TSH-suppressive Therapy Research Articles

Bone mineral density (BMD), bone turnover markers (BTMS) and evaluation of musculoskeletal system in patients with differentiated thyroid cancer undergoing TSH suppressive therapy

Bone mineral density (BMD), bone turnover markers (BTMS) and evaluation of musculoskeletal system in patients with differentiated thyroid cancer undergoing TSH suppressive therapy

Factors influencing TSH suppression efficacy in postoperative papillary thyroid carcinoma patients: a retrospective cohort study

ObjectivesWhile surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC.MethodsThis study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy.ResultsThere were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P < 0.05), and the ROC curve analysis indicated that the area under the curve for the preoperative TSH index was 0.610 (P < 0.05). The proportion of patients in the TSH level conforming group who took oral levothyroxine sodium tablets at a dose of ≥ 1.4 µg/kg·d after surgery was higher (P < 0.05). The postoperative levels of FT3 and FT4 were higher in the TSH level conforming group (P < 0.05). The results of binary logistic regression analysis indicated that factors “Postoperative TSH level ≥ 2 mU/L”, “Levothyroxine sodium tablet dose<1.4 µg/kg·d”, and “Combined with Hashimoto thyroiditis” were significantly associated with an elevated risk of postoperative TSH levels failing to reach the target (P < 0.05).ConclusionOptimal thyroid function in patients with PTC post-surgery is best achieved when adjusting the dose of levothyroxine sodium in a timely manner to reach the target TSH level during follow-up visits.

Comparison of Bone Mineral Density and Trabecular Bone Score in Patients with and without Vertebral Fractures and Differentiated Thyroid Cancer with Long-Term Serum Thyrotrophin-Suppressed Therapy.

The study of BMD provides only partial information on bone health in patients undergoing TSH suppression therapy due to differentiated thyroid cancer (DTC). The trabecular bone score (TBS), a new parameter assessing bone microarchitecture, is proposed for studying bone in this context. This study aimed to analyze their long-term use in patients with DTC. Bone mineral density (BMD) was measured by dual X-ray densitometry (DXA) and TBS was assessed with iNsigth software (version 2.0, MediImaps, France) in 145 postmenopausal patients with DTC. Vertebral fractures (VFs) were identified using a semi-quantitative X-ray method. The BMD at the end of this study did not differ from the initial measurement. However, the TBS decreased from 1.35 ± 0.1 to 1.27 ± 0.1 (p = 0.002). Increased levels of PTH, osteocalcin, and bone alkaline phosphatase (BAP) were observed, suggesting enhanced bone remodeling. There was an increase in the prevalence of osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%, respectively). The proportion of patients with partially degraded and totally degraded TBS increased from 31% and 15.1% to 48.9% and 24.8% by the end of this study. Among the 30 patients with VFs, there were no significant differences in age, body mass index (BMI), calcium intake, alcohol consumption, smoking, radioiodine, therapy, or thyroid parameters compared to those without VFs. The odds ratio for VFs increased with osteopenia (OR 2.63). Combining TBS with BMD did not improve discrimination. The TBS decreased while the BMD remained unchanged. The percentage of patients with osteoporosis and osteopenia, whether partially degraded or totally degraded, increased by the end of this study. The predominant discordance was found in partially degraded microarchitectures, with a higher proportion of osteopenic patients compared to those with normal or osteoporotic bone density. The AUC of the combination of TBS and BMD did not enhance discrimination. TBS, radioactive iodine therapy, and sedentary lifestyle emerged as the main distinguishing factors for DTC patients with VFs.

Association between serum TSH concentration and bone mineral density: an umbrella review.

