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Open Access Research article

Comparison of metabolic ratios of urinary estrogens between benign and malignant thyroid tumors in postmenopausal women

Ju-Yeon Moon12, Eun Jig Lee3, Woong Youn Chung4, Myeong Hee Moon2, Bong Chul Chung1 and Man Ho Choi1*

Author Affiliations

1 Future Convergence Research Division, Korea Institute of Science and Technology, 39–1 Hawolkok-dong, Seoul 136-791, Korea

2 Department of Chemistry, Yonsei University, Seoul 120-749, Korea

3 Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Korea

4 Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea

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BMC Clinical Pathology 2013, 13:25  doi:10.1186/1472-6890-13-25

Published: 25 October 2013

Abstract

Background

Estrogen metabolism may be associated with the pathophysiological development of papillary thyroid carcinoma (PTC).

Methods

To evaluate the differential estrogen metabolism between benign and malignant PTCs, estrogen profiling by gas chromatography–mass spectrometry was applied to urine samples from postmenopausal patients with 9 benign tumors and 18 malignant stage I and III/IV PTCs.

Results

The urinary concentration of 2-methoxyestradiol was significantly lower in the stage I malignant patients (3.5-fold; P < 0.025) than in the benign group. The metabolic ratios of 16α-OH-estrone/estrone and estriol/estradiol, which are responsible for 16α-hydroxylase activity, were increased more than 2.5-fold in the advanced-stage malignant PTC (P < 0.02 each). The more than 6.2-fold decrease in the urinary 2-/16α-hydroxylase ratio in stage III/IV malignant PTC was consistent with the ratio in postmenopausal patients with endocrine gland cancers. In addition, reductive 17β-hydroxysteroid dehydrogenase (17β-HSD; estradiol/estrone or estriol/16α-OH-estrone) was present at significantly higher levels in subjects with stage III/IV malignant PTCs than in benign subjects (>3.5-fold difference; P < 0.002). In particular, the estriol/16α-OH-estrone ratio differentiated between the benign and early-stage malignant patients (P < 0.01).

Conclusions

Increased 16α-hydroxylation and/or a decreased 2-/16α-ratio, as well increased reductive 17β-HSD, with regard to estrogen metabolism could provide potential biomarkers. The devised profiles could be useful for differentiating malignant thyroid carcinomas from benign adenomas in postmenopausal women.

Keywords:
Estrogens; Postmenopause; Thyroid cancer; 16α-hydroxylation; 17β-hydroxysteroid dehydrogenase