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      We thank Santhanam for his interesting thoughts on our study.
      • Pecina J.
      • Garrison G.M.
      • Bernard M.E.
      Levothyroxine Dosage Is Associated with Stability of Thyroid-stimulating Hormone Values.
      While we are aware that there is significant controversy in the literature on what constitutes the upper limits of normal for a thyroid-stimulating hormone (TSH) value, we chose to use the range of 0.3-5.0 mIU/L to define normal in our study, as this is the reference range for the test used at our institution. This is in accordance with the 2012 American Association of Clinical Endocrinologist's guidelines for management of hypothyroidism state, “In patients who are not pregnant, the target range should be within the normal range. If upper and lower normal values for a third generation TSH assay are not available [emphasis added], the range used should be based on the NHANES [National Health and Nutrition Examination Survey] III reference population range of 0.45-4.12.”
      • Garber J.R.
      • Cobin R.H.
      • Gharib H.
      • et al.
      Clinical Practice Guidelines for Hypothyroidism in Adults: Co-sponsored by American Association of Clinical Endocrinologists and the American Thyroid Association.
      We agree with Santhanam's insightful comment that lower levothyroxine dosages could be a surrogate marker for some patients having subclinical hypothyroidism rather than overt hypothyroidism. However, we do not feel this changes the important finding of our study that in our Cox Proportional Hazard Model, we found that both levothyroxine dose >125 μg/d, and a TSH further from the midpoint of the normal range were associated with higher odds of an abnormal TSH test sooner than patients on low-dose levothyroxine with mid-range TSH values.
      • Pecina J.
      • Garrison G.M.
      • Bernard M.E.
      Levothyroxine Dosage Is Associated with Stability of Thyroid-stimulating Hormone Values.
      The fact remains that all the patients in the study were diagnosed with hypothyroidism (whether subclinical or not) and treated with replacement therapy. Thus, they all require periodic monitoring typically performed by their primary care physician. Our findings are clinically useful evidence to support monitoring patients with mid-range TSH values on low-dose levothyroxine less frequently than patients on higher-dose levothyroxine or those who have borderline TSH values.

      References

        • Pecina J.
        • Garrison G.M.
        • Bernard M.E.
        Levothyroxine Dosage Is Associated with Stability of Thyroid-stimulating Hormone Values.
        Am J Med. 2014; 127: 240-245
        • Garber J.R.
        • Cobin R.H.
        • Gharib H.
        • et al.
        Clinical Practice Guidelines for Hypothyroidism in Adults: Co-sponsored by American Association of Clinical Endocrinologists and the American Thyroid Association.
        Endocr Pract. 2012; : 1-207

      Linked Article

      • Levothyroxine Dose and Measurement of TSH
        The American Journal of MedicineVol. 128Issue 1
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          The article by Pecina et al1 raises several issues that need further clarification, especially in the light of the new guidelines by the American Association of Clinical Endocrinologists for management of hypothyroidism.2 The reference range of thyroid stimulating hormone (TSH) used in the study to classify the normal range (0.3-5.0) may not be entirely accurate given that the National Health and Nutrition Examination Surveys III (NHANES III) database has shown significant ethnic and age-related differences in the 97.5th percentile values of TSH, with the upper limit of TSH being 4.5 mIU/L.
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