Endocrine Abstracts (2012) 28 P247

A case series of corticotroph macroadenomas and Cushing's: clinical characteristics and management

Sam O'Toole1, Karl Metcalfe2, Piers Plowman3, Jane Evanson4, Robert Carpenter1 & Will Drake1


1Department of Endocrinology, St Bartholomew's Hospital, London, United Kingdom; 2Department of Endocrinology, Southend University Hospital, Westcliff-on-Sea, United Kingdom; 3Department of Oncology, St Bartholomew's Hospital, London, United Kingdom; 4Department of Radiology, St Bartholomew's Hospital, London, United Kingdom.


Background: Pituitary macroadenomas are an uncommon cause of Cushing’s disease. They present with a higher cortisol burden, are more aggressive and harder to cure and manage than microadenomas.

Aims: To review the demographics, clinical features, biochemistry, radiology and required treatment modalities of a single-centre case series of corticotroph macroadenomas.

Methods: Retrospective analysis and review of the case records of a series of patients diagnosed with pituitary corticotroph macroadenomas at St Bartholomew’s Hospital from 2001–2011 was performed.

Results: Nine patients with Cushing’s disease due to a macroadenoma were identified. Six (66.6%) were female, mean age at diagnosis 50.7 +13.8 years (range 35–75). Baseline biochemical evaluation confirmed severe cortisol excess in all patients: mean 9 AM cortisol 957.8 nmol/l +533.8, mean 9 AM ACTH 151.4 ng/L +112.1, mean asleep midnight free cortisol 600.4 nmol/l+ 140.3, mean cortisol-day curve burden 732.0 nmol/l +430.4. All patients failed to suppress on a 48 hour low dose dexamethasone suppression test. At baseline, 5 patients had hyperprolactinaemia (mean 567 mIU/L +393) and 5 were deficient in at least one anterior pituitary hormone. There was a high prevalence of supra-sellar and cavernous sinus extension at diagnosis. Management strategies were varied: trans-sphenoidal hypophysectomy (8), external beam radiotherapy (8), gamma-knife stereotactic radiosurgery (5), bilateral adrenalectomy (2), chemotherapy (2). 7 of the 9 patients required multi-modality therapy. At final follow-up (mean duration 36 months), outcomes were as follows: 2 had developed Nelson’s syndrome (1 of whom had passed away), 4 had been rendered hypopituitary, 3 had an acceptable cortisol burden on adrenalytic therapy and 1 patient did not.

Discussion: This case series highlights the severe and often clinically aggressive phenotype of Cushing’s disease secondary to pituitary macroadenomas. Potential for surgical cure is restricted by para- and supra-sellar extension and can necessitate the use of additional lines of therapy including chemotherapy.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

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