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Contact in Context 2023Thyrotropin alfa is a heterodimeric glycoprotein containing human thyroid stimulating hormone (TSH). It is used as an adjunctive diagnostic tool for serum thyroglobulin...
Thyrotropin alfa is a heterodimeric glycoprotein containing human thyroid stimulating hormone (TSH). It is used as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer who have previously undergone thyroidectomy. Inter-lot variability in the Fourier transform near-infrared spectra of 30 samples obtained from four separate lots of Thyrogen was detected in the Drug Quality Study (DQS). The vials fell into two distinct groups (r = 0.90, r= 0.98, =0.02). In addition, one vial of the 30 (3%) appeared 4.7 multidimensional SDs from all of the other vials, suggesting that it also represents a different material.
PubMed: 37396298
DOI: 10.6084/m9.figshare.23524530 -
Japanese Journal of Radiology Nov 2023Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the...
PURPOSE
Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the glomerular filtration rate. Using recombinant human thyrotropin (rhTSH) may avoid these changes; however, these two preparation methods have not been compared in the literature. The purpose of this study was to reveal whether THW and rhTSH as preparation methods for RIT affect serum electrolytes differently. We also evaluated clinical factors influencing the onset of hyponatremia and hyperkalemia during RIT.
MATERIALS AND METHODS
From April 2005 to December 2020, we analyzed 278 patients with thyroid cancer who received RIT. The patients were classified into two groups based on the preparation method, and renal function and serum electrolytes were compared between the groups. We also evaluated clinical factors that may affect overt hyponatremia (serum sodium level < 134 mmol/L) and hyperkalemia (serum potassium level ≥ 5.0 mmol/L).
RESULTS
Serum sodium and chloride levels in the THW group were significantly lower than those in the rhTSH group (p < 0.001 and p = 0.002, respectively). In contrast, the serum potassium level in the THW group was significantly higher than that in the rhTSH group (p = 0.008). As for clinical factors that may influence hyponatremia, age and estimated glomerular filtration rate (eGFR) were significantly associated with serum sodium level in the univariate analysis (p = 0.033 and p = 0.006, respectively). In the multivariate analysis, only age was significantly associated with serum sodium level (p = 0.030). Regarding hyperkalemia, distant metastases, the preparation method and eGFR were significantly associated with the serum potassium level in the univariate analysis (p = 0.005, p = 0.005 and p = 0.001, respectively). In the multivariate analysis, only eGFR was significantly associated with hyperkalemia (p = 0.019).
CONCLUSION
THW and rhTSH affect serum sodium and potassium levels differently. Renal function may be risk factors for hyperkalemia, whereas older age may be a risk factor for hyponatremia.
Topics: Humans; Thyroid Neoplasms; Thyrotropin Alfa; Iodine Radioisotopes; Hyperkalemia; Hyponatremia; Retrospective Studies; Thyrotropin; Potassium; Sodium; Electrolytes
PubMed: 37184818
DOI: 10.1007/s11604-023-01444-9 -
Clinical Cancer Research : An Official... Jul 2023To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with...
PURPOSE
To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation.
PATIENTS AND METHODS
A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq-150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months.
RESULTS
Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3-4 AEs in 7 patients.
CONCLUSIONS
Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Proto-Oncogene Proteins B-raf; Thyrotropin Alfa; Prospective Studies; Pyridones; Pyrimidinones; Oximes; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Mutation
PubMed: 37074727
DOI: 10.1158/1078-0432.CCR-23-0046 -
Renal Failure Dec 2023This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia.
PURPOSE
This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia.
METHODS
The study involved 110 patients with renal anemia. Thyroid profile and baseline investigations were carried out for each patient. The patients were divided into two groups: 60 patients taking erythropoietin served as the control group (rHuEPO group) and 50 patients using roxadustat served as the experimental group (roxadustat group).
