Effect of Thyroid-Stimulating Hormone Suppression on Muscle Function After Total Thyroidectomy in Patients With Thyroid Cancer

ContextThyroid-stimulating hormone (TSH) suppression is recommended to reduce tumor recurrence following surgery for differentiated thyroid cancer (DTC). However, prolonged subclinical hyperthyroidism caused by levothyroxine treatment has deleterious effects on various organs.ObjectiveTo evaluate the relationships of TSH concentration with muscle mass, muscle strength, and physical performance related to sarcopenia in patients with DTC undergoing TSH suppression following surgery.MethodsWe studied 134 patients of >60 years who were undergoing TSH suppression therapy following surgery for DTC. We evaluated muscle mass and muscle function-related parameters and diagnosed sarcopenia using the threshold for Asian people.ResultsThe participants were 68.3 ± 7.2 years old and 36/134 (26.9%) were diagnosed with sarcopenia. They were allocated to high-TSH and low-TSH groups using a threshold concentration of 0.40 μU/mL, and grip strength was significantly lower in the low-TSH group. The data were further analyzed according to age and sex, and in the low-TSH group, male participants and those of <70 years were found to have significantly lower grip strength.ConclusionsLow-TSH concentrations is associated with low grip strength, and this is most pronounced in individuals of <70 years of age. Therefore, muscle function should be considered an adverse effect of TSH suppression in patients with DTC who undergo TSH suppression therapy, especially in men of <70 years.

Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis

CONTEXT As subclinical hyperthyroidism increases the risk of osteoporosis and fractures, concerns are growing about the long-term skeletal safety of thyrotropin (TSH) suppression therapy after total thyroidectomy in patients with differentiated thyroid cancer (DTC). OBJECTIVE We aimed to determine the effect of TSH suppression therapy on bone mineral density (BMD) in DTC patients. METHODS We searched PubMed, Embase, the Cochrane library, and other sources. Eligible observational studies included DTC patients who underwent TSH suppression therapy and BMD measurement. Two independent reviewers extracted data on the studies’ characteristics and outcomes and determined their risk of bias. Data were extracted from each study for postmenopausal/premenopausal women’s and men’s lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD and summed using a random-effects meta-analysis model. The weighted mean difference (WMD) with 95% confidence intervals (CI) are expressed for the differences in outcome measurements between groups. RESULTS Seventeen studies (739 patients and 1085 controls) were included for quantitative analysis. In postmenopausal women, TSH suppression therapy showed a significant decrease in LS BMD (-0.03; -0.05, -0.02), and a similar trend was seen in TH. In premenopausal women, TSH suppression therapy significantly increased LS BMD (0.04; 0.02, 0.06) and FN BMD (0.02; 0.01, 0.04). In men, there was no significant association between TSH suppression therapy and BMD at any site compared to the controls. CONCLUSION Evidence from observational studies suggests that postmenopausal women treated with TSH suppression therapy are at risk for lower BMD. Attention should be paid to long-term skeletal safety in DTC survivors.

Risk Factors for Cardiovascular Disease Among Thyroid Cancer Survivors: Findings From the Utah Cancer Survivors Study

ContextThyroid cancer survivors are at high risk of developing multiple cardiac and vascular conditions as consequence of cancer diagnosis and treatment. However, it is still unclear how the baseline and prognostic factors, as well as cancer treatments, play a role in increasing cardiac and vascular disease risk among thyroid cancer survivors.ObjectiveTo investigate the association between potential risk factors, treatment effects, and cardiovascular disease (CVD) outcomes in thyroid cancer survivors.Design, Setting, PatientsPrimary thyroid cancer survivors, diagnosed from 1997 to 2012 (n = 3822), were identified using the statewide Utah Population Database. The medical records were used to ascertain information on risk factors and CVD outcomes. Cox proportional hazards models were used to assess the risk of CVD with baseline demographic data and clinical factors.ResultsAmong thyroid cancer survivors, age and year at cancer diagnosis, cancer stage, sex, baseline body mass index, baseline comorbidities, and TSH suppression therapy were significantly associated with CVD risk 1 to 5 years after cancer diagnosis. Patients who were male, overweight or obese, older at cancer diagnosis, and diagnosed with cancer since 2005 had an increased risk of CVD compared with patients who were female, had a normal body mass index, were younger at cancer diagnosis, and diagnosed with cancer from 1997 to 1999. Administration of TSH suppression therapy, distant metastases at cancer diagnosis, and a higher Charlson comorbidity index score were associated with an increased CVD risk among thyroid cancer survivors.ConclusionsOur findings suggest that examining the effect of thyroid cancer diagnosis, cancer treatment, and demographic characteristics on the risk of CVD is critical.

Coexistence of resistance to thyroid hormone and papillary thyroid carcinoma

Summary Resistance to thyroid hormone (RTH) is a syndrome of reduced tissue responsiveness to thyroid hormones. RTH is majorly caused by mutations in the thyroid hormone receptor beta (THRB) gene. Recent studies indicated a close association of THRB mutations with human cancers, but the role of THRB mutation in carcinogenesis is still unclear. Here, we report a rare case of RTH with a papillary thyroid carcinoma (PTC). A 26-year-old woman was referred to our hospital due to a thyroid tumor and hormonal abnormality. She had elevated serum thyroid hormones and non-suppressed TSH levels. Genetic analysis of THRB identified a missense mutation, P452L, leading to a diagnosis of RTH. Ultrasound-guided fine-needle aspiration biopsy of the tumor and lymph nodes enabled the cytological diagnosis of PTC with lymph node metastases. Total thyroidectomy and neck lymph nodes dissection were performed. Following surgery, thyroxine replacement (≥500 μg) was necessary to avoid the symptoms of hypothyroidism and to maintain her TSH levels within the same range as before the operation. During the follow-up, basal thyroglobulin (Tg) levels were around 6 ng/ml and TSH-stimulated Tg levels were between 12 and 20 ng/ml. Up to present, the patient has had no recurrence of PTC. This indicates that these Tg values are consistent with a biochemical incomplete response or an indeterminate response. There is no consensus regarding the management of thyroid carcinoma in patients with RTH, but aggressive treatments such as total thyroidectomy followed by radioiodine (RAI) and TSH suppression therapy are recommended. Learning points There are only a few cases reporting the coexistence of RTH and thyroid carcinoma. Moreover, our case would be the first case presenting one with lymph node metastases. Recent studies indicated a close association of THRB mutations with human cancers, but the role of THRB mutation in carcinogenesis is still unclear. When total thyroidectomy is performed in patients with RTH, a large amount of thyroxine is needed to maintain their thyroid function. There is no consensus regarding the management of thyroid carcinoma in patient with RTH, but effective treatments such as total thyroidectomy followed by RAI and TSH suppression therapy are recommended.