Outcome variables included TSH levels in the therapeutic range vs outside of the therapeutic range. This study was approved under the Mayo Clinic IRB protocol #09-008343.
Statistical analysis
We used a Student’s t-test to identify any association between age or BMI and a normal repeat TSH value, and a chi-square calculation to test for an association between medication dosage or sex and TSH level at follow-up. We used multiple logistic regression analysis to estimate adjusted odds ratios (ORs) for each independent variable.
Results
Three hundred eighty-six (85.4%) patients were women and 66 (14.6%) were men. Three hundred ten patients were taking levothyroxine at <125 mcg/d, and 142 patients were taking dosages ≥125 mcg/d. At approximately one year, 85.6% of all patients had a normal repeat TSH level.
Results of the 2-way tests are shown in TABLE 1. We found no mean differences in age, sex, or BMI between patients with normal repeat TSH levels and those with abnormal levels at follow-up. However, the percentage of normal repeat TSH values was inversely proportional to medication dosage (P=.01). Of patients whose dosage was <75 mcg/d, 90.8% had normal repeat TSH values, compared with 77.5% of patients taking ≥125 mcg/d. Percentages of low, normal, and high TSH values for each dosage range are shown in TABLE 2.
These findings were confirmed with multiple logistic regression analysis (TABLE 3). Age at index, BMI at index, and sex were not significantly associated with normal TSH at follow-up. However, patients with dosages ≥125 mcg/d had significantly lower odds of normal repeat TSH (OR=0.31, 95% confidence interval [CI]=0.13-0.76, P=.01).
Table 1
Normal TSH levels at one year were more often associated with levothyroxine dosages <125 mcg/d
| TSH normal* | TSH not normal | N | P value | |
|---|---|---|---|---|
| Age at index, mean | 54.7 | 54.9 | 452 | .91 |
| BMI at index, mean | 28.9 | 29.0 | 452 | .93 |
| Sex, % | .57 | |||
| Women | 85.2 | 14.8 | 386 | |
| Men | 87.9 | 12.1 | 66 | |
| Total | 85.6 | 14.4 | 352 | |
| Dosage, mcg/d | .01 | |||
| 0–74.9 | 90.8 | 9.2 | 76 | |
| 75–99.9 | 89.6 | 10.4 | 106 | |
| 100–124.9 | 88.3 | 11.7 | 128 | |
| ≥125 | 77.5 | 22.5 | 142 | |
| Total | 85.6 | 14.4 | 452 | |
| BMI, body mass index; TSH, thyroid-stimulating hormone. *Normal range=0.3-5.0 mIU/L. | ||||
Table 2
Levothyroxine dosages and associated TSH levels* at one year follow-up
| Dosage, mcg/d | Low TSH, n (%) | Normal TSH, n (%) | High TSH, n (%) | Total, n |
|---|---|---|---|---|
| 0-74.9 | 0 | 69 (90.8%) | 7 (9.2%) | 76 |
| 75-99.9 | 5 (4.7%) | 95 (89.6%) | 6 (5.7%) | 106 |
| 100-124.9 | 9 (7.0%) | 113 (88.3%) | 6 (4.7%) | 128 |
| ≥125 | 22 (15.5%) | 110 (77.5%) | 10 (7.0%) | 142 |
| Total | 36 (8.0%) | 387 (85.6%) | 29 (6.4%) | 452 |
| TSH, thyroid-stimulating hormone. *Low TSH=<0.3 mIU/L; normal TSH=0.3-5.0 mIU/L; high TSH=>5.0 mIU/L. | ||||
Table 3
Patients with dosages ≥125 mcg/d had significantly lower odds of normal repeat TSH* (N=452)
| Variable | Odds ratio | Confidence interval | P value |
|---|---|---|---|
| Age at index | 0.99 | 0.98-1.01 | .46 |
| BMI at index | 1.02 | 0.98-1.05 | .41 |
| Men (vs women) | 1.53 | 0.68-3.48 | .31 |
| Dosage, mcg/d | |||
| 0–74.9 | 1 | ||
| 75–99.9 | 0.87 | 0.32-2.37 | .79 |
| 100–124.9 | 0.76 | 0.29-1.97 | .58 |
| ≥125 | 0.31 | 0.13-0.76 | .01 |
| BMI, body mass index; TSH, thyroid-stimulating hormone. *Using multiple logistic regression analysis. | |||
DISCUSSION
Our retrospective study showed that patients taking <125 mcg/d levothyroxine were likely to have a normal TSH value at one year. Thus we propose that TSH values may be measured less frequently in this population. Given that the fee for testing TSH averages $50, there is potential for savings in costs, as well as in patient and provider time. A prospective, randomized controlled trial of less frequent TSH measurements in asymptomatic patients treated for hypothyroidism with replacement levothyroxine <125 mcg/d would yield more definitive conclusions.
Our study also revealed that patients requiring ≥125 mcg/d levothyroxine were less likely than patients requiring lower dosages to have a normal repeat TSH value at one year. The reasons for this are unclear. Although excess body weight may be a reason for patients to be on higher replacement dosages, we did not find BMI to be predictive of continued normal TSH values after one year. Other potential reasons for patients to require higher dosages of thyroid replacement include noncompliance, drug interference, and malabsorption.12 A change in any of these factors could presumably lead to a change in thyroid replacement needs and a change in TSH upon recheck one year later. Based on this finding, we suggest that TSH levels for patients requiring ≥125 mcg/d levothyroxine be repeated at maximum intervals of 12 months.
Limitations of this study
Study limitations were primarily a consequence of the retrospective design. Selection bias may have occurred by capturing patients with higher compliance. Patients who had repeat testing approximately one year later may reflect a population with more monitoring and better medication adherence. Interestingly, our retrospective review revealed that a large number of patients in our study did not have an annual TSH measurement; out of the 780 patients initially identified with a normal TSH value in 2006, 177 (23%) had repeat TSH values obtained more than 14 months later.
Other limitations of this study include an inability to control for, or detect, any changes in levothyroxine brand between the 2 data points. Because different levothyroxine formulations may differ in bioequivalence, a change in brands between measured values has the potential to affect outcomes.7 Additionally, the retrospective design could not address whether patients had any concurrent symptoms of over- or undertreated hypothyroidism or had sustained a serious, recent health status change that may have affected their TSH levels. Another limitation was the possible inclusion of women started on levothyroxine replacement for postpartum thyroiditis who may have subsequently recovered full thyroid function but continued on levothyroxine treatment.