Establishing and Monitoring an Effective Management of Benign Nontoxic Multinodular Goitre in Kuwait "Utilizing Two Different Dose Levels of Recombinant Human TSH in Combination with Radioactive Iodine".

INTRODUCTION: rhTSH-assisted radioiodine therapy of multinodular goiter is not fully known and only a few studies, with a limited number of patients have evaluated the effect of rhTSH assisted radioiodine therapy beyond 1 year. Though there is an effective and safe management of benign non-toxic MNG available, it is not applicable to all patient categories in Kuwait covering the impact of the past environmental events (Gulf War) and the genetic relation. The proposed project aims to address those points raised, that is exclusive to the Kuwait population. MATERIALS AND METHODS: In this cohort study, 2 groups of patients, group one (G1) and group two (G2) patients (N=50, ≥18 years old) went undergo evaluated according to a proposed criteria followed by FNA to exclude cancer, toxicity and those who have refused surgery. All patients had a CT scan, TSH, T3, T4 and CBC and complete biomedical tests at a 6-months interval during the treatment period and the follow up. The Volumetric application of GE 670 SPECT/CT (i.e. Xeleris) and in-house developed MATLAB used for quantitative measurement. All patients had a 131-I uptake at baseline and 24 intervals post intramuscular a single dose of 0.3mg or 0.1mg (group 1, group 2) of rhTSH. RESULTS: There was no significant difference in TSH levels at 24-month follow-up between the two groups (p=0.327), whereas there was a statistically significant difference at the baseline and at the 6-months interval between the 2 groups for T4. Post treatment follow up at the 24-hour time point, Group 1 displayed significantly higher uptake than Group 2 (G1:41.74 ± 6.27 vs. G2:34.80 ± 3.84, p < 0.001). The change in I131 uptake from baseline to 24 hours was significantly greater in Group 1compared to Group 2 (p < 0.001). The ROC analysis (AUC) post treatment indicated an excellent discriminatory power for AUC (0.960) and (p < 0.001). There was a much better correlation posttreatment between BMI and thyroid volume for group 1 (R2=0.661) than for group 2 (R2=0.008). Our results suggest 42.1% thyroid volume reduction for group 1 and 20% for group 2. CONCLUSION: The study underscores the potential benefits of the higher rhTSH dose (0.3mg) in managing multinodular non-toxic goiter for the Kuwaiti population and the region considering the impact of dietary, and experience to the drastic environmental exposure.

Recombinant or endogenous thyroid-stimulating hormone for radioactive iodine therapy in thyroid cancer: state of knowledge and current controversies.

For patients undergoing radioiodine therapy (RIT) of differentiated thyroid carcinoma (DTC), thyroid-stimulating hormone (TSH) stimulation prior to RIT can be achieved using thyroid hormone withdrawal (THW) or administration of recombinant human TSH (rhTSH). As THW can lead to nausea, headaches, vomiting, fatigue, and dizziness secondary to transient acute hypothyroidism, rhTSH could be a good alternative. Recombinant human TSH has been administered in patients in order to stimulate TSH for RIT since 2005. According to the Martinique criteria formulated by the leading professional societies involved in care of patients with DTC, rhTSH can be applied in 3 settings: for remnant ablation, adjuvant treatment, and treatment of known disease. Numerous studies have investigated the effects of rhTSH as a method of TSH stimulation on the thyroid cell, the systemic effects, biokinetics, and clinical outcomes; however, no consensus has been reached about many aspects of its potential use. Recombinant human TSH is able to stimulate sufficient TSH levels (>30 mIU L-1) and is hypothesized to decrease risks of tumor cell proliferation. As rhTSH-use avoids the transiently impaired renal function associated with THW, radioiodine excretion is faster with the former, leading to a lower iodine-131 uptake and a difference in fractional remnant uptake, effective half-life, mean residence time, and dose to the blood. Differences between rhTSH and THW were observed in radioiodine genotoxic effects and endothelial-dependent vasodilation and inflammation. For thyroid remnant ablation, THW and rhTSH lead to similar remnant ablation rates. For adjuvant therapy and treatment of known disease, insufficient trials have been conducted and future prospective studies are recommended. The current review provides a state-of-the-science overview on the issues and debates surrounding TSH stimulation through either rhTSH adminsitration orendogenous TSH production after levothyroxin withdrawal.