The aim of this study was to summarize the results of previous studies, standardize the data, and present new statistical results in orderto provide physicians with clinically significant outcomes regarding the association between serum TSH concentration and bone mineral density (BMD). To perform this umbrella review, a systematic search was conducted in which major online medical databases, such as PubMed, Web of Science, Embase, Scopus, Cochrane Library, and Google Scholar, were searched for meta-analyses and systematic reviews regarding the effect of TSH on BMD. Furthermore, all primary studies were screened for statistical analysis. The statistical outcomes of the present study were based on the data of 75,898 patients. The pooled risk ratio of any kind of fracture in patients with subclinical hyperthyroidism was estimated to be 1.36 (95% CI: 1.18-1.56; p < 0.001). The SMD for BMD in the distal radius in male patients receiving L-thyroxine suppression therapy was estimated to be -0.61 (95% CI: -1.10-(-0.11); p = 0.02). Furthermore, the pooled risk ratio of any fracture in patients receiving L-thyroxine suppression therapy was estimated to be 1.98 (95% CI: 0.98 - 3.98; p = 0.06). In these patients, the BMD may significantly differ from that in non-treated patients. However, the difference depends on the type of bone. Our data confirmed that subclinical hyperthyroidism has a detrimental effect on bones, causing decreased BMD. Based on the obtained results, the authors suggest that a reduced TSH serum level itself may be an individual factor associated with decreased BMD and, thus, with a greater risk of bone fracture. Nevertheless, it should be noted that the effects of TSH suppression therapy differ between areas of interest for assessing BMD. Furthermore, the results have shown that this issue may, in specific areas, concern not only postmenopausal women but also male patients. These conclusions should contribute to a careful consideration of the application of TSH suppressive therapy in all patients. Particular attention should be given to patients after DTC, while all the advantages and disadvantages of implementing L-thyroxine therapy should be individually considered.

Short-Term Postoperative Depression and Anxiety in Patients with Differentiated Thyroid Carcinoma: Assessment of Potential Oncologic-Psycho Relevance.

Objective: To understand whether TSH suppressive therapy affect short-term postoperative cancer-related depression and anxiety among DTC patients. To evaluate short-term postoperative psychological problems and its relationship with baseline parameters, fatigue, sleep quality, illness perception, and patients' quality of life. Study Design and Methods: This was a prospective, observational, single center study. This study involved 831 TC patients who consecutively admitted to the inpatient department of hospital between 1st June 2020 and 31th February 2021. Results: Mean scores of the self-rated anxiety scale (SAS) (49.04 vs. 40.69) and self-rated depression scale (SDS) (44.61 vs. 39.86), as well as the incidence of anxiety (41.5% vs. 22.1%) and depression (22.5% vs. 2.4%) significantly decreased 3 months after surgery. For personal and clinical characteristics, low educational background (SAS, β = 1.392; SDS, β = 1.622; and p < 0.05), without children (SAS, β = 4.068; SDS, β = 1.873, and p < 0.01), FNAC (SAS, β = -0.981; SDS, β = -2.583; and p < 0.05), and multifocal tumor (SAS, β = -1.287; SDS, β = -2.681; and p < 0.05) were the main effects for both short-term postoperative anxiety and depression. Multiple linear regression analysis identified the serum TSH level as a significant variable associated with worse SAS (Beta = -0.695 and p=0.043) and SDS (Beta = -3.133 and p < 0.001) scores 3 months after surgery. FT4 was independently associated with SAS scores (Beta = -0.202 and p < 0.001). Patients with middle ATA risk had a significantly higher level of SDS scores (p=0.033). Conclusion: We confirmed that cancer-related anxiety and depression among DTC patients significantly alleviated 3 months after surgery. TSH suppression therapy has profound effects on cancer-related anxiety and depression, and the degree of anxiety and depression significantly deteriorated with the decrease of TSH level.

Two synchronous paraneoplastic endocrine syndromes in a 53-year-old male with broadly metastatic widely invasive Hürthle cell carcinoma.

Unlike medullary thyroid carcinomas, follicular cell-derived thyroid malignancies have rarely been associated with paraneoplastic endocrine syndromes. An ultrarare case of a middle-aged man with heavily treated broadly metastatic radioactive iodine-refractory widely invasive Hürthle cell carcinoma (HCC) of the thyroid with two synchronous paraneoplastic endocrine syndromes, T3 thyrotoxicosis and hypercalcemia of malignancy, is discussed here. The levothyroxine-induced T3 thyrotoxicosis was a gradual process that became more noticeable as the tumor burden, refractory to different modalities of therapy, expanded. The 1,25-dihydroxyvitamin-D-mediated hypercalcemia, on the other hand, developed in a manner of weeks, as it usually happens. It is important to emphasize that in patients with metastatic Hürthle cell and follicular carcinomas of the thyroid, on TSH suppressive therapy, the unexplained and progressive decline in FT4 and rise in FT3 levels, resulting in an elevated FT4/FT3 ratio, could be an indication of augmented type 1 (D1) and/or type 2 (D2) deiodinase expression in tumoral tissue, causing an increased conversion from the prohormone T4 into the active metabolite T3 via outer ring deiodination. Albeit extremely rare, some patients with thyroid cancer can present with more than one concomitant paraneoplastic syndrome. Although medullary thyroid carcinoma is the thyroid malignancy that is usually associated with paraneoplastic endocrine syndromes, follicular cell-derived thyroid cancers have been rarely described as being the culprit. In patients with metastatic Hürthle cell and follicular thyroid carcinomas, the unexplained and progressive decline in FT4 and rise in FT3 levels could be an indication of augmented type 1 (D1) and/or type 2 (D2) deiodinase expression in tumoral tissue, causing an increased conversion from T4 into T3 leading to T3 thyrotoxicosis.

