal deficiencies. Management is controversial and includes either a conservative medical treatment versus a more aggressive surgical approach. We present a case of a PA induced by Apixaban, an orally active factor Xa inhibitor. Clinical Case: This is the case of a 45 years-old male patient with prior medical history of hyperthyroidism treated with radioiodine ablation, systolic heart failure and atrial fibrillation, receiving Apixaban for stroke risk reduction. The patient presented initially to the ER after developing an acute, pulsatile frontal headache, associated with nausea and vomiting. He was treated for a suspected acute gastroenteritis and was discharged home. Two days later the patient returned to the ER, with persistent headaches unresponsive to oral analgesics. This time, the patient also complained of decreased energy, difficulty concentrating, and memory problems. He denied visual changes, galactorrhea, decreased libido or polyuria. Vital signs were unremarkable and there was no orthostatic hypotension. Physical examination showed a male in mild distress due to pain. There were no visual field defects on confrontation, no neurological deficits, and an intact mental status. Brain imaging showed hemorrhage within the pituitary gland with associated edema, compatible with PA. There was no obvious evidence of a pre-existing pituitary adenoma. Laboratory workup did not reveal any hormonal deficiencies. The patient was managed conservatively with close neurological follow up and empiric high dose dexamethasone. Headaches improved significantly after treatment and eventually resolved. After clinical improvement, the patient was discharged home on physiologic replacement of glucocorticoids with outpatient follow up and plans for re-evaluation of hormonal axis. Conclusion: Oral anticoagulants can increase the risk of PA, even in the absence of a pre-existing pituitary adenoma, as other case reports have shown. Management is controversial, and although there are agents for reversal of Apixaban effects (recombinant factor Xa), their use in PA has not been described. This case was managed conservatively with excellent results. Although we cannot exclude a pre-existing pituitary adenoma in this patient, this case shows that Apixaban increases the risk of PA.

Antiplatelet and anticoagulation therapy and the risk of pituitary apoplexy in pituitary adenoma patients

“…A particular focus was given to antiplatelet/anticoagulant (AP/AC) therapy as AP/AC medications are increasingly prescribed to an aging population [28,29]. Furthermore, the relationship between PA and AP/AC therapy is controversial and inadequately established in the literature [4,6,10,[13][14][15][16][17][18][19][20][21][22][23][24][25][26].…”

“…The age at apoplectic presentation is also varied, ranging from the rst to the eighth decade of life with peak incidence occurring in the fth decade of life [1,9]. The use of antiplatelets/anticoagulants (AP/AC) in patients with pituitary adenomas is controversial and may be associated with increased risk of apoplexy [6,10,[14][15][16][17][18][19][20][21][22][23][24][25][26]. Using one of the largest series of PA patients to date, we investigated risk factors for apoplexy, with a focus on AP/AC use, to determine whether it is safe to put patients on AP/AC medications in the presence of a known pituitary lesion.…”

Pituitary Apoplexy (PA): Delayed Diagnosis of a Rare Clinical Syndrome in a Patient With a Known Pituitary Adenoma

“…Pituitary adenomas are typically benign; however, their high metabolic requirements coupled with limited vascularization and poor angiogenesis increases their susceptibility to hemorrhage and infarction [4,8]. Pituitary adenomas are thus sensitive to changes in perfusion and several of the precipitating risk factors for PA are those which may affect hemodynamic stability or increase intratumoral or intrasellar pressure [1,4,[8][9][10]. Although asymptomatic hemorrhage of a pituitary adenoma is not uncommon, hemorrhage or infarction of a pituitary adenoma typically occurs acutely, resulting in sudden onset of severe headache [3].…”