American Thyroid Association Continues to Recommend Levothyroxine as First-Line Therapy for Hypothyroidism

This article is Part I in a series covering the American Thyroid Association guidelines on the treatment of hypothyroidism. This section covers recommendations regarding levothyroxine therapy.

Standard of Care and Goals for Treating Hypothyroidism
In reviewing the latest literature on hypothyroidism treatment, the American Thyroid Association (ATA) concluded that levothyroxine should remain the current standard of care, noting that no consistently strong evidence supports the superiority of alternative therapies. The goal of levothyroxine treatment should be to improve the biologic and physiologic markers of hypothyroidism, achieve normalization of serum TSH level, and avoid over-treatment.

How Should Efficacy of Levothyroxine Be Measured?
While it may be helpful to follow clinical symptoms over time (eg, cold sensitivity, dry skin, constipation), these symptoms lack the sensitivity and specificity to judge the adequacy of levothyroxine therapy and should be considered in the context of serum TSH values, relevant comorbidities, and other biochemical assessments. In addition, routine clinical use of tissue biomarkers of thyroid hormone action is not recommended.  Patients treated for hypothyroidism with levothyroxine may have T3 levels at the lower end or below the reference range even if TSH is normal.  However, the clinical significance of this is not known.

It is recommended that patients not switch between formulations of levothyroxine if possible because of differences in therapeutic equivalence that could lead to changes in serum TSH level. Patients who do undergo changes in levothyroxine formulations should be re-evaluated for serum TSH levels. Use of gelatin capsule formulations to promote absorption is not recommended because of a lack of long-term controlled studies assessing outcomes.

Optimal Dosing of Levothyroxine
The starting dose of levothyroxine should be based on the patient’s weight, lean body mass, pregnancy status, etiology of hypothyroidism, degree of TSH elevation, age, general clinical context (eg, cardiac disease), and serum TSH goal, according to the ATA. Treatment can begin with a full replacement dose, or by starting with a low dose and titrating higher to achieve serum TSH goals.  This latter strategy may be especially helpful for patients who are elderly or have cardiovascular disease. Levothyroxine dosage may need to be adjusted if there are large changes in body weight, aging, and pregnancy.

The dose should be given consistently either 60 minutes before breakfast or at bedtime for optimal absorption, and should not be given at the same time as medications and supplements that might interfere with absorption (eg, aluminum-containing antacids, calcium carbonate, ferrous sulfate, phosphate binders, proton pump inhibitors, and sucralfate).

Patients who require higher than expected levothyroxine levels should be evaluated for gastrointestinal disorders, including Helicobacter pylori–related gastritis, atrophic gastritis, or celiac disease. Re-evaluation of thyroid function and levothyroxine dose should be performed following treatment of these conditions.

For the minority of patients who achieve normal serum TSH values with levothyroxine treatment but still report residual symptoms, the ATA recommends acknowledging patients’ symptoms and evaluating the patients for other potential causes of the symptoms. The ATA encourages future research into subgroups of patients who might benefit from combination therapy.

Thyrotoxicosis can lead to atrial fibrillation and osteoporosis. Thus, the ATA recommends avoiding excess thyroid hormone levels as well as subnormal serum TSH values (eg, <0.1 mIU/L), especially in the elderly and postmenopausal women. On the other hand, under-treatment with levothyroxine can lead to dyslipidemia and progression of cardiovascular disease.

Patients who are allergic to or intolerant of levothyroxine can be managed with a dose, formulation change (eg, gel capsules), or product change and may possibly benefit from treating concomitant iron deficiency anemia. 

Reassess TSH Level With Initiation of Select Concomitant Medications
Reassessment of serum TSH at steady state should be performed during levothyroxine treatment in patients starting or discontinuing estrogen or androgen therapy, as well as when starting carbamazepine, phenobarbital, phenytoin, rifampin, sertraline, and tyrosine kinase inhibitors (and other agents that affect thyroxine metabolism and thyroxine or triiodothyronine deiodination).

March 12, 2015

American Thyroid Association Hypothyroidism Guideline Summary Continues at:

Part II: American Thyroid Association Guideline for Treatment of Hypothyroidism

Part III: American Thyroid Association Guideline: Treatment of Hypothyroidism Other Than Levothyroxine Monotherapy

Part IV: American Thyroid Association Guideline: Treatment of Hospitalized Patients with Hypothyroidism and Use of Thyroid Hormone Analogs

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