Subclinical Hypothyroidism: To Screen or Not to Screen?

August 17, 2011

By Addie Peretz, MD

Faculty Peer Reviewed

Despite the ease of screening for hypothyroidism with hormone assays and the availability of thyroxine replacement therapy, no recommendations regarding routine screening for hypothyroidism in adults are universally accepted. The American Academy of Family Physicians [1] and the American Association of Clinical Endocrinologists [2] recommend periodic assessment of thyroid function in older women.  The American Thyroid Association advocates for more frequent earlier screening, recommending measurement of thyroid stimulating hormone (TSH) beginning at age 35 and every 5 years thereafter.[3]

Whereas screening adults for hypothyroidism is controversial, screening infants for congenital hypothyroidism is routinely done.  The reasons for the universal acceptance of congenital hypothyroidism screening include its high prevalence (1:4000 births), the severity of the consequences if even mild hypothyroidism is left untreated, and the efficacy of treatment with levothyroxine replacement.  Adults have a lower prevalence of overt disease, and the necessity, efficacy, and cost -effectiveness of treating subclinical hypothyroidism are uncertain.[4]

Subclinical hypothyroidism (SCH) is defined as a normal serum free thyroxine (T4) concentration in the presence of an elevated serum thyrotropin (TSH) concentration.[5]  In the United States National Health and Examination Survey (NHANES III), 4.3% of the 16 533 people studied, excluding those subjects with known thyroid disease, were found to have SCH.[6] Other population-based studies report the prevalence of subclinical hypothyroidism to be as high as 15%.  A higher prevalence has been reported among women, Caucasian populations, those over 50 years of age, and men and women with a family history of thyroid disease.

One of the most compelling reasons to screen for hypothyroidism is to reduce the risk of the  potential consequences of SCH.  In a prospective study of patients with subclinical hypothyroidism with 10-20 years of follow-up, approximately 33-55% of patients went on to develop overt hypothyroidism.  The risk of progression tended to correlate with the initial serum TSH concentration and the presence of antithyroid peroxidase antibodies.[7]

Another clinically relevant potential consequence of SCH is cardiovascular disease.  While data are inconsistent, some observational studies have reported an increased risk of cardiovascular disease among subjects with SCH.[8]  This increased risk may be related to the reported association between elevated TSH and elevated total and LDL-cholesterol concentrations.[9]  Other proposed mechanisms point to the link between SCH and other cardiovascular risk factors, including markers of inflammation, vascular reactivity, endothelial function, and carotid intima media thickness.[10]

While the development of overt hypothyroidism or cardiovascular disease are two of the more severe potential consequences of SCH, the disease also has an impact on quality of life and has been associated with neuropsychiatric disease.  SCH has been linked to defects in verbal memory and executive function, defects which improve upon treatment with levothyroxine.[11]  In addition, the lifetime frequency of depression has been found to be higher in subjects who have SCH compared with those who do not.[12]

Though the potential consequences of SCH can be severe, standardized treatment recommendations are lacking. Levothyroxine replacement therapy is recommended for all patients with a TSH greater than 10 mlU/L; however, treatment recommendations are controversial for those patients with a serum TSH level between 5 and 10 mIU/L.  Large-scale randomized trials establishing a benefit of treatment of SCH have yet to be conducted.  Studies are necessary to confirm that detection of SCH will allow physicians to implement effective interventions with levothyroxine therapy.

Despite the lack of randomized trials, screening is nonetheless important.  Until these trials are conducted, clinicians ought to have an especially low threshold for screening higher risk populations, including women with vague symptoms suggestive of hypothyroidism (such as fatigue or depression), women who are pregnant or anticipate becoming pregnant, those with a strong family history of autoimmune thyroid disease,[13] and patients with type 1 diabetes.[14],[15]

Dr.  Addie Peretz is a former medical student at NYU School of Medicine,

Peer reviewed by Manfred Blum, MD, Medicine, Endocrinology, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References

1. American Academy of Family Physicians. Age charts for periodic health examination. Kansas City, MO; American Academy of Family Physicians, 1994. (Reprint no. 510).

2. American Association of Clinical Endocrinologists and American College of Endocrinology. AACE clinical practice guidelines for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract.1995;1:54-62.
3.  Ladenson PW, Singer PA, Ain KB, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med. 2000;160:1573–1575.

4. Weetman AP. Hypothyroidism: screening and subclinical disease. BMJ. 1997;314(7088):1175-1178.

5. An elevated TSH concentration is defined as above the upper limit of the normal TSH reference range of 4-5mU/L.  The majority of patients with subclinical hypothyroidism have a serum TSH level <10mU/L and are asymptomatic.

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. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf);1995;43(1):55-68.  http://www.ncbi.nlm.nih.gov/pubmed/7641412
8. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med. 2000;132(4):270-278. http://www.ncbi.nlm.nih.gov/pubmed/10681281
9. . Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29(1):76-131.  http://www.ncbi.nlm.nih.gov/pubmed/17991805
10. Cikim AS, Oflaz H, Ozbey N, et al. Evaluation of endothelial function in subclinical hypothyroidism and subclinical hyperthyroidism. Thyroid. 2004;14(8):605-609.
11. . Samuels MH, Schuff KG, Carlson NE, Carello P, Janowsky JS. Health status, mood, and cognition in experimentally induced subclinical hypothyroidism. J Clin Endocrinol Metab. 2007;92(7):2545-2551.
12. . Haggerty JJ Jr, Stern RA, Mason GA, Beckwith J, Morey CE, Prange AJ Jr. Subclinical hypothyroidism: a modifiable risk factor for depression? Am J Psychiatry. 1993;150(3):508-510. http://ajp.psychiatryonline.org/cgi/content/abstract/150/3/508
13. Glinoer D, Riahi M, Grün JP, Kinthaert J. Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab. 1994;79(1):197–204. http://http://www.ncbi.nlm.nih.gov/pubmed/8027226
14. . Perros P, McCrimmon RJ, Shaw G, Frier BM. Frequency of thyroid dysfunction in diabetic patients: value of annual screening. Diabet Med. 1995;12(7):622–627. http://http://www.ncbi.nlm.nih.gov/pubmed/7554786

15. Fatourechi V. Subclinical hypothyroidism: an update for primary care physicians. Mayo Clin Proc. 2009;84(1):65-71.

One Response to Subclinical Hypothyroidism: To Screen or Not to Screen?

  1. [...] including elevated total and LDL-cholesterol concentrations. Several months ago, an article in Clinical Correlations evaluated the recommendation for SCH screening. [6]  Although there are no uniformly accepted guidelines, general consensus is to periodically [...]

Leave a Reply

Your email address will not be published. Required fields are marked *

*