TSH Stimulation Research Articles

TSH Stimulation before PET/CT as Our Frenemy in Detecting Thyroid Cancer Metastases-Final Results of a Retrospective Analysis.

Introduction: Non-iodine avid metastases of differentiated thyroid cancer (DTC) can be found using PET/CT with a fluorine-18-labeled glucose analog ([18F]FDG). There are ongoing discussions on the appropriateness of using exogenous thyrotropin (TSH) stimulation before this examination. Material and Methods: In a retrospective study, 73 PET/CT scans with [18F]FDG performed after exogenous stimulation with recombinant human TSH (rhTSH) and without such stimulation were analyzed. All analyzed patients were suspected of having non-iodine-avid foci of DTC. Results: The stimulation with rhTSH before the PET/CT did not affect the percentage of positive results: 37.5% (18/48) with rhTSH and 40% (10/25) without rhTSH (p = 0.83). The analysis of the ROC curves established the cut-off thyroglobulin point for a positive PET/CT result separately for both subgroups. There was no statistically significant difference between obtaining a positive PET/CT result and the baseline thyroglobulin concentration (both stimulated and unstimulated). The exogenous stimulation of TSH prior to the PET/CT had no effect on the [18F]FDG uptake in the PET/CT lesions. Conclusions: PET/CT with [18F]FDG remains a useful method for the diagnosis of non-iodine-avid DTC lesions; in the presented group, a positive effect of rhTSH stimulation on the number of DTC foci visible in the PET/CT was found, but without affecting its effectiveness.

7771 Surveillance Role in Differentiated Thyroid Cancer Through Ultrasensitive Thyroglobulin IRMA with High Negative Prediction Value

Abstract Disclosure: J. Jang: None. H. Kim: None. S. Ha: None. K. Jung: None. G. Jung: None. S. Cho: None. D. Park: None. G. Cheon: None. Y. Park: None. TSH-stimulated serum thyroglobulin (s-Tg) is a well-established marker for monitoring differentiated thyroid cancer (DTC) following remnant ablation therapy. The 2nd-generation immunoradiometric assay for Tg (ultrasensitive Tg, uTg) was developed to detect Tg with higher sensitivity compared with the 1st generation (conventional Tg, cTg). This study aimed to compare efficacy of both methods, cTg and uTg, to determine whether unstimulated Tg (us-Tg) could predict s-Tg levels. Paired serum samples were collected from 274 DTC patients before (us-Tg) and after (s-Tg) TSH stimulation for 1st radioiodine therapy after surgery (1st Tg) or both 1st therapy and 2nd therapy/diagnostic test (1st and 2nd Tg, respectively). Both cTg (Dynotest Tg-plus, BRAHMS Gmbh, Germany, LOD 0.1 ng/mL and functional sensitivity (FS) 0.2 ng/mL) and uTg (RIAKEY, Shinjin Medics, South Korea; LOD 0.01 ng/mL and FS 0.06 ng/mL) were measured. For analysis, samples with inadequate TSH stimulation (<30 μIU/mL) or with anti-thyroglobulin antibody levels > 60 U/mL were excluded. Ultimately, the included samples consisted of 296 for us-Tg and 352 for s-Tg.. Among these, paired samples for us-Tg and s-Tg were available in 260 cases (189 for 1st Tg and 71 for 2nd Tg). Comparing all Tg values, cTg and uTg levels had a correlation (Intraclass correlation coefficient r=0.752, P < 0.001), with no significant difference between us-Tg (r=0.803, P < 0.001) and s-Tg (r= 0.752, P < 0.001). The optimal cut-off level for predicting s-cTg at 1 ng/mL was 0.12 ng/mL in uTg or 0.16 ng/mL in cTg tests using AUC-ROC curve analysis. Considering the FS for cTg, diagnostic performance was assessed with a cut-off level of 0.2 ng/mL for cTg and 0.16 ng/mL for uTg. For s-cTg positivity as ≥ 1 ng/mL, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of uTg were 72.1%, 59.8%. 52.0%, and 78.0%, respectively, while for cTg, they were 33.3%, 95.3%, 78.4%, and 73.9%, respectively. Similar trends were observed for s-cTg ≥ 2 ng/mL (69.0%, 71.4%, 35.0%, and 91.2% for uTg, respectively; 49.0%, 93.8%, 64.9%, and 88.7% for cTg, respectively). In essence, uTg demonstrated higher sensitivity than cTg, while having lower specificity and PPV, with a similar NPV. Of the 71 patients with paired 2nd Tg levels, 7 (9.8%) had biochemical disease (BCD) by s-cTg (1 ng/mL), whereas only 1 (1.4%) showed BCD using us-cTg ≥ 0.2 ng/mL. Conversely, 40 (56.0%) were classified as BCD using us-uTg ≥ 0.16 ng/mL. During the 6.48 years of follow-up, 4 patients developed structural recurrence; all had positive us-Tg levels with uTg tests, while only 1 patient demonstrated positivity with cTg tests. Although, the ultrasensitive Tg is sensitive in predicting positive stimulated Tg and recurrence, the specificity is very low resulting high frequency of BCD cases without clinical significance. Therefore, the clinical utility of uTg appears to be limited. Presentation: 6/2/2024