Feasibility of Recombinant Human TSH as a Preparation for Radioiodine Therapy in Patients with Distant Metastases from Papillary Thyroid Cancer: Comparison of Long-Term Survival Outcomes with Thyroid Hormone Withdrawal.

BACKGROUND: this study was designed to compare the long-term survival outcomes of patients prepared for radioiodine (RAI) therapy using either thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH) stimulation, by specifically focusing on cases with distant metastases from papillary thyroid cancer (PTC). METHODS: A retrospective analysis was performed on 88 patients with distant metastases from PTC. Fifty-one and thirty-seven patients were prepared for RAI treatment by either THW or rhTSH stimulation, respectively. The primary endpoints were progression-free survival (PFS) and disease-specific survival (DSS). RESULTS: The 10-year DSS rates of patients prepared for RAI therapy using either THW or rhTSH stimulation were 62.2% and 73.3%, respectively. Using multivariate analysis, RAI-avid metastases (p = 0.025) and preparation with rhTSH (p = 0.041) were identified as independent prognostic factors for PFS. Notably, PFS in the group of patients with RAI-avid metastases and preparation with rhTSH was significantly better than that in the other groups (p = 0.025). CONCLUSIONS: Preparation for RAI therapy using rhTSH stimulation is not inferior to THW preparation in terms of long-term survival outcomes experienced by patients with PTC and distant metastasis. Patients with RAI-avid metastases and preparation with rhTSH had the most favorable PFS.

Radio-Iodide Treatment: From Molecular Aspects to the Clinical View.

Thyroid radio-iodide therapy (RAI) is one of the oldest known and used targeted therapies. In thyroid cancer, it has been used for more than eight decades and is still being used to improve thyroid tumor treatment to eliminate remnants after thyroid surgery, and tumor metastases. Knowledge at the molecular level of the genes/proteins involved in the process has led to improvements in therapy, both from the point of view of when, how much, and how to use the therapy according to tumor type. The effectiveness of this therapy has spread into other types of targeted therapies, and this has made sodium/iodide symporter (NIS) one of the favorite theragnostic tools. Here we focus on describing the molecular mechanisms involved in radio-iodide therapy and how the alteration of these mechanisms in thyroid tumor progression affects the diagnosis and results of therapy in the clinic. We analyze basic questions when facing treatment, such as: (1) how the incorporation of radioiodine in normal, tumor, and metastatic thyroid cells occurs and how it is regulated; (2) the pros and cons of thyroid hormonal deprivation vs. recombinant human Thyroid Stimulating Hormone (rhTSH) in radioiodine residence time, treatment efficacy, thyroglobulin levels and organification, and its influence on diagnostic imaging tests and metastasis treatment; and (3) the effect of stunning and the possible causes. We discuss the possible incorporation of massive sequencing data into clinical practice, and we conclude with a socioeconomical and clinical vision of the above aspects.

Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal preparation for radioiodine ablation in differentiated thyroid cancer in children, adolescents and young adults.

OBJECTIVE: Recombinant human TSH (rhTSH) is commonly used to prepare patients for postoperative radioiodine (I-131) ablation after surgery for differentiated thyroid cancer (DTC). In adults, rhTSH is associated with equivalent oncologic efficacy in comparison to thyroid hormone withdrawal (THW), but its use has not been well studied in children. We aimed to measure time to disease progression after rhTSH stimulation vs. THW in paediatric patients under the age of 21 with DTC following total thyroidectomy. DESIGN: Retrospective cohort study (March 2001-July 2018). PATIENTS: Sixteen children and adolescents (75% female, median age, 17.4 years) who received rhTSH were compared to 29 historical controls (72% female, median age, 18.5 years) prepared with THW, followed for a median of 2.4 years (range, 0.5-14). MEASUREMENTS: Stimulated serum TSH concentrations prior to I-131 ablation and time to disease progression, as determined by a component outcome variable encompassing both structural and biochemical disease persistence/recurrence. RESULTS: No differences were observed in tumour characteristics and I-131 dose (median 2.3 [1.8-2.90] mCi/kg rhTSH) between groups. Patients who received rhTSH achieved a similar median stimulated TSH level (163 [127-184] mU/L), compared to those who underwent THW (136 [94.5-197] mU/L; p = .20). Both groups exhibited similar time to progression (p = .13) and disease persistence/recurrence rates (rhTSH 31% vs. THW 59%, p = .14). CONCLUSION: In this cohort of children and adolescents with DTC, we observed similar time to disease progression among those who received rhTSH or underwent THW prior to postoperative I-131 ablation.

