Clinical and biochemical characteristics of adrenocorticotropin-secreting macroadenomas

Context: Cushing's disease as a result of a pituitary macroadenoma is an uncommon cause of Cushing's syndrome, and reports in the published literature are few and of limited size. Objective: Our objective was to establish the clinical and biochemical characteristics of macroadenomas associated with Cushing's disease compared with a large cohort of microadenomas and to assess their response to therapy. Design: We conducted a retrospective case-records study for the years 1964-2001. Setting: The study occurred at a tertiary referral hospital center. Patients: Patients had Cushing's disease presenting with a pituitary macroadenoma, in comparison with a large group of microadenoma patients. Interventions: Interventions included therapy with surgery and radiotherapy. Main Outcome Measures: Outcome measures included basal and dynamically responsive plasma ACTH and cortisol levels and response to treatment. Results: We identified 18 patients with Cushing's disease secondary to a macroadenoma; basal 0900 h plasma ACTH was 135.8 +/- 32.5 and 45.0 +/- 4.3 ng/liter (mean +/- SEM), respectively, in macroadenomas and microadenomas (P = 0.013). Mean 0900 h serum cortisol was significantly increased in the macroadenomas (27.5 +/- 3.0 mu g/dl, 759.6 +/- 82.6 nmol/liter, vs. 22.6 +/- 0.6 mu g/dl, 624.7 +/- 16.4 nmol/liter) (P = 0.021). Testing with high-dose dexamethasone showed less suppression in the macroadenomas (57.6 +/- 8.7% vs. 74.4 +/- 2.1%; P = 0.02) and an attenuated ACTH response to CRH. For all biochemical variables there was considerable overlap between the two groups. Few patients with macroadenomas were cured by surgery. Conclusions: Pituitary macroadenomas causing Cushing's disease have biochemical features largely distinct from patients harboring microadenomas but represent one end of a continuum.