Ectopic ACTH-secreting pituitary adenoma of the sphenoid sinus: case report of endoscopic endonasal resection and systematic review of the literature

Ectopic pituitary adenomas are exceedingly rare entities that are often misdiagnosed. The resulting delay in diagnosis may be particularly concerning in the case of Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Although the total resection of ectopic adenomas results in rapid and durable remission, persistent Cushing syndrome is often associated with permanently damaging invasive procedures and significantly higher risk of mortality. The authors report the case of a 48-year-old man with ACTH-dependent Cushing syndrome. On the morning before surgery, his serum cortisol measured 51 mu g/dl, his ACTH level was 195.7 pg/ml, and his urinary free cortisol level was 2109 mu g/day. Serum cortisol was not suppressed with the administration of high-dose dexamethasone. Imaging showed separate masses in both the sphenoid sinus and the pituitary gland, complicating the diagnostic process and requiring pathological assessment of both masses. No other abnormalities were found on thoracic, abdominal, or pelvic scans. Gross-total resection of both lesions was accomplished via an endoscopic endonasal transsphenoidal approach. Pathology confirmed an ectopic ACTH pituitary adenoma of the sphenoid sinus and a Crooke hyaline change of the pituitary gland. The patient achieved stable hormonal remission without significant postoperative complications, returned to full activity within 3 months, and remained disease free nearly 1 year after tumor resection. In a systematic literature review, the authors identified 41 cases of ectopic ACTH-secreting pituitary adenomas, including 18 arising in the sphenoid sinus without direct involvement of the sella. Including the case described here, the total number of ectopic ACTH pituitary adenomas arising in the sphenoid sinus was 19, and the total number of ectopic ACTH pituitary adenomas without regard to location was 42. For the 19 patients with adenomas found in the sphenoid sinus, ages ranged from 16 to 76 years, and there were 15 women and 4 men. The mean and median diameters of the resected sphenoid masses were 13.9 and 8 mm, respectively, with a range of 3-55 mm. Seven were microadenomas (< 1 cm). Fifteen of the 19 cases reported serum ACTH and morning cortisol levels, the means of which were 106.7 pg/ml and 32.5 mu g/dl, respectively. Gross-total tumor resection was achieved in all patients except one, and in all of them durable hormonal remission of Cushing syndrome was achieved (mean follow-up time 20 months). Ectopic pituitary adenomas are rare but important causes of Cushing syndrome and related endocrinopathies, particularly because of the rapid onset and severity of symptoms with atypical presentation. Ectopic pituitary adenomas, especially those in the nasal cavity, nasopharynx, or paranasal sinuses, are easily misidentified. Any patient presenting with signs and symptoms of Cushing syndrome without any obvious pituitary adenoma or other sources of hypercortisolemia should be thoroughly screened for an ectopic adenoma. However, as with the case presented here, the coincident existence of a sellar mass should not preclude the possibility of an ectopic source. There should be a high degree of clinical suspicion for any mass in the general area surrounding the sella when evaluating Cushing syndrome.