Higher serum TSH in thyroid cancer patients occurs independent of age and correlates with extrathyroidal extension

Division of Metabolism, Endocrinology, and Diabetes (MEND), University of Michigan, Ann Arbor, MI 48109, USA.
Clinical Endocrinology (Impact Factor: 3.46). 09/2009; 71(3):434-9. DOI: 10.1111/j.1365-2265.2008.03489.x
Source: PubMed


It has previously been shown that higher serum TSH is associated with increased thyroid cancer incidence and advanced-stage disease. In the healthy adult population, mean TSH increases with age. As age over 45 years is a known prognostic indicator for thyroid cancer, it is important to know whether higher TSH in patients with thyroid cancer occurs independent of age.
To determine the relationship between higher TSH, cancer and age.
A retrospective cohort study.
A total of 1361 patients underwent thyroid surgery between May 1994 and December 2007 at a single institution. Of these patients, 954 had pathological data, preoperative TSH and complete surgical history available. Data were analysed in relation to age and TSH.
Mean TSH was significantly higher in cancer patients regardless of age < 45 years or >or= 45 years (P = 0.046 and P = 0.027, respectively). When examining age groups < 20, 20-44, 45-59 and >or= 60 years, there was a trend of rising mean TSH with age. Despite the rise in the benign subgroups, mean TSH was consistently higher in those with cancer vs. those without. On multivariate analysis, higher TSH was independently associated with cancer (P = 0.039) and pathological features of Hashimoto's thyroiditis (P = 0.001) but not with age (P = 0.557). On multivariate analysis of high-risk features associated with poor prognosis, there was a significant association between higher TSH and extrathyroidal extension (P = 0.002), whereas there was no clear relationship with age, tumour size > 4 cm, and distant metastases.
Independent of age, thyroid cancer incidence correlates with higher TSH. Higher TSH is associated with extrathyroidal extension of disease.

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    • "Haymart et al. [7] found that the preoperative mean TSH level is significantly higher in patients with a final diagnosis of thyroid cancer. The same group has shown that this relationship is independent from age [13]. Jonklaas et al. [14] reported that this association remained in a strictly euthyroid population (after subclinical hypo- and hyperthyroidism cases were excluded) who underwent thyroid surgery for NTD. "
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    ABSTRACT: We evaluated the preoperative serum thyrotropin (TSH) levels in 386 patients operated on for nodular thyroid disease (NTD). TSH levels for cases with final benign disease and differentiated thyroid carcinoma (DTC) were compared. No evidence of cancer was detected in 310 patients (80.3%), whereas malignancy was present in 76 cases (19.7%). Mean TSH concentration was 1.36 ± 1.62 mU/L in benign patients and 2.08 ± 2.1 in cases with malignant lesions (P = 0.0013). The group of malignancy was subdivided in papillary thyroid carcinoma (PTMC) versus thyroid cancer of larger size (TCLS). Mean TSH was 1.71 ± 1.52 in PTMC and 2.42 ± 2.5 in TCLS. Significant differences were found when all groups (benign, PTMC and TCLS) were compared (P < 0.001). However, pairwise comparisons between them showed that differences were only significant between benign and TCLS groups (P < 0.01). In conclusion, TSH levels were higher in patients with a final diagnosis of DTC. Moreover, it appears that there exists an increment in tumor size as a function of increment in the TSH level.
    Journal of Thyroid Research 01/2012; 2012:530721. DOI:10.1155/2012/530721
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    • "Interestingly, several studies in recent years have demonstrated a strong association of high TSH levels with an increased malignancy risk of thyroid nodules (Boelaert et al. 2006, Haymart et al. 2009). The mechanism of this association has been unclear. "
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    ABSTRACT: Oxidative stress (OS) is a state of excessive free radicals and reactive metabolites among which the most important class is reactive oxygen species (ROS) - radicals derived from oxygen - as represented by the superoxide anion radical (O2(·-)) and its reactive metabolites, hydroxyl radical (·OH) and hydrogen peroxide (H(2)O(2)). In essence, OS represents an imbalance between the production of oxidants - ROS - and their elimination by antioxidative systems in the body. Many studies have linked OS to thyroid cancer by showing its association with abnormally regulated oxidative or antioxidative molecules. The study by Wang et al. in the December 2011 issue of Endocrine-Related Cancer (18, 773-782) further supports this relationship by demonstrating a high total oxidant status and OS index in thyroid cancer patients. The origin of ROS in thyroid cancer patients has not been defined, but thyroid cancer itself can be one since inflammation, a major event in it, is a classical source of ROS. ROS may in turn enhance the mitogen-activated protein (MAP) kinase and phosphatidylinositol-3-kinase (PI3K) pathways, forming a vicious cycle propelling thyroid tumorigenesis. Regardless of the mechanism, the clinical implication of the association of OS with thyroid cancer is severalfold: one, OS is a new risk factor for thyroid cancer; two, OS confers thyroid cancer patients an increased risk for cardiovascular diseases, degenerative neurological disorders, and other cancers that are classically associated with OS; and three, interference with OS may reduce this risk and be therapeutically beneficial to thyroid cancer itself in thyroid cancer patients. These interesting possibilities deserve further studies.
    Endocrine Related Cancer 12/2011; 19(1):C7-11. DOI:10.1530/ERC-11-0360 · 4.81 Impact Factor
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    • "Some studies find Hashimoto thyroiditis as associated with thyroid cancer [22,23] as examples, while others do not report an association [24,25] as examples. Since higher TSH level in patients with thyroid nodules has been found to be associated with risk of differentiated thyroid cancer [26,27], we hypothesized that active remodeling of thyroid epithelium in cytological Hashimoto's may explain in part the increased risk for differentiated thyroid cancer observed in patients with elevated but within normal TSH [26,27]. "
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    ABSTRACT: Our Thyroid-Multidisciplinary Clinic is a large referral site for thyroid diseases. Thyroid biopsies are mainly performed for thyroid cancer screening. Yet, Hashimoto thyroiditis (HT) is being too frequently diagnosed. The prevalence of HT is reported as 0.3-1.2% or twice the prevalence of type 1 diabetes. However, the prevalence of HT confirmed by cytology is still uncertain. To evaluate different aspects of thyroid physiopathology including prevalence of Hashimoto's, a database of clinical features, ultrasound images and cytology results of patients referred for FNA of thyroid nodules was prospectively developed. We retrospectively studied 811 consecutive patients for whom ultrasound guided thyroid FNA biopsies were performed at our clinic over 2.5 year period (Mar/2006-Sep/2008). The analysis of our database revealed that from 761 patients, 102 (13.4%) had HT, from whom 56 (7.4%) were euthyroid or had sub-clinical (non-hypothyroid) disease, and 46 (6%) were clinically hypothyroid. This is the first study to show such a high prevalence of HT diagnosed by ultrasound-guided FNA. More strikingly, the prevalence of euthyroid HT, appears to be >5% similar to that of type 2 diabetes. Based on our results, there might be a need to follow up on cytological Hashimoto's to monitor for thyroid failure, especially in high risk states, like pregnancy. The potential risk for thyroid cancer in patients with biopsy-proven inflammation of thyroid epithelium remains to be established prospectively. However, it may explain the increased risk for thyroid cancer observed in patients with elevated but within normal TSH.
    Thyroid Research 12/2010; 3(1):11. DOI:10.1186/1756-6614-3-11
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