Applied Evidence

Refining your approach to hypothyroidism treatment

J Fam Pract. 2020 March;69(2):84-89

References

1. Aoki Y, Belin RM, Clickner R, et al. Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002). Thyroid. 2007;17:1211-1223.

2. Vaidya B, Pearce SH. Management of hypothyroidism in adults. BMJ. 2008;337:a801.

3. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18:988-1028.

4. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014;24:1670-1751.

5. Toft AD. Thyroxine therapy. N Engl J Med. 1994;331:174-180.

6. Floriani C, Gencer B, Collet TH, et al. Subclinical thyroid dysfunction and cardiovascular diseases: 2016 update. Eur Heart J. 2018;39:503-507.

7. Lexi-Comp, Inc. (Lexi-Drugs®). https://online.lexi.com/lco/action/login. Accessed July 7, 2017.

8. Okosieme O, Gilbert J, Abraham P, et al. Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee. Clin Endocrinol (Oxf). 2016;84:799-808.

9. Fish LH, Schwartz HL, Cavanaugh J, et al. Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. Role of triiodothyronine in pituitary feedback in humans. N Engl J Med. 1987;316:764-770.

10. John-Kalarickal J, Pearlman G, Carlson HE. New medications which decrease levothyroxine absorption. Thyroid. 2007;17:763-765.

11. Sachmechi I, Reich DM, Aninyei M, et al. Effect of proton pump inhibitors on serum thyroid-stimulating hormone level in euthyroid patients treated with levothyroxine for hypothyroidism. Endocr Pract. 2007;13:345-349.

12. Sperber AD, Liel Y. Evidence for interference with the intestinal absorption of levothyroxine sodium by aluminum hydroxide. Arch Intern Med. 1992;152:183-184.

13. Zamfirescu I, Carlson HE. Absorption of levothyroxine when coadministered with various calcium formulations. Thyroid. 2011;21:483-486.

14. Campbell NR, Hasinoff BB, Stalts H, et al. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med. 1992;117:1010-1013.

15. Bugdaci MS, Zuhur SS, Sokmen M, et al. The role of Helicobacter pylori in patients with hypothyroidism in whom could not be achieved normal thyrotropin levels despite treatment with high doses of thyroxine. Helicobacter. 2011;16:124-130.

16. Centanni M, Gargano L, Canettieri G, et al. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med. 2006;354:1787-1795.

17. Centanni M, Marignani M, Gargano L, et al. Atrophic body gastritis in patients with autoimmune thyroid disease: an underdiagnosed association. Arch Intern Med. 1999;159:1726-1730.

18. Collins D, Wilcox R, Nathan M, et al. Celiac disease and hypothyroidism. Am J Med. 2012;125:278-282.

19. Azizi F, Belur R, Albano J. Malabsorption of thyroid hormones after jejunoileal bypass for obesity. Ann Intern Med. 1979;90:941-942.

20. Gkotsina M, Michalaki M, Mamali I, et al. Improved levothyroxine pharmacokinetics after bariatric surgery. Thyroid. 2013;23:414-419.

21. Hennessey JV, Espaillat R. Diagnosis and management of subclinical hypothyroidism in elderly adults: a review of the literature. J Am Geriatr Soc. 2015;63:1663-1673.

22. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017;27:315-389.

23. Carney LA, Quinlan JD, West JM. Thyroid disease in pregnancy. Am Fam Physician. 2014;89:273-278.

24. Fröhlich E, Wahl R. Thyroid autoimmunity: role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Front Immunol. 2017;8:521.

25. Aksoy DY, Kerimoglu U, Okur H, et al. Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto’s thyroiditis. Endocr J. 2005;52:337-343.

26. Padberg S, Heller K, Usadel KH, et al. One-year prophylactic treatment of euthyroid Hashimoto’s thyroiditis patients with levothyroxine: is there a benefit? Thyroid. 2001;11:249-255.

27. Rugge B, Balshem H, Sehgal R, et al. Screening and Treatment of Subclinical Hypothyroidism or Hyperthyroidism [Internet]. Comparative Effectiveness Reviews, No. 24. Rockville, MD: Agency for Healthcare Research and Quality; October 2011. www.ncbi.nlm.nih.gov/books/NBK83492/. Accessed February 21, 2020.

28. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87:489-499.

29. Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab. 2007;92:4575-4582.

30. Pasqualetti G, Tognini S, Polini A, et al. Is subclinical hypothyroidism a cardiovascular risk factor in the elderly? J Clin Endocrinol Metab. 2013;98:2256-2266.

A history of gastric bypass surgery alone is not considered a risk factor for poor absorption of thyroid hormone, given that the majority of levothyroxine absorption occurs in the ileum.^19,20 However, advancing age (> 70 years) and extreme obesity (BMI > 40) are independent risk factors for decreased levothyroxine absorption.^20,21

Women of reproductive age and pregnant women. Overt untreated or undertreated hypothyroidism can be associated with increased risk of maternal and fetal complications including decreased fertility, miscarriage, preterm delivery, lower birth rates, and infant cognitive deficits.^3,22 Therefore, the main focus should be optimization of thyroid hormone levels prior to and during pregnancy.^3,4,8,22 Thyroid hormone replacement needs to be increased during pregnancy in approximately 50% to 85% of women using thyroid replacement prior to pregnancy, but the dose requirements vary based on the underlying etiology of thyroid dysfunction.

One initial option for patients on a stable dose before pregnancy is to increase their daily dose by a half tablet (1.5 × daily dose) immediately after home confirmation of pregnancy, until finer dose adjustments (usually increases of 25%-60% ) can be made by a physician. Experts recommend that a TSH level be obtained every 4 weeks until mid-gestation and then at least once around 30 weeks’ gestation to ensure specific targets are being met with dose adjustments.²² Optimal thyrotropin reference ranges during conception and pregnancy can be found in the literature.²³

Iron and calcium supplements can interfere with the absorption of levothyroxine, so a 3- to 4-hour gap between taking these supplements and levothyroxine is recommended.

Patients who have positive antibodies and normal thyroid function tests. Patients who are screened for thyroid disorders may demonstrate normal thyroid function (ie, euthyroid) with TSH, free T4, and, if checked, free T3, all within normal ranges. Despite these normal lab results, patients may have additional test results that demonstrate positive thyroid autoantibodies including thyroglobulin antibodies and/or thyroid peroxidase antibodies. Thyroid autoimmunity itself has been associated with a range of other autoimmune conditions as well as an increased risk of thyroid cancer in those with Hashimoto thyroiditis.²⁴Two studies showed that prophylactic treatment of euthyroid patients with levothyroxine led to a reduction in antibody levels and a lower TSH level.^25,26 However, no studies have focused on patient-oriented outcomes such as hospitalizations, quality of life, or symptoms. If the patient remains asymptomatic, we recommend no treatment, but that the patient’s TSH levels be monitored every 12 months.²⁷

Elderly patients. Population data have shown that TSH increases normally with age, with a TSH level of 7.5 mIU/L being the upper limit of normal for a population of healthy adults > 80 years of age.^28,29 Overall, studies have failed to show any benefit in treating elderly patients with subclinical hypothyroidism unless their TSH level exceeds 10 mIU/L.^6,21 The one exception is elderly patients with heart failure in whom untreated subclinical hypothyroidism has been shown to be associated with higher mortality.³⁰

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