Family history of malignant or benign thyroid tumors: implications for surgical procedure management and disease-free survival.

Current guidelines lack a standardized management for patients with family history of thyroid carcinoma (fTC),particularly benign thyroid neoplasm (fBTN). Our objective was to investigate the influence of various family histories on the selection of surgical approaches and disease-free survival (DFS). A cohort study was conducted involving 2261 patients diagnosed with differentiated thyroid carcinoma including those with fTC (n=224), fBTN (n=122), and individuals without a family history of thyroid carcinoma (nfTC; n=1915). Clinicopathological characteristics were collected. DFS was estimated using Kaplan-Meier analysis and factors affecting DFS were identified using Cox proportional hazard model. Compared to nfTC, small tumor size, clinically lymph node-positive, extrathyroidal extension, vascular invasion, Hashimoto's disease and nodular goiter were more common in fTC and fBTN groups. They had lower T stage and a lower rate of good response to TSH suppression therapy but received more radioiodine therapy. It is worth noting that fTC is associated with male, bilateral and multifocal tumors, as well as central lymph node metastasis and distant metastasis. Both fTC (aHR = 2.45, 95% CI=1.11-5.38; P = 0.03) and fBTN (aHR = 3.43, 95% CI=1.27-9.29; P = 0.02) were independent predictors of DFS in patients who underwent lobectomy, but not total thyroidectomy. For 1-4cm thyroid carcinomas with clinically node-negative, fTC was identified as an independent predictor, whereas fBTN was not. Our findings indicate that a family history, particularly of malignancy, is associated with a more aggressive disease. Family history does not affect the prognosis of patients who undergo total thyroidectomy, but it may increase the risk of postoperative malignant events in those who have a lobectomy. Additionally, it may be necessary to monitor individuals with a family history of benign thyroid neoplasms.

Association between TSH suppression therapy and type 2 deiodinase gene polymorphism in differentiated thyroid carcinoma.

Oral levothyroxine (L-T4) suppression of thyroid-stimulating hormone (TSH) levels is the most commonly used clinical approach to manage and treat patients after thyroid cancer surgery. This study aimed to investigate the association between TSH suppression therapy and type 2 deiodinase gene (DIO2) polymorphism in differentiated thyroid carcinoma (DTC). A total of 240 patients with DTC who received total thyroidectomy (TT; 120) and hemithyroidectomy (HT; 120) were enrolled in this study. The serum TSH, free triiodothyronine (FT3), and free thyroxine (FT4) levels were detected using an automatic serum immune analyser and electrochemiluminescence immunoassay. Based on the results of DIO2 gene detection, 3 genotypes of Thr92Ala were detected. The serum TSH levels were inhibited after oral L-T4 treatment, but the proportion of patients who reached the TSH suppression standard in the hemithyroidectomy group was higher than in the total thyroidectomy group. After TSH suppression treatment, serum FT4 levels were increased in both total thyroidectomy and hemithyroidectomy. The difference in serum TSH, FT3, and FT4 levels was associated with different genotypes, and patients with high cytosine cytosine (CC) genotypes may have difficulty meeting the TSH suppression criteria. Patients who underwent total thyroidectomy exhibited higher postoperative serum FT4 levels than patients in the hemithyroidectomy group after TSH suppression therapy. The Thr92Ala polymorphism of type 2 deiodinase (D2) was associated with TSH suppression therapy.