Voice Outcome of Total Thyroidectomy in Comparison With Administration of Recombinant Human TSH.

BACKGROUND AND OBJECTIVES: The larynx is an end-organ target for hormones, and thyroid hormone may act on the larynx. We objectively compared and analyzed the phonetic characteristics of patients who underwent total thyroidectomy before and after radioiodine therapy (RIT) according to administration of recombinant human TSH (rh-TSH). SUBJECTS AND METHODS: Ninety-one patients who had undergone a total thyroidectomy participated (50 patients without rh-TSH, 41 patients with rh-TSH). Voice samples were obtained postoperatively (Post-OP), before high-dose RIT (Pre-RIT), and after high-dose RIT (Post-RIT). Frequency-, perturbation-, and noise-related parameters were evaluated for acoustic analysis, and the voice handicap index (VHI) was used for the subjective evaluation. RESULTS: Frequency-related parameters decreased significantly in patients without rh-TSH administration, but not changed at three periods in patients with rh-TSH administration. Pitch perturbation parameters were not changed at each period in two groups, but amplitude perturbation parameters were changed significantly in two groups. The functional scores of the VHI increased significantly at Pre-RIT in two groups and physical scores increased in patients without rh-TSH at Pre-RIT. CONCLUSION: The hypothyroidism after total thyroidectomy affects phonation significantly. Our results suggest that rh-TSH administration during RIT resulted in improving voice results during RIT in the patients with total thyroidectomy.

Clinical Outcomes After Radioiodine Therapy, According to the Method of Preparation by Recombinant TSH vs. Endogenous Hypothyroidism, in Thyroid Cancer Patients at Intermediate-High Risk of Recurrence.

Background: To effectively treat differentiated thyroid carcinoma (DTC) with radioiodine therapy (RAI), it is necessary to raise serum thyrotropin levels, either by thyroid hormone withdrawal (THW) or by administration of recombinant human TSH (rhTSH). The use of rh-TSH is controversial in DTC patients at intermediate to high risk of recurrence. Even more controversial is the question of whether is alters progression-free survival rates and overall survival in more aggressive patients. Objective: The primary objective of this study was comparing clinical outcomes according to the method of preparation of RAI in intermediate to high DTC patients who presented progression of structural disease. Methods: This retrospective study included 81 patients with initial intermediate to high DTC and progression of structural disease at the end of follow-up. In 21 patients, all RAI treatments were done with only rhTSH stimulation. In 11, RAI treatments were done either with thyroid hormone withdrawal (THW) or rhTSH. In 49 patients, all RAI treatments were done only THW. Results: After a median follow-up time of 83 months, there were no statistical differences in the clinical outcomes (status of structural disease at the end of the follow-up, death rate, overall survival curve, and progression-free survival curve). Conclusions: Preparation for RAI therapy using either rhTSH stimulation or THW was associated with no inferiority in the clinical outcomes in progressive DTC patients at higher risk of recurrence.

Familial Longevity is Associated with an Attenuated Thyroidal Response to Recombinant Human Thyroid Stimulating Hormone.

CONTEXT: Longevity is associated with higher circulating levels of TSH in the absence of differences in circulating thyroid hormones (TH), as previously observed in F2 members of long-lived families (F2-LLS) and their partners (F2-Con). The mechanism underlying this observed difference remains unknown. OBJECTIVE: We hypothesized that the thyroid gland of members from long-lived families are less responsive to TSH stimulation, thereby requiring higher circulating TSH levels to maintain adequate TH levels. METHODS: We performed a case-control intervention study with a single intramuscular (gluteal) injection with 0.1 mg recombinant human TSH in a subgroup of 14 F2-LLS and 15 similarly aged F2-Con. They were followed for 4 days. No serious adverse events were reported. For analyses, we compared time trajectories of TSH and TH, and the ratio of TH to TSH using area under the curve (AUC) calculations. RESULTS: The AUC free T4/AUC TSH ratio was significantly lower in F2-LLS than in F2-Con (estimated mean [95% confidence interval] 1.6 [1.2-1.9] and 2.2 [1.9-2.6], respectively, P = 0.01). The AUC thyroglobulin/AUC TSH ratio was also lower in F2-LLS than in F2-Con (median [interquartile range] 2.1 [1.4-3.6] and 3.2 [2.7-7.4], respectively, P = 0.04). We observed the same trend with the AUC free T3/AUC TSH ratio, although the difference was not statistically significant (estimated mean [95% confidence interval] 0.6 [0.4-0.7] and 0.7 [0.6-0.8], respectively, P = 0.07). CONCLUSIONS: The present findings show that members of long-living families have a lower thyroid responsivity to TSH compared with their partners.

