Transsphenoidal surgery for Cushing's disease: does what is removed determine the endocrine outcome?

Fifty-seven patients with pituitary-dependent Cushing's syndrome and eight with Nelson's syndrome underwent transsphenoidal pituitary exploration, with removal of macroscopically abnormal tissue in 64 patients and detailed histology of this in 63. The cure rate by stringent criteria 1 month later was 48 (83%) of the 58 with assessable data, who were followed for 225 patient-years. Two patients relapsed later, a rate of one per 112 patient-years of follow-up. In 27% of patients, the macroscopically abnormal tissue removed was histologically indistinguishable from normal pituitary gland but the cure rate was 82%, and a quarter of the patients in this group assessable for recovery of normal ACTH function gained it. Another 53% of biopsies showed corticotroph adenomas, and the cure rate in these was 89% though rather more (69%) recovered normal ACTH function. The remaining 20% of biopsies were consistent with corticotroph hyperplasia. The cure rate varied little whether the lesion was diffuse or localized, whether or not it was in the invasion zone/interlobar cleft, whether or not there was pituitary enlargement, or whether the surgery was radical or selective. Six patients, of whom three are cured, showed surgical or radiological evidence of invasion outside the pituitary fossa. The data are consistent with the idea that pituitary adenoma is merely the end stage of some other process in the corticotrophs, and cure often follows removal of a lesion other than adenoma. Of patients who were permanently cured, 47% regained normal ACTH function within 3 years of operation (none later), 53% remaining ACTH-deficient at 3 years or more. Of all patients 48% acquired gonadotrophin deficiency, 28% have TSH deficiency and 25% permanent diabetes insipidus. All these pituitary function deficits were more common after radical surgery and in patients with normal histology, The literature contains so little objective data on these functions that we cannot say whether the endocrine damage in our patients is exceptional or not.