Title

Treatment of Hypothyroidism

Authoring Organization

American Thyroid Association

Publication Month/Year

December 12, 2014

Last Updated Month/Year

October 17, 2024

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps.

Target Provider Population

Clinicians providing care to patients with hypothyroidism

PICO Questions

  1. Is levothyroxine monotherapy considered to be the standard of care for hypothyroidism?

  2. What are the clinical and biochemical goals for levothyroxine replacement in primary hypothyroidism?

  3. Are clinical parameters such as cold sensitivity and dry skin useful by themselves for assessing adequacy of levothyroxine replacement in primary hypothyroidism?

  4. Are tissue markers of thyroid hormone action helpful in determining the adequacy of levothyroxine replacement in primary hypothyroidism?

  5. Is there a clinical rationale for prescribing brand-name levothyroxine preparations in preference to generic levothyroxine?

  6. Are there situations in which therapy with levothyroxine dissolved in glycerin and supplied in gelatin capsules may have advantages over standard levothyroxine?

  7. How should levothyroxine administration be timed with respect to meals and beverages in order to maintain maximum, consistent absorption?

  8. Are there medications and supplements that should not be co-administered with levothyroxine in order to avoid impaired absorption?

  9. Are there gastrointestinal conditions that should be considered when a patient's levothyroxine dose is much higher than expected?

  10. Are different levothyroxine products associated with different absorption, such that a switch to a different brand name or generic is associated with a significantly different serum thyrotropin?

  11. What medications may alter a patient's levothyroxine requirement by affecting either metabolism or binding to transport proteins?

  12. What factors determine the levothyroxine dose required by a hypothyroid patient for reaching the appropriate serum thyrotropin goal?

  13. What is the best approach to initiating and adjusting levothyroxine therapy?

  14. What are the potential deleterious effects of excessive levothyroxine?

  15. What are the potential deleterious effects of inadequate levothyroxine?

  16. What is the appropriate management of perceived allergy to the constituents of levothyroxine or intolerance to levothyroxine?

  17. How do co-existent medical conditions (e.g., atherosclerotic coronary artery disease) affect the management of levothyroxine replacement therapy?

  18. How do coexistent psychosocial, behavioral, and mental health conditions (such as addiction, somatization disorder, and depression) affect the management of levothyroxine therapy?

  19. How should levothyroxine therapy be managed in the elderly with hypothyroidism?

  20. How should levothyroxine therapy be managed in pregnant women with hypothyroidism?

  21. How should levothyroxine therapy be managed in infants and children with overt hypothyroidism?

  22. How should levothyroxine therapy be managed in children with subclinical hypothyroidism?

  23. How should levothyroxine therapy be managed in individuals who have elevated thyrotropin values due to nonadherence?

  24. Are variations in serum triiodothyronine concentrations within the reference range of physiologic or clinical significance?

  25. Does levothyroxine therapy that returns the serum thyrotropin levels of hypothyroid patients to the reference range also result in normalization of their serum triiodothyronine levels?

  26. Is there evidence of discordance between the thyroid hormone status of different tissues and the serum thyrotropin concentration?

  27. Should levothyroxine therapy for hypothyroidism, particularly in specific subgroups such as those with obesity, depression, dyslipidemia, or who are athyreotic, be targeted to achieve high-normal serum triiodothyronine levels or low-normal serum thyrotropin levels?

  28. What biochemical goals should be employed for levothyroxine replacement in patients with secondary hypothyroidism?

  29. Are clinical parameters useful for assessing adequacy of levothyroxine replacement in patients with secondary hypothyroidism?

  30. Are tissue markers of thyroid hormone action helpful for management of levothyroxine replacement in patients with secondary hypothyroidism?

  31. What tools may be useful in the clinical or research setting, to measure the impact of levothyroxine replacement for primary hypothyroidism on patients' physical or psychological well-being, treatment satisfaction, or treatment preferences?

  32. What approach should be taken in patients treated for hypothyroidism who have normal serum thyrotropin values but still have unresolved symptoms?

  33. Is there a role for the use of levothyroxine to treat biochemically euthyroid patients with symptoms that overlap with those of hypothyroidism?