68 Ga-DOTATATE PET/CT Versus 18 F-FDG PET/CT in TENIS Syndrome: A Head-to-Head Comparison With Elevated and Suppressed TSH Levels in Papillary Thyroid Carcinoma-A Pilot Study.

TENIS syndrome is characterized by reduced expression of sodium-iodine symporter, rising serum thyroglobulin (Tg) levels, and negative whole-body 131 I scans. In such patients, somatostatin receptor imaging with 68 Ga-DOTATATE PET/CT (somatostatin receptor [SSR] PET/CT) and 18 F-FDG PET/CT (FDG PET/CT) can identify metastases and were compared under 2 conditions: elevated (eTSH) and suppressed (sTSH) TSH serum levels. Potential candidates for peptide receptor radionuclide therapy (PRRNT) were identified in 15 patients prospectively enrolled. All patients underwent 4 examinations. Images were blindly evaluated for differences in SUV max values and lesion detectability. Reference standard consisted of neck ultrasound, CT, MRI, PET/CT, biopsy, and follow-up. Three patients were received PRRNT. sTSH SSR PET/CT detected a greater number of cervical ( P = 0.0253 and P = 0.0176) and distant LNs ( P = 0.0253 and P = 0.0391) when compared with sTSH FDG PET/CT, respectively, in a per-patient and on a per-lesion based analysis. Likewise, eTSH SSR PET/CT detected a greater number of patients with local recurrences ( P = 0.0455) and distant LN metastases ( P = 0.0143). Per-lesion analysis revealed greater number of cervical and distant LNs ( P = 0.0337 and P = 0.0039, respectively) when compared with eTSH FDG PET/CT. There was no difference in detection of distant metastases by both tracers for lung and bone metastases (κ = 1). Both skeletal and pulmonary lesions were also detected by conventional CT part of FDG or DOTATATE PET/CT scans. TSH stimulation had no additional value in a per-patient analysis for both FDG and DOTATATE PET scans (κ varying from 0.6087 to 1). However, TSH stimulation led to more lesion identifications in DOTATATE PET/CT; most of those metastases were not confirmed by the reference standard leading to a decrease in specificity (84% vs 74%). One of 3 patients submitted to 3 cycles of PRRNT presented with a visual partial response, a 20% reduction in quantitative analyses, and stable disease regarding Tg and TgAb levels. Patients with TENIS syndrome can be imaged with SSR PET/CT as well as FDG PET/CT with high overall accuracy regardless of TSH levels (86% to 92% and 92% to 85%, respectively, with eTSH and sTSH). SSR PET/CT detected a greater number of locoregional and distant LN metastases than FDG PET/CT with both sTSH and eTSH. One of 3 patients submitted to PRRNT presented a partial response to treatment. Our findings may impact in patient restaging, management, and theranostics strategies with radiolabeled somatostatin analogs.

Thyroid scintigraphy: establishing a clinically useful normal range for 99mTc pertechnetate uptake.

