Dual bronchial carcinoids and Cushing's syndrome with a paradoxical response to dexamethasone and a false positive outcome of inferior petrosal sinus sampling

http://www.eje.org/cgi/content/abstract/159/4/483

DOI: 10.1530/EJE-08-0385
European Journal of Endocrinology, Vol 159, Issue 4, 483-488
Copyright © 2008 by European Society of Endocrinology

CASE REPORT

Dual bronchial carcinoids and Cushing's syndrome with a paradoxical response to dexamethasone and a false positive outcome of inferior petrosal sinus sampling

Pia Burman, ÅsaLinda Lethagen, Krasnodar Ivancev, Leif Johansson and Anders Sundin

Departments of Endocrinology , Radiology Pathology, University Hospital MAS, SE-205 02 Malmö, Sweden4 Department of Diagnostic Radiology, University Hospital, Uppsala, Sweden

(Correspondence should be addressed to P Burman; Email: pia.a.burman@skane.se)

Abstract
Context: Establishing the cause of Cushing's syndrome (CS) can be a considerable challenge, in particular in ectopic adrenocorticotropic hormone (ACTH) syndrome, and often requires a combination of biochemical tests and imaging procedures.

Subject: A 27-year-old man presented with signs of CS. P-ACTH levels were three times above the upper limit of normal (ULN) and free urinary cortisol around 2000 nmol/24 h. The work-up showed remarkable results.

Results: A 2-day low-dose dexamethasone suppression test demonstrated paradoxical increases in cortisol. Sampling from the bilateral inferior petrosal sinus sampling (BIPSS) showed a central to peripheral ACTH ratio of 4.7 after corticotrophin-releasing hormone (CRH) stimulation, i.e. indicated pituitary disease, but magnetic resonance imaging of the pituitary was normal. Computed tomography (CT) scan of the lungs showed two oval-shaped masses, 1.3x1.8 and 1.3x2 cm, in the middle lobe. Both were positive at somatostatin receptor scintigraphy, compatible with tumors or inflammatory lesions. Subsequently, 11C-5-hydroxytryptophan-PET showed distinct uptake in the tumors but not elsewhere. Two carcinoids situated 3 cm apart, both staining for ACTH, were removed at surgery.

Conclusion: This unique case with dual bronchial carcinoids inducing hypercortisolism illustrates the problems with identifying the source of ACTH in CS. Possibly, an abnormal regulation of ACTH production in response to dexamethasone, or steroid-induced tumor necrosis, explains the paradoxical outcome at dexamethasone suppression, and the false positive result at BIPSS reflects an unusual sensitivity of the pituitary corticotrophs to CRH in this patient. The work-up illustrates the great value of 11C-5-hydroxytryptophan-PET as a diagnostic procedure when other investigations have produced ambiguous results.