Treatment of Cushing's Disease by Transsphenoidal Microsurgery

Six patients of ACTH dependant Cushing's disease were treated by transsphenoidal resection of pituitary adenomas. Preoperative endocrinological results showed that both plasma ACTH and cortisol were maintained at higher levels and their normal diurnal rhythms were lost. Urinary 17-OHCS excretion was partially suppressed by larger doses of dexamethasone (8 mg). These data was suggestive of pituitary dependent Cushing's disease, rather than ectopic ACTH-producing tumors. The sella volume was measured by Di Chiro's method and in 3 cases it exceeded minimally above the upper limit of the normal value, but the other 3 showed completely normal sella. Localized bulging of the sella floor was found in 2 cases by midline lateral tomography. In the A-P tomogram asymmetry of the sella floor was found in one case and localized bulging in other 2 cases. Minimal suprasellar expansion of the tumor was found only in one case by midline pneumotomography. Magnified cerebral angiography with subtraction method or computed tomography was not diagnostic to verify pituitary microadenomas. The indication of pituitary surgery had to be decided mainly by endocrinological findings. In only one case the adenoma occupied most of the intrasellar space, but in the other 5 they were microadenomas and 3 of them were buried in the normal glands. Complete resection of the adenoma was attempted, but macroscopically normal tissue was tried to be left as much as possible. Typical Crooke's hyaline changes were found in the normal adenohypophysis in one case and immunohistochemical studies using anti-ACTH serum revealed that the Crooke's cells are still reactive. After surgery most patients showed decreased plasma ACTH and cortisol levels and substitution therapy of adrenocortical hormones was necessary for the first one or two months. Rapid clinical remission of Cushing's syndrome was observed in all but one, who might have residual tumor cells due to technical incompleteness. Successive endocrinological reevaluation showed that pituitary-adrenal function has been normal or subnormal in 5 cases. One showed no significant improvement. None had pan-hypopituitarism nor any serious side effects, such as liquorrhea and continuous diabetes insipidus. Overall results suggest that transsphenoidal resection of pituitary adenomas in Cushing's disease should be located in the center of the treatment.