This study aims to establish a normal range for the thyroid uptake derived from 99mTc pertechnetate scans. In particular, variations of uptake with TSH stimulation and other factors such as urinary iodine concentration are taken into account and compared with the calculation of a raw uptake value. Clinical multicentric (center A, B and C) prospective study on 125 consecutive healthy patients undergoing thyroid scans for thyroid nodules. Normal functional thyroid status was assured by normal TSH, normal thyroid size, no thyroid antibodies and no symptoms of thyroid functional disorders. Calculations of raw Tc-uptake (uptake) and modified uptake values regarding current TSH value (uptakeTSH1), urinary iodine concentration (uptakeTSH1&uic), gland volume, age, smoking status, weight and tissue thickness ventral to the thyroid were performed. There is a positive correlation of thyroid uptake with TSH allowing for the calculation of a normalized uptake value (uptakeTSH1). The normal range for uptakeTSH1 compares favourable to that for raw uptake in that it yields a clear distinction from thyroid functional disorders. The additional normalization for urinary iodine concentration (uptakeTSH1&uic) may even improve the distinctive power whereas further normalizations such as for gland volume, age and others are not warranted by this study. The 95% CI of uptakeTSH1 for sites A, A&B, and A&B&C were 0.21%-2.06%, 0.22%-2.38% and 0.24%-2.40%. A normal range for the thyroid uptake can be established with respect to the current TSH stimulation. This normalization (uptakeTSH1) overcomes the drawback of raw uptake by yielding a clinically useful parameter with obviously high distinctive power against functional thyroid disorders.

Effect of TSH on aromatase expression of ovarian granulosa cells in obese mice.

Aromatase plays an important role in ovarian development, the normal progress of the menstrual cycle, and fertility status. Elevated aromatase activity is linked to obesity. There is a bidirectional relationship between obesity and thyroid function. Few studies have investigated the relationship between TSH and ovarian aromatase in obesity. Our aim was to investigate the effect of TSH on aromatase expression of ovarian granulosa cells in obese mice. Female mice pups were divided into an obesity group and a control group. Obese parameters and the time of pubertal onset were recorded. At the age of 5weeks, blood and tissues were obtained. Serum aromatase and hormone concentrations were measured using ELISA. The granulosa cells were isolated and exposed to variable concentrations (0μM, 1μM, 10μM, 100μM) of TSH. The expression of CYP19A1 mRNA and protein were assessed via RT-qPCR and western blot. In female mice, body weight, Lee's obesity index, and serum levels of E2, aromatase, and TSH were significantly higher in the obesity group compared to the control group, whereas the time of pubertal onset and serum T3 and T4 concentrations were significantly lower (all P < 0.001). In granulosa cells, the expression of CYP19A1 mRNA in the obesity group was lower than that in the control group at 1μM and 100μM concentrations of TSH (both P < 0.001). The expression of CYP19A1 protein in the obesity group was higher than that in the control group after TSH stimulation (P = 0.014, P < 0.001, and P = 0.004, respectively). With the increase of TSH concentrations, the expression of CYP19A1 mRNA and protein in the two groups significantly increased (all P < 0.001). Early puberty and elevated serum aromatase and TSH levels were found in obese female mice. In the granulosa cells of obese mice, TSH directly regulates aromatase expression in a dose-dependent manner.

The Presence of Anti-TPO Antibodies Increase the Likelihood of Post-I131 Hypothyroidism.

The use of radioactive iodine in the treatment of hyperthyroidism is common practice. However, a standardized treatment protocol with regard to radioactive iodine treatment (RAI) remains subject to discussion. We retrospectively analyzed 100 patient records. Patient diagnosis, age, gender, body mass index (BMI), dose of radioactive iodine, thyroid size, the 24 h radioiodine uptake (24 h RAIU) and protein bound iodine (PBI) were deducted, as well as the use of antithyroid drugs prior to RAI. Biochemical parameters were obtained, such as TSH, fT4, fT3, Anti-TPO, Anti-TG antibodies and thyroid stimulating antibodies. After 5 years of follow-up, 46% of the patients proved to be hypothyroid, whereas 8% of the patients were not cured after one dose of RAI. One year after RAI, a larger proportion of patients with a toxic nodule developed hypothyroidism compared to patients with a multinodular goiter (MNG) (44.2% vs. 21.2%). Radioactive iodine dose, PBI, RAIU, BMI, size of the thyroid gland, diagnosis, age and TPO-antibodies showed statistically significant differences in the development of hypothyroidism. Furthermore, thiamazole pretherapy was shown to be a predictor of hypothyroidism, as well as a high PBI value, exhibiting a positive predictive value of 85.2% when the PBI exceeded 0.16. We suggest a standardized measurement of TPO-Ab's to further determine their role in the development of hypothyroidism after RAI. The empirical dosing regimen was very effective, illustrating a 92% cure rate after 1 dose.

