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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0070
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 8 4963-4969
Copyright © 2005 by The Endocrine Society


EXTENSIVE CLINICAL EXPERIENCE

Clinical and Biochemical Characteristics of Adrenocorticotropin-Secreting Macroadenomas

Y. Sammy Woo, Andrea M. Isidori, Winnie Z. Wat, Gregory A. Kaltsas, Fari Afshar, Ian Sabin, Paul J. Jenkins, John P. Monson, G. Michael Besser and Ashley B. Grossman

Departments of Endocrinology (Y.S.W., A.M.I., W.Z.W., G.A.K., 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

Address all correspondence and requests for reprints to: Prof. Ashley B. Grossman, Department of Endocrinology, St. Bartholomew’s Hospital, London EC1A 7BE, United Kingdom. E-mail: A.B.Grossman{at}qmul.ac.uk.

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 µg/dl, 759.6 ± 82.6 nmol/liter, vs. 22.6 ± 0.6 µg/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.




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