Intracavernous sinus ectopic adrenocorticotropin-secreting tumours causingtherapeutic failure in transsphenoidal surgery for Cushing's disease

Background. The major cause of surgical failure in the treatment of Gushing 's disease lies in unsuccessful identification of adenomas. In the present study, we investigated the pathogenesis of negative exploration in transsph enoidal surgery for Gushing's disease by analyzing neuro-imaging studies, e ndocrinological examination and selective venous sampling. Methods. Thirty patients with ACTH-dependent Gushing's syndrome that met th e endocrinological criteria for Gushing's disease were treated by transsphe noidal microsurgery. Depending on positive or negative identification of ad enomas during the surgery, selective adenomectomy, partial hypophysectomy o r subtotal hypophysectomy was performed. Findings. All nine patients who underwent selective adenomectomy showed end ocrinological remission and did not need any hormone replacement therapy. O f the 12 patients who underwent partial hypophysectomy, 11 showed normaliza tion of hypercortisolism but seven needed permanent replacement of hydrocor tisone. Four patients underwent subtotal hypophysectomy because no adenoma could be identified in spite of detailed exploration, and three of them sho wed remission but with permanent requirements of hydrocortisone and other p ituitary hormones. Five patients, whose hypercortisolism persisted after in itial surgery, underwent total hypophysectomy as secondary transsphenoidal surgery, and only one of them showed endocrinological remission. Of the six patients with surgical failure, four were thought to be rare cases in whom the ACTH-secreting tumours may have occurred ectopically in the cavernous sinus without direct contact with the pituitary gland. Endocrinologically, these four patients showed a low or no response to corticotropin releasing hormone (CRH) stimulation, and for three of them, radiation therapy to the sellar region including the cavernous sinus was effective for persistent hy percortisolemia. Interpretation. Recognition of an ectopic intracavernous sinus ACTH-secreti ng tumour as a pathological entity for Gushing's disease may not only enhan ce the diagnostic accuracy but also be important for determining the optima l surgical mode for persistent Gushing's disease.