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1 Treatment LEVOTHYROXINE THERAPY Î Levothyroxine is recommended as the preparation of choice for the treatment of hypothyroidism due to its efficacy in resolving the symptoms of hypothyroidism, long-term experience of its benefits, favorable side effect profile, ease of administration, good intestinal absorption, long serum half-life, and low cost. (S-M) Î Levothyroxine replacement therapy has three main goals. These are: • To provide resolution of the patients' symptoms and hypothyroid signs, including biological and physiologic markers of hypothyroidism • To achieve normalization of serum TSH with improvement in thyroid hormone concentrations • To avoid overtreatment (iatrogenic thyrotoxicosis), especially in the elderly. (S-M) Î Although it may be helpful to follow changes in clinical symptoms longitudinally in patients treated for hypothyroidism, symptoms alone lack sensitivity and specificity and therefore are not recommended for judging adequacy of replacement in the absence of biochemical assessment. Therefore, symptoms should be followed but considered in the context of serum TSH values, relevant comorbidities, and other potential causes. (W-L) Î Tissue biomarkers of thyroid hormone action are not recommended for routine clinical use, outside of the research setting, since these parameters are not sensitive, specific, readily available, or standardized. (W-L) Î Prescription of brand name levothyroxine, or alternatively maintenance of the same generic preparation (i.e., maintenance of an identifiable formulation of levothyroxine [See Table 1]), is advised. • General populations (W-L) • Frail patients, high-risk thyroid cancer patients, pregnant patients (S-L) • Early childhood hypothyroidism (S-M) Note: Switches between levothyroxine products could potentially result in variations in the administered dose and should generally be avoided for that reason. Î Because use of different levothyroxine products may sometimes be associated with altered serum TSH values, a change in an identifiable formulation of levothyroxine (brand name or generic [See Table 1]) should be followed by re-evaluation of serum TSH at steady state. (W-L) Î Although there are preliminary small studies suggesting that levothyroxine dissolved in glycerin and supplied in gelatin capsules may be better absorbed than standard levothyroxine in selected circumstances such as concomitant use of proton pump inhibitors or concomitant coffee consumption, the present lack of controlled long- term outcome studies does not support a recommendation for the use of such preparations in these circumstances. (W-L) Note: Switch to a gel capsule might be considered in the rare case of putative allergies to excipients.

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