Usefulness of second 131I treatment in biochemical persistent differentiated thyroid cancer patients.

Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment. The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR). One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated. After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment. Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.

The Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Differentiated Thyroid Cancer Patients with Elevated Thyroglobulin/Thyroglobulin Antibody Levels and Negative Iodine Scintigraphy: A Systematic Review and Meta-Analysis.

Background: The objective of this study is to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in detecting recurrence in patients with differentiated thyroid cancer (DTC) who have negative whole-body scans (WBSs) but elevated serum thyroglobulin (Tg) or thyroglobulin antibody (TgAb) levels. Methods: This systematic review/meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy criteria (International Prospective Register of Systematic Reviews registration number: CRD42022340924). A comprehensive search of the MEDLINE, EMBASE, and Cochrane databases identified articles reporting the diagnostic accuracy of FDG PET/CT for the detection of recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels published between January 2012 and June 2023. Meta-analyses were performed to determine the diagnostic accuracy of FDG PET/CT on the total target population as well as on subgroups stratified by serum Tg or TgAb, and thyrotropin (TSH) stimulation status at the time of FDG PET/CT. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was applied to evaluate the quality of evidence and the strength of recommendations to facilitate translation of the meta-analysis results into practical recommendations for clinical guidelines. Results: A total of 24 studies involving 1988 patients were included for analysis. The overall pooled sensitivity and specificity values were 0.87 (95% confidence interval [CI] = 0.83-0.92; I2 = 75%) and 0.84 (CI = 0.80-0.89; I2 = 44%), respectively. Subgroup analyses revealed no significant differences in the diagnostic accuracy of FDG PET/CT in patients stratified by serum Tg or TgAb levels, and TSH stimulation status at the time of PET/CT. Treatment plans were changed following FDG PET/CT imaging in 40% (CI = 34-47%; I2 = 39%) of cases. The quality level of evidence for using FDG PET/CT was moderate in both sensitivity and specificity according to the GRADE system. Conclusion: There is moderate quality evidence demonstrating the high diagnostic accuracy of FDG PET/CT in detecting recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels. This evidence corroborates the current guidelines' endorsement of FDG PET/CT as a diagnostic tool in such patients.

Efficiance of radioiodine remnant ablation in cases of locally differentiated thyroid cancer

On the territory of Russia has increased the of thyroid cancer after Chernobyl NPP incidence at 1986, and currently accounts for up to 14,000 newly identified cases. Postoperative radioiodine (RAI) remnant ablation is the second stage of combine treatment of differentiated thyroid cancer, except for the prevalence of pT1N0M0, with minimal level of TG and AT-TG, according to international guidelines. In the past 20 years a significant number of published practice guidelines for the treatment of this disease. However, the discussion is the amount of medication for administration activity (GBq) 131I, is required for successful ablation of thyroid remnants. The study analyzed 353 clinical cases after radical surgical treatment for DTC. In our study, the effectiveness of radioiodablation was compared with certain indicators of specific therapeutic activity 131I (MBq/kg), in groups of patients with different levels of TSH stimulation (less than 30 mME/ml, and more than 30 mME/ml). We evaluated the absorbed dose in the thyroid remnant in patients with residual thyroid tissue volume determined by US when administering 131I empirical therapeutic activity. The control of the WBS with 131I was carried out in 6 months. The average eղciency RAI was 85.5 %, there were no significant differences in the TSH stimulation groups of more than 30 mME/ml and 4-30 mME/ml (p &gt; 0.05). If the thyroid remnant is not detected by US, the effective range of 131I specific therapeutic activity is 30-40 MBq/ kg against a background of TTG stimulation greater than 4 ՏME/ml and strict adherence to a 14-day low iodine diet. Direct radiometry followed by neck scintigraphy (1200 kBq 131I) and calculation of therapeutic activity is recommended when determining thyroid remnant by US to plan for TAD = 300 Gy and reduce the risk of radiation sialoadenitis. At the time of RAI, 3.9 % of patients had previously undetectable X-rays lung metastases with stimulated TG levels greater than 124 ng/mL after surgical treatment with SPECT/CT.