RESULTS
The results indicated that there were no significant differences in serum total thyroxine (TT4), total triiodothyronine (TT3), free triiodothyronine (FT3), free thyroxine (FT4) or thyroid stimulating hormone (TSH) between the two groups at baseline. After treatment, TSH, FT3, and FT4 were significantly lower in the roxadustat group than in the rHuEPO group ( < 0.05). After adjusting for age, sex, dialysis modality, thyroid nodules and causes of kidney disease, Cox regression showed that roxadustat was an independent influencing factor on thyroid dysfunction (HR 3.37; 95% CI 1.94-5.87; < 0.001). After 12 months of follow-up, the incidence of thyroid dysfunction was higher in the roxadustat group than in the rHuEPO group (log-rank < 0.001).
CONCLUSION
Roxadustat may lead to a higher risk of thyroid dysfunction, including low TSH, FT3 and FT4, than rHuEPO in patients with renal anemia.
Topics: Humans; Triiodothyronine; Thyroxine; Thyroid Gland; Cohort Studies; Thyrotropin; Erythropoietin; Chronic Disease; Kidney Diseases; Epoetin Alfa; Anemia
PubMed: 37051660
DOI: 10.1080/0886022X.2023.2199093 -
Endocrine Jul 2023To evaluate the predictive value of the rhTSH thyroglobulin stimulation test (rhTSH-Tg) compared to basal high-sensitive thyroglobulin (hs-Tg) under TSH suppressive...
PURPOSE
To 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.
METHODS
Prospective 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.
RESULTS
hs-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.
CONCLUSIONS
Both 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.
Topics: Adult; Female; Humans; Male; Middle Aged; Iodine Radioisotopes; Prospective Studies; Risk Assessment; Thyroglobulin; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Thyrotropin Alfa
PubMed: 36820996
DOI: 10.1007/s12020-023-03320-y -
Frontiers in Endocrinology 2022The 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...
INTRODUCTION
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
Topics: Male; Humans; Female; Adult; Middle Aged; Aged; Thyrotropin; Thyroid Nodule; Thyrotropin Alfa; Thyroxine
PubMed: 36714577
DOI: 10.3389/fendo.2022.1066379 -
Scientific Reports Jan 2023This study was conducted to investigate the effects of thyroid hormone withdrawal (THW) and recombinant human thyroid-stimulating hormone (rhTSH) administration on renal...
This study was conducted to investigate the effects of thyroid hormone withdrawal (THW) and recombinant human thyroid-stimulating hormone (rhTSH) administration on renal function in patients with thyroid cancer after total thyroidectomy. This study included 202 patients who discontinued thyroid hormone therapy and/or received rhTSH after total thyroidectomy. Creatinine (Cr), blood urea nitrogen (BUN) levels, and estimated glomerular filtration rate (eGFR) were assessed at the following three time points: before thyroidectomy, at least 3 weeks after THW, and 1 day after the second injection of rhTSH. The median serum Cr level was significantly higher following THW compared to that before thyroidectomy (0.95 versus 0.70). In contrast, the median BUN level was significantly lower after THW compared to that before thyroidectomy (9.8 versus 11.3). Over a fifth (22.2%) of patients had abnormal eGFR values after THW, which was significantly greater than that before thyroidectomy. In contrast, renal parameter values after rhTSH administration were not significantly different than those before thyroidectomy. In conclusion, THW affects renal function in patients with thyroid cancer who have undergone total thyroidectomy. However, renal function in such patients is not affected by rhTSH administration.
Topics: Humans; Thyrotropin Alfa; Thyrotropin; Thyroid Neoplasms; Thyroid Hormones; Kidney; Recombinant Proteins
PubMed: 36604466
DOI: 10.1038/s41598-023-27455-0 -
The Kaohsiung Journal of Medical... Feb 2023This retrospective study was designed to compare the treatment response of patients with differentiated thyroid cancer (DTC) prepared for radioiodine ablation (RIA) with... (Comparative Study)
Comparative Study
Recombinant human thyrotropin versus thyroid hormone withdrawal preparation for radioiodine ablation in differentiated thyroid cancer: Experience in a South Taiwanese medical center.