  34. Is there a role for the use of levothyroxine to treat euthyroid patients with depression?

  35. Is there a role for the use of levothyroxine to treat euthyroid patients with obesity?

  36. Is there a role for the use of levothyroxine to treat euthyroid patients with urticaria?

  37. What is the recommended approach to treating factitious thyrotoxicosis?

  38. What are the ethical obligations of clinicians in treating hypothyroidism?

  39. In adults requiring thyroid hormone replacement treatment for primary hypothyroidism, is treatment with thyroid extracts superior to treatment with levothyroxine alone?

  40. Do genetic variants in thyroid hormone pathway genes (deiodinases or thyroid hormone transporters) affect the serum or tissue levels of thyroid hormones in healthy euthyroid individuals or hypothyroid patients taking replacement therapy?

  41. In adults requiring thyroid hormone replacement treatment for primary hypothyroidism, is combination treatment including levothyroxine and liothyronine superior to the use of levothyroxine alone?

  42. In adults requiring thyroid hormone replacement treatment for primary hypothyroidism who feel unwell while taking levothyroxine, is combination treatment including levothyroxine and liothyronine superior to the use of levothyroxine alone?

  43. Should genetic characterization according to type 2 deiodinase gene polymorphism status be used to guide the use of combination synthetic levothyroxine and liothyronine therapy in hypothyroidism, in order to optimize biochemical and clinical outcomes?

  44. Are there data regarding therapy with triiodothyronine alone, either as standard liothyronine or as sustained release triiodothyronine, that support the use of triiodothyronine therapy alone for the treatment of hypothyroidism?

  45. Is there a role for the use of liothyronine to treat biochemically euthyroid patients with depression?

  46. Is there a role for the use of liothyronine to treat biochemically euthyroid patients with obesity?

  47. What is the recommendation regarding therapy with compounded thyroid hormones (either levothyroxine or liothyronine) for treatment of hypothyroidism based on current evidence?

  48. Is there a role for the use of dietary supplementation, nutraceuticals, and over-the-counter products in either hypothyroid or euthyroid individuals?

  49. What are the research ethics issues involved in evaluating or designing clinical trials for the treatment of hypothyroidism?

  50. Is there evidence for the existence of “Wilson's temperature syndrome” and a rationale for use of escalating doses of triiodothyronine?

  51. In hospitalized but not critically ill patients with known pre-existing hypothyroidism, should levothyroxine therapy be re-evaluated based on an elevated serum thyrotropin measurement?

  52. In hospitalized but not critically ill patients in whom levothyroxine replacement is instituted or increased, should the therapeutic goal be normalization of serum thyrotropin?

  53. In hospitalized but not critically ill patients treated with levothyroxine replacement what formulation and route of administration are recommended?

  54. In hospitalized but not critically ill patients about to be treated with levothyroxine should the possibility of adrenal insufficiency be excluded?

  55. In patients with myxedema coma being treated with levothyroxine, what route of administration should be used?

  56. In patients with myxedema coma being treated with levothyroxine, should empiric glucocorticoid coverage be provided?

  57. In patients with myxedema coma being treated with levothyroxine, should liothyronine therapy also be initiated?

  58. In patients with myxedema coma being treated with levothyroxine, what therapeutic endpoints should be targeted?

  59. In hospitalized adult patients exhibiting the “nonthyroidal illness syndrome,” should thyroid hormone replacement be instituted with levothyroxine?

  60. In hospitalized adult patients with cardiac dysfunction, such as advanced heart failure, and low serum triiodothyronine concentrations, should thyroid hormone replacement be instituted with liothyronine?

  61. Should thyroid hormone analog therapy be used in euthyroid individuals with non–hypothyroid-related medical conditions (such as dyslipidemia) based on current evidence?

  62. What are the clinical and biochemical goals for treatment of patients who have genetic syndromes of resistance to thyroid hormone?

  63. What is the role of thyroid hormone analogs in treating patients who have genetic syndromes of resistance to thyroid hormone?

Inclusion Criteria

Male, Female, Adolescent, Adult, Child, Infant, Older adult

Health Care Settings

Ambulatory

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Treatment, Management

Keywords

hypothyroidism, thyroid stimulating hormone (TSH), hypothyroid, FNA