HYPERTHYROIDISM SECONDARY TO GESTATIONAL TROPHOBLASTIC DISEASE : A LITERATURE REVIEW

Gestational trophoblastic disease (GTD) is a rare form of pregnancy-related cancer that is effectively treatable. GTD is accompanied by the potentially fatal complication of hyperthyroidism. We created a review consisting of five case reports. This case report was conducted on women who became pregnant when they were &gt;35 years old. They showed consistent laboratory results, in which there was an increase in hCG levels. TSH and thyroid stimulating antibodies cannot account for the hyperthyroidism associated with GTD. The source of the thyroid stimulating agent is trophoblastic tissue. The thyrotropic effects of ?-hCG mediate GTD hyperthyroidism. Other research examined the prevalence of hyperthyroidism in women with normal pregnancy, hydatidiform mole, and choriocarcinoma who had ?-hCG serum levels below 100,000 IU/ml. Early prenatal screening may significantly reduce hyperthyroidism rates. Thyroid hormone synthesis inhibitors treat hyperthyroidism in pregnancy. Thioamides, propylthiouracil (PTU), and methimazole (MMI) are the most prevalent U.S. antithyroid medications (ATD). Plasmaphoresis may be an option for people who are resistant to therapy or need emergency surgery. GTD can cause fatal hyperthyroidism. Anti-thyroid medicines can handle most GTD hyperthyroidism. Surgery may be a possibility for patients refractory to medical treatment.

Thyroid Hormone Withdrawal versus Recombinant Human TSH as Preparation for I-131 Therapy in Patients with Metastatic Thyroid Cancer: A Systematic Review and Meta-Analysis.

Differentiated thyroid carcinoma (DTC) is characterized by an excellent prognosis with a 10-year survival rate > 90%. However, when DTC develops in a metastatic form, it has been shown to significantly impact patient survival and quality of life. Although I-131 has been shown to be an effective therapy in patients with metastatic DTC, whether its efficacy after recombinant human TSH (rhTSH) is comparable to endogenous TSH stimulation by thyroid hormone deprivation (THW) is still debated. Our present study was prompted to compare clinical results obtained in metastatic DTC by I-131 administered after rhTSH and THW stimulation protocols, respectively. A systematic search on PubMed, Web of Science, and Scopus was performed from January to February 2023. Pooled risk ratios with 95% CI were determined for evaluating the initial response after to I-131 therapy after preparation with rhTSH or THW and the disease progression. To track the accumulation of evidence and reduce type I errors because of small data, a cumulative meta-analysis was performed. A sensitivity analysis was also performed to examine the impact of individual studies on overall prevalence results. Ten studies were included with a total of 1929 patients pre-treated with rhTSH (n = 953) and THW (n = 976), respectively. The cumulative data of our systematic review and meta-analysis showed an increase in the risk ratio over the years without any change in favour of a pre-treatment or the other on the effectiveness of I-131 therapy of metastatic DTC. Our data suggest that pretreatment with rhTSH or THW has no significant impact on the effectiveness of I-131 therapy for metastatic DTC. This implies that concerns about the use of one or the other pretreatment should be deferred to clinical evaluations made considering patient characteristics and reduction in side effects.

The Mediation Role of Thyrotropin Receptor Antibody in the Relationship Between Age and Severity of Hyperthyroidism in Graves' Disease.