Outcomes of Patients with an Intermediate-Risk Group According to the Japanese Risk Classification of Papillary Thyroid Carcinoma

BackgroundThe management of intermediate-risk group of papillary thyroid cancer (PTC) is still vague, particularly regarding whether or not total thyroidectomy, postoperative radioactive iodine ablation (RAI-a), and postoperative TSH suppression are mandatory.MethodsThis retrospective study evaluated 680 PTC patients from 2010 to 2017, who were classified into the three risk groups as low, intermediate, and high-risk groups according to the criteria of the Japanese Association of Endocrine Surgeons (JAES) 2010 and underwent surgery according to the JAES guidelines. We retrospectively collected patient data for analyses of disease-free survivals in the intermediate-risk group patients.ResultsWe performed surgery on 680 PTC patients from 2010 to 2017. Of them, 297 were classified as the intermediate-risk group. DFS was not statistically significantly different in patients with/without total thyroidectomy and postoperative TSH suppression therapy. For RAI-a, DFS (95% confidence interval) at 3, 5, and 8 years were 93.2% (84.6 ~ 97.2), 81.6% (68,3 ~ 90.2), and 70.7% (51.4 ~ 84.6) in patients with postoperative RAI-a and 100%, 100%, and 100% in patients without postoperative RAI-a after total thyroidectomy, respectively. DFS of patients without RAI-a was superior to those with RAI-a (P < 0.0004). Multivariable analysis by stepwise selection method revealed that postoperative RAI-a was a risk factor with a hazard ratio of 5.69. (95% CI 1.998–16.21) (P = 0.001131).ConclusionsOur study did not show the efficacy of RAI-a in patients with intermediate-risk PTC. This study implies that judging the efficacy of adjuvant therapy such as RAI or TSh suppression in intermediate-risk patients is difficult.

The Etiology of Abnormal TSH in Veterans Cared by a VA Medical Center – One High Serum Thyrotropin is Associated with Higher 5-Years Mortality

Objective: By analyzing the etiology of abnormal TSH in randomly selected veteran patients, we set our heart on improving future clinical care/management of the clinical/subclinical hyper- and hypothyroidism in the aging veteran population. Methods: A total of 1100 patients’ charts in alphabetical order were selected. Excluded cases of insufficient information, 897 patients’ charts were reviewed and analyzed for causes of abnormal TSH. Among them, 602 for the cause of low TSH (below 0.55 uU/mL) and 295 for high TSH (above 4.78 uU/mL) were reviewed retrospectively. Findings: Among the 1100 patients selected, 680 (61.8%) were 60 y or older (female=44, 6.8%); 420 were under 60 y (female=80, 19.0%); significantly more female patients were found in the younger age group (P&lt;0.001). After excluding patients with insufficient data, the most common cause of suppressed TSH is iodine-induced, CT iodinated contrast and betadine use caused 35.0% in the older group (n=126) compared to 23.6% in the younger group(n=57) (P = 0.027). The significant difference is that older veterans received more contrast CTs (P &lt; 0.05 compared to the younger group). In both age groups with concurrent FT4 study, we found four high FT4 among 90 studies, 4.4% overt hyperthyroidism. The second most common cause of suppressed TSH is due to thyroid hormone (TH) replacement in the older group (119 patients, 33.1%) with age &gt; 60y, significantly more frequent compared to the younger group, P&lt;0.001. There is significantly more overt hyperthyroidism, 27.8/%, than the iodine-load induced suppression of TSH, P&lt;0.001, due to 17 patients on TSH suppression therapy after total thyroidectomy for thyroid cancer. Among the 295 patients with elevated TSH, the most common cause of high TSH was due to hypothyroidism on T4 replacement: a total of 128 (59.3%) in the older group (N=216) is, similar to 47 (59.5%) in the younger group (N=79). In both age groups, there were 139 patients with concomitant FT4 measurement; 17 overt hypothyroidism were found, 12.2%. No significant difference is seen in the two age groups. The next most common causes of elevated TSH are CT contrast infusion, 23 (10.6%) in the older group and 7 (8.9%) in the younger group. We find high TSH is associated with a higher death rate of 101/238 (42.4%) in a 5-year follow-up (from 2016 to 2021), as compared to low TSH of 68/238 (28.6%), in the older age group, p&lt;0.03； both were significantly higher than the age- and sex-matched general US population, 19.7%, P&lt;0.01. Conclusion: Even though most, ~ 90%, were subclinical, the suppressed and elevated TSH are associated with severe consequences in CV/CNS and immune-suppression complications in aging veterans. Therefore, cautious use (and more frequent check of TSH) of TH replacement and CT contrast in aging veterans is recommended. The alarming increase in the 5-year death rate in older patients with elevated TSH deserves further study.

