Applied Evidence

Refining your approach to hypothyroidism treatment

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

Author(s):

Thyroid hormone supplementation can be complicated by a number of factors. These tips can help to ensure that you provide the best treatment possible.

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PRACTICE RECOMMENDATIONS

› Prescribe levothyroxine 1.6 mcg/kg/d for healthy adult patients < 50 years of age with overt hypothyroidism. B

› Consider lower initial doses of levothyroxine in patients with cardiac disease (12.5-50 mcg/d) or subclinical hypothyroidism (25-75 mcg/d). B

› Titrate levothyroxine by 12.5 to 25 mcg/d at 6- to 8-week intervals based on thyroid-stimulating hormone measurements, comorbidities, and symptoms. C

› Closely monitor and provide thyroid supplementation to female patients who are pregnant or of reproductive age with concomitant hypothyroidism. C

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

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.

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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.

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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.

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CASE

A 38-year-old woman presents for a routine physical. Other than urgent care visits for 1 episode of influenza and 2 upper respiratory illnesses, she has not seen a physician for a physical in 5 years. She denies any significant medical history. She takes naproxen occasionally for chronic right knee pain. She does not use tobacco or alcohol. Recently, she has started using a meal replacement shake at lunchtime for weight management. She performs aerobic exercise 30 to 40 minutes per day, 5 days per week. Her family history is significant for type 2 diabetes mellitus, arthritis, heart disease, and hyperlipidemia on her mother’s side. She is single, is not currently sexually active, works as a pharmacy technician, and has no children. A high-risk human papillomavirus test was normal 4 years ago.

A review of systems is notable for a 20-pound weight gain over the past year, worsening heartburn over the past 2 weeks, and chronic knee pain, which is greater in the right knee than the left. She denies weakness, fatigue, nausea, diarrhea, constipation, or abdominal pain. Vital signs reveal a blood pressure of 146/88 mm Hg, a heart rate of 63 bpm, a temperature of 98°F (36.7°C), a respiratory rate of 16, a height of 5’7’’ (1.7 m), a weight of 217 lbs (98.4 kg), and a peripheral capillary oxygen saturation (SpO₂) of 99% on room air. The physical exam reveals a body mass index (BMI) of 34, warm dry skin, and coarse brittle hair.

Lab results reveal a thyroid-stimulating hormone (TSH) level of 11.17 mIU/L (reference range, 0.45-4.5 mIU/L) and a free thyroxine (T4) of 0.58 ng/dL (reference range, 0.8-2.8 ng/dL). A basic metabolic panel and hemoglobin A1C level are normal.

What would you recommend?

In the United States, the prevalence of overt hypothyroidism (defined as a TSH level > 4.5 mIU/L and a low free T4) among people ≥ 12 years of age was estimated at 0.3% based on National Health and Nutrition Examination Survey (NHANES) data from 1999-2002.¹ Subclinical hypothyroidism (TSH level > 4.5 mIU/L but < 10 mIU/L and a normal T4 level) is even more common, with an estimated prevalence of 3.4%.¹ Hypothyroidism is more common in females and occurs more frequently in Caucasian Americans and Mexican Americans than in African Americans.¹

The most common etiologies of hypothyroidism include autoimmune thyroiditis (eg, Hashimoto thyroiditis, atrophic autoimmune thyroiditis) and iatrogenic causes (eg, after radioactive iodine ablation or thyroidectomy) (TABLE 1).^2-4

Initiating thyroid hormone replacement

Factors to consider when starting a patient on thyroid hormone replacement include age, weight, symptom severity, TSH level, goal TSH value, adverse effects from thyroid supplements, history of cardiac disease, and, for women of child-bearing age, the desire for pregnancy vs the use of contraceptives. Most adult patients < 50 years with overt hypothyroidism can begin a weight-based dose of levothyroxine: ~1.6 mcg/kg/d (based on ideal body weight).³

Continue to: For adults with cardiac disease...