title: Phaeochromocytoma and ACTH-dependent cushing's syndrome: tumour crf secretion can mimic pituitary cushing's disease.
abstract: BACKGROUND
  10% of corticotrophin (ACTH)-dependent Cushing's syndrome arises from secretion by extrapituitary tumours, with phaeochromocytoma implicated in a few cases. Ectopic secretion by phaeochromocytoma of corticotropin-releasing hormone (CRF), with secondary corticotroph hyperplasia, is even rarer, with only five cases in the literature hitherto. However, such cases may be classified as 'ectopic ACTH' due to incomplete verification.
  
  
  METHODS
  We describe three patients with phaeochromocytoma and ACTH-dependent Cushing's syndrome in whom biochemical cure was achieved following unilateral adrenalectomy. Although unable to access a validated CRF assay within the timeframe for sample storage, we nevertheless inferred CRF secretion in 2 of 3 cases by tumour immunostaining (positive for CRF; negative for ACTH), supported in one case by pre-operative inferior petrosal sinus sampling (IPSS) indicative of pituitary ACTH source. Both cases were characterized by rapid postoperative wean off glucocorticoids, presumed to reflect the pituitary stimulatory-effect of CRF outweighing central negative feedback inhibition by hypercortisolaemia. By contrast, the tumour excised in a third case exhibited positive immunostaining for ACTH - negative for CRF - and postoperative recovery of hypothalamic-pituitary-adrenal axis took significantly longer.
  
  
  CONCLUSIONS
  Ectopic CRF production is biochemically indistinguishable from ectopic ACTH secretion, except that IPSS mimics pituitary Cushing's disease and cortisol dynamics may normalize rapidly postadrenalectomy. CRF secretion can be inferred through tumour immunohistochemistry, even if no CRF assay is available. Unrecognized phaeochromocytoma ACTH secretion may underpin some cases of cardiovascular collapse postadrenalectomy through acute hypocortisolaemia. Despite advances in phaeochromocytoma genetics since previous reports, we were unable to identify somatic DNA defects associated with either ACTH or CRF secretion.
authors.affiliation: Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors.forename: Konstantinos B
authors.initials: KB
authors.lastname: Lois
authors.affiliation: Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors.forename: Anjali
authors.initials: A
authors.lastname: Santhakumar
authors.affiliation: Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati (MP), India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Vaikkakara
authors.affiliation: Department of Surgery, Oman Health Services, Sohar Hospital, Muscat, Oman.
authors.forename: Sajjan
authors.initials: S
authors.lastname: Mathew
authors.affiliation: Department of Cellular Pathology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Long
authors.affiliation: Department of Cellular Pathology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Johnson
authors.affiliation: Department of Clinical Biochemistry, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors.forename: Rovert
authors.initials: R
authors.lastname: Peaston
authors.affiliation: Department of Clinical Biochemistry, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors.forename: R Dermot G
authors.initials: RDG
authors.lastname: Neely
authors.affiliation: Department of Radiology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors.forename: David L
authors.initials: DL
authors.lastname: Richardson
authors.affiliation: Department of Radiology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors.forename: James
authors.initials: J
authors.lastname: Graham
authors.affiliation: Department of Endocrine Surgery, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.|Newcastle Bioscience, University of Newcastle-upon-Tyne, Newcastle Upon Tyne, UK.
authors.forename: Thomas W J
authors.initials: TWJ
authors.lastname: Lennard
authors.affiliation: Department of Endocrine Surgery, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Bliss
authors.affiliation: Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Miller
authors.affiliation: Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.|Newcastle Bioscience, University of Newcastle-upon-Tyne, Newcastle Upon Tyne, UK.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ball
authors.affiliation: Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.|Newcastle Bioscience, University of Newcastle-upon-Tyne, Newcastle Upon Tyne, UK.
authors.forename: Simon H S
authors.initials: SHS
authors.lastname: Pearce
authors.affiliation: Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.|Royal Centre for Defence Medicine, Birmingham, UK.|Department of Endocrinology & Diabetes, Northumbria NHS Trust, UK.|Carnegie Research Institute, Leeds Beckett University, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Woods
authors.affiliation: Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.|Newcastle Bioscience, University of Newcastle-upon-Tyne, Newcastle Upon Tyne, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Quinton