Abstract #1400018: Genetic Alterations in NRAS, TERT, PIK3CA and SPEN Genes Leading to an Aggressive Metastatic RAI Refractory Follicular Thyroid Cancer

Follicular thyroid cancer (FTC) is a well-differentiated thyroid tumor and the second most common type after papillary thyroid cancer (PTC) with higher incidence of distant metastases, more aggressive behavior, and poorer outcome than PTC Patient is 43-year-old female with 6.2 cm TR4 left thyroid nodule on Neck US. On Exam, Cricoid is deviated to the right with left thyroid firm nodule. FNA showed Follicular neoplasm. TSH level was 1.59 (0.45-4.70 mIU/L) and Free T4 level: 1.19 (0.78-2.20 ng/dl) CT scan of neck with contrast and MRI thoracic spine: Large, solid heterogenous mass in left thyroid lobe causing lateral displacement and mild narrowing of the trachea with retrosternal extension, Osteolytic lesion of T4 vertebral body and right sided pleura-based mass at the level of T7-T8 with No enlarged cervical lymph nodes. IR biopsy of vertebra: thyroid Origin Metastatic Carcinoma, Patient underwent total thyroidectomy with central neck dissection. Follicular thyroid cancer (STAGE II pT3A,pN1B,pM1) Mutational Testing: Negative BRAF and KRAS with Positive NRAS, PIK3CA, SPEN and TERT. Patient started on TSH suppression therapy. 1 month Later: Thyroglobulin: 2443.4 ng/ml (1.3-31.8), Thyroglobulin Ab< 0.9 (0.0-4.0 IU/ml), TSH 0.02 with Free T4 2.53 FDG PET: Multifocal osseous metastatic disease, predominantly in the axial skeleton Thyrogen stimulated WBS I-123 showed No evidence of residual or metastatic disease. Patient recieved 214 mCi of iodine-131. Post treatment MN scan showed accumulation of iodine in the metastatic bone lesions with small focal activity in the thyroidectomy bed. Post RAI treatment: TG trended to 1102.7 then 1307 Patient Completed 10 fractions of external beam radiation on T4 spine Ultrasound thyroid: No residual thyroid tissue or suspicious lymph nodes Oncology started Bone directed therapy with zoledronate with consideration of PIK3CA mutation targeted therapy with Everolimus or Temsirolimus FTC is more aggressive with poorer prognosis than PTC that is more likely to hematogenously disseminate, with mortality rate of 50%. The neoplastic proliferation of thyroid follicular cells develops by altering multiple molecular pathways such as the PI3K/AKT pathway involving the RAS, RAF, RET, and NTRK1 genes. RAS is a dual activator of the mitogen activated protein kinase and PI3K/AKT pathways TERT is a catalytic subunit of the telomerase complex. Reported in 11–17% of FTC. TERT promoter mutations associated with tumor aggressiveness and mortality PIK3CA encodes p110-alpha, is a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) involves in thyroid cancer tumorigenesis and progression, reported in 7.7% of FTC with sensitivity to therapies targeting PI3K49-56, AKT57-58, or mTOR59-66. In our patient, pretreatment MN scan failed to show RAI avid lesions but PET showed increase FDG uptake and since receiving RAI treatment helped in lowering TG that indicate a possibility of mixture of RAI avid and non-RAI avid lesions existing at same time so RAI treatment is still recommended despite negative Diagnostic Scan for persistent elevated TG.

Predictive value and dynamic risk stratification of high sensitive basal or stimulated thyroglobulin assay in a long-term thyroid carcinoma cohort

PurposeTo evaluate the predictive value of the rhTSH thyroglobulin stimulation test (rhTSH-Tg) compared to basal high-sensitive thyroglobulin (hs-Tg) under TSH suppressive therapy at 12 months after the completion of initial treatment to predict the long-term response and Dynamic Risk Stratification (DRS) at the last follow-up visit in a long-term DTC cohort.MethodsProspective study in 114 DTC patients (77.2% women, mean age 46.4 ± 14.1 years old, median/IQR evolution 6.7[3.1–8.0] years) from 2013 to 2020 undergoing total thyroidectomy and radioiodine ablation in whom hs-Tg and rhTSH-Tg was performed 12 months after completing initial treatment. Pearson correlation, receiving operating characteristics (ROC) and DRS at initial and last follow-up visit were analyzed.Resultshs-Tg and rhTSH-Tg show a strong positive linear correlation (r = 0.864, p < 0.001). The diagnostic performance of initial hs-Tg and rhTSH-Tg levels were evaluated via ROC-AUC as a predictor of excellent response (ER) in the last follow-up visit. Hs-Tg showed a better AUC (0.969, 95%CI = 0.941–0.997) than rhTSH-Tg (0.944, 95%IC = 0.905–0.984; p < 0.001). The hs-Tg and rhTSH-Tg cutoff point of highest sensitivity (S) and specificity (E) was 0.110 and 0.815 ng/dl, respectively. Hs-Tg showed a higher diagnostic accuracy than rhTSH-Tg (S = 100% vs 96.8%, E = 84.3% vs 84.3%, NPV = 100% vs 98.6%, PPV = 70.5% vs 69.7%; p < 0.05). The DRS based on initial hs-Tg showed better ability to predict ER (93.3% vs 86.7%) and biochemical incomplete response (53.3%vs13.3%) in the last follow-up visit compared to rhTSH-Tg.ConclusionsBoth initial hs-Th and rhTSH-Tg were good predictors of long-term ER. In patients with hs-Tg, the rhTSH-test did not provide relevant prognosis information. An ER after initial treatment was associated with a very high NPV at subsequent follow-up.

