Thyroid-stimulating Hormone Suppression Research Articles

Clinical inertia in thyrotropin suppressive therapy for low-risk differentiated thyroid cancer: A real-world experience at an endocrine center in Bangkok.

The management of low-risk differentiated thyroid cancer (DTC) has evolved over time toward treatment de-escalation. However, overtreatment with supraphysiological dose of levothyroxine (LT4) continues to be observed despite current clinical guideline. This study aimed to assess the actual thyrotropin suppressive therapy for low-risk DTC patients at an endocrine center in Bangkok. This retrospective study included patients with low-risk DTC who were regularly follow-up for at least 18 months at Theptarin Hospital between 2016 and 2022. The serum thyroid stimulating hormone (TSH) levels were stratified as TSH < 0.1 mIU/L; TSH 0.1 to 0.5 mIU/L; TSH 0.5 to 2.0 mIU/L; and TSH > 2.0 mIU/L. The initial risk stratification (IRS) and dynamic risk stratification were determined at 12 months of follow-up after completing the initial treatment and at the last visit. The clinical factors associated with overtreatment with LT4 were analyzed. A total of 102 patients (83.3% female, age at diagnosis 41.8 ± 13.6 years, mean tumor size 1.6 ± 1.0 cm) were evaluated with a mean follow-up of 5.9 years. The IRS classified 92.2% of patients after the initial treatment and 93.1% of patients at the last follow-up visit into the excellent response category. The mean LT4 daily dosage at the last follow-up was 121.3 ± 44.8 µg/day. Serum TSH levels were in an appropriate target range according to IRS in only 8.8% (9/102) of the patients and then improved to 19.6% (20/102) at the last follow-up visit. Further analysis showed that treating physicians with ≥10 years of practice was associated with severe TSH suppression therapy (TSH < 0.1 mIU/L). Despite the current clinical guideline recommendations and scientific evidences, less than one-fifth of low-risk DTC patients achieved the appropriate serum TSH target. While the proportion of an optimum LT4 suppressive had improved during the study period, further efforts are needed to overcome this clinical inertia.

Clinical Manifestations of Malignant Struma Ovarii: A Retrospective Case Series in a Tertiary Hospital in Korea.

Malignant struma ovarii (MSO) is a very rare disease in which thyroid cancer originates from the ovary. Because it is rare for endocrinologists to encounter patients with MSO, endocrinologists may have a limited understanding of the disease. Therefore, we analyzed and introduced its incidence and clinical course in a tertiary hospital in Korea. We retrospectively investigated the clinical data of 170 patients who underwent surgery for struma ovarii at the Department of Obstetrics and Gynecology of Samsung Medical Center from 1994 to May 2023. Among 170 patients with struma ovarii, 15 (8.8%) were diagnosed with MSO. The median age of patients with MSO was 48 years (range, 30 to 74), and the median tumor size was 3.3 cm (range, 0.5 to 11.0). Papillary thyroid carcinoma (46.7%) was the most common subtypes followed by follicular thyroid carcinoma (26.7%). All patients were diagnosed after surgery, with no predictions from preoperative imaging. The surgical extent of gynecological surgery was variable. Four patients (26.7%) underwent thyroidectomy for thyroid cancer, while one underwent total thyroidectomy and radioactive iodine therapy for MSO with peritoneal metastasis. Except for one patient who underwent hemithyroidectomy, thyroid stimulating hormone suppression therapy was performed in four patients. Only 53% of MSO patients were consulted by an endocrinologist. With a median follow-up period of 33 months (range, 4 to 156), 11 patients remained disease-free, one experienced progression with peritoneal seeding, and the remaining one was in treatment. There have been no recurrences or deaths due to MSO. An endocrinologist should be involved in establishing a therapeutic plan for MSO, for which the overall prognosis is generally favorable.

The Effect of Thyrotropin Suppression on Survival Outcomes in Patients with Differentiated Thyroid Cancer: A Systematic Review and Meta-Analysis.

Background: Long-term management of intermediate- and high-risk differentiated thyroid cancer (DTC) involves thyrotropin (TSH) suppression with thyroid hormone to prevent potential stimulation of TSH receptors on DTC cells, leading to tumor growth. However, the current guidelines recommending TSH suppression are based on low- to moderate-quality evidence. Methods: We performed a systematic review and meta-analysis of studies evaluating the role of TSH suppression in intermediate- and high-risk DTC patients (≥18 years) treated as per regional guideline-based therapy with a follow-up duration of 5 years (PROSPERO #252396). TSH suppression was defined as "below normal reference range" or, when known, <0.5 mIU/L. Primary outcome measures included (i) composite of progression-free survival (PFS), disease-free survival (DFS), and relapse-free survival (RLFS), and (ii) composite of disease-specific survival (DSS), and overall survival (OS). Secondary outcome included a composite of cardiac or skeletal adverse events. All outcomes and comparisons were represented as TSH suppression versus TSH nonsuppression. Randomized controlled trials, cohort studies, and case-control studies were included for analysis. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using random-effects model. Results: Abstract screening was performed on 6,369 studies. After the exclusion of irrelevant studies and full-text screening, nine studies were selected for the final meta-analysis. Based on seven studies (3,591 patients), the composite outcome of PFS, DFS, and RLFS was not significantly different between TSH suppression and nonsuppression groups (HR: 0.75; 95% CI: 0.48-1.17; I2 = 76%). Similarly, a DSS and OS composite outcome assessment based on four studies (3,616 patients) did not favor TSH suppression (HR: 0.69; 95% CI: 0.31-1.52; I2 = 88%). Even after excluding studies of lower quality, the primary outcomes were not significantly different between the TSH suppression and nonsuppression cohorts. The secondary outcome, obtained from two studies (1,294 patients), was significantly higher in the TSH-suppressed groups (HR: 1.82; 95% CI: 1.30-2.55; I2 = 0%). Significant study heterogeneity was noted for primary outcomes. Conclusion: TSH suppression in intermediate- and high-risk DTC may not improve survival outcomes but may increase the risk of secondary complications. However, the limited evidence and study heterogeneity warrant cautious interpretation of our findings. Registration: PROSPERO #252396.

3. Thyrotropin Suppression During Intoxication Mediates a Positive Effect of Alcohol on Kidney Function in Males

3. Thyrotropin Suppression During Intoxication Mediates a Positive Effect of Alcohol on Kidney Function in Males

Risk of Subsequent Primary Cancers in Thyroid Cancer Survivors according to the Dose of Levothyroxine: A Nationwide Cohort Study.

Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients. We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy. A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05-1.24 and 1.17- 1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence. High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy.

Five-Year Follow-Up of Health-Related Quality of Life in Differentiated Thyroid Cancer Patients Treated with Total Thyroidectomy and Radioiodine in Sweden: A Nationwide Prospective Cohort Study.

Background: Despite a good prognosis, survivors of differentiated thyroid cancer (DTC) may have reduced health-related quality of life (HRQOL) many years after treatment, and it is unclear how suppression of thyroid-stimulating hormone (TSH) may contribute to HRQOL. This study investigated changes in HRQOL in the 5 years following DTC treatment, the association between HRQOL and TSH suppression, and how HRQOL compares to the general population. Methods: In this nationwide prospective cohort study, 487 patients with DTC were identified between 2012 and 2017 from all Swedish hospitals treating patients with DTC. Patients treated with total thyroidectomy and planned for radioiodine answered the Swedish version of the Short Form-36 Health Survey (SF-36) and a study specific questionnaire at treatment and after 1, 3, and 5 years. Summary measures for physical and mental QOL were derived from the SF-36, and TSH values were collected from patient records. To study changes in HRQOL over time, linear mixed models were fitted on multiply imputed data, with all patients and measurement points included in the model. Results: In total, 351 patients consented to participate in the study. In the 5 years following DTC treatment, physical QOL did not change significantly with time, while mental QOL improved by on average 0.61 (p < 0.001) per year. TSH levels were not predictive of either physical or mental QOL, or their change over time. At 5 years, there was a significant difference in physical and mental QOL compared with the Swedish general population, but effect sizes were small (Cohen's d = 0.29 and -0.21, respectively). The SF-36 domains general health, vitality, social functioning, and mental health were lower at 5 years compared with the general population (difference 8.7-13.3), and these differences were clinically significant. Conclusions: The mental component of HRQOL improves over time following DTC treatment. HRQOL in patients with DTC is not explained by TSH suppression. Although overall differences in physical and mental HRQOL compared with the general population were small 5 years after treatment, several specific psychosocial HRQOL domains were clinically meaningfully reduced. Psychosocial health issues should be screened for during DTC follow-up.

Effect of TSH Suppression Therapy on Sex Hormone Levels after Thyroid Cancer Surgery

Objective: To analyze the effect of thyroid-stimulating hormone (TSH) suppression therapy on sex hormone levels in patients undergoing postoperative treatment for thyroid cancer. Methods: A total of 40 patients undergoing postoperative thyroid cancer treatment were selected for data analysis. TSH suppression therapy was implemented during the postoperative period. Patients were grouped according to the TSH level: TSH &lt; 0.1, 0.1 ≤ TSH &lt; 0.5, and TSH ≥ 0.5. Results: Among male patients, there were no significant differences in sex hormone levels at different dosing times and TSH levels (P &gt; 0.05). For female patients, testosterone levels at different dosing times showed no significant differences under the same circumstances (P &gt; 0.05). The comparison of testosterone levels at different TSH levels over 5 years of TSH suppression therapy did not yield significant differences (P &gt; 0.05). However, the comparison of testosterone levels within 5 years of TSH suppression therapy yielded significant differences (P &lt; 0.05), with the lowest levels observed at 0.1 ≤ TSH &lt; 0.5. Conclusion: The use of TSH suppression therapy in postoperative thyroid cancer treatment minimally affects sex hormone levels in male patients. However, it has a significant impact on female patients. Therefore, preoperative sex hormone testing is recommended, and postoperative monitoring should include regular sex hormone testing.

Effect of thyroid-stimulating hormone suppression on quality of life in thyroid lobectomy patients: interim analysis of a multicenter, randomized controlled trial in low- to intermediate-risk thyroid cancer patients (MASTER study).

Current clinical practices favor less or no thyroid-stimulating hormone (TSH) suppression for low- to intermediate-risk thyroid cancer patients who receive thyroid lobectomy. The association of TSH suppression on health-related quality of life (HR-QoL) in patients after thyroid lobectomy is not well studied. This study aimed to evaluate the effect of TSH suppression on patient HR-QoL after thyroid lobectomy. This study included patients enrolled in an ongoing, multicenter, randomized controlled study investigating the effects of TSH suppression. Patients were randomized to either the low-TSH group (TSH target range, 0.3-1.99 µIU/mL) or the high-TSH group (TSH target range, 2.0-7.99 µIU/mL). The HR-QoL, hyperthyroidism symptom, and depression symptom questionnaires performed preoperatively and 2 weeks and 3 months postoperatively were evaluated. Total of 669 patients (low-TSH group, 340; high-TSH group, 329) were included. Although total HR-QoL score changes were not different between the 2 groups, the high-TSH group had a significantly higher score in the physical domain at postoperative 3 months (P = 0.046). The 2 groups did not have significant differences in hyperthyroidism and depression scores. In the short-term postoperative period, the physical HR-QoL scores in thyroid lobectomy patients were better when they did not receive TSH suppression. This study suggests the importance of considering HR-QoL when setting TSH suppression targets in thyroid lobectomy patients.

