Are endogenously lower serum thyroid hormones new predictors for thyroid malignancy in addition to higher serum thyrotropin?
Department of Endocrinology and Metabolism, Ankara Ataturk Education and Research Hospital, Bilkent, Ankara, Turkey. Endocrine
(Impact Factor: 3.88).
04/2010; 37(2):253-60. DOI: 10.1007/s12020-010-9316-6
It is well known that TSH plays a major role in the secretion of thyroid hormones, maintenance of thyroid specific gene expression, and gland growth. In this study, we aimed to evaluate association between tests of thyroid functions (fT3, fT4, TSH) and differentiated thyroid carcinoma. 441 patients operated for nodular goiter between 2005 and 2008 were analyzed. Thyroid functions were studied in the period of 1-30 days prior to surgery. In postoperative histopathological examination, differentiated thyroid carcinoma and benign thyroid disease were detected in 166 (37.6%) and 275 (62.4%) patients, respectively. Patients with thyroid malignancy had significantly lower serum fT3 (P = 0.001), lower fT4 (P = 0.022), and higher TSH levels (P < 0.001) compared to patients with benign disease, although all analytes were within the normal range. We subdivided by quartile serum fT3, fT4, and TSH in normal limits into three groups. The odds ratio (ORs) for the risk of thyroid cancer with a serum TSH between 0.63 and 1.67 μIU/ml and 1.68-4.00 μIU/ml, compared with a serum TSH between 0.40 and 0.62 μIU/ml were calculated as 2.60 (95% CIs 1.49-4.54) and 6.50 (95% CIs 3.51-12.03), respectively. There was also a greater risk of thyroid cancer in patients with fT3 levels of 1.57-3.00 pg/ml, compared with patients with fT3 levels of 3.89-4.71 pg/ml (OR 2.95, 95% CIs 1.68-5.20). For fT4, OR for the risk of thyroid cancer between 0.85 and 1.17 ng/dl compared with 1.48-1.78 ng/dl was 2.14 (95% CIs 1.22-3.74). In conclusion, lower fT3, fT4, and higher TSH concentrations within normal limits were related with increased thyroid cancer independent from sex and nodule type. Particularly, the association between lower fT3, fT4 levels and a diagnosis of thyroid cancer is a novel finding.
Available from: Marene IB Landström
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ABSTRACT: Anaplastic thyroid carcinoma (ATC) is one of the most malignant tumors in humans, and currently there is no effective treatment. In the present study we investigated the effect of an endogenous estrogen metabolite, 2-methoxyestradiol (2-ME), on the growth of human ATC cells. 2-ME treatment had a strong growth inhibitory effect on five human ATC cell lines (HTh7, HTh 74, HTh83, C643, and SW1736), but showed no effect on one cell line (KAT-4). Cell cycle analysis of the growth-inhibited cells showed that 2-ME induced a G(2)/M-arrest, followed by an increased fraction of cells in sub-G(1). Analysis of internucleosomal DNA laddering as well as DNA fragmentation in a terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay demonstrated a high number of cells undergoing apoptosis after 2-ME treatment. An increased activation of caspase-3 and caspase-8 by 2-ME was observed, and inhibition of caspase-3 decreased the apoptotic effect. Addition of 2-ME increased activity of p38 mitogen-activated protein kinase (MAPK) in the sensitive HTh7 as well as the refractory KAT-4 cells, however, activation of stress-activated protein kinase/c-jun aminoterminal kinase (SAPK/JNK) was seen only in the HTh7 cells. Inhibitors of p38 MABK and SAPK/JNK significantly attenuated the 2-ME effect. Taken together, our data demonstrate an antiproliferative and apoptotic effect of 2-ME on ATC cells involving activation of MAPKs.
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ABSTRACT: There is scant data concerning surgeon-performed thyroid fine-needle aspiration (FNA), and controversy regarding its accuracy in larger nodules. This study aimed to specifically assess accuracy of surgeon-performed ultrasound (US)-guided FNA on a per-nodule basis, with a subanalysis of nodule size.
Data of 1,000 surgeon-performed US-guided thyroid FNAs at a single institution from 2000 to 2010 were prospectively collected. Standard clinical information, FNA results using the Bethesda criteria, and final histology were recorded.
Fine-needle aspiration results were reported as: cancer (7%), suspicious for cancer (2%), suspicious for follicular neoplasm (17%), atypia of unknown significance (AUS) (1%), benign (67%), and insufficient (6%). Of nodules with FNA results of cancer, suspicious for cancer, suspicious for follicular neoplasm, and atypia of unknown significance, 94% were operated on, with malignancy rates of 97%, 58%, 21%, and 12%, respectively. Of nodules with benign FNA, 26% underwent surgery for associated symptoms, concerning features, or other remote pathology. A total of 56% were followed, and 18% were lost to follow-up. Of nodules with insufficient FNA, 46% had repeat FNA (yielding a diagnosis in 81%), 23% underwent surgery, 21% with hypocellular features were followed, and 9% were lost to follow-up. In size subanalysis, there was no statistically significant difference in risk of malignancy or increased rate of falsely negative FNA with increasing nodule size.
The Bethesda system appropriately stratified lesions for risk of malignancy, and repeat FNA had high diagnostic yield in lesions with inadequate FNA. The results suggest no trend toward larger lesions harboring thyroid malignancy nor an increased likelihood of false-negative benign FNA.
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ABSTRACT: TSH is the main factor involved in the control of proliferation of thyrocytes. Recently, a strong relationship between serum TSH and risk of thyroid malignancy has been reported.
The aim was to review published papers about the relationship between serum TSH and frequency of differentiated thyroid cancer.
PubMed was used to identify studies focused on the relationship between TSH and differentiated thyroid cancer.
In patients with nodular thyroid disease, the risk of thyroid malignancy increases with serum TSH, and even within normal ranges, higher TSH values are associated with a higher frequency and more advanced stage of thyroid cancer. The likelihood of papillary thyroid carcinoma is reduced when TSH is lower, as in thyroid autonomy, and increased when TSH is higher, as in thyroid autoimmunity. Treatment with l-thyroxine (LT4), which reduces serum TSH, is associated with significantly lower risk of developing clinically detectable thyroid cancer.
TSH plays a key role in the development of clinically detectable thyroid cancer, and LT4 treatment reduces the risk of thyroid malignancy in patients with nodular thyroid disease. According to the guidelines of the main scientific societies, LT4 therapy is not currently recommended for the treatment of patients with nodular goiter. Even if the available data are not sufficient to advise LT4 treatment in all patients with nodular goiter with the aim of reducing the risk of papillary thyroid carcinoma, we propose that this indication should be reconsidered, taking into account recent evidence reported in the literature.
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