Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successfuI treatment

Abstract

Summary: OBJECTIVE We tested the hypothesis that in Cushing's disease, ACTH secretion from the normal pituitary surrounding an ACTH‐secreting adenoma is inhibited and hence removal of the entire adenoma should result in an undetectable serum cortisol in the immediate post‐operative period. DESIGN A retrospective study of patients undergoing transsphenoidal selective adenomectomy, hemi‐hypophysectomy or total hypophysectomy for Cushing's disease at St Bartholomew's Hospital between 1985 and 1990. PATIENTS Forty‐eight consecutive patients (33 women, mean age 43, range 7–69 years) undergoing transsphenoidal hypophysectomy for Cushing's disease. Ten patients who underwent a second operation were re‐evaluated; the patients were followed for a median time of 40 months after operation (range 15–70). MEASUREMENTS Post‐operatively, serum cortisol was measured daily at 0900 h. Serum TSH, T4, prolactin, LH, FSH, testosterone or oestradiol plus plasma and urine osmolality were measured. RESULTS After initial surgery, post‐operative serum cortisol was undetectable (>50 nmol/l) in 20 out of 48 patients (42%) and >300 nmol/l in 32 out of 48 patients (67%). Re‐exploration of the pituitary fossa in 10 patients found undetectable cortisol levels in 25 (52%) and levels >300 nmol/l in 39 (81%) patients. Cushing's syndrome has not recurred, clinically or biochemically, in any patient in whom the post‐operative cortisol was > 50 nmol/l. Post‐operatively, hypothyroidism was present in 40% of patients and hypogonadism in 53% of men and 30% of premenopausal women. Diabetes insipidus, persisting for at least six months, occurred in 46% of patients. CONCLUSIONS Cushing's disease has not recurred in any patient with an undetectable serum cortlsol (>50 nmol/l) post‐operatively. Serum cortisol should be regarded as a tumour marker in Cushing's disease and the aim of transsphenoidal hypophysectomy for Cushing's disease should be to render the immediate post‐operative serum cortisol undetectable.