Thyrotropin Suppression Increases the Risk of Osteoporosis Without Decreasing Recurrence in ATA Low- and Intermediate-Risk Patients with Differentiated Thyroid Carcinoma
Open accessAbstract
BACKGROUND: Levothyroxine suppression of thyrotropin (TSH) is broadly applied to patients with thyroid cancer despite lack of consensus on the optimal TSH concentration necessary to reduce cancer recurrence while minimizing toxicity from subclinical hyperthyroidism. The objectives of this study were to examine the beneficial effects and the cardiac and skeletal toxicity of TSH suppression in well-differentiated thyroid carcinoma (DTC). METHODS: A total of 771 patients (569 women) at ATA low or intermediate risk of recurrence, with a mean age of 48±14 years, and undergoing total thyroidectomy at a tertiary care center between 2000 and 2006 were followed for a median of six and a half years. They were divided into a suppressed TSH group (median TSH ≤0.4 mIU/L) and a nonsuppressed group (median TSH >0.4 mIU/L). Structural recurrence of thyroid cancer, postoperative atrial fibrillation (AF), and osteoporosis were examined in the two groups. Osteoporosis was only examined in women. RESULTS: A total of 43/771 (5.6%) patients recurred, 29/739 (3.9%) patients were diagnosed with postoperative osteoporosis, and 17/756 (2.3 %) were diagnosed with postoperative AF. Despite similar rates of recurrence (HR 1.02, p=0.956 [CI 0.54-1.91]), patients treated to a median TSH ≤0.4 mIU/L were at increased postoperative risk of a composite outcome of AF and osteoporosis (HR 2.1, p=0.05 [CI 1.001-4.3]) compared to those not suppressed. A differential risk of AF alone (HR 0.78, p=0.63 [CI 0.3-2.1]) was not detected, but postoperative osteoporosis was increased among women with a suppressed TSH compared to those not suppressed (HR 3.5, p=0.023 [CI 1.2-10.2]). The increased risk of postoperative osteoporosis disappeared when the patient's median TSH was maintained around 1 mIU/L. CONCLUSION: TSH suppression significantly increases the risk of postoperative osteoporosis without changing tumor recurrence in ATA low- and intermediate-risk patients with DTC. Future interventions should focus on avoiding harm in indolent disease.
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Several large cohorts or prospective studies reporting the prevalence of osteoporosis or fractures in patients with TSH suppression therapy were not included because they did not provide accurate data.
“In addition, several large cohorts or prospective studies reporting the prevalence of osteoporosis or fractures in patients with TSH suppression therapy were not included because they did not provide the accurate data (52)(53)(54)(55).”
From Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis (2021) · cites this paper as [54]
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References 47 · Cited by 161
- Authors
- Wang, L. Y., Smith, A. W., Palmer, F. L., Tuttle, R. M., Mahrous, A., Nixon, I. J., Patel, S. G., Ganly, I., Fagin, J. A., & Boucai, L.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Boucai, Laura
- ORCID
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2015-03
- Volume
- 25
- Issue
- 3
- Pages
- 300-307
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- PMC
- PMC6916125
- OpenAlex
- W2153327849
- Cited by
- 161
- References
- 47
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 10 · 2023: 12 · 2022: 15 · 2021: 22 · 2020: 13 · 2019: 21 · 2018: 10 · 2017: 13 · 2016: 9 · 2015: 13
- FWCI
- 9.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Thyroid (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- TSH suppression, levothyroxine, differentiated thyroid cancer, recurrent thyroid cancer, postoperative atrial fibrillation, subclinical hyperthyroidism, total thyroidectomy, thyroid cancer risk stratification, women, cardiotoxicity, skeletal toxicity, long-term follow-up
- MeSH terms
- Adult, Aged, Bone and Bones, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Osteoporosis, Postoperative Complications, Recurrence, Risk Factors, Thyroid Neoplasms, Thyroidectomy, Thyrotropin, Thyroxine, Multivariate Analysis, Disease-Free Survival
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