Benign thyroid nodules respond to a single administration of 0.3mg recombinant human thyrotropin with highly variable volume increase.

The nature of thyroid nodules is heterogenous. Most of them are benign and, in the absence of pressure symptoms of adjunct structures, no treatment is needed. Our objective was to investigate the acute effects of a low dose of recombinant human TSH (rhTSH) on the volume of benign thyroid nodules. we studied 27 nodules (14 isoechoic and 13 hypoechoic) in 15 (11 women and 4 men; mean age: 51.0 ± 15.9 years) consecutive patients with one to three well-separated asymptomatic benign thyroid nodules. All subjects were euthyroid, with negative thyroid antibodies, and none received levothyroxine. The total thyroid volume and thyroid nodule volume were sonographically determined by two independent examiners (P.B. and M.M.) before, 48 hours and 6 months post intramuscular (IM) administration of 0.3mg rhTSH, and the mean values of the two examiners' measurements were used; thyroid function tests were obtained at the same time points. The mean volume of isoechoic nodules increased by 57.3%, of hypoechoic nodules by 46.6% and of the surrounding thyroid parenchyma by 70.4% 48 hours post-rhTSH; mean volumes had returned to baseline levels 6 months later. A large variance in the volume change responses was observed. The relative change in nodule volume (defined as the percent change in nodule volume divided by the percent change in the surrounding parenchyma) from baseline to 48 hours was significantly higher in isoechoic versus hypoechoic nodules (p<0.05). A single dose of 0.3 mg rhTSH transiently increased the volume of benign thyroid nodules. The increase was more pronounced in isoechoic nodules and had a great variability. Our findings could be useful in the management of benign thyroid nodules, by helping in understanding which nodules would be more responsive to TSH suppression therapy.

Meta-analysis of TSH suppression therapy and the risk of cardiovascular events after thyroid cancer surgery.

To investigate the relationship between TSH suppression therapy and cardiovascular events in patients with thyroid cancer after surgery. Pub Med, Web of Science, and Embase databases were retrieved to collect studies related to the risk of cardiovascular events in patients treated with TSH suppression after thyroid cancer surgery. RevMan statistical software was used for meta-analysis. A total of 14 studies were included. The mean heart rate of patients after thyroid cancer surgery was higher than that of the control group (SMD=2.59, 95% CI: -0.37,.54), and the risk of atrial fibrillation was increased compared with the control group (RR = 1.52, 95%CI, 1.28-1.81; I = 63%). Ejection fraction and left ventricular end-diastolic diameter were not significantly different between the two groups, ejection fraction SMD = -0.10, 95% CI: -3.73, 3.52, left ventricular end-diastolic diameter SMD = -0.09, 95% CI: - 1.29, 1.11. Patients with TSH suppression after thyroid cancer had higher mean systolic blood pressure than controls (SMD = 1.97, 95% CI: -1.09, 5.03) and mean diastolic blood pressure (SMD = 1.85, 95% CI: -0.15, 3.85). Meta-analysis concluded that TSH suppression therapy after thyroid cancer surgery increases the risk of atrial fibrillation in patients. In addition, the heart rate, systolic blood pressure and diastolic blood pressure are higher than those in the control group, and there is no significant difference in ejection fraction and left ventricular end-diastolic diameter.