This retrospective study was designed to compare the treatment response of patients with differentiated thyroid cancer (DTC) prepared for radioiodine ablation (RIA) with thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH) stimulation. Patients with DTC were followed-up retrospectively between 2013 and 2018 in Kaohsiung Chang Gung Memorial Hospital, Taiwan. We compared the excellent response ratios between THW (49.9%) and rhTSH (50.1%) stimulation. Patients were then divided into subgroups, on the basis of age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage, for analysis. In all, 647 patients were followed-up after RIA. The ratios of THW or rhTSH use in the different subgroups were not statistically significant. In all the patients, the excellent response rate with THW and rhTSH was 80% and 76.5%, respectively, which was not statistically significant. The subgroup analysis, including age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage (low and high risk), showed similar results. Furthermore, the logistic regression analysis revealed no statistically significant differences among the subgroups. The multivariate analysis showed extrathyroidal extension, lymph node metastasis, and high I dose were the prognostic factors affecting the excellent response rate. In conclusion, the THW and rhTSH preparations for RIA were similar in terms of the excellent response rates and subgroup clinical outcomes.
Topics: Humans; Adenocarcinoma; Iodine Radioisotopes; Lymphatic Metastasis; Recombinant Proteins; Retrospective Studies; Thyroid Hormones; Thyroid Neoplasms; Thyrotropin; Thyrotropin Alfa; Treatment Outcome; Withholding Treatment
PubMed: 36448726
DOI: 10.1002/kjm2.12621 -
Journal of Nuclear Medicine : Official... Oct 2022It is well known that ionizing radiation can induce genetic damage and that oxidative stress is a major factor inducing it. Our aim was to investigate whether thyroid...
Analysis of Short-Term and Stable DNA Damage in Patients with Differentiated Thyroid Cancer Treated with I in Hypothyroidism or with Recombinant Human Thyroid-Stimulating Hormone for Remnant Ablation.
It is well known that ionizing radiation can induce genetic damage and that oxidative stress is a major factor inducing it. Our aim was to investigate whether thyroid remnant ablation with low activities of I (1,850 MBq) is associated with DNA damage by evaluating the CometAssay, micronuclei, and chromosome aberrations with multicolor fluorescent in situ hybridization. We studied 62 patients prepared with recombinant human thyroid-stimulating hormone (rhTSH) or by thyroid hormone withdrawal. In both groups, we analyzed stable and unstable genetic alterations before I therapy and 1 wk and 3 mo after I administration. We also correlated the genetic damage with several variables, including the degree of radiation-induced oxidative stress, genetic polymorphisms of enzymes involved in DNA repair, and antioxidative stress. We found a comparable amount of DNA breaks evaluated by CometAssay and micronuclei testing in both groups of patients at different time points, but there was a significant increase in stable chromosome aberrations evaluated by multicolor fluorescent in situ hybridization (breaks and translocations) in patients prepared with thyroid hormone withdrawal. Overall, high chromosome damage was associated with higher retained body radioactivity and unfavorable gene polymorphism. A high level of free oxygen radicals and a low level of antioxidants were found in all patients at any time point. In particular, patients prepared with thyroid hormone withdrawal, at 3 mo, had significantly higher levels of free oxygen radicals than those prepared with rhTSH. An increase in stable chromosome aberrations with respect to baseline is detectable after administration of low doses of I in patients prepared with thyroid hormone withdrawal but not in patients prepared with rhTSH. The clinical significance of these chromosomal alterations remains to be determined.
Topics: Adenocarcinoma; Chromosome Aberrations; DNA Damage; Humans; Hypothyroidism; In Situ Hybridization, Fluorescence; Iodine Radioisotopes; Reactive Oxygen Species; Thyroid Hormones; Thyroid Neoplasms; Thyrotropin; Thyrotropin Alfa
PubMed: 35115370
DOI: 10.2967/jnumed.121.263442