Download เฉลย ข้อที่ 2 Ectopic Cushing`s Syndrome due to Medullary Thyroid

เฉลย ข้ อที่ 2
Ectopic Cushing’s Syndrome due to Medullary Thyroid Carcinoma
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MTC is reported up to 1-7.5% of all cases of ectopic Cushing’s syndrome (ECS) (ACTH or CRH).
ECS is rare in patients with MTC, seen in 0.07%-0.6% of MTC cases.
It has been described in sporadic and familial cases.
In most cases, MTC diagnosis precedes that of ECS.
Variable periods have been reported between the onset of MTC and ECS.
The site of ACTH and/or CRH production may be the primary tumor or its metastases.
Advanced MTC with Cushing’s syndrome is associated with poor survival because the syndrome can
be severe and debilitating.
 ACTH staining may not detect ACTH, but measuring POMC mRNA by in situ hybridization is helpful
in confirming the source of ectopic ACTH production.
 Treatment options
A. Control of elevated cortisol level
- Debulking of large hepatic metastases by surgery or chemoembolization
- Medical therapy (ketoconazole, mifepristone, aminoglutethimide, metyrapone, mitotane;
- Bilateral adrenalectomy (in cases refractory to medical treatment)
B. Correct metabolic derangement
- Correct hypokalemia, hypertension, diabetes, and gastritis.
 Targeted therapy with tyrosine kinase inhibitor: vandetanib and cabozantinib
- 3 recent reports of reversal of Cushing’s syndrome following the administration of vandetanib to
patients with advanced MTC.
Reference
1.
Ilias I, Torpy DJ, Pacak K et al. 2005 Cushing’s syndrome due to ectopic corticotropin secretion: twenty years’ experience at the National Institutes
of Health. J Clin Endocrinol Metab 90: 4955-4962.
2.
Barbosa SL-S, Rodien P, Schlumberger M et al. 2001 Ectopic ACTH-syndrome due to medullary carcinoma of the thyroid. Program of the 83rd
Annual Meeting of The Endocrine Society, Denver, CO, p 432 (Abstract P2-647)
3.
Wajchenberg BL, Mendonca BB, Liberman B et al. 1994 Ectopic adrenocorticotropic hormone syndrome. Endocr Rev 15: 752–787
4.
Pozza C, Graziadio C, Giannetta E et al. 2012 Management strategies for aggressive Cushing’s syndrome: from macroadenomas to ectopics. J
Oncol 2012: 685213
5.
Baudry C, Paepegaey AC, Groussin L 2013 Reversal of Cushing’s syndrome by vandetanib in medullary thyroid carcinoma. N Engl J Med 369:
584–586.
6.
Fox E, Widemann BC, Chuk MK et al. 2013 Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated
medullary thyroid carcinoma. Clin Cancer Res 19: 4239–4248.
7.
Samuel A. Wells Jr.,Sylvia L. Asa, Henning Dralle et al. 2015 Revised American Thyroid Association Guidelines for the Management of Medullary
Thyroid Carcinoma : The American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma. Thyroid 25(6): 567-610.
8.
Sheikh-Ali M, Krishna M, Lloyd R et al. 2007 Predicting the development of Cushing's syndrome in medullary thyroid cancer: utility of
proopiomelanocortin messenger ribonucleic acid in situ hybridization. Thyroid.;17(7):631-6.