The risk between thyrotropin suppression and bone mineral density in differentiated thyroid cancer

The effect of thyroid stimulating endocrine (TSH) suppression medical aid on bone mineral density (BMD) of patients with differentiated thyroid carcinoma (DTC) or differentiated thyroid malignant neoplastic disease is still controversial. Our aim was to investigate the effect of TSH suppression therapy on BMD of patients with DTC. A total of 1651 DTC patients with TSH-suppression medical care were analyzed by RevMan 5.3 software (https://training.cochrane.org/online-learning/core-software/revman/revman-5-download) in the present study. The PubMed and Embase databases were consistently hunted for works revealed through July 29, 2022. The results indicated that a significant association between femoral bone mineral density (FN-BMD) (P = .02) or lumbar spine bone mineral density (L-BMD) (P = .04) and DTC patients with TSH-suppression therapy. However, the total hip bone mineral density (TH-BMD) was not significantly related to DTC patients with TSH-suppression therapy (P = .11). For premenopausal women, it was shown that TH-BMD (P = .02) or L-BMD (P = .01) were closely related to DTC patients with TSH-suppression therapy. However, there was no relationship between FN-BMD and DTC patients with TSH-suppression therapy (P = .06). For postmenopausal women, TH-BMD was closely related to DTC patients with TSH-suppression therapy (P = .02). It was revealed that there was no significant difference between L-BMD (P = .16) or FN-BMD (P = .26) and DTC patients with TSH-suppression therapy. For men, there was no relationship between FN-BMD (P = .94) or L-BMD (P = .29) and DTC patients with TSH-suppression therapy. Our systematic review has demonstrated that TSH inhibition treatment mainly influence the TH-BMD or L-BMD of the DTC patients who were premenopausal women; the TH-BMD of the DTC patients who were postmenopausal women. In addition, there was no influence on the FN-BMD or L-BMD of the DTC patients who were men.

Evolution of suppressing TSH therapy at diagnosis and in the long-term follow-up in a cohort of differentiated thyroid cancer

IntroductionTo evaluate the adequacy of TSH suppression therapy (TSHst) at the first disease assessment and the last follow-up visit. MethodsRetrospective observational study of those patients under follow-up of DTC in a reference hospital. Results216 patients (79.2% women) were evaluated, with a mean age 59.0 ± 13.1 years-old and a mean follow-up of 6.9 ± 4.3 years. 88.4% were papillary carcinomas.At diagnosis, 69.2% had a low risk of recurrence (RR) compared to 13.6% with a high RR. Dynamic risk stratification (DRS) classified patients at first disease assessment and the last visit as excellent response (ER) in 60.0% and 70.7%, respectively.Those patients with ER in the first and last follow-up control maintained TSHst in 30.7% and 16.3% of the cases, respectively (p < 0.001).The factors associated with maintaining TSHst at the last control were younger age, higher RR at diagnosis, DRE at follow-up, presence of multifocality and histological vascular invasion (p < 0.05).In a logistic regression analysis adopting tsTSH at follow-up as the dependent variable, exclusively age (β = −0.062; p < 0.001), RR at diagnosis (β = 1.074; p < 0.05) and EDR during follow-up (β = 1.237; p < 0.05) maintained statistical significance. ConclusionsDespite the current recommendations, 30.7% of patients with low RR and initial ER are under TSHst. This percentage reduced to 16.3% in those patients with ER after a mean follow-up of 6.9 years. Age, baseline RR, and DRE during follow-up were associated to maintaining tsTSH.

PSAT276 A Case of Malignant Struma Ovarii: Management After Surgery

Abstract Background Struma ovarii is a highly specialized and extremely rare monodermal ovarian teratoma that comprises 0.3 to 1% of all ovarian tumors. It consists of greater than 50% of mature thyroid tissue that is usually benign, but malignancy has been reported in up to 5- 23% of the cases. Even after surgery, recurrence rates of malignant struma ovarii can be as high as 35%. [1] Adjuvant thyroid targeting therapies such as radioiodine ablation after total thyroidectomy and TSH suppression therapy have been shown to reduce the risk of tumor recurrence similar to that of primary thyroid cancer. Case Description A 46-year-old healthy lady presented with a 3-month history of non-specific lower abdominal pain and inter-menstrual bleeding. An extensive review of systems was otherwise unremarkable. Ultrasound of the pelvis showed a 4 cm left adnexal mass. An MRI of the pelvis revealed a 2.2×3.6×2.4 cm solid, enhancing mass within the left ovary with an adjacent cystic component. Tumor markers including CEA, CA 19-9, and CA 125 were unremarkable. Due to suspicion for malignancy, she underwent laparoscopic left salpingo-oophorectomy and resection of the mass. Histopathology revealed papillary thyroid carcinoma approximately 1 cm in size with a background of struma ovarii. Immunohistochemistry staining showed positivity for thyroglobulin and Thyroid Transcription Factor-1 (TTF-1). BRAF mutation analysis was negative. An ultrasound of the thyroid gland disclosed two low-risk nodules. TSH was 1.070 mcIU/ml (0.450-4.500), and thyroglobulin level was 6.8ng/ml (1.5-38.5). We performed an Iodine-123 whole-body scan which was negative for abnormal radioiodine uptake. Based on these results, we classified this patients’ recurrence risk as low to intermediate. We initiated TSH suppression therapy with thyroid hormone to maintain TSH in the low normal range. We deferred total thyroidectomy and radioiodine ablation given the low recurrence risk. She will be monitored for recurrence with TSH and thyroglobulin panel at 6 and 12 months in the first year and then annually for at least the next ten years. Discussion Given the rarity of malignant struma ovarii, there are no consensus guidelines for identifying patients with a high recurrence risk who would benefit from thyroid targeting therapy. While some authors recommend total thyroidectomy and radioiodine ablation for all patients, a recent review [2] recommended an algorithm based on imaging, laboratory, and pathologic characteristics of the tumor to risk-stratify patients and treat them depending on their recurrence risk. Improved strategies for risk-stratification and follow-up are essential to provide optimal treatment for malignant struma ovarii patients without over-treating them.