Concomitant medullary thyroid carcinoma with paraganglioma-like pattern and papillary thyroid carcinoma.

SUMMARY: A 74-year-old man was referred to the Endocrinology Unit because of multinodular goiter. The dominant nodule (1.7 × 1.9 × 2.4 cm), at the medium-superior third of the left lobe, was inhomogeneously hypoechoic, with irregular margins, macrocalcifications and intranodular vascularization. Fine-needle aspiration biopsy (FNAB) was performed. The cytological diagnosis was TIR 2, benign, according to the 2013 Italian thyroid cytology classification system. Moderately high serum calcitonin (s-Ct) (61.5 pg/mL, n.r. 0-7.5) and normal CEA were detected. The Ct level in FNAB wash-out fluid (Ct-FNAB) was 1450 pg/mL. Based on s-Ct and Ct-FNAB levels, patient underwent total thyroidectomy. Macroscopically, a dominant circumscribed nodule of 2 ecm was described; the histological and immunohistochemical features identified medullary thyroid carcinoma (MTC) with paraganglioma (PG)-like pattern positive for Ct, CEA and chromogranin and negative for S-100 sustentacular cells (SC). Moreover, papillary carcinoma of 3 mm in the right lobe was also associated. No areas of hyperaccumulation of the tracer were documented at Ga68 PET/CT. No RET-proto-oncogene mutations were found. Post-surgery s-Ct levels were within normal range (4 pg/mL). Two years after thyroidectomy, the patient is still disease-free. We reported a case of sporadic and rare variant of MTC: this is the ninth described case of PG-like MTC. In this case, cytologically benign, the clinical suspicion arose from high Ct values at FNAB wash-out fluid. Even if clinical behavior of this variant seems indolent, additional studies are necessary to understand prognoses and predictive factors. LEARNING POINTS: Several unusual histological variants of medullary thyroid carcinoma (MTC) have been described such as spindle cell, giant cell, clear cell, melanotic, squamous, angiosarcoma-like variants; even rarer is the paraganglioma (PG)-like pattern. We here describe a case of medullary PG-like thyroid carcinoma in a 74-year-old man. This is a rare histological variant of MTC hardly diagnosed by cytology, since immunohistochemical investigations are necessary. Measurement of calcitonin both in serum and in wash-out fluid from fine-needle aspiration could be an additional tool for an early and non-invasive identification of these variants.

Conventional Radioiodine Therapy for Differentiated Thyroid Cancer.

This article presents an overview of the use of radioactive iodine (131-I) in the treatment of patients with differentiated thyroid cancer. Topics reviewed include definitions; staging; the 2 principal methods for selection of 131-I dosage; the indications for ablation, adjuvant treatment, and treatment; the recommendations for the use of 131-I contained in the guidelines of the American Thyroid Association and the Society of Nuclear Medicine and Molecular Imaging; the dosage recommendations and selection of dosage approach for 131-I by these organizations; the use of recombinant human thyrotropin for radioiodine ablation, adjuvant therapy, or treatment; and the MedStar Washington Hospital Center approach.

Pattern of urine iodine excretion with low iodine diet during preparation for radioactive iodine ablation in patients with thyroid cancer.

BACKGROUND: The optimal period of low iodine diet during preparation for radioactive iodine (RAI) ablation in an area with iodine-rich diet was investigated. METHODS: Ninety-four patients with thyroid cancer who underwent low iodine diet and RAI were prospectively allocated into 2 groups-thyroxine withdrawal or using recombinant human thyroid stimulating hormone (rhTSH) for TSH stimulation. Their urinary iodine excretion (UIE) patterns were analyzed. RESULTS: There was no clinicopathological difference between the 2 groups except for tumor size and lymph node status. The UIE (median iodine to creatinine ratio, I/Cr) in the withdrawal group on the 7th and 14th day were 18.3 and 17.9 µg/gCr, respectively, with adequate preparation rate of 93.3% on both days (cutoff value 100 µg/gCr). In the rhTSH group, the median I/Cr on the 7th and 14th day were 48.0 and 45.7 µg/gCr (adequate preparation rates 91.8% and 93.8%), respectively. CONCLUSION: One week of low iodine diet is sufficient preparation for RAI regardless of method of TSH stimulation.

Indirect Basal Metabolism Estimation in Tailoring Recombinant Human TSH Administration in Patients Affected by Differentiated Thyroid Cancer: A Hypothesis-Generating Study.

PURPOSE: Recombinant human TSH (rhTSH) is currently used in follow-up of patients affected by differentiated thyroid cancer (DTC). Age, sex, weight, body mass index, body surface area (BSA) and renal function are known factors affecting serum TSH peak levels, but the proper rhTSH dose to deliver to single patient remains elusive. In this study, the correlations of basal metabolic rates with serum TSH peak following rhTSH administration were investigated. METHODS: We evaluated 221 patients affected by thyroid cancer that received a standard dose rhTSH. Blood samples were collected at pre-established time points. Data on body weight, height, and BSA were collected. The Mifflin-St Jeor and Fleisch equations were used to assess basal metabolism. RESULTS: The median value (range) of serum TSH peaks was 142 ± 53 µU/ml. Serum TSH peaks were significantly lower in males than in females (p = 0.04). TSH values also increased with age. Data showed a significant decrease of TSH peak levels at day 3 from the administration of rhTSH when basal metabolic rates increased (p = 0.002 and p = 0.009, respectively). Similar findings were observed at day 5 (p = 0.004 and p = 0.04, respectively). A multivariate analysis of several factors revealed that patients' basal metabolism (obtained using the Mifflin-St Jeor but not Fleisch equation) predicts serum TSH level peak at day 3 (p < 0.001). These results were used to generate a new formula based on Mifflin-StJeor equation which reveals as a promising tool in tailoring rhTSH dose. CONCLUSION: Basal metabolism appears an improving factor in tailoring diagnostic rhTSH dose in patients affected by DTC.

Incidence of salivary side effects after radioiodine treatment using a new specifically-designed questionnaire.

Sialadenitis is one of the common complications of radioiodine treatment for thyroid malignancy. The aim of this study was to evaluate the prevalence of radioiodine-induced sialadenitis and other side effects by using a self-administered questionnaire. From 1 January 2011 to 31 December 2012 all consecutive patients with a newly-established diagnosis of thyroid cancer who were treated with adjuvant radioiodine at La Timone University Hospital were sent a self-administered questionnaire on salivary complaints that had been specifically designed for this study. A total of 413 patients sent the questionnaire back, of whom 100 (24%) had experienced pain, 116 (28%) discomfort or swelling, and 147 (36%) dry mouth or xerostomia. This survey has highlighted the number of side effects of radioiodine treatment in a large group of patients and corroborates previous observations. Our new self-administered questionnaire may be useful to others for follow-up and research.

Single-Photon Emission Computed Tomography for Preclinical Assessment of Thyroid Radioiodide Uptake Following Various Combinations of Preparative Measures.

BACKGROUND: MicroSPECT/CT imaging was used to quantitatively evaluate how iodide uptake in the mouse thyroid is influenced by (i) route of iodine administration; (ii) injection of recombinant human thyrotropin (rhTSH); and (iii) low iodide diet (LID) in euthyroid and triiodothyronine (T3)-treated mice. METHODS: Pertechnetate (99mTcO4-) and 123I thyroid uptake in euthyroid and T3-treated animals fed either a normal-iodine diet (NID) or an LID, treated or not with rhTSH, and radiotracer administered intravenously, subcutaneously, intraperitoneally or by gavage, were assessed using microSPECT/CT imaging. Western blotting was performed to measure sodium/iodide symporter expression levels in the thyroid. RESULTS: Systemic administration of radioiodide resulted in a higher (2.35-fold in NID mice) accumulation of iodide in the thyroid than oral administration. Mice fed LID with systemic radioiodide administration showed a further two-fold increase in thyroid iodide uptake to yield a ∼5-fold increase in uptake compared to the standard NID/oral route. Although rhTSH injections stimulated thyroid activity in both euthyroid and T3-treated mice fed the NID, uptake levels for T3-treated mice remained low compared with those for the euthyroid mice. Combining LID and rhTSH in T3-treated mice resulted in a 2.8-fold higher uptake compared with NID/T3/rhTSH mice and helped restore thyroid activity to levels equivalent to those of euthyroid animals. CONCLUSIONS: Systemic radioiodide administration results in higher thyroidal iodide levels than oral administration, particularly in LID-fed mice. These data highlight the importance of LID, both in euthyroid and T3-treated, rhTSH-injected mice. Extrapolated to human patients, and in the context of clinical guidelines for the preparation of differentiated thyroid cancer patients, our data indicate that LID can potentiate the efficacy of rhTSH treatment in T3-treated patients.

