The
n e w e ng l a n d j o u r na l
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m e dic i n e
Subclinical Hypothyroidism To the Editor: In his article on the management of subclinical hypothyroidism, Peeters (June 29 issue)1 considers the presence of circulating antibodies to thyroid peroxidase to be an indication for levothyroxine therapy in patients with a thyrotropin level of 7 mIU per liter or higher, on the basis of the increased risk of progression to overt hypothyroidism. The author does not say that findings on ultrasonographic examination of the thyroid suggestive of chronic thyroiditis are an indication for treatment in these patients.1 In studies of the natural history of subclinical hypothyroidism in which levels of antibodies to thyroid peroxidase were measured and ultrasonographic examination of the thyroid was performed, the results were consistent: ultrasonographic findings were as important as2,3 or even more important than4 levels of antibodies to thyroid peroxidase as predictors of the evolution of subclinical hypothyroidism. Thus, many authors recommend that patients with ultrasonographic findings suggestive of chronic thyroiditis, even in the absence of antibodies to thyroid peroxidase, should receive the same treatment for subclinical hypothyroidism as patients who test positive for antibodies to thyroid peroxidase.5 Peeters also indicates that female sex and free thyroxine concentrations in the low-normal range are predictors of progression to overt hypothyroidism.1 However, the studies cited by the author do not actually confirm the predictive value of these factors in multivariate analysis. Pedro W. Rosario, M.D.
The author replies: I agree with Rosario’s comment that ultrasonographic examination of the thyroid can provide additional evidence of thyroid autoimmunity.1 However, this examination is associated with a risk of incidental findings. A large proportion of diagnoses of thyroid cancer in the past two decades were probably due to diagnostic changes after the introduction of ultrasonographic examination of the neck in the 1980s.2 This is best illustrated by data from South Korea, where a large-scale introduction of ultrasonographic examination of the thyroid (ultrasonographic examination of the neck was offered at a low cost in addition to organized screening programs for other cancers) resulted in a rate of thyroid-cancer diagnoses in 2011 that was 15 times that observed in 1993.3 Despite this dramatic increase in incidence, thyroid cancer–specific mortality remained stable; this clearly suggests overdiagnosis of indolent thyroid cancers. It is estimated that overdiagnosis accounts for the majority of cases of thyroid cancer in many Western countries.4 In the context of guidelines from professional societies that emphasize avoidance of both overdiagnosis and overtreatment of thyroid cancer,5 ultrasonographic examination of the neck should not be performed routinely in the management of subclinical hypothyroidism unless there are additional clinical indications. Robin P. Peeters, M.D., Ph.D. Erasmus Medical Center Rotterdam, the Netherlands Since publication of his article, the author reports no further potential conflict of interest.
Santa Casa de Belo Horizonte Belo Horizonte, Brazil
1. Pedersen OM, Aardal NP, Larssen TB, Varhaug JE, Myking O, Vik-Mo H. The value of ultrasonography in predicting autoimNo potential conflict of interest relevant to this letter was re- mune thyroid disease. Thyroid 2000;10:251-9. ported. 2. Vaccarella S, Dal Maso L, Laversanne M, Bray F, Plummer M, Franceschi S. The impact of diagnostic changes on the rise in 1. Peeters RP. Subclinical hypothyroidism. N Engl J Med 2017; thyroid cancer incidence: a population-based study in selected 376:2556-65. high-resource countries. Thyroid 2015;25:1127-36. 2. Rosário PW, Bessa B, Valadão MM, Purisch S. Natural his- 3. Ahn HS, Kim HJ, Welch HG. Korea’s thyroid-cancer “epidemtory of mild subclinical hypothyroidism: prognostic value of ul- ic” — screening and overdiagnosis. N Engl J Med 2014;371:1765-7. trasound. Thyroid 2009;19:9-12. 4. Vaccarella S, Franceschi S, Bray F, Wild CP, Plummer M, Dal 3. Rosário PW, Carvalho M, Calsolari MR. Natural history of Maso L. Worldwide thyroid-cancer epidemic? The increasing imsubclinical hypothyroidism with TSH ≤10 mIU/l: a prospective pact of overdiagnosis. N Engl J Med 2016;375:614-7. study. Clin Endocrinol (Oxf) 2016;84:878-81. 5. Haugen BR, Alexander EK, Bible KC, et al. 2015 American 4. Imaizumi M, Sera N, Ueki I, et al. Risk for progression to Thyroid Association management guidelines for adult patients overt hypothyroidism in an elderly Japanese population with with thyroid nodules and differentiated thyroid cancer: the Amersubclinical hypothyroidism. Thyroid 2011;21:1177-82. ican Thyroid Association Guidelines Task Force on Thyroid Nod5. Biondi B, Cooper DS. The clinical significance of subclinical ules and Differentiated Thyroid Cancer. Thyroid 2016;26:1-133. thyroid dysfunction. Endocr Rev 2008;29:76-131. DOI: 10.1056/NEJMc1709853
DOI: 10.1056/NEJMc1709853
1404
Correspondence Copyright © 2017 Massachusetts Medical Society.
n engl j med 377;14 nejm.org October 5, 2017
The New England Journal of Medicine Downloaded from nejm.org on October 4, 2017. For personal use only. No other uses without permission. Copyright © 2017 Massachusetts Medical Society. All rights reserved.