Bone Density Testing Intervals in TSH Suppression Therapy for Differentiated Thyroid Cancer

Bone Density Testing Intervals in TSH Suppression Therapy for Differentiated Thyroid Cancer

Bone-density testing interval and transition to osteoporosis in differentiated thyroid carcinoma patients on TSH suppression therapy.

Thyrotropin (TSH) suppression therapy is a standard treatment after surgery for differentiated thyroid carcinoma (DTC). It may be associated with osteoporosis in postmenopausal women. However, there are no guidelines for bone mineral density (BMD) testing intervals to screen for osteoporosis in these patients. Therefore, we evaluated the timing of repeated BMD testing in DTC patients with TSH suppression according to baseline T-scores. We retrospectively evaluated 658 DTC patients who underwent BMD testing more than twice between January 2007 and January 2020. A 1:3 propensity score matching was conducted to compare the timing of repeated BMD tests between the DTC and non-DTC groups. We stratified the participants into four groups based on their baseline T-scores: normal (-1.00 or higher), mild osteopenia (-1.01 to -1.49), moderate osteopenia (-1.50 to -1.99), and severe osteopenia (-2.00 to -2.49). Additionally, the 10% of patients in each group that transitioned to osteoporosis were analysed. The estimated BMD testing interval for 10% of patients who developed osteoporosis was 85 months for patients with initially mild osteopenia, 65 months for those with moderate osteopenia, and 15 months for those with severe osteopenia in the DTC group. In the non-DTC group, the testing intervals for mild, moderate, and severe osteopenia were 98, 57, and 13 months, respectively. On multivariate analysis, baseline T-score (mild osteopenia: hazard ratio [HR] 5.91, p = .105; moderate osteopenia: HR, 25.27, p = .02; and severe osteopenia: HR, 134.82, p < .001) and duration of TSH suppression (tertile 2: HR, 2.25, p = .005; Tertile 3: 1.78, p = .033) were independent risk factors for osteoporosis in the DTC group. This study provides guidance for the timing of repeated BMD tests in women over 50 years of age with TSH suppression. The rescreening interval for BMD testing can be modified based on the baseline T-score. The appropriate BMD testing intervals in female DTC patients were similar to those in non-DTC females.

A synchronous medullary and papillary thyroid carcinoma

&lt;p&gt;The synchronous occurrence of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) is rare (&amp;lt;1%). The medullary component determines the prognosis. A 31-year-old female with no relevant personal or family cancer history presented with swelling on the right side of the neck. A fine-needle aspiration biopsy was positive for MTC and PTC. Mass sequencing of 322 genes associated with cancer came back negative. The histopathological examination revealed synchronous MTC and PTC with thymic and bilateral lymph node metastasis. The patient underwent total thyroidectomy with bilateral radical neck dissection (II-V), central dissection, and mediastinal dissection including the thymus. The extent of surgery is determined by MTC and the analysis of RET and BRAF mutations. Post-operative treatment must include monitoring for specific markers (calcitonin and thyroglobulin, respectively, for MTC and PTC). Based on histopathological results and recurrent PTC, TSH suppression and iodine-131 therapy should be considered. Recurrent MTC must be treated with new targeted therapies.&lt;/p&gt;