Neuroendocrinological Outcomes Following Early versus Delayed Surgery for Acute Pituitary Apoplexy

Introduction: Acute pituitary apoplexy is a clinical syndrome consisting of neurological and endocrinological abnormalities secondary to hemorrhage or ischemia of an underlying pituitary adenoma. We report our experience at the University of California, San Francisco, in the early versus delayed management of acute pituitary apoplexy, with a particular focus on the time course of intervention and subsequent neurological and endocrine recovery.

Methods: We reviewed the records of all patients undergoing treatment of pituitary adenoma from 2003–14 and identified 37 patients who presented with acute pituitary apoplexy and underwent endonasal transsphenoidal resection of a radiologically and pathologically confirmed necrotic and/or hemorrhagic pituitary adenoma. Neurological deficits, partial or complete endocrinopathy, and non-neuroendocrine abnormalities were analyzed both pre- and postoperatively, including among patients receiving early (< 72h) and delayed (> 72h) surgical resection following onset of acute apoplexy symptoms.

Results: Thirty-seven patients were identified with acute pituitary apoplexy, with a mean age of 46 years. All tumors were macroadenomas, and 16% were clinically functional with evidence of hormone hypersecretion. Ninety-seven percent showed radiographic evidence of suprasellar invasion, and 32% showed evidence of cavernous sinus invasion. Preoperatively, neurological deficits were found in 36 patients (97%), endocrinopathy in 33 patients (89%), and non-neuroendocrine symptoms and signs including headache in 36 patients (97%). Fifteen patients (42%) were hyponatremic. Early surgery, occurred in 12 patients (32%), while delayed surgery occurred in 25 patients (68%), including 4 patients (11%) in whom surgery was performed at 1–4 weeks, and 3 patients (8%) in whom surgery was performed more than 1 month from onset of symptoms. Gross total resection was achieved in 10 of 10 patients (100%) undergoing early surgery (p = 0.011) versus 10 of 20 patients (50%) undergoing delayed surgery, despite no significant baseline differences between the early and delayed groups in tumor size (p = 0.288), cavernous sinus invasion (p = 0.263), or suprasellar invasion (p = 1.0). Early versus delayed surgical resection did not appear to significantly reverse visual loss (58% versus 80%, p = 0.240), resolve cranial neuropathies (42% versus 32%, p = 0.716), improve endocrinopathy (20% versus 24%, p = 0.673), or non-neuroendocrine signs and symptoms (75% verus 87%, p = 0.391). Notably, there was a significant association between apoplexy and increased tumor size and suprasellar invasion; apoplectic patients had a mean tumor diameter of 2.93 cm versus 2.27 cm for non-apoplectic patients (p < 0.0001), and 97% of tumors showed suprasellar invasion versus 18% of non-apoplexy patients (p < 0.0001). There was no difference in the time until recurrence between apoplectic and non-apoplectic tumors (p = 0.760, log-rank).

Conclusion: Acute pituitary apoplexy can present with derangements of neurological and endocrinological function, presents more commonly in middle aged men, and is more often associated with larger tumors with suprasellar invasion. Neurological deficits such as visual loss and cranial neuropathies show moderate improvement following surgical decompression, as does preoperative hypopituitarism. Nevertheless, most patients require long-term hormone replacement. The timing of surgical intervention does not appear to significantly affect the resolution of neurological or endocrinological deficits.