OUTCOMES OF THERAPY FOR CUSHINGS-DISEASE DUE TO ADRENOCORTICOTROPIN-SECRETING PITUITARY MACROADENOMAS

We reviewed our experience with 21 patients who had Cushing's disease due to ACTH-secreting macroadenomas to clarify the natural history of this disease. All patients had typical clinical and biochemical featur es of ACTH-dependent hypercortisolism. Their mean maximal tumor diamet er was 1.6 +/- 0.1 cm, and the range was 1.0-2.7 cm. Six patients had cavernous sinus invasion, three had invasion of the floor of their sel la, and nine had suprasellar extension. The observed remission rate wa s significantly lower in macroadenoma patients than in microadenoma pa tients (67% vs. 91%; chi(2) = 5.7; P < 0.02). Cavernous sinus invasion (odds ratio, 35; 95% confidence interval, 2.6-475; P < 0.008) and pre sence of a maximum tumor diameter 2.0 cm or more (odds ratio, 12.9; 95 % confidence interval, 1.4-124; P < 0.02) emerged as the only predicto rs of residual disease after surgery. The observed recurrence rate was significantly higher in macroadenoma patients than in microadenoma pa tients (36% vs. 12%; chi(2) = 4.2; P < 0.05). Macroadenoma patients te nded to suffer from recurrences earlier than did microadenoma patients (16 vs. 49 months). Stepwise multiple logistic regression did not ide ntify any predictors of disease recurrence in macroadenoma patients. E ight macroadenoma patients underwent a total of nine repeat surgical p rocedures, but none of these resulted in clinical remissions. Only fou r of seven (57%) patients followed for a sufficient period of time ach ieved normal urinary free cortisol levels after conventional radiother apy. Three (75%) of these four patients had re-recurrent hypercortisol ism after brief periods of eucortisolism. Pharmacological agents and a drenalectomy were effective in the management of hypercortisolism in p atients with residual and recurrent disease. Our results indicate that ACTH-secreting macroadenomas are more refractory to conventional trea tments than are ACTH-secreting microadenomas.