Hypothyroidism: Diagnosis and Treatment


Am Fam Physician. 2021 May 15;103(10):605-613.

  Patient information: A handout on this topic is available at https://familydoctor.org/condition/hypothyroidism/.

Clinical hypothyroidism affects one in 300 people in the United States, with a higher prevalence among female and older patients. Symptoms range from minimal to life-threatening (myxedema coma); more common symptoms include cold intolerance, fatigue, weight gain, dry skin, constipation, and voice changes. The signs and symptoms that suggest thyroid dysfunction are nonspecific and nondiagnostic, especially early in disease presentation; therefore, a diagnosis is based on blood levels of thyroid-stimulating hormone and free thyroxine. There is no evidence that population screening is beneficial. Symptom relief and normalized thyroid-stimulating hormone levels are achieved with levothyroxine replacement therapy, started at 1.5 to 1.8 mcg per kg per day. Adding triiodothyronine is not recommended, even in patients with persistent symptoms and normal levels of thyroid-stimulating hormone. Patients older than 60 years or with known or suspected ischemic heart disease should start at a lower dosage of levothyroxine (12.5 to 50 mcg per day). Women with hypothyroidism who become pregnant should increase their weekly dosage by 30% up to nine doses per week (i.e., take one extra dose twice per week), followed by monthly evaluation and management. Patients with persistent symptoms after adequate levothyroxine dosing should be reassessed for other causes or the need for referral. Early recognition of myxedema coma and appropriate treatment is essential. Most patients with subclinical hypothyroidism do not benefit from treatment unless the thyroid-stimulating hormone level is greater than 10 mIU per L or the thyroid peroxidase antibody is elevated.

Hypothyroidism occurs when there is inadequate thyroid hormone production by the thyroid gland or insufficient stimulation by the hypothalamus or pituitary gland. Causes may include primary gland failure or can be iatrogenic, transient, or central (Table 1).14 Central causes, such as low levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4), are rare.

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Clinical recommendationEvidence ratingComments

Screening for thyroid dysfunction in nonpregnant, asymptomatic adults has uncertain risks and benefits.13


No studies have directly compared the benefits and harms of screening vs. no screening

Patients with hypothyroidism should not be treated with triiodothyronine, alone or in combination with levothyroxine.5,26


Evidence-based guidelines generated from consistent, prospective, randomized trials

Patients with hypothyroidism should not be treated with iodine supplementation unless they are from an area with known iodine insufficiency.5


Patient-oriented evidence from nonprospective studies and consensus evaluation of those data

In newly diagnosed patients with hypothyroidism who are older than 60 years or with known or suspected ischemic heart disease, levothyroxine therapy should be initiated at 12.5 to 50 mcg per day.2,3,5,21


Consensus, expert opinion

In women with controlled hypothyroidism who become pregnant, the levothyroxine dosage should be increased by 30%, from seven to nine doses per week, with the thyroid-stimulating hormone level checked every four weeks.22,23


Consistent high-quality randomized trials

Nonpregnant patients with subclinical hypothyroidism should not be treated with thyroid hormone therapy unless the thyroid-stimulating hormone level is greater than 10 mIU per L or the thyroid peroxidase antibody is elevated.16,17,34


Consistent, prospective, randomized data and meta-analysis

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

The Authors

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STEPHEN A. WILSON, MD, MPH, FAAFP, is the chair of and a professor in the Department of Family Medicine at Boston (Mass.) University School of Medicine. At the time this article was initiated, he was the executive vice chair of the Department of Family Medicine at the University of Pittsburgh (Pa.)....

LEAH A. STEM, MD, MS, is a faculty member at the University of Pittsburgh Medical Center St. Margaret Family Medicine Residency Program.

RICHARD D. BRUEHLMAN, MD, is the director of Community Preceptors and a faculty member at the University of Pittsburgh Medical Center St. Margaret Family Medicine Residency Program.

Address correspondence to Stephen A. Wilson, MD, MPH, Boston Medical Center, 1 Boston Medical Center Pl., Dowling 5, Room 5309, Boston, MA 02118 (email: stephen.wilson@bmc.org). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


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1. Gaitonde DY, Rowley KD, Sweeney LB. Hypothyroidism: an update. Am Fam Physician. 2012;86(3):244–251. Accessed December 9, 2020. https://www.aafp.org/afp/2012/0801/p244.html...

2. Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet. 2017;390(10101):1550–1562.

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

4. So M, MacIsaac RJ, Grossmann M. Hypothyroidism. Aust Fam Physician. 2012;41(8):556–562.

5. Garber JR, Cobin RH, Gharib H, et al.; American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults [published correction appears in Endocr Pract. 2013;19(1):175]. Endocr Pract. 2012;18(6):988–1028.

6. 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(2):489–499.

7. Stott DJ, Rodondi N, Kearney PM, et al.; TRUST Study Group. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med. 2017;376(26):2534–2544.

8. Nygaard B. Primary hypothyroidism. Am Fam Physician. 2015;91(6):359–360. Accessed December 31, 2020. https://www.aafp.org/afp/2015/0315/p359.html

9. Kitahara CM, Linet MS, Beane Freeman LE, et al. Cigarette smoking, alcohol intake, and thyroid cancer risk: a pooled analysis of five prospective studies in the United States. Cancer Causes Control. 2012;23(10):1615–1624.

10. Ladenson PW, Singer PA, Ain KB, et al. American Thyroid Association guidelines for detection of thyroid dysfunction [published correction appears in Arch Intern Med. 2001;161(2):284]. Arch Intern Med. 2000;160(11):1573–1575.

