Although only thyrotropin values at the time of nodule diagnosis and most recent thyrotropin values were analyzed, thyrotropin trends over time were considered. Some patients did have transient abnormal thyrotropin values; however, a search of the patients’ records showed that these transient abnormalities did not lead to any initiation of hypothyroidism or hyperthyroidism treatment.
Another consideration is that changes in the sample type processed and in the normal thyrotropin ranges over time could have been confounding variables. However, statistical analyses showed that the abnormal and normal most recent thyrotropin groups did not show any significant differences in sample type or reference range for either the initial or most recent thyrotropin values. Hospitals change the laboratory assays they use for clinical tests over time, but these changes likely did not affect the results of this study.
The data from this study showed similar results to previously reported research. This study found that 6% of patients developed abnormal thyrotropin levels over time. A study of 157 patients with nonfunctioning benign thyroid nodules found that 8.3% of patients developed thyroid dysfunction.5 In another follow-up study on patients with thyroid nodules who were otherwise euthyroid, 2 of 118 patients eventually received treatment for hyperthyroidism.6 In the current study, we report that just 1 of 100 included patients had to begin treatment for hyperthyroidism.
The literature also includes research on using thyrotropin and age to predict malignancy in patients with thyroid nodules. One study suggested that a thyrotropin cutoff point of ≥ 2.1 mU/I and an age cutoff point of ≥ 47 years were significantly associated with a diagnosis of malignancy.7 Although the current study did not study malignancy, the results showed that the mean age at nodule diagnosis was higher in patients who had abnormal vs normal most recent thyrotropin levels: 69 vs 62 years, respectively. Future studies could determine whether a certain initial thyrotropin value or age could be used as a cutoff for requiring further thyrotropin monitoring to check for development of hyperthyroidism or hypothyroidism.
Limitations
This study was limited by its small size of 100 subjects. Most patients had to be excluded to focus on the aim of determining whether thyrotropin monitoring is needed in the specific group of patients without medical history that would be expected to affect thyroid function. Another limitation was that 83% of the patients included in the study were male, which does not reflect the general population. Future studies should include a greater number of patients and aim for a balance of 50% male and 50% female patients.
Additionally, it is important to note that the changing definition of the normal thyrotropin range was a limitation. It is possible that some patients who were considered normal at the time of a particular thyrotropin measurement may have had an abnormal reading if measured at a different time. Another consideration is that the VADHS changed the type of blood sample used to generate thyrotropin values from serum to plasma during the time that analyzed thyrotropin values were measured. This could have led to different thyrotropin values and, therefore, different results of this study compared with if the sample type had stayed the same. However, a previous study showed very similar thyrotropin values generated from serum and plasma samples in 17 patients.8 Therefore, possibly the change in sample type in the current study only minimally affected the results.
CONCLUSIONS
Current American Thyroid Association guidelines do not specify recommendations for follow-up thyrotropin testing in patients with thyroid nodules who do not have a history of conditions or medications known to affect thyroid hormone levels.1 This study suggests that repeat thyrotropin monitoring may not be necessary for this group of patients. Individuals who had an abnormal most recent thyrotropin had an older age at thyroid nodule diagnosis compared with patients who had a normal most recent thyrotropin, so it is possible that thyrotropin monitoring may be recommended for people with nodules who are above a certain age. The results of this study as well as future studies could help create new clinical recommendations for thyrotropin monitoring in patients with thyroid nodules that clinicians can use to make evidence-based clinical decisions. There would also be a decreased financial, physical, and time burden on the patients if guidelines specify that they are not required to get continued blood thyrotropin testing.
Acknowledgments
The authors acknowledge Ronald J. Markert, PhD, formerly of Wright State University Boonshoft School of Medicine, for his contributions to the statistical analysis of this research.