Ectopic corticotropin-releasing hormone (CRH) syndrome from metastatic small cell carcinoma: a case report and review of the literature.
BACKGROUND
Cushing's Syndrome (CS) which is caused by isolated corticotropin-releasing hormone (CRH) production, rather than adrenocorticotropin (ACTH) production, is extremely rare.


METHODS
We describe the clinical presentation, course, laboratory values and pathologic findings of a patient with isolated ectopic CRH causing CS. We review the literature of the types of tumors associated with this unusual syndrome and the behavior of these tumors by endocrine testing.


RESULTS
A 56 year old woman presented with clinical and laboratory features consistent with ACTH-dependent CS. Pituitary imaging was normal and cortisol did not suppress with a high dose dexamethasone test, consistent with a diagnosis of ectopic ACTH. CT imaging did not reveal any discrete lung lesions but there were mediastinal and abdominal lymphadenopathy and multiple liver lesions suspicious for metastatic disease. Laboratory testing was positive for elevated serum carcinoembryonic antigen and the neuroendocrine marker chromogranin A. Serum markers of carcinoid, medullary thyroid carcinoma, and pheochromocytoma were in the normal range. Because the primary tumor could not be identified by imaging, biopsy of the presumed metastatic liver lesions was performed. Immunohistochemistry was consistent with a neuroendocrine tumor, specifically small cell carcinoma. Immunostaining for ACTH was negative but was strongly positive for CRH and laboratory testing revealed a plasma CRH of 10 pg/ml (normal 0 to 10 pg/ml) which should have been suppressed in the presence of high cortisol.


CONCLUSIONS
This case illustrates the importance of considering the ectopic production of CRH in the differential diagnosis for presentations of ACTH-dependent Cushing's Syndrome.
Shahani
Sadeka
S
Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Nudelman
Rodolfo J
RJ
Nalini
Ramaswami
R
Kim
Han-Seob
HS
Samson
Susan L
SL
D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000737:chemistry / Q000150:complications* / Q000378:metabolism / Q000556:secondary; D003346:Corticotropin-Releasing Hormone / Q000097:blood / Q000378:metabolism*; D003480:Cushing Syndrome / Q000097:blood / Q000209:etiology*; D003940:Diagnostic Techniques, Endocrine; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000737:chemistry / Q000150:complications* / Q000378:metabolism / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000737:chemistry / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D009384:Paraneoplastic Endocrine Syndromes / Q000097:blood / Q000209:etiology*
D014408:Biomarkers, Tumor; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone
J Clin Endocrinol Metab. 2001 Jan;86(1):117-23
11231987
J Clin Endocrinol Metab. 1998 Feb;83(2):305-8
9467532
J Endocrinol Invest. 1994 Jun;17(6):447-52
7930390
J Clin Endocrinol Metab. 2006 Feb;91(2):371-7
16303835
J Endocrinol Invest. 2006 Feb;29(2):177-81
16610247
Endocrinol Metab Clin North Am. 2008 Mar;37(1):135-49, ix
18226734
J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):139-51
7626446
Arq Bras Endocrinol Metabol. 2007 Nov;51(8):1245-52
18209862
J Clin Endocrinol Metab. 2005 Aug;90(8):4955-62
15914534
Exp Clin Endocrinol Diabetes. 2006 Sep;114(8):444-7
17039427
Hormones (Athens). 2008 Jul-Sep;7(3):259-62
18694866
J Clin Endocrinol Metab. 2009 Sep;94(9):3121-31
19734443
Zentralbl Pathol. 1993 Jun;139(2):157-63
8396419
Eur J Histochem. 2009 Jan-Mar;53(1):1-6
19351607
J Endocrinol. 1987 Apr;113(1):133-8
3035046
J Clin Endocrinol Metab. 2003 Oct;88(10):4565-8
14557423
Horm Res. 2002;57(5-6):200-4
12053094
Endocr Pract. 1999 Mar-Apr;5(2):84-7
15251695