Clinical outcomes of therapeutic approaches to subclinical hypothyroidism: An integrative review




Hypothyroidism; Pharmacological treatment; Levothyroxine.


Subclinical hypothyroidism is characterized by high levels of thyroid-stimulating hormone in addition to normal levels of free thyroxine. Patients need to be monitored in order to find the most effective clinical and therapeutic approach for each individual. The most commonly used therapeutic approach is levothyroxine, which has no clear evidence of its benefits. Therefore, this study is an integrative literature review, which aim to synthesize the studies related to the possible benefits or not of using levothyroxine in the therapeutic approach to subclinical hypothyroidism, evaluating various clinical aspects. The MEDLINE (via PubMed), EMBASE and SCIELO databases were included in the search, focusing on original articles, especially randomized clinical trials in English and Spanish, covering the last 5 years, including 2023. From the results, it was possible to discuss clinical outcomes related to the cardiovascular, musculoskeletal and hematopoietic systems, as well as psychiatric manifestations and effects on laboratory aspects. In addition, other therapies for managing the disease were discussed. The analysis made shows that levothyroxine replacement does not present significant results for the treatment of subclinical hypothyroidism, as well as the other therapeutic options discussed. 


Azim, S., & Nasr, C. (2019). Subclinical hypothyroidism: When to treat. Cleve Clin J Med, 86(2), 110.101-

Bekkering, G. E., Agoritsas, T., Lytvyn, L., Heen, A. F., Feller, M., Moutzouri, E., & Vermandere, M. (2019). Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. Bmj, 365.

Bernal de Lázaro, E., & Díaz-Perera Fernández, G. (2022). Efectos del tratamiento sustitutivo del hipotiroidismo subclínico en el grosor intima-media carotideo. Revista Cubana de Medicina, 61(1).

Blum, M. R., Bauer, D. C., Collet, T. H., Fink, H. A., Cappola, A. R., Da Costa, B. R., & Thyroid Studies Collaboration. (2015). Subclinical thyroid dysfunction and fracture risk: a meta-analysis. Jama, 313(20), 2055-2065.

Blum, M. R., Gencer, B., Adam, L., Feller, M., Collet, T. H., da Costa, B. R., & Rodondi, N. (2018). Impact of thyroid hormone therapy on atherosclerosis in the elderly with subclinical hypothyroidism: a randomized trial. The Journal of Clinical Endocrinology & Metabolism, 103(8), 2988-2997.

Büchi, A. E., Feller, M., Netzer, S., Blum, M. R., Rodriguez, E. G., Collet, T. H., & Aeberli, D. (2022). Bone geometry in older adults with subclinical hypothyroidism upon levothyroxine therapy: A nested study within a randomized placebo controlled trial. Bone, 161, 116404.

Calissendorff, J., & Falhammar, H. (2020). To treat or not to treat subclinical hypothyroidism, what is the evidence? Medicina, 56(1), 40.

Costantine, M. M., Smith, K., Thom, E. A., Casey, B. M., Peaceman, A. M., Varner, M. W., & Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. (2020). Effect of thyroxine therapy on depressive symptoms among women with subclinical hypothyroidism. Obstetrics and gynecology, 135(4), 812.

Du Puy, R. S., Poortvliet, R. K., Mooijaart, S. P., Stott, D. J., Quinn, T., Sattar, N., & den Elzen, W. P. (2022). No effect of levothyroxine on hemoglobin in older adults with subclinical hypothyroidism: pooled results from 2 randomized controlled trials. The Journal of Clinical Endocrinology & Metabolism, 107(6), e2339-e2347.

Feller, M., Snel, M., Moutzouri, E., Bauer, D. C., de Montmollin, M., Aujesky, D., & Dekkers, O. M. (2018). 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, 320(13), 1349-1359.

Gao, N., Zhang, W., Zhang, Y. Z., Yang, Q., & Chen, S. H. (2013). Carotid intima-media thickness in patients with subclinical hypothyroidism: a meta-analysis. Atherosclerosis, 227(1), 18-25.

Gencer, B., Moutzouri, E., Blum, M. R., Feller, M., Collet, T. H., Delgiovane, C., & Rodondi, N. (2020). The impact of levothyroxine on cardiac function in older adults with mild subclinical hypothyroidism: a randomized clinical trial. The American journal of medicine, 133(7), 848-856.

Gonzalez Rodriguez, E., Stuber, M., Del Giovane, C., Feller, M., Collet, T. H., Löwe, A. L., & Rodondi, N. (2020). Skeletal effects of levothyroxine for subclinical hypothyroidism in older adults: a TRUST randomized trial nested study. The Journal of Clinical Endocrinology & Metabolism, 105(1), 336-343.

Han, L., Ma, Y., Liang, Z., & Chen, D. (2021). Laboratory characteristics analysis of the efficacy of levothyroxine on subclinical hypothyroidism during pregnancy: a single-center retrospective study. Bioengineered, 12(1), 4183-4190.

Jabbar, A., Ingoe, L., Junejo, S., Carey, P., Addison, C., Thomas, H., & Razvi, S. (2020). Effect of levothyroxine on left ventricular ejection fraction in patients with subclinical hypothyroidism and acute myocardial infarction: a randomized clinical trial. Jama, 324(3), 249-258.

