Thyroid hormone suppressive therapy for thyroid nodules and benign goiter
- Douglas S Ross, MD
Douglas S Ross, MD
- Section Editor — Thyroid Disease
- Professor of Medicine
- Harvard Medical School
The efficacy of thyroid hormone suppressive therapy in euthyroid patients with solitary benign thyroid nodules or sporadic nontoxic multinodular goiters is controversial. Most studies have shown that few thyroid nodules regress in patients taking thyroid hormone. However, suppressive therapy does appear to interfere with goitrogenesis in many patients, and recent speculation suggests that it could reduce the risk of thyroid oncogenesis, as well. The American Thyroid Association does not recommend suppression therapy of benign thyroid nodules in iodine sufficient populations .
This topic will review potential benefits and risks of thyroid hormone suppressive therapy and suggest therapeutic approaches to patients with goiter. The overall approach to the evaluation and treatment of patients with goiter and with thyroid nodules is discussed separately. (See "Clinical presentation and evaluation of goiter in adults" and "Diagnostic approach to and treatment of thyroid nodules".)
Suppression of thyroid-stimulating hormone (TSH) secretion in normal subjects by the administration of thyroid hormone results in thyroid atrophy . Although the pathogenesis of thyroid nodules and sporadic nontoxic multinodular goiters is poorly understood, TSH is presumed to be necessary if not sufficient and, therefore, suppression of TSH secretion might be expected to result in a decrease in nodule or goiter size or at least prevent further enlargement.
The importance of TSH in goiter formation varies with the cause of the goiter. For example, in patients with iodine deficiency or chronic autoimmune (Hashimoto's) thyroiditis, an increase in TSH secretion is the predominant cause of goiter. In contrast, most patients with thyroid nodules or sporadic nontoxic multinodular goiters have normal serum TSH concentrations. In them, particularly those with nontoxic multinodular goiters, the thyroid enlargement is probably caused by several growth factors (including TSH) that act over time on thyroid follicular cells that have different synthetic and growth potentials. The result is diffuse and later multinodular thyroid enlargement; some nodules eventually become autonomous , and others may undergo cystic degeneration.
Because thyroid hormone is presumed to reduce goiter size by reducing TSH secretion, suppressive therapy would be expected to be ineffective in patients in whom serum TSH concentrations were already subnormal due to autonomous thyroid hormone production.
- American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19:1167.
- Rienhoff, WF Jr. Microscopic changes induced in thyroid gland by oral administration of desiccated thyroid. Arch Surg 1940; 41:487.
- Studer H, Peter HJ, Gerber H. Natural heterogeneity of thyroid cells: the basis for understanding thyroid function and nodular goiter growth. Endocr Rev 1989; 10:125.
- Berghout A, Wiersinga WM, Drexhage HA, et al. Comparison of placebo with L-thyroxine alone or with carbimazole for treatment of sporadic non-toxic goitre. Lancet 1990; 336:193.
- Cesareo R, Iozzino M, Isgrò MA, et al. Short term effects of levothyroxine treatment in thyroid multinodular disease. Endocr J 2010; 57:803.
- Grussendorf M, Reiners C, Paschke R, et al. Reduction of thyroid nodule volume by levothyroxine and iodine alone and in combination: a randomized, placebo-controlled trial. J Clin Endocrinol Metab 2011; 96:2786.
- Wémeau JL, Caron P, Schvartz C, et al. Effects of thyroid-stimulating hormone suppression with levothyroxine in reducing the volume of solitary thyroid nodules and improving extranodular nonpalpable changes: a randomized, double-blind, placebo-controlled trial by the French Thyroid Research Group. J Clin Endocrinol Metab 2002; 87:4928.
- Koc M, Ersoz HO, Akpinar I, et al. Effect of low- and high-dose levothyroxine on thyroid nodule volume: a crossover placebo-controlled trial. Clin Endocrinol (Oxf) 2002; 57:621.
- Murphy ED, Scanlon EF, Garces RM, et al. Thyroid hormone administration in irradiated patients. J Surg Oncol 1986; 31:214.
- DeGroot LJ. Radiation and thyroid disease. Baillieres Clin Endocrinol Metab 1988; 2:777.
- Subbiah S, Collins BJ, Schneider AB. Factors related to the recurrence of thyroid nodules after surgery for benign radiation-related nodules. Thyroid 2007; 17:41.
- Chow EJ, Friedman DL, Stovall M, et al. Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 2009; 53:432.
- Sklar C, Whitton J, Mertens A, et al. Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 2000; 85:3227.
