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Cited by 34Thyroid Cancer Diagnosis and TreatmentBone health and osteoporosis researchThyroid and Parathyroid Surgery

Effects of thyroid-stimulating hormone suppression after thyroidectomy for thyroid cancer on bone mineral density in postmenopausal women: a systematic review and meta-analysis

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Kwak, Donghee, Ha, Jane, Won, Yousun, Kwon, Yeongkeun, Park, Sungsoo·2021·BMJ Open
DOI 10.1136/bmjopen-2020-043007PMC PMC8126273
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Abstract

Objectives: We assessed thyroid-stimulating hormone (TSH) suppression effects on bone mineral density (BMD) in postmenopausal women who underwent thyroidectomy. Data sources: PubMed, EMBASE, Cochrane Library, Web of Science and SCOPUS were searched from inception to 24 February 2021. Study selection: Case-control studies were included. Data extraction and synthesis: Two authors independently reviewed the studies, extracted the data and performed meta-analysis of eligible studies. Research design and methods: Studies evaluating BMD in postmenopausal women with thyroid cancer who had thyroidectomy and levothyroxine therapy were included. Differences in BMD were presented as standardised mean differences (SMDs). Meta-analyses were conducted using a random-effects model. Results: Analysis of 16 case-control studies (426 patients and 701 controls without thyroid cancer) showed that stringent TSH suppression (TSH <0.10 mIU/L) after thyroidectomy had deleterious effects on the BMD of the lumbar spine in postmenopausal women compared with controls (SMD −0.55; 95% CI −0.99 to −0.10; I 2=75.8%). There was no significant difference in patients with moderate TSH suppression (TSH 0.10–0.49 mIU/L). TSH suppression in postmenopausal women was not significantly associated with lower femoral neck BMD. Subgroup analysis of the lumbar spine showed that the association between stringent TSH suppression and lower BMD was consistent among studies with >10 years of follow-up (SMD −0.32; 95% CI −0.50 to −0.14). Subgroup analysis of the femoral neck showed that total thyroidectomy was related to detrimental effects on the BMD of the femoral neck (SMD −0.60; 95% CI −0.89 to −0.31; I 2=90.4%), but near-total thyroidectomy was not (SMD 0.00; 95% CI −0.30 to 0.30; I 2=55.6%). Conclusions: Stringent TSH suppression had deleterious effects on the BMD of the lumbar spine after thyroidectomy in postmenopausal women. Further studies are needed to determine whether stringent TSH suppression after thyroidectomy increases the fracture risk.