Klaver, E. I., van Loon, H. C., Stienstra, R., Links, T. P., Keers, J. C., Kema, I. P., & Wolffenbuttel, B. H. (2013). Thyroid hormone status and health-related quality of life in the LifeLines Cohort Study. Thyroid, 23(9), 1066-1073.

Livingston, E. H. (2019). Subclinical hypothyroidism. Jama, 322(2), 180-180.

Lyko, C., Blum, M. R., Abolhassani, N., Stuber, M. J., Del Giovane, C., Feller, M., & Rodondi, N. (2022). Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism: A pooled analysis of two randomized controlled trials. Journal of internal medicine, 292(6), 892-903.

Mazeto, G. M. F. D. S., Sgarbi, J. A., Ramos, H. E., Villagelin Neto, D. G. P., Nogueira, C. R., Vaisman, M., & Carvalho, G. A. D. (2022). Approach to adult patients with primary hypothyroidism in some special situations: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM). Archives of Endocrinology and Metabolism, 66, 871-882.

Nakova, V. V., Krstevska, B., Kostovska, E. S., Vaskova, O., & Ismail, L. G. (2018). The effect of levothyroxine treatment on left ventricular function in subclinical hypothyroidism. Archives of endocrinology and metabolism, 62, 392-398.

Ouyang, Q., Xu, Y., Ban, Y., Li, J., Cai, Y., Wu, B., & Zhao, Y. (2023). Probiotics and Prebiotics in Subclinical Hypothyroidism of Pregnancy with Small Intestinal Bacterial Overgrowth. Probiotics and Antimicrobial Proteins, 1-10.

Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., & Moher, D. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. International journal of surgery, 88, 105906.

Palui, R., Sahoo, J., Kamalanathan, S., Kar, S. S., Sridharan, K., Durgia, H., & Patil, M. (2019). Effect of metformin on thyroid function tests in patients with subclinical hypothyroidism: an open-label randomised controlled trial. Journal of Endocrinological Investigation, 42, 1451-1458.

Pirola, I., Rotondi, M., Cristiano, A., Maffezzoni, F., Pasquali, D., Marini, F., & Cappelli, C. (2020). Selenium supplementation in patients with subclinical hypothyroidism affected by autoimmune thyroiditis: Results of the SETI study. Endocrinología, Diabetes y Nutrición (English ed.), 67(1), 28-35.

Rodondi, N., den Elzen, W. P., Bauer, D. C., Cappola, A. R., Razvi, S., Walsh, J. P., & Thyroid Studies Collaboration, F. T. (2010). Subclinical hypothyroidism and the risk of coronary heart disease and mortality. Jama, 304(12), 1365-1374.

Sgarbi, J. A., Teixeira, P. F., Maciel, L. M., Mazeto, G. M., Vaisman, M., Montenegro Junior, R. M., & Ward, L. S. (2013). Consenso brasileiro para a abordagem clínica e tratamento do hipotireoidismo subclínico em adultos: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia. Arquivos Brasileiros de Endocrinologia & Metabologia, 57, 166-183.

Soto-García, A., Elizondo-Riojas, G., Rodriguez-Gutiérrez, R., Mancillas-Adame, L., & Gonzalez-Gonzalez, J. G. (2020). Carotid intima-media thickness in patients with subclinical hypothyroidism: A prospective controlled study. Authorea Preprints.

Stuber, M. J., Moutzouri, E., Feller, M., Del Giovane, C., Bauer, D. C., Blum, M. R., & Rodondi, N. (2020). Effect of thyroid hormone therapy on fatigability in older adults with subclinical hypothyroidism: a nested study within a randomized placebo-controlled trial. The Journals of Gerontology: Series A, 75(9), e89-e94.

Vilar, L., & Kater, C. E. (2021). Endocrinologia Clínica. (7a ed.). Editora Guanabara.

Wildisen, L., Feller, M., Del Giovane, C., Moutzouri, E., Du Puy, R. S., Mooijaart, S. P., & Rodondi, N. (2021). Effect of levothyroxine therapy on the development of depressive symptoms in older adults with subclinical hypothyroidism: an ancillary study of a randomized clinical trial. JAMA network Open, 4(2), e2036645-e2036645.

Zijlstra, L. E., Jukema, J. W., Westendorp, R. G., Du Puy, R. S., Poortvliet, R. K., Kearney, P. M., & Mooijaart, S. P. (2021). Levothyroxine treatment and cardiovascular outcomes in older people with subclinical hypothyroidism: pooled individual results of two randomised controlled trials. Frontiers in endocrinology, 12, 674841.



How to Cite

LOPES, R. M. .; BATISTA, J. G. de M. .; MONTEIRO, A. C. .; SOUZA, J. G. R. de .; PORTUGAL, C. G. .; VIEIRA, F. J. M. .; SILVA, J. L. N. da .; DALLAGO, C. M. . Clinical outcomes of therapeutic approaches to subclinical hypothyroidism: An integrative review. Research, Society and Development, [S. l.], v. 12, n. 12, p. e128121244025, 2023. DOI: 10.33448/rsd-v12i12.44025. Disponível em: Acesso em: 17 jun. 2024.



Health Sciences