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11 Unanswered Questions UNANSWERED QUESTIONS (Areas Needing Further Research) Î The significance of perturbations in serum triiodothyronine concentrations within the reference range or of mildly low serum triiodothyronine concentrations is unknown. Î Patients with hypothyroidism treated with levothyroxine to achieve normal serum TSH values may have serum triiodothyronine concentrations that are at the lower end of the reference range, or even below the reference range. The clinical significance of this is unknown. Î There are specific instances in which there appears to be discordance between the thyroid status of the pituitary gland, as reflected by the serum TSH, and the thyroid status of other tissues as indicated by various biomarkers. The clinical significance of this is not known. Î Specific polymorphisms in the deiodinases are consistently associated with very small changes in serum thyroid hormone levels. Insufficient data exist to draw any conclusion about the clinically relevant effects of deiodinase or transporter polymorphisms on tissue thyroid hormone levels.

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