Effects of levothyroxine therapy on bone mineral density and bone turnover markers in premenopausal women with thyroid cancer after thyroidectomy
Abstract
Introduction: We investigated the impact of long-term levothyroxine (LT4) treatment on bone mineral density (BMD) and bone turnover markers (BTMs) in premenopausal women with differentiated thyroid cancer (DTC) after thyroidectomy.
Material and methods: Sixty-five premenopausal women who received LT4 therapy at least one year (range, 1.5–9.0 years) after thyroidectomy for DTC and 50 premenopausal women without thyroid diseases were enrolled in this study. We measured the Z-scores of lumbar and hip BMD, serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), intact parathyroid hormone (iPTH), N-terminal propeptide of type 1 N procollagen (P1NP), C terminal telopeptide of type 1 collagen (CTX-1), calcium (Ca), phosphorus (P), vitamin D3, and alkaline phosphatase (ALP) in all participants.
Results: In DTC subjects, serum TSH levels were lower, and serum FT4, P1NP, CTX-1, and ALP levels were higher compared with controls. The prevalence of low BMD was higher in DTC subjects than in controls. Multivariate logistic regression analysis showed that serum TSH levels were negatively associated with CTX-1 and ALP.
Conclusions: We found a high prevalence of low BMD among premenopausal women who received long-term LT4 therapy for DTC after thyroidectomy. Long-term TSH suppression therapy was a significant risk factor for decreased bone strength, mainly by increasing bone turnover.
Keywords: levothyroxinebone mineral densitywomenbone turnover markersthyroid cancerthyroidectomy
References
- Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016; 388(10061): 2783–2795.
- Lim H, Devesa SS, Sosa JA, et al. Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974-2013. JAMA. 2017; 317(13): 1338–1348.
- Mirian C, Grønhøj C, Jensen DH, et al. Trends in thyroid cancer: Retrospective analysis of incidence and survival in Denmark 1980-2014. Cancer Epidemiol. 2018; 55: 81–87.
- Daniels GH. Follicular Thyroid Carcinoma: A Perspective. Thyroid. 2018; 28(10): 1229–1242.
- Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014; 159(3): 676–690.
- Tam S, Boonsripitayanon M, Amit M, et al. Survival in Differentiated Thyroid Cancer: Comparing the AJCC Cancer Staging Seventh and Eighth Editions. Thyroid. 2018; 28(10): 1301–1310.
- Schmidbauer B, Menhart K, Hellwig D, et al. Differentiated Thyroid Cancer-Treatment: State of the Art. Int J Mol Sci. 2017; 18(6).
- Takami H, Ito Y, Okamoto T, et al. Revisiting the guidelines issued by the Japanese Society of Thyroid Surgeons and Japan Association of Endocrine Surgeons: a gradual move towards consensus between Japanese and western practice in the management of thyroid carcinoma. World J Surg. 2014; 38(8): 2002–2010.
- Biondi B, Cooper DS. Thyroid Hormone Suppression Therapy. Endocrinol Metab Clin North Am. 2019; 48(1): 227–237.
- Roman BR, Morris LG, Davies L. The thyroid cancer epidemic, 2017 perspective. Curr Opin Endocrinol Diabetes Obes. 2017; 24(5): 332–336.
- Biondi B, Cooper DS. Benefits of thyrotropin suppression versus the risks of adverse effects in differentiated thyroid cancer. Thyroid. 2010; 20(2): 135–146.
- Freudenthal B, Williams GR. Thyroid Stimulating Hormone Suppression in the Long-term Follow-up of Differentiated Thyroid Cancer. Clin Oncol (R Coll Radiol). 2017; 29(5): 325–328.
- Reverter JL, Colomé E. [Potential risks of the adverse effects of thyrotropin suppression in differentiated thyroid carcinoma]. Endocrinol Nutr. 2011; 58(2): 75–83.
- Williams GR, Bassett JHD. Thyroid diseases and bone health. J Endocrinol Invest. 2018; 41(1): 99–109.
- Bassett JH, Williams GR. Role of thyroid hormones in skeletal development and bone maintenance. Endocr Rev. 2016; 37(2): 135–187.
