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Submitted on January 12, 2005
Accepted on May 2, 2005
Departments of Endocrinology (Y.S.W., A.M.I., W.Z.W., P.J.J., J.P.M., G.M.B., A.B.G.) and Neurosurgery (F.A., I.S.), St Bartholomew's Hospital, London ECIA 7BE, United Kingdom
* To whom correspondence should be addressed. E-mail: A.B.-Grossman{at}qmul.ac.uk.
1. Context: Cushing's disease due to a pituitary macroadenoma is an uncommon cause of Cushing's syndrome, and reports in the published literature are few and of limited size.
2. Objective: 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.
3. Design: Retrospective case-records study for the years 1964-2001.
4. Setting: Tertiary referral hospital center.
5. Patients: Patients with Cushing's disease presenting with a pituitary macroadenoma, in comparison to a large group of microadenoma patients.
6. Interventions: Therapy with surgery and radiotherapy.
7. Main Outcome Measures: Basal and dynamically-responsive plasma ACTH and cortisol levels, and response to treatment.
8. Results: We identified 18 patients with Cushing's disease secondary to a macroadenoma: basal 09.00 h plasma ACTH was 135.8 ± 32.5 and 45.0 ± 4.3 ng/L (mean ± SEM) respectively in macroadenomas and microadenomas (P = 0.013). Mean 09.00 h serum cortisol was significantly increased in the macroadenomas (27.5 ± 3.0 µg/dL, 759.6 ± 82.6 nmol/L vs. 22.6 ± 0.6 µg/dL, 624.7 ± 16.4 nmol/L) respectively; P = 0.021). Testing with high-dose dexamethasone showed less suppression in the macroadenomas (57.6 ± 8.7% vs. 74.4 ± 2.1% respectively; 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.
9. Conclusions: Pituitary macroadenomas causing Cushing's disease have biochemical features largely distinct from patients harboring microadenomas, but represent one end of a continuum.
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