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

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 cortisol (< 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.