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  1. [1]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– 133. 10.1089/thy.2015.0020 26462967 PMC4739132 · DOI · Paper page
  2. [2]Sugitani I, Fujimoto Y. Effect of postoperative thyrotropin suppressive therapy on bone mineral density in patients with papillary thyroid carcinoma: a prospective controlled study. Surgery 2011; 150: 1250– 7. 10.1016/j.surg.2011.09.013 22136848 · DOI
  3. [3]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: 300– 7. 10.1089/thy.2014.0287 25386760 PMC6916125 · DOI · Paper page
  4. [4]Lim H, Devesa SS, Sosa JA, et al. Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. JAMA 2017; 317: 1338– 48. 10.1001/jama.2017.2719 28362912 PMC8216772 · DOI · Paper page
  5. [5]Mazzaferri EL, Kloos RT. Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 2001; 86: 1447– 63. 10.1210/jcem.86.4.7407 11297567 · DOI
  6. [6]Biondi B, Filetti S, Schlumberger M. Thyroid-Hormone therapy and thyroid cancer: a reassessment. Nat Clin Pract Endocrinol Metab 2005; 1: 32– 40. 10.1038/ncpendmet0020 16929364 · DOI
  7. [7]Jódar E, Begoña López M, García L, et al. Bone changes in pre- and postmenopausal women with thyroid cancer on levothyroxine therapy: evolution of axial and appendicular bone mass. Osteoporos Int 1998; 8: 311– 6. 10.1007/s001980050069 10024900 · DOI · Paper page
  8. [9]Vestergaard P, Mosekilde L. Hyperthyroidism, bone mineral, and fracture risk-a meta-analysis. Thyroid 2003; 13: 585– 93. 10.1089/105072503322238854 12930603 · DOI · Paper page
  9. [10]Nicholls JJ, Brassill MJ, Williams GR, et al. The skeletal consequences of thyrotoxicosis. J Endocrinol 2012; 213: 209– 21. 10.1530/JOE-12-0059 22454529 · DOI · Paper page
  10. [11]Frusciante V, Carnevale V, Scillitani A, et al. Global skeletal uptake of technetium-99m methylene diphosphonate in female patients receiving suppressive doses of L-thyroxine for differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 1998; 25: 139– 43. 10.1007/s002590050206 9473261 · DOI
  11. [12]Toivonen J, Tahtela R, Laitinen K, et al. Markers of bone turnover in patients with differentiated thyroid cancer with and following withdrawal of thyroxine suppressive therapy. Eur J Endocrinol 1998; 138: 667– 73. 10.1530/eje.0.1380667 9678534 · DOI
  12. [13]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: 973– 81. 10.1677/erc.1.01072 16322336 · DOI
  13. [14]Goerres G, Theiler R, Müller-Brand J. Interfemur variation of bone mineral density in patients receiving high-dose thyroxin therapy. Calcif Tissue Int 1998; 63: 98– 101. 10.1007/s002239900496 9685511 · DOI · Paper page
  14. [15]Kung AWC, Lorentz T, Tam SCF. Thyroxine suppressive therapy decreases bone mineral density in post-menopausal women. Clin Endocrinol 1993; 39: 535– 40. 10.1111/j.1365-2265.1993.tb02405.x 8252741 · DOI
  15. [16]Diamond T, Nery L, Hales I. A therapeutic dilemma: suppressive doses of thyroxine significantly reduce bone mineral measurements in both premenopausal and postmenopausal women with thyroid carcinoma. J Clin Endocrinol Metab 1991; 72: 1184– 8. 10.1210/jcem-72-6-1184 2026740 · DOI
  16. [17]Tuttle RM, Haddad RI, Ball DW, et al. Thyroid carcinoma, version 2.2014. J Natl Compr Canc Netw 2014; 12: 1671– 80. 10.6004/jnccn.2014.0169 25505208 · DOI
  17. [18]Perros P, Boelaert K, Colley S, et al. Guidelines for the management of thyroid cancer. Clin Endocrinol 2014; 81: 1– 122. 10.1111/cen.12515 24989897 · DOI
  18. [21]Heemstra KA, Hamdy NAT, Romijn JA, et al. The effects of thyrotropin-suppressive therapy on bone metabolism in patients with well-differentiated thyroid carcinoma. Thyroid 2006; 16: 583– 91. 10.1089/thy.2006.16.583 16839260 · DOI
  19. [22]Parker WAE, Edafe O, Balasubramanian SP. Long-Term treatment-related morbidity in differentiated thyroid cancer: a systematic review of the literature. Pragmat Obs Res 2017; 8: 57– 67. 10.2147/POR.S130510 28553154 PMC5440065 · DOI
  20. [23]Quan ML, Pasieka JL, Rorstad O. Bone mineral density in well-differentiated thyroid cancer patients treated with suppressive thyroxine: a systematic overview of the literature. J Surg Oncol 2002; 79: 62– 70. 10.1002/jso.10043 11754378 · DOI
  21. [25]Uzzan B, Campos J, Cucherat M, et al. Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. J Clin Endocrinol Metab 1996; 81: 4278– 89. 10.1210/jcem.81.12.8954028 8954028 · DOI · Paper page
  22. [26]Wang M-Y, Han Z-Q, Gong X-W, et al. TSH-suppressive therapy can reduce bone mineral density in patients with differentiated thyroid carcinoma: a meta-analysis. Eur Rev Med Pharmacol Sci 2020; 24: 922– 9. 10.26355/eurrev_202001_20077 32016999 · DOI
  23. [27]Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009; 151: 264– 9. 10.7326/0003-4819-151-4-200908180-00135 19622511 · DOI · Paper page
  24. [28]Higgins JPT, Green S, Cochrane Collaboration. Cochrane Handbook for systematic reviews of interventions. Chichester: Wiley-Blackwell, 2009.
  25. [31]Recker DP, Shapiro B. The effect of thyroidectomy on bone mineral content in perimenopausal women. Thyroidol 1989; 1: 59– 65. 2484864
  26. [32]Franklyn JA, Betteridge J, Daykin J, et al. Long-Term thyroxine treatment and bone mineral density. Lancet 1992; 340: 9– 13. 10.1016/0140-6736(92)92423-D 1351654 · DOI
  27. [33]Abugassa S, Nordenström J, Eriksson S, et al. Bone mineral density in patients with chronic hypoparathyroidism. J Clin Endocrinol Metab 1993; 76: 1617– 21. 10.1210/jcem.76.6.8501170 8501170 · DOI
