Clinical and biochemical characteristics of adrenocorticotropin-secreting macroadenomas.
BACKGROUND
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.


METHODS
We conducted a retrospective case-records study for the years 1964-2001.


METHODS
The study occurred at a tertiary referral hospital center.


METHODS
Patients had Cushing's disease presenting with a pituitary macroadenoma, in comparison with a large group of microadenoma patients.


METHODS
Interventions included therapy with surgery and radiotherapy.


METHODS
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.
Woo
Y Sammy
YS
Department of Endocrinology, St. Bartholomew's Hospital, London EC1A 7BE, United Kingdom.
Isidori
Andrea M
AM
Wat
Winnie Z
WZ
Kaltsas
Gregory A
GA
Afshar
Fari
F
Sabin
Ian
I
Jenkins
Paul J
PJ
Monson
John P
JP
Besser
G Michael
GM
Grossman
Ashley B
AB
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D000310:Adrenal Gland Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D047748:Pituitary ACTH Hypersecretion / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone