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 microg/dl, 759.6 +/- 82.6 nmol/liter, vs. 22.6 +/- 0.6 microg/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.