  28. [34]Giannini S, Nobile M, Sartori L, et al. Bone density and mineral metabolism in thyroidectomized patients treated with long-term L-thyroxine. Clin Sci 1994; 87: 593– 7. 10.1042/cs0870593 7874849 · DOI
  29. [35]Hawkins F, Rigopoulou D, Papapietro K, et al. Spinal bone mass after long-term treatment with L-thyroxine in postmenopausal women with thyroid cancer and chronic lymphocytic thyroiditis. Calcif Tissue Int 1994; 54: 16– 19. 10.1007/BF00316283 8118747 · DOI
  30. [36]Chen C-H, Chen J-F, Yang B-Y, et al. Bone mineral density in women receiving thyroxine suppressive therapy for differentiated thyroid carcinoma. J Formos Med Assoc 2004; 103: 442– 7. 15278189
  31. [37]Eftekhari M, Asadollahi A, Beiki D, et al. The long term effect of levothyroxine on bone mineral density in patients with well differentiated thyroid carcinoma after treatment. Hell J Nucl Med 2008; 11: 160– 3. 19081859
  32. [38]Tournis S, Antoniou JD, Liakou CG, et al. Volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in women with differentiated thyroid cancer under TSH suppression. Clin Endocrinol 2015; 82: 197– 204. 10.1111/cen.12560 25040693 · DOI
  33. [39]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– 10. 10.1016/j.bone.2015.10.015 26518742 · DOI
  34. [40]Kim EH, Jeon YK, Pak K, et al. Effects of thyrotropin suppression on bone health in menopausal women with total thyroidectomy. J Bone Metab 2019; 26: 31– 8. 10.11005/jbm.2019.26.1.31 30899722 PMC6416151 · DOI · Paper page
  35. [41]Berger C, Langsetmo L, Joseph L, et al. Association between change in BMD and fragility fracture in women and men. J Bone Miner Res 2009; 24: 361– 70. 10.1359/jbmr.081004 18847328 PMC5104566 · DOI
  36. [42]Cooper DS, Specker B, Ho M, et al. Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National thyroid cancer treatment cooperative registry. Thyroid 1998; 8: 737– 44. 10.1089/thy.1998.8.737 9777742 · DOI
  37. [43]Jonklaas J, Sarlis NJ, Litofsky D, et al. Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid 2006; 16: 1229– 42. 10.1089/thy.2006.16.1229 17199433 · DOI
  38. [44]Biondi B, Cooper DS. Benefits of thyrotropin suppression versus the risks of adverse effects in differentiated thyroid cancer. Thyroid 2010; 20: 135– 46. 10.1089/thy.2009.0311 20151821 · DOI · Paper page
  39. [45]Flynn RW, Bonellie SR, Jung RT, et al. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab 2010; 95: 186– 93. 10.1210/jc.2009-1625 19906785 · DOI · Paper page
  40. [46]Viniol A, Hickstein L, Walker J, et al. Influence of thyroid hormone therapy on the fracture rate — a claims data cohort study. Bone 2016; 86: 86– 90. 10.1016/j.bone.2016.03.002 26946131 · DOI
  41. [47]Lin S-Y, Lin C-L, Chen H-T, et al. Risk of osteoporosis in thyroid cancer patients using levothyroxine: a population-based study. Curr Med Res Opin 2018; 34: 805– 12. 10.1080/03007995.2017.1378174 28884595 · DOI
  42. [48]Faber J, Galløe AM. Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis. Eur J Endocrinol 1994; 130: 350– 6. 10.1530/eje.0.1300350 8162163 · DOI · Paper page
  43. [49]Pacifici R, Estrogen PR. Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res 1996; 11: 1043– 51. 10.1002/jbmr.5650110802 8854239 · DOI · Paper page
  44. [50]Abe E, Marians RC, Yu W, et al. Tsh is a negative regulator of skeletal remodeling. Cell 2003; 115: 151– 62. 10.1016/S0092-8674(03)00771-2 14567913 · DOI · Paper page
  45. [51]Albright F, Smith PH, Richardson AM. Postmenopausal osteoporosis: its clinical features. JAMA 1941; 116: 2465– 74.
  46. [52]Schaadt O, Bohr H. Different trends of age-related diminution of bone mineral content in the lumbar spine, femoral neck, and femoral shaft in women. Calcif Tissue Int 1988; 42: 71– 6. 10.1007/BF02556337 3127027 · DOI
  47. [53]Ensrud KE. Epidemiology of fracture risk with advancing age. J Gerontol A Biol Sci Med Sci 2013; 68: 1236– 42. 10.1093/gerona/glt092 23833201 · DOI · Paper page
  48. [54]Ensrud KE, Thompson DE, Cauley JA, et al. Prevalent vertebral deformities predict mortality and hospitalization in older women with low bone mass. J Am Geriatr Soc 2000; 48: 241– 9. 10.1111/j.1532-5415.2000.tb02641.x 10733048 · DOI
  49. [55]Melton LJ, Ardila E, Crowson CS, et al. Fractures following thyroidectomy in women: a population-based cohort study. Bone 2000; 27: 695– 700. 10.1016/S8756-3282(00)00379-3 11062358 · DOI
  50. [56]Ojomo KA, Schneider DF, Reiher AE, et al. Using body mass index to predict optimal thyroid dosing after thyroidectomy. J Am Coll Surg 2013; 216: 454– 60. 10.1016/j.jamcollsurg.2012.12.002 23318118 PMC3658157 · DOI
  51. [57]Ballinger CB, Browning MCK, Smith AHW. Hormone profiles and psychological symptoms in peri-menopausal women. Maturitas 1987; 9: 235– 51. 10.1016/0378-5122(87)90006-5 3431475 · DOI
  52. [58]Mosekilde L, Christensen MS. Decreased parathyroid function in hyperthyroidism: interrelationships between serum parathyroid hormone, calcium-phosphorus metabolism and thyroid function. Acta Endocrinol 1977; 84: 566– 75. 10.1530/acta.0.0840566 576531 · DOI
  53. [59]Goichot B, Sapin Rémy, Schlienger JL. Subclinical hyperthyroidism: considerations in defining the lower limit of the thyrotropin reference interval. Clin Chem 2009; 55: 420– 4. 10.1373/clinchem.2008.110627 19147733 · DOI
  54. [60]Hakami Y, Khan A. Hypoparathyroidism. Front Horm Res 2019; 51: 109– 26. 10.1159/000491042 30641528 · DOI