11. Pluta RM, Burke AE, Glass RM. JAMA patient page. Subclinical hypothyroidism. JAMA. 2010;304(12):1402.

12. Dietrich JW, Landgrafe G, Fotiadou EH. TSH and thyrotropic agonists: key actors in thyroid homeostasis. J Thyroid Res. 2012;2012:351864.

13. LeFevre ML; U.S. Preventive Services Task Force. Screening for thyroid dysfunction: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;162(9):641–650.

14. Iyer PC, Cabanillas ME, Waguespack SG, et al. Immune-related thyroiditis with immune checkpoint inhibitors. Thyroid. 2018;28(10):1243–1251.

15. Cohen BM, Sommer BR, Vuckovic A. Antidepressant-resistant depression in patients with comorbid subclinical hypothyroidism or high-normal TSH levels. Am J Psychiatry. 2018;175(7):598–604.

16. Thayakaran R, Adderley NJ, Sainsbury C, et al. Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study. BMJ. 2019;366:l4892.

17. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291(2):228–238.

18. Kravets I. Hyperthyroidism: diagnosis and treatment. Am Fam Physician. 2016;93(5):363–370. Accessed December 31, 2020. https://www.aafp.org/afp/2016/0301/p363.html

19. Rivas AM, Lado-Abeal J. Thyroid hormone resistance and its management. Proc (Bayl Univ Med Cent). 2016;29(2):209–211.

20. Synthroid (levothyroxine sodium tablets, USP) [package insert]. Abbott Laboratories. Accessed November 19, 2019. https://www.rxabbvie.com/pdf/synthroid.pdf

21. Jonklaas J, Bianco AC, Bauer AJ, et al.; American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670–1751.

22. Yassa L, Marqusee E, Fawcett R, et al. Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. J Clin Endocrinol Metab. 2010;95(7):3234–3241.

23. 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 [published correction appears in Thyroid. 2017;27(9):1212]. Thyroid. 2017;27(3):315–389.

24. Mathew V, Misgar RA, Ghosh S, et al. Myxedema coma: a new look into an old crisis. J Thyroid Res. 2011;2011:493462.

25. Kwaku MP, Burman KD. Myxedema coma. J Intensive Care Med. 2007;22(4):224–231.

26. American College of Obstetricians and Gynecologists. Practice bulletin no. 148: thyroid disease in pregnancy. Obstet Gynecol. 2015;125(4):996–1005.

27. Pecina J, Bernard M, Furst J, et al. Hypothyroidism management: is an annual check of TSH level always necessary? J Fam Pract. 2012;61(10):E1–E5.

28. Doucet J, Trivalle C, Chassagne P, et al. Does age play a role in clinical presentation of hypothyroidism? J Am Geriatr Soc. 1994;42(9):984–986.

29. Aggarwal N, Razvi S. Thyroid and aging or the aging thyroid? An evidence-based analysis of the literature. J Thyroid Res. 2013;2013:481287.

30. Hyland KA, Arnold AM, Lee JS, et al. Persistent subclinical hypothyroidism and cardiovascular risk in the elderly: the Cardiovascular Health Study. J Clin Endocrinol Metab. 2013;98(2):533–540.

31. Lazarus JH, Bestwick JP, Channon S, et al. Antenatal thyroid screening and childhood cognitive function [published correction appears in N Engl J Med. 2012;366(17):1650]. N Engl J Med. 2012;366(6):493–501.

32. Grozinsky-Glasberg S, Fraser A, Nahshoni E, et al. Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2006;91(7):2592–2599.

33. Díez JJ, Iglesias P. Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure. J Clin Endocrinol Metab. 2004;89(10):4890–4897.

34. Huber G, Staub JJ, Meier C, et al. Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab. 2002;87(7):3221–3226.

35. Grossman A, Feldhamer I, Meyerovitch J. Treatment with levothyroxin in subclinical hypothyroidism is associated with increased mortality in the elderly. Eur J Intern Med. 2018;50:65–68.

36. Meier C, Staub JJ, Roth CB, et al. TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study). J Clin Endocrinol Metab. 2001;86(10):4860–4866.

37. Feller M, Snel M, Moutzouri E, et al. Association of thyroid hormone therapy with quality of life and thyroid-related symptoms in patients with subclinical hypothyroidism: a systematic review and meta-analysis. JAMA. 2018;320(13):1349–1359.

38. Akhtar MA, Agrawal R, Brown J, et al. Thyroxine replacement for subfertile women with euthyroid autoimmune thyroid disease or subclinical hypothyroidism. Cochrane Database Syst Rev. 2019;(6):CD011009.

39. Nazarpour S, Ramezani Tehrani F, Simbar M, et al. Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with autoimmune thyroid disease. Eur J Endocrinol. 2017;176(2):253–265.

40. Casey BM, Thom EA, Peaceman AM, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network. Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. N Engl J Med. 2017;376(9):815–825.

41. Loh HH, Lim LL, Yee A, et al. Association between subclinical hypothyroidism and depression: an updated systematic review and meta-analysis. BMC Psychiatry. 2019;19(1):12.

42. Bekkering GE, Agoritsas T, Lytvyn L, et al. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019;365:I2006.

43. Hueston WJ. Treatment of hypothyroidism [published correction appears in Am Fam Physician. 2002;65(12):2438]. Am Fam Physician. 2001;64(10):1717–1725. Accessed December 9, 2020. https://www.aafp.org/afp/2001/1115/p1717.html



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