Serum TSH as a novel predictor of thyroid malignancy?


Title Serum Thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by a fine-needle aspiration.

Authors: Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, & Franklyn JA.

Reference: Journal of Clinical Endocrinology and Metabolism 91: 4295-4301, 2006



Thyroid nodules are common but thyroid malignancy is rare. Predictors of malignancy include historical information, FNA result and US findings.


The objective of the study was to asses clinical and biochemical information that can predict the probability of malignancy in thyroid nodules.

Material and methods

1,500 consecutive patients with goiter including diffuse thyroid enlargement, multiple nodules and solitary nodules, were studied between 1984 and 2002. All patients were evaluated by FNA and serum TSH measurement. Serum TSH was measured in a sensitive assay and final cytologic or histologic diagnosis was determined after surgery in 553 patients or a minimum 2-year clinical follow-up.


The overall sensitivity and specificity of FNA in predicting malignancy were 88 and 84 percent, respectively. The risk of diagnosis of malignancy rose in parallel with the serum TSH at presentation, with significant increases evident in patients > 0.9, compared with those with lower TSH. The findings suggest that independent risk factors for thyroid malignancy include patient-s gender, age, goiter type, and serum TSH level.


The risk of malignancy in a thyroid nodule increases with serum TSH concentration within the normal range. This finding can serve as an adjunct to FNA in predicting risk of thyroid malignancy.


Features that help predict malignancy in thyroid nodules include hard nodule on palpation, rapid growth of a nodule, a history of prior head/neck radiation, and age <20 or > 70 years. Additionally, clinically solitary nodules are more likely to be malignant than multinodular goiters. Of note, approximately 50% of patients with a single nodule on palpation have other nodules when examined by US. Clearly, FNA is the gold standard in the evaluation of patients with thyroid nodules. The recent guidelines published by the American Association of Clinical Endocrinologists (AACE) and American Thyroid Association (ATA) suggest that evaluation of all patients with thyroid nodules should include TSH measurement, US examination, and FNA biopsy.

In this report, serum TSH concentration, even when within the normal range, is shown to be an independent predictor for thyroid malignancy. The authors use TSH to calculate the risk of malignancy in a hypothetical patient with differing TSH levels: a 40-year old woman with a solitary nodule and serum TSH 0.3 has a calculated risk of malignancy at 8.1%; the same patient with serum TSH 3.0 has a malignancy risk of 14.6%; and if serum TSH is 6.0, that risk increases to 26.4%. The results illustrate that predicted probability of diagnosis of cancer increases from <10% for serum TSH level at the lower end of normal range up to 25% if the same patient has a TSH at the upper end of normal range. Of note, between 1984 and 2002 these authors did not use routine US examinations for thyroid evaluation. Moreover, the final diagnosis of benign or malignant disease was not confirmed histologically in all subjects. TSH is necessary to maintain normal thyroid function and growth. It is also established that TSH has a growth-promoting effect on differentiated thyroid cancer and its suppression leads to reduced cancer recurrence and mortality. In this context, the observation by Boelaert and colleagues is important because they suggests that higher TSH levels , by inducing thyroid cell growth, increase the risk of cancer in patients with thyroid nodules. The serum TSH concentration data by Boelaert et al suggest that patients with serum TSH levels in the high-normal range should be more carefully evaluated and followed. More prospective studies are required to confirm this important observation. ( Summary and commentary prepared by Hossein Gharib ) Present summary and commentary are related to Chapter N- 18 of TDM Full paper obtainable at

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