Cited by

Sorted by citations

Authors
Kwak, D., Ha, J., Won, Y., Kwon, Y., & Park, S.
Affiliations
Korea University (KR)
Corresponding author
Kwon, Yeongkeun
ORCID
Venue
BMJ Open
Publisher
BMJ
Published
2021-05
Volume
11
Issue
5
Pages
e043007
ISSN
2044-6055 (ISSN-L)
DOI
10.1136/bmjopen-2020-043007
PMC
PMC8126273
OpenAlex
W3162451528
Cited by
34
References
5
Citations by year
2026: 7 · 2025: 7 · 2024: 9 · 2023: 3 · 2022: 7 · 2021: 1
FWCI
0.77
Type
journal article
Language
en
Open access
Licence
Locations
  • BMJ Open (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Research Foundation of Korea (2020R1I1A1A01070106)
  • The Korea government (Project Number: 9991007295, KMDF_PR_202012D13-02)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Keywords
TSH suppression, bone mineral density, thyroidectomy, thyroid cancer, postmenopausal women, levothyroxine, lumbar spine, femoral neck, total thyroidectomy, near-total thyroidectomy, fracture risk, osteoporosis, hormone replacement therapy
MeSH terms
Female, Humans, Thyroid Neoplasms, Thyroidectomy, Thyrotropin, Thyroxine, Bone Density, Osteoporosis, Postmenopausal, Postmenopause

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