Chapter 6: Risk Stratification and Surveillance in Differentiated Thyroid Cancers

ABSTRACT Surveillance strategies in differentiated thyroid cancers (DTCs) differ from other head-and-neck subsites by virtue of their excellent prognosis. Guidelines in this chapter are based on a comprehensive literature review, particularly in the Indian setting concurred upon by experts in the field. Key recommendations include serial measurement of thyroglobulin values, thyroglobulin antibodies, and risk-based suppression of thyroid-stimulating hormone during follow-up of treated DTCs, with radioactive iodine scan and structural imaging based on dynamic risk stratification. These recommendations take into consideration prevailing Indian scenario related to reliability of follow-up, insurance coverage, as well as burden on health-care systems.

Determination of Frequency of Type 2 Deiodinase Thr92Ala Polymorphism (rs225014) in 131I-treated Differentiated Thyroid Cancer Patients Undertaking L-thyroxine (L-T4) Suppression Therapy

Introduction: Type 2 deiodinase (DIO2) enzyme plays a vital role in peripheral T4 to T3 conversion and in the negative feedback regulation of pituitary thyroid-stimulating hormone (TSH) secretion. Thr92Ala polymorphism (rs225014) is a common single-nucleotide polymorphism (SNP) that lowers DIO2 activity and is associated with diverse physiological disorders. Differentiated thyroid cancer (DTC) patients are given L-T4 therapy after total thyroidectomy and 131I treatment to suppress TSH levels. Aim: The aim of the study was to determine the frequency of rs225014 in DTC patients and to investigate its effect on the thyroid function tests (TFTs) and L-T4 dose required to suppress TSH levels. Materials and Methods: The study included a DTC patient group and a control group. TFTs were estimated by RIA/IRMA kits. Genomic DNA of all the subjects was screened for rs225014 SNP by polymerase chain reaction. Results: The frequency of Thr/Thr (wild type), Thr/Ala (heterozygous mutant), and Ala/Ala (homozygous mutant) genotypes in the DTC patients’ group was 0.21, 0.52, and 0.27, respectively. T3 levels and T3/T4 ratio were significantly low in the Ala/Ala genotype in the DTC group indicating impaired DIO2 activity. L-T4 dose requirement to suppress TSH levels in the DTC patients harboring rs225014 SNP was not statistically different from the wild-type genotype. Conclusion: The SNP rs225014 was observed to be associated with T3 and T3/T4 ratio but not with the L-T4 dose in DTC harboring SNP suggesting the presence of a compensatory pathway to overcome DIO2 impairment. However, it is essential to study the genetic makeup of DTC patients showing reduced response to TSH suppression to enable quicker decision-making in the implementation of personalized L-T4 dose to prevent any adverse effects.

Effects of short- and long-term TSH suppression on lumbar bone mineral density in both genders using PET/CT

Iatrogenic subclinical hyperthyroidism is induced intentionally in patients with differentiated thyroid cancer to reduce the risk of tumor recurrence. This retrospective study aimed to investigate the effect of thyroid-stimulating hormone (TSH) suppressive therapy on bone mineral density in men and women. Two cohorts of endocrine cancer patients were compared. In cohort A, 42 patients with long-lasting suppressed serum TSH were assessed. Cohort B consisted of 41 euthyroid patients. Bone density was measured in the L1-L4 lumbar vertebrae of all patients using PET/CT scans performed for cancer staging. In 17 patients of cohort A who received a second PET/CT scan, bone density was measured again to provide longitudinal analysis. A non-significant difference in age (p = .572) and equal distribution of sex (p = .916) was determined when comparing both cohorts. A significant difference (p = .011) with a moderate effect (η2 = .08; 20.4%) was observed regarding higher bone mineral density (BMD^HU) in cohort B with normal TSH levels (M 160.63 ± 54.7 HU) versus cohort A under TSH suppression therapy (M 127.9 ± 59.5 HU) for a mean duration of 4.45 ± 2.64 years. Furthermore, no significant change in BMD^HU (p = .786) was found in those patients who received a second PET/CT scan after a mean observation time of 2.3 ± 1.2 years. In conclusion, long-lasting TSH suppression therapy caused a statistically significant decrease in BMD^HU while short-lasting therapy didn't. Therefore, we can assume a higher likelihood of osteoporosis in those patients under prolonged TSH suppression.