n e w e ng l a n d j o u r na l
of
m e dic i n e
Subclinical Hypothyroidism To the Editor: In his article on the management of subclinical hypothyroidism, Peeters (June 29 issue)1 considers the presence of circulating antibodies to thyroid peroxidase to be an indication for levothyroxine therapy in patients with a thyrotropin level of 7 mIU per liter or higher, on the basis of the increased risk of progression to overt hypothyroidism. The author does not say that findings on ultrasonographic examination of the thyroid suggestive of chronic thyroiditis are an indication for treatment in these patients.1 In studies of the natural history of subclinical hypothyroidism in which levels of antibodies to thyroid peroxidase were measured and ultrasonographic examination of the thyroid was performed, the results were consistent: ultrasonographic findings were as important as2,3 or even more important than4 levels of antibodies to thyroid peroxidase as predictors of the evolution of subclinical hypothyroidism. Thus, many authors recommend that patients with ultrasonographic findings suggestive of chronic thyroiditis, even in the absence of antibodies to thyroid peroxidase, should receive the same treatment for subclinical hypothyroidism as patients who test positive for antibodies to thyroid peroxidase.5 Peeters also indicates that female sex and free thyroxine concentrations in the low-normal range are predictors of progression to overt hypothyroidism.1 However, the studies cited by the author do not actually confirm the predictive value of these factors in multivariate analysis. Pedro W. Rosario, M.D.
The author replies: I agree with Rosario’s comment that ultrasonographic examination of the thyroid can provide additional evidence of thyroid autoimmunity.1 However, this examination is associated with a risk of incidental findings. A large proportion of diagnoses of thyroid cancer in the past two decades were probably due to diagnostic changes after the introduction of ultrasonographic examination of the neck in the 1980s.2 This is best illustrated by data from South Korea, where a large-scale introduction of ultrasonographic examination of the thyroid (ultrasonographic examination of the neck was offered at a low cost in addition to organized screening programs for other cancers) resulted in a rate of thyroid-cancer diagnoses in 2011 that was 15 times that observed in 1993.3 Despite this dramatic increase in incidence, thyroid cancer–specific mortality remained stable; this clearly suggests overdiagnosis of indolent thyroid cancers. It is estimated that overdiagnosis accounts for the majority of cases of thyroid cancer in many Western countries.4 In the context of guidelines from professional societies that emphasize avoidance of both overdiagnosis and overtreatment of thyroid cancer,5 ultrasonographic examination of the neck should not be performed routinely in the management of subclinical hypothyroidism unless there are additional clinical indications. Robin P. Peeters, M.D., Ph.D. Erasmus Medical Center Rotterdam, the Netherlands Since publication of his article, the author reports no further potential conflict of interest.
Santa Casa de Belo Horizonte Belo Horizonte, Brazil
1. Pedersen OM, Aardal NP, Larssen TB, Varhaug JE, Myking O, Vik-Mo H. The value of ultrasonography in predicting autoimNo potential conflict of interest relevant to this letter was re- mune thyroid disease. Thyroid 2000;10:251-9. ported. 2. Vaccarella S, Dal Maso L, Laversanne M, Bray F, Plummer M, Franceschi S. The impact of diagnostic changes on the rise in 1. Peeters RP. Subclinical hypothyroidism. N Engl J Med 2017; thyroid cancer incidence: a population-based study in selected 376:2556-65. high-resource countries. Thyroid 2015;25:1127-36. 2. Rosário PW, Bessa B, Valadão MM, Purisch S. Natural his- 3. Ahn HS, Kim HJ, Welch HG. Korea’s thyroid-cancer “epidemtory of mild subclinical hypothyroidism: prognostic value of ul- ic” — screening and overdiagnosis. N Engl J Med 2014;371:1765-7. trasound. Thyroid 2009;19:9-12. 4. Vaccarella S, Franceschi S, Bray F, Wild CP, Plummer M, Dal 3. Rosário PW, Carvalho M, Calsolari MR. Natural history of Maso L. Worldwide thyroid-cancer epidemic? The increasing imsubclinical hypothyroidism with TSH ≤10 mIU/l: a prospective pact of overdiagnosis. N Engl J Med 2016;375:614-7. study. Clin Endocrinol (Oxf) 2016;84:878-81. 5. Haugen BR, Alexander EK, Bible KC, et al. 2015 American 4. Imaizumi M, Sera N, Ueki I, et al. Risk for progression to Thyroid Association management guidelines for adult patients overt hypothyroidism in an elderly Japanese population with with thyroid nodules and differentiated thyroid cancer: the Amersubclinical hypothyroidism. Thyroid 2011;21:1177-82. ican Thyroid Association Guidelines Task Force on Thyroid Nod5. Biondi B, Cooper DS. The clinical significance of subclinical ules and Differentiated Thyroid Cancer. Thyroid 2016;26:1-133. thyroid dysfunction. Endocr Rev 2008;29:76-131. DOI: 10.1056/NEJMc1709853
DOI: 10.1056/NEJMc1709853
1404
Correspondence Copyright © 2017 Massachusetts Medical Society.
n engl j med 377;14 nejm.org October 5, 2017
The New England Journal of Medicine Downloaded from nejm.org on October 4, 2017. For personal use only. No other uses without permission. Copyright © 2017 Massachusetts Medical Society. All rights reserved.