- BERGFELT G, RISHOLM L. POSTOPERATIVE THYROID HORMONE THERAPY IN NONTOXIC GOITRE. Acta Chir Scand 1963; 126:531.
- Anderson PE, Hurley PR, Rosswick P. Conservative treatment and long term prophylactic thyroxine in the prevention of recurrence of multinodular goiter. Surg Gynecol Obstet 1990; 171:309.
- Bellantone R, Lombardi CP, Boscherini M, et al. Predictive factors for recurrence after thyroid lobectomy for unilateral non-toxic goiter in an endemic area: results of a multivariate analysis. Surgery 2004; 136:1247.
- Bistrup C, Nielsen JD, Gregersen G, Franch P. Preventive effect of levothyroxine in patients operated for non-toxic goitre: a randomized trial of one hundred patients with nine years follow-up. Clin Endocrinol (Oxf) 1994; 40:323.
- Hegedüs L, Nygaard B, Hansen JM. Is routine thyroxine treatment to hinder postoperative recurrence of nontoxic goiter justified? J Clin Endocrinol Metab 1999; 84:756.
- Svensson J, Ericsson UB, Nilsson P, et al. Levothyroxine treatment reduces thyroid size in children and adolescents with chronic autoimmune thyroiditis. J Clin Endocrinol Metab 2006; 91:1729.
- Fiore E, Vitti P. Serum TSH and risk of papillary thyroid cancer in nodular thyroid disease. J Clin Endocrinol Metab 2012; 97:1134.
- Fiore E, Rago T, Provenzale MA, et al. L-thyroxine-treated patients with nodular goiter have lower serum TSH and lower frequency of papillary thyroid cancer: results of a cross-sectional study on 27 914 patients. Endocr Relat Cancer 2010; 17:231.
- Zelmanovitz F, Genro S, Gross JL. Suppressive therapy with levothyroxine for solitary thyroid nodules: a double-blind controlled clinical study and cumulative meta-analyses. J Clin Endocrinol Metab 1998; 83:3881.
- Castro MR, Caraballo PJ, Morris JC. Effectiveness of thyroid hormone suppressive therapy in benign solitary thyroid nodules: a meta-analysis. J Clin Endocrinol Metab 2002; 87:4154.
- Gharib H, Mazzaferri EL. Thyroxine suppressive therapy in patients with nodular thyroid disease. Ann Intern Med 1998; 128:386.
- Puzziello A, Carrano M, Angrisani E, et al. Evolution of benign thyroid nodules under levothyroxine non-suppressive therapy. J Endocrinol Invest 2014; 37:1181.
- Gharib H, James EM, Charboneau JW, et al. Suppressive therapy with levothyroxine for solitary thyroid nodules. A double-blind controlled clinical study. N Engl J Med 1987; 317:70.
- Mainini E, Martinelli I, Morandi G, et al. Levothyroxine suppressive therapy for solitary thyroid nodule. J Endocrinol Invest 1995; 18:796.
- Lima N, Knobel M, Cavaliere H, et al. Levothyroxine suppressive therapy is partially effective in treating patients with benign, solid thyroid nodules and multinodular goiters. Thyroid 1997; 7:691.
- Cheung PS, Lee JM, Boey JH. Thyroxine suppressive therapy of benign solitary thyroid nodules: a prospective randomized study. World J Surg 1989; 13:818.
- Reverter JL, Lucas A, Salinas I, et al. Suppressive therapy with levothyroxine for solitary thyroid nodules. Clin Endocrinol (Oxf) 1992; 36:25.
- Larijani B, Pajouhi M, Bastanhagh MH, et al. Evaluation of suppressive therapy for cold thyroid nodules with levothyroxine: double-blind placebo-controlled clinical trial. Endocr Pract 1999; 5:251.
- La Rosa GL, Lupo L, Giuffrida D, et al. Levothyroxine and potassium iodide are both effective in treating benign solitary solid cold nodules of the thyroid. Ann Intern Med 1995; 122:1.
- La Rosa GL, Ippolito AM, Lupo L, et al. Cold thyroid nodule reduction with L-thyroxine can be predicted by initial nodule volume and cytological characteristics. J Clin Endocrinol Metab 1996; 81:4385.
- Papini E, Petrucci L, Guglielmi R, et al. Long-term changes in nodular goiter: a 5-year prospective randomized trial of levothyroxine suppressive therapy for benign cold thyroid nodules. J Clin Endocrinol Metab 1998; 83:780.
- Sdano MT, Falciglia M, Welge JA, Steward DL. Efficacy of thyroid hormone suppression for benign thyroid nodules: meta-analysis of randomized trials. Otolaryngol Head Neck Surg 2005; 133:391.