Assessment for bone health in patients with differentiated thyroid carcinoma after postoperative thyroid-stimulating hormone suppression therapy: a new fracture risk assessment algorithm.

The fracture risk assessment tool (FRAX) is used to assess the 10-year risk of major site and hip fractures; however, whether this tool can be applied to patients receiving levothyroxine-based thyroid-stimulating hormone (TSH) suppressive therapy for postoperative differentiated thyroid cancer (DTC) patients is yet to be clarified. A total of 64 patients with DTC following thyroidectomy and oral levothyroxine for TSH suppression therapy and 30 gender- and age-matched controls were collected. The fracture risk was compared between the affected groups with different TSH levels. FRAX was used to calculate the fracture risk with and without bone mineral density (BMD). The TSH level was converted to an age-weighted score to estimate the fracture risk of postoperatively differentiated thyroid cancer patients. The sensitivity, specificity, and area under the AUC curve of the traditional FRAX and the new algorithm for osteoporosis diagnosis were compared. The dual-energy X-ray bone mineral density measurement T score was used as the gold standard to diagnose osteoporosis. There were 24 patients in the T ≥ -1-2.5 group, 23 in the -2.5 < T < -1 group, and 17 in the T ≤ -2.5 group. The T score of BMD in the disease group was significantly lower than that in the control group (p < 0.05). The risk of MOF and hip fracture without a T score were significantly different under various TSH levels (p < 0.05). The area under the curve (AUC) of FRAX without BMD for predicting major osteoporotic fractures (PMOF) and major hip fractures (PHF) was 0.694 and 0.683, respectively. The cutoff values were 2.15% and 0.25%, respectively. The AUC of FRAX with BMD for PMOF and PHF was 0.976 and 0.989, respectively, and the cutoff values were 4.15% and 1.1%, respectively. The AUC of FRAX without BMD for PMOF and PHF was 0.708 and 0.72, respectively, and the cutoff values were 5.5% and 1.55%, respectively. FRAX is suitable for postoperative DTC patients after TSH suppressive therapy. In the absence of BMD, TSH weighted by age can improve the specificity of FRAX in the diagnosis of osteoporosis in this population.

Differentiated thyroid cancer: a focus on post-operative thyroid hormone replacement and thyrotropin suppression therapy.

This review focuses on post-operative thyroid hormone replacement and thyrotropin suppression therapy in patients with differentiated thyroid cancer. A clinical review. Differentiated thyroid cancers (DTC), including papillary and follicular thyroid cancers, have an excellent prognosis and their management leverages a unique set of clinical tools arising from homology to the normal thyroid follicular cell. Surgery is the cornerstone of initial management, and post-operative care often requires thyroid hormone replacement therapy, which may be approached with the intent of physiologic normalization or used pharmacologically to suppress TSH as part of a DTC treatment. Management of DTC and approaches to TSH suppression are tailored to an individual's risk of DTC recurrence and are adjusted to a patient's clinical status and comorbidities over time with the goal of mitigating risk and maximizing benefit.