Background: The severity of hyperthyroidism in Graves' disease (GD) has been reported to be worse in younger patients and to gradually improve with advancing age, accompanied by declining thyrotropin (TSH) receptor antibody (TRAb) values. This study was conducted to explore the extent to which the declining TRAb production may contribute to a decrease in severe hyperthyroidism with advancing age in patients with GD. Methods: This study was a cross-sectional analysis of retrospectively reviewed data. The medical records of patients newly diagnosed with GD at Ito Hospital, between January 2005 and June 2019, were examined. Patients were divided into age-stratified groups for evaluation. Multivariable logistic regression was performed to estimate the odds ratio (OR) of severe hyperthyroidism by increasing age. Mediation analyses were also conducted to quantify the association between age and declining severity of hyperthyroidism mediated through decreased TRAb productivity. Results: A total of 21,018 patients with newly diagnosed GD (3848 male and 17,170 female) were included. A correlation was observed between TRAb value and thyroid hormone values in each age-stratified group, which became weaker with an increase in age. Patients aged <40 years had a higher risk of severe hyperthyroidism (free thyroxine [fT4] level >7.0 ng/dL [n = 5616], OR [confidence interval, CI] = 1.80 [1.68-1.92]; free triiodothyronine [fT3] level >25 pg/mL [n = 4501], OR [CI] = 2.06 [1.92-2.23]) than those aged ≧40 years. In examining the relationship between age and severe hyperthyroidism, the proportion mediated through TRAb productivity was 8.5% and 8.4% using fT4 and fT3 as an outcome index, respectively. Conclusions: Declining TRAb value mediated only 8.5% of the negative association between age and severity of hyperthyroidism. The presence of other underlying mechanisms, such as the decline in the reactivity of thyrocytes to TSH stimulation, requires further investigation.

Abstract #1167579: A Case of Thyroid Ectopia

Prevalence of Ectopic Thyroid (ET) tissue is one per 100,000-300,000 in the general population, and 1 in 4,000-8,000 in patients with thyroid dysfunction. Lingual and submandibular locations account for 90%, while 10% occur at other sites. Most cases of ET are euthyroid, but one third can be complicated by hypothyroidism. In some of these, the ET tissue can enlarge due to TSH stimulation. For most, medical treatment is sufficient but surgical excision may be required if local compression, nodular disease or cancer complicates the presentation.

Transcription Factor CREB3L1 Regulates the Expression of the Sodium/Iodide Symporter (NIS) in Rat Thyroid Follicular Cells

The transcription factor CREB3L1 is expressed in a wide variety of tissues including cartilage, pancreas, and bone. It is located in the endoplasmic reticulum and upon stimulation is transported to the Golgi where is proteolytically cleaved. Then, the N-terminal domain translocates to the nucleus to activate gene expression. In thyroid follicular cells, CREB3L1 is a downstream effector of thyrotropin (TSH), promoting the expression of proteins of the secretory pathway along with an expansion of the Golgi volume. Here, we analyzed the role of CREB3L1 as a TSH-dependent transcriptional regulator of the expression of the sodium/iodide symporter (NIS), a major thyroid protein that mediates iodide uptake. We show that overexpression and inhibition of CREB3L1 induce an increase and decrease in the NIS protein and mRNA levels, respectively. This, in turn, impacts on NIS-mediated iodide uptake. Furthermore, CREB3L1 knockdown hampers the increase the TSH-induced NIS expression levels. Finally, the ability of CREB3L1 to regulate the promoter activity of the NIS-coding gene (Slc5a5) was confirmed. Taken together, our findings highlight the role of CREB3L1 in maintaining the homeostasis of thyroid follicular cells, regulating the adaptation of the secretory pathway as well as the synthesis of thyroid-specific proteins in response to TSH stimulation.

Circulating MicroRNA Profiles as Potential Biomarkers for Differentiated Thyroid Cancer Recurrence.