- Tsourdi E, Lademann F, Siggelkow H. [Impact of thyroid diseases on bone]. Internist (Berl). 2018; 59(7): 661–667.
- Baliram R, Sun Li, Cao J, et al. Hyperthyroid-associated osteoporosis is exacerbated by the loss of TSH signaling. J Clin Invest. 2012; 122(10): 3737–3741.
- Donangelo I, Suh SeY. Subclinical Hyperthyroidism: When to Consider Treatment. Am Fam Physician. 2017; 95(11): 710–716.
- Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016; 26(10): 1343–1421.
- de Melo TG, da Assumpção LV, Santos Ad, et al. Low BMI and low TSH value as risk factors related to lower bone mineral density in postmenospausal women under levothyroxine therapy for differentiated thyroid carcinoma. Thyroid Res. 2015; 8: 7.
- Wang LY, Smith AW, Palmer FL, et al. Thyrotropin suppression increases the risk of osteoporosis without decreasing recurrence in ATA low- and intermediate-risk patients with differentiated thyroid carcinoma. Thyroid. 2015; 25(3): 300–307.
- Kim CW, Hong S, Oh SeH, et al. Change of Bone Mineral Density and Biochemical Markers of Bone Turnover in Patients on Suppressive Levothyroxine Therapy for Differentiated Thyroid Carcinoma. J Bone Metab. 2015; 22(3): 135–141.
- Rossini M, Adami S, Bertoldo F, et al. Guidelines for the diagnosis, prevention and management of osteoporosis. Reumatismo. 2016; 68(1): 1–39.
- World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013; 310(20): 2191–2194.
- Reverter JL, Holgado S, Alonso N, et al. Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma. Endocr Relat Cancer. 2005; 12(4): 973–981.
- Yoon BH, Lee Y, Oh HJ, et al. Influence of Thyroid-stimulating Hormone Suppression Therapy on Bone Mineral Density in Patients with Differentiated Thyroid Cancer: A Meta-analysis. J Bone Metab. 2019; 26(1): 51–60.
- Moon JH, Jung KY, Kim KM, et al. The effect of thyroid stimulating hormone suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma. Bone. 2016; 83: 104–110.
- Cauley JA. Estrogen and bone health in men and women. Steroids. 2015; 99(Pt A): 11–15.
- Zhang P, Xi H, Yan R. Effects of thyrotropin suppression on lumbar bone mineral density in postmenopausal women with differentiated thyroid carcinoma. Onco Targets Ther. 2018; 11: 6687–6692.
- Cohen A. Premenopausal Osteoporosis. Endocrinol Metab Clin North Am. 2017; 46(1): 117–133.
- Melton LJ, Ardila E, Crowson CS, et al. Fractures following thyroidectomy in women: a population-based cohort study. Bone. 2000; 27(5): 695–700.
- Lin SY, Lin CL, Chen HT, et al. Risk of osteoporosis in thyroid cancer patients using levothyroxine: a population-based study. Curr Med Res Opin. 2018; 34(5): 805–812.
- Babu RP, Christy A, Hegde A, et al. Do premenopausal hypothyroid women on levothyroxine therapy need bone status monitoring? Clin Med Insights Womens Health. 2015; 8: 1–6.
- Baqi L, Payer J, Killinger Z, et al. Thyrotropin versus thyroid hormone in regulating bone density and turnover in premenopausal women. Endocr Regul. 2010; 44(2): 57–63.
- Abrahamsen Bo, Jørgensen HL, Laulund AS, et al. The excess risk of major osteoporotic fractures in hypothyroidism is driven by cumulative hyperthyroid as opposed to hypothyroid time: an observational register-based time-resolved cohort analysis. J Bone Miner Res. 2015; 30(5): 898–905.
- Amato G, Mazziotti G, Sorvillo F, et al. High serum osteoprotegerin levels in patients with hyperthyroidism: effect of medical treatment. Bone. 2004; 35(3): 785–791.
- Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016; 26(1): 1–133.
![](https://journals.viamedica.pl/plugins/generic/popups/images/icons/close.png)