FRI511 Bexarotene: A Deceptive Cause Of Iatrogenic Hypothyroidism

Abstract Disclosure: S. Ghaith: None. A. Ramachandran: None. C. Alcorn: None. F. Amer: None. A. Thompson: None. A. Ramachandran: None. Background: Bexarotene, an antineoplastic agent used for the treatment of cutaneous T cell lymphoma, is associated with a rapid and profound suppression of thyrotropin, which may lead to central hypothyroidism. Case: A Seventy-four-year-old female with a recent diagnosis of Cutaneous T cell lymphoma presented with a 1-week history of progressive fatigue, lightheadedness, and night sweats. She was found to have hypotension and hypothermia. She was started on oral Bexarotene chemotherapy 225 mg daily five days prior to admission. The physical exam was unremarkable except for sinus bradycardia and hypothermia. Labs were significant for TSH 0.48 [0.4-4.2 uIU/mL] dropped from 3.3 uIU/mL one week prior, FT4 0.5 [0.8-1.7 ng/dL] and Total T3 111 ng/dL [87- 187 ng/dL] consistent with central hypothyroidism. Bexarotene was held during her hospitalization per hematology recommendations. The patient was started on Levothyroxine 50 mcg, which was later advanced to 75 mcg daily based on free T4 levels. At one month follow up, free T4 level normalized while on Levothyroxine and Bexarotene was restarted again by her hematologist. Discussion: Bexarotene, an antineoplastic agent approved for treating cutaneous T cell lymphoma, can rapidly suppress TSH levels by directly inhibiting its secretion and affect thyroid hormone metabolism, leading to central hypothyroidism. The degree of suppression of TSH increases with higher doses of Bexarotene while reduction in free T4 and TSH are reversible. Patients already receiving thyroid hormone therapy may require increased thyroid hormone doses to achieve therapeutic levels. If bexarotene is permanently discontinued, levothyroxine can either be stopped or can be resumed to doses used prior to bexarotene therapy. Recovery of thyroid function usually occurs within weeks of Bexarotene discontinuation. Conclusion: Oral Bexarotene can cause central hypothyroidism therefore, thyroid function tests should be measured at baseline and treatment. Thyroid hormone replacement should be considered if central hypothyroidism is suspected. Presentation: Friday, June 16, 2023

Factors related to bone mineral density in female patients receiving TSH-suppressive doses of levothyroxine for thyroid cancer

Background: Patients with thyroid cancer receive a high-dose thyroid hormone therapy after total thyroidectomy for suppression of thyroid stimulating hormone (TSH); this may affect bone mineral density (BMD). Identifying the common factors that affect BMD (including the duration of a high dose of thyroid hormone treatment) may, therefore, aid the delivery of appropriate and comprehensive care in such cases. Objective: To identify the factors related to BMD in female patients with thyroid cancer. Materials and Methods: This cross-sectional study evaluated data pertaining to the BMD and demographic characteristics of female patients with thyroid cancer. The patients were aged at least 40 years and received a high-dose thyroid hormone replacement therapy after total thyroidectomy at the Rajavithi Hospital between January 2004 and December 2019. The relationships between BMD and associated factors were analyzed using Pearson’s correlation and multiple linear regression. A p-value of less than 0.05 was considered statistically significant. Results: A total of 100 female patients with a mean age of 55.37 ± 11.36 (40-82) years and mean body mass index (BMI) of 24.8 ± 4.96 (15-40) were included; 60 and 56 of them were postmenopausal and coffee drinkers, respectively. High-dose thyroid hormone replacement therapy was received for a mean duration of 94.59±50.36 (3-210) months and 13 patients had a history of fractures; 60%, 30%, and 10% had normal BMD, osteopenia, and osteoporosis, respectively. The factors affecting BMD included the BMI (p-value &lt;0.001) and postmenopausal status(p-value &lt;0.001). Subgroup analyses showed the BMI to be the factor affecting BMD in the premenopausal group (p-value &lt;0.001). Age, BMI, and calcium supplement intake were found to have an effect on the BMD in the postmenopausal group (p-value= 0.003, 0.002, and 0.020, respectively). The duration of high-dose thyroid hormone intake had no effect on the BMD in both the overall population (p-value= 0.558) and the subgroups based on the menopausal status (p-value = 0.437 and 0.380 in premenopausal and postmenopausal groups, respectively). Conclusion: In female patients who were treated for thyroid cancer, the factors affecting the BMD included the BMI in the premenopausal group and the age, BMI, and calcium supplementation in the postmenopausal group.