Circulating microRNAs (miRNAs) are emerging biomarkers of thyroid cancer. This study sought to identify the profile of circulating miRNAs and its response to human recombinant TSH (rhTSH) in thyroid cancer patients with recurrent/persistent disease. We obtained serum samples from 30 patients with differentiated thyroid cancer, 14 with recurrent/persistent disease and 16 with complete remission. We used next-generation sequencing to define the miRnomes along with a comprehensive quantitative PCR (qPCR) validation using 2 different platforms. We made a transversal study by comparing serum miRNA profiles of patients with or without recurrent/persistent disease and a longitudinal study looking at differences before and after rhTSH stimulation. Selected miRNAs were then studied in human thyroid cancer cell lines TPC-1, FTC-133, and OCUT-2 in response to TSH stimulation. We could not demonstrate any consistent differences in serum profiles of known miRNAs between patients with and without recurrent/persistent disease or before and after rhTSH stimulation. However, our sequencing data revealed 2 putative novel miRNAs that rise with rhTSH stimulation in the serums of patients with recurrent/persistent disease. We further confirmed by qPCR the upregulation of these putative miRNAs both in serums and in TSH-stimulated cells. We also show miRNAs that are good candidates for housekeeping genes in the serum of patients independently of the levels of TSH. The present study does not provide evidence that known miRNAs can be used as circulating markers for recurrence of thyroid cancer. However, we suggest that novel miRNA molecules may be related to thyroid cancer pathogenesis.

KARAKTERISTIK FUNGSI KELENJAR TIROID PASCA TIROIDEKTOMI TOTAL PADA PASIEN NODUL TIROID DI RSUP SANGLAH

ABSTRACT&#x0D; The thyroid nodule is an enlargement because of the impact of TSH stimulation in order to produce thyroxine. The thyroid nodule is a case of benign and malignant neoplasm with a prevalence rate of 5-10%. The thyroid nodule causes obstruction and cosmetic disturbance so that these need thyroid gland surgery or thyroidectomy. Thyroidectomy is categorized into two methods which are partial and total thyroidectomy. After thyroidectomy procedure is performed, it needs subsequent examination post thyroidectomy in order to check the thyroid gland functions (hypothyroid, euthyroid and hyperthyroid). Such examination consists of the examination of TSH and FT4 levels. This study aims to understand the characteristics in terms of age, sex, classification and thyroid gland post total thyroidectomy.&#x0D; This study is of a descriptive research type with cross-sectional design towards thyroid nodule patients in RSUP Sanglah from November 2018 until November 2019. This study uses secondary data in the form of thyroid nodule patients’ medical records to get the characteristics in terms of age, sex, classification and thyroid gland post total thyroidectomy.&#x0D; In this study, it was found that 59 patients’ medical records with highest category which is with the age 50-59 years (30.5%); thyroid nodule cases are suffered more by female patients (84.7%) and was found more to be malignant (59.3%) which the domination of papillary thryroid carcinoma (45.8%). The thyroid gland function characteristics which are with the most cases are hypothyroid (44.1%), as followed by hyperthyroid (37.3%) and euthyroid (18.6%). It can be concluded that the thyroid nodule cases happen most in 50-59 years old with case with more prevalence in female patients. The thyroid nodule is found more to be in malignant classification. The thyroid gland function post thyroidectomy being found to be with most prevelence is hyperthyroid.&#x0D; &#x0D; Keywords : Thyroid nodule, thyroidectomy, thyroid function

TSH stimulation of human thyroglobulin and thyroid peroxidase gene transcription is partially dependent on internalization

The TSH receptor (TSHR) is the major regulator of thyroid hormone biosynthesis in human thyrocytes by regulating the transcription of a number of genes including thyroglobulin (TG) and thyroperoxidase (TPO). Until recently, it was thought that TSHR initiated signal transduction pathways only at the cell-surface and that internalization was primarily involved in TSHR desensitization and downregulation. Studies primarily in mouse cells showed that TSHR internalization regulates gene transcription at an intracellular site also. However, this has not been shown for genes involved in thyroid hormone biosynthesis in human thyrocytes. We used human thyrocytes in primary culture. In these cells, the dose-response to TSH for gene expression is biphasic with low doses upregulating gene expression and higher doses decreasing gene expression. We used two approaches to inhibit internalization. In the first, we used inhibitors of dynamins, dynasore and dyngo-4a. Pretreatment with dynasore or dyngo-4a markedly inhibited TSH upregulation of TG and TPO mRNAs, as well as TG secretion. In the second, we used knockdown of dynamin 2, which is the most abundant dynamin in human thyrocytes. We showed that dynamin 2 knockdown inhibited TSHR internalization and decreased the TSH-stimulated levels of TG and TPO mRNAs and proteins. Lastly, we showed that the level of the activatory transcription factor phosphorylated cAMP response element binding protein (pCREB) in the cell nuclei was reduced by 68% when internalization was inhibited. We conclude that upregulation of genes involved in thyroid hormone synthesis in human thyrocytes is, in part, dependent on internalization leading to nuclear localization of an activated transcription factor(s).

