Clinical Implications of Giant Pituitary Adenomas: Surgical Approach to Diagnosis and Endocrine Treatment

Background Silent pituitary adenomas (SPAs) are clinically nonfunctioning neoplasms. Although they do not produce clinically apparent endocrinopathies, SPAs can express low levels of hormones, while others, termed null cell adenomas, do not express any hormones. Patients with SPAs are typically not diagnosed until mass lesion effect is exerted on surrounding tissues. Medical management of giant (> 4 cm) SPAs based strictly on blood prolactin (PRL) levels is further complicated by stalk and hook effects, which can lead to an erroneous diagnosis without further biochemical evaluation. Here, we report diagnostic work-up and the expanded endoscopic endonasal transtuberculum approach (EEET-TA) to resecting a giant SPA with significant third ventricle (TV) involvement in a single operation.

Case Illustration A 55-year-old man presented to our emergency department with imaging that revealed a giant adenoma encasing the right cavernous carotid artery (KNOSP 4), extending from the sella into the suprasellar region and into the TV causing obstructive hydrocephalus. The pituitary component of the mass measured 3.6 × 2.8 cm and the TV component measured 3.4 × 2.9 cm, with a 5.9-cm craniocaudal aspect. On physical examination, the patient was lethargic and demonstrated dense bitemporal hemianopsia. He had no clinical history consistent with hyperprolactinemia. Preoperatively, the patient had panhypopituitarism and a prolactin level (PRL) of 99 ng/dL. The diagnosis of PRL-SPA was made.

Methods A single-staged EEET-TA was used to resect the tumor. Pre- and postoperative pituitary hormones and clinical exam was assessed. The cytoarchitecture, reticulin, and SF-1 stains were evaluated.

Results Sections of the lesion showed disrupted acinar architecture and sheets of monomorphic adenoma cells that strongly express PRL. The tumor was categorized as a densely granulated PRL-containing pituitary adenoma. Focal nuclear and more extensive cytoplasmic steroidogenic factor 1 expression was also noted. The patient’s mental status and visual acuity improved immediately after the procedure (20/200 preoperatively to 20/50 postoperatively). Patient’s 15-month follow-up MRI revealed robust decompression of the optic chiasm and optic nerves, gross total resection of the tumor within the TV, and stable-appearing residual mass seen within the right cavernous. He continues on hormonal replacement for adrenal insufficiency, hypothyroidism, diabetes insipidus, and low-dose 1.25 mg po qd of bromocriptine.

Discussion Serum PRL levels are generally proportional to tumor size in prolactinomas, and macroprolactinomas are usually associated with PRL levels more than 250 ng/mL. In this unusual case, where serum PRL was 99 ng/mL, we concluded that mild PRL elevation was most likely due to the stalk effect, resulting from disruption of normal dopaminergic inhibition of PRL secretion. Therefore, the unexpected histological findings of a PRL-staining adenoma with focal SF-1 expression suggest that this was a clinically silent PRL adenoma.

Conclusion This case highlights the benefit of accurate subtyping of pituitary adenomas. It not only confirms clinical disease and identifies patients at higher risk of recurrent disease but in some instances, may also indicate therapeutic responses. Perhaps, treating postoperatively with a low-dose dopamine agonist should be considered given the high recurrence rate of SPA.