The Effect of TSH Suppression Therapy on the Efficacy and Immune Function of Postoperative Patients with Thyroid Cancer

Objective: To investigate the efficacy and immune function of thyroid stimulating hormone (TSH) suppression therapy in postoperative thyroid cancer patients. Methods: Sixty thyroid cancer patients admitted from July 2020–July 2022 were recruited and randomly divided into two groups. The control group (30 patients) received hormone replacement therapy, while the study group (30 patients) received TSH suppression therapy. The thyroid function, clinical efficacy, immune function, and tumor markers of the two groups were compared. Results: After treatment, the levels of free triiodothyronine (FT3) and thyroxine (FT4) in both groups increased significantly, while TSH levels decreased significantly. Moreover, the magnitude of change in the study group was greater than that in the control group (P &lt; 0.05). The total effective rate in the study group was significantly higher as compared to the control group (P &lt; 0.05). After treatment, the levels of CD3+ and CD4+ cells in both groups of patients increased significantly, with the study group showing significantly higher levels than the control group, whereas the level of CD8+ cells decreased significantly, with the study group having lower levels than the control group (P &lt; 0.05). After treatment, the levels of Tg and CEA in both groups were significantly lowered as compared to before treatment, and the levels of Tg and CEA in the study group were significantly lower than the control group (P &lt; 0.05). Conclusion: TSH suppression therapy in postoperative thyroid cancer patients can improve thyroid function, suppress the levels of tumor markers, and enhance immune function, thereby achieving good clinical outcomes.

Transiently impaired endothelial function during thyroid hormone withdrawal in differentiated thyroid cancer patients.

Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD(P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (ΔLDL) was the only factor correlated negatively with the change of FMD (ΔFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029). Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy.

40-LB: The Association between Changes in Physical Activity Before and After Thyroidectomy and Incident Type 2 Diabetes in Patients with Thyroid Cancer

Background: Thyroid cancer patients who underwent thyroid-stimulating hormone suppression therapy after thyroidectomy is increased a risk for type 2 diabetes mellitus (T2DM). However, whether the changes in physical activity (PA) before and after thyroidectomy in patients with thyroid cancer are associated with T2DM has not been evaluated yet. We investigated the association between changes in PA before and after thyroidectomy and incident T2DM in patients with thyroid cancer. Methods: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy between 2010 and 2016 was performed using the Korean National Health Information Database. PA was defined as mid-term or vigorous exercise at least 1 day in a week. PA changes over time were divided into four groups: persistent non-exercisers (n = 18,441), new exercisers (n = 14,599), exercise dropouts (n = 11,023), and exercise maintainers (n = 25,463). Results: During mean 4.5 years of follow-up, the incidences per 1,000 person years of T2DM were lower in patients who performed PA before or after thyroidectomy than persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the exercise dropout group (adjusted hazard ratio [aHR] 0.81, 95% confidence interval [CI], 0.72-0.91), new exerciser group (aHR 0.87, 95% CI 0.78-0.97), and the exercise maintainer group (aHR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. When we stratified patients according to energy expenditure, PA with &amp;lt; 1,500 metabolic equivalent of task (MET)-min/week in exercise maintainers was associated with lower risk of incident T2DM than non-exercisers, but PA with ≥ 1,500 MET-min/week was not. Conclusion: In patients with thyroid cancer, PA before or after thyroidectomy was associated with lower risk of incident T2DM. Disclosure J. Park: None. H. Park: None. S. Kim: None. Y. Cho: None. K. Han: None. K. Kim: None.

Age-based factors modulating the required thyroxine dose to achieve thyrotropin suppression in intermediate-and high-risk papillary thyroid cancer.