Diagnostic utility of basal serum T4 and TSH concentrations in dogs with hypothyroidism confirmed by TSH stimulation test

Diagnostic utility of basal serum T4 and TSH concentrations in dogs with hypothyroidism confirmed by TSH stimulation test

Radiation exposure to allied health personnel handling blood specimens from patients receiving radioactive iodine-131 and recombinant human TSH (thyrogen®) stimulation

With increasing use of recombinant human TSH (rhTSH) stimulation protocol in radioactive iodine-131 treatment of thyroidectomised differentiated thyroid carcinoma (DTC), there is increasing concern regarding radiation safety during collection and processing of radioactive blood samples. Our study aims to quantify this radiation exposure in the context of current radiation guidelines to provide a practical safety framework. We analysed 45 patients prospectively referred to a tertiary centre in Singapore, who had histologically proven DTC, and who were thyroidectomised and planned for I-131 with rhTSH stimulation. Each patient received rhTSH for two consecutive days, with I-131 administered 24 h after, and a stimulated Thyroglobulin blood sample collected and processed 72 h after the last rhTSH dose. We measured radiation exposures with dosimeters. Based on the average and maximum exposure rates calculated, we extrapolated and derived the number of radioactive blood samples that could be safely collected and processed. Mean hand and body radiation exposures during venepuncture and blood processing were generally significantly higher than background radiation. Based on average exposure rates, the permissible number of blood samples that can be collected and processed is 9.09 × 103 per year (24 per day) and 8.70 × 104 per year (238 per day), respectively. This is the first study to date to extrapolate permissible thresholds that can serve as a practical guideline to the number of radioactive blood samples which can be safely collected and processed, following radioactive iodine therapy, within the limits of current radiation guidelines. Once validated, generalisations to other radioactive therapies may be considered.

Comparative Efficacy of Haizao Yuhu Decoction Composed of Different Varieties of Glycyrrhiza in Goiter Rats.

In traditional Chinese medicine, Glycyrrhiza and Sargassum are one pair of the “18 incompatible medicaments,” which in theory cannot be used together. However, since ancient times, many reports have described using compounds containing both Glycyrrhiza and Sargassum to treat diseases. Haizao Yuhu Decoction (HYD), which contains both ingredients, is mainly used to treat goiter. Chinese Pharmacopoeia officially recorded three varieties of Glycyrrhiza: Glycyrrhiza uralensis, Glycyrrhiza inflata, and Glycyrrhiza glabra. These three varieties have certain differences in chemical composition and pharmacological effects. The purpose of the present study was to investigate whether the HYD containing different varieties of Glycyrrhiza and Sargassum had different therapeutic effects in rats with goiter and to elucidate the underlying mechanism of any difference. In this study, propylthiouracil (PTU) was used to replicate the goiter model, then HYDs containing different varieties of Glycyrrhiza were used for treatment for four weeks, and then the relevant indicators were tested. The results demonstrated that HYD had antigoiter effects, alleviated the pathological changes in the thyroid tissue, and restored the abnormal serum levels of hormones related to thyroid function induced by PTU. HYD containing Glycyrrhiza uralensis had the best therapeutic effect in rats with PTU-induced goiter. The antigoiter effect of HYD may function through the hypothalamic-pituitary-thyroid (HPT) axis, inhibit the expression of the Tg and NIS genes, and regulate the synthesis of thyroid hormones, thereby reducing the excessive stimulation of TSH in thyroid cells. In addition, HYD also prevented goiter by promoting thyroid cell apoptosis and inhibiting the ERK/RSK1 pathway of cell proliferation. In conclusion, three types of HYD had different therapeutic effects in rats with goiter, which might be caused by the compatibility of different varieties of Glycyrrhiza and Sargassum.