Guidelines widely recommend thyrotropin suppression to reduce the risk of recurrence in intermediate- and high-risk papillary thyroid cancer (PTC) after total thyroidectomy. However, an insufficient or excessive dosage may result in a number of symptoms/complications especially in older patients. We constructed a retrospective cohort including 551 PTC patient encounters. Using propensity score matching and logistic regression models, we determined the independent risk factors affecting levothyroxine therapy at different ages. Our outcomes included: expected TSH level and an unexpected TSH level, which was based on the initial thyroid-stimulating hormone (TSH) goal< 0.1 mIU/L with usual dosage of L-T4 (1.6 μg/kg/day). From our analysis, more than 70% of patients undergoing total thyroidectomy did not achieve the expected TSH level using an empirical medication regimen, and the effect of the drug was affected by age (odds ratio [OR], 1.063; 95% CI, 1.032-1.094), preoperative TSH level (OR, 0.554; 95% CI, 0.436-0.704) and preoperative fT3 level (OR, 0.820; 95% CI, 0.727-0.925). In patients with age < 55 years old, preoperative TSH level (OR, 0.588; 95% CI, 0.459-0.753), and preoperative fT3 level (OR, 0.859; 95% CI, 0.746-0.990) were two independent protective factors, while, in patients with age ≥ 55 years old, only preoperative TSH level (OR, 0.490; 95% CI, 0.278-0.861) was the independent protective factors to achieve expected TSH level. Our retrospective analysis suggested the following significant risk factors of getting TSH suppression in PTC patients: age (≥55 years), lower preoperative TSH and fT3 levels.

#4846 ROXADUSTAT-INDUCED HYPOTHYROIDISM: THE EFFECT OF ROXADUSTAT ON SUPPRESSION OF THYROID FUNCTION

Abstract Background and Aims There have been only two case reports of hypothyroidism in patients treated with roxadustat, a HIF-PH inhibitor as new renal anemia drug. However, there has yet been no studies to examine the effect of roxadustat on thyroid function. Method In this study, we retrospectively examined the effects of roxadustat on thyroid-stimulating hormone (TSH) in hemodialysis patients by two blood examinations, before and during treatment with roxadustat. We included patients who had TSH levels measured after at least two consecutive weeks of roxadustat treatment and before. We excluded patients with a history of taking other HIF-PH inhibitors before roxadustat. The period was from September 2021 to November 2022 in this interim analysis. A p value of&amp;lt;0.05 was considered statistically significant. Analyses were performed using SPSS. Results 93 patients were included in this analysis. TSH levels significantly decreased after treatment with roxadustat. A total of 58.1% of patients had decreased TSH levels (2.23 ± 1.18 v.s. 1.81 ± 1.35, μIU/mL, p value = 0.040, Wilcoxon signed-rank test), and 18.3% of patients had a significant decrease below the normal range. Additionally, patients treated with thyroid hormone replacement therapy in primary hypothyroidism had a higher frequency (81.0%) of TSH decrease compared to patients without (p value = 0.013, Pearson's chi-square test). Conclusion This is the first study to examine that roxadustat has a suppressive effect on TSH secretion in hemodialysis patients. We also found that roxadustat-induced hypothyroidism is prevalent in the high frequency of TSH suppression, especially in primary hypothyroidism patients treated with thyroid hormone replacement therapy. Thyroid hormone receptor beta (THRβ), which is expressed in the hypothalamus and pituitary gland, plays an important role in regulating thyroid hormone through feedback mechanisms. Yao et al. have reported that roxadustat has a similar structure to T3 and acts as a THRβ-selective ligand, particularly activating THRβ. Therefore, it is possible that roxadustat suppresses TSH secretion through negative feedback via THRβ. It is important to monitor thyroid function in patients receiving roxadustat. Roxadustat should be avoided in patients with primary hypothyroidism, since it is inferred that roxadustat-induced hypothyroidism cannot be improved by enhancement of thyroid hormone replacement therapy.