Comparison of Therapeutic Efficacy and Clinical Parameters Between Recombinant Human Thyroid Stimulating Hormone and Thyroid Hormone Withdrawal in High-Dose Radioiodine Treatment with Differentiated Thyroid Cancer.

PURPOSE: High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer. METHODS: We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6-8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (-), and thyroid US or F-18 FDG PET/CT (-). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups. RESULTS: The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change of body mass index was 0.4 (±0.7) kg/m(2) in the THW group and was decreased by -0.6 (±0.6) kg/m(2) in the rh-TSH group. CONCLUSIONS: Consistent with previous studies, the rates of complete ablation between the THW and rh-TSH groups were not significantly different. The clinical parameters, as we mentioned above, were elevated for THW group but were irrelevant for the rh-TSH group. The findings favor HD-RIT after rh-TSH, especially for patients with chronic liver and kidney disease.

Does (131)I Radioactivity Interfere with Thyroglobulin Measurement in Patients Undergoing Radioactive Iodine Therapy with Recombinant Human TSH?

OBJECTIVES: Recombinant human thyroid-stimulating hormone (rhTSH) is widely used in radioactive iodine therapy (RIT) to avoid side effects caused by hypothyroidism during the therapy. Owing to RIT with rhTSH, serum thyroglobulin (Tg) is measured with high (131)I concentrations. It is of concern that the relatively high energy of (131)I could interfere with Tg measurement using the immunoradiometric assay (IRMA). We investigated the effect of (131)I administration on Tg measurement with IRMA after RIT. METHODS: A total of 67 patients with thyroid cancer were analysed retrospectively. All patients had undergone rhTSH stimulation for RIT. The patients' sera were sampled 2 days after (131)I administration and divided into two portions: for Tg measurements on days 2 and 32 after (131)I administration. The count per minute (CPM) of whole serum (200 µl) was also measured at each time point. Student's paired t-test and Pearson's correlation analyses were performed for statistical analysis. RESULTS: Serum Tg levels were significantly concordant between days 2 and 32, irrespective of the serum CPM. Subgroup analysis was performed by classification based on the (131)I dose. No difference was noted between the results of the two groups. CONCLUSIONS: IRMA using (125)I did not show interference from (131)I in the serum of patients stimulated by rhTSH.

Systemic oxidative stress to nucleic acids is unaltered following radioiodine therapy of patients with benign nodular goiter.

BACKGROUND: Little is known about the whole body oxidative stress burden following radioactive iodine ((131)I) therapy of thyroid diseases. METHODS: We studied 17 patients with benign nodular goiter treated with (131)I therapy. The targeted thyroid dose was 50 Gy in 11 patients pretreated with 0.1 mg of recombinant human TSH (rhTSH). In 6 patients, the applied thyroid dose was 100 Gy without rhTSH prestimulation. Well-established biomarkers of oxidative stress to RNA (8-oxo-7,8-dihydroguanosine; 8-oxoGuo) and DNA (8-oxo-7,8-dihydro-2'-deoxyguanosine; 8-oxodG) were measured in freshly voided morning urine (normalized against the creatinine concentration) at baseline, and 7 and 21 days after rhTSH (not followed by (131)I), and 7 and 21 days after (131)I therapy, respectively. RESULTS: The baseline urinary excretions of 8-oxoGuo and 8-oxodG were 2.20 ± 0.84 and 1.63 ± 0.70 nmol/mmol creatinine, respectively. We found no significant changes in the excretion of any of the metabolites, neither after rhTSH stimulation alone nor after (131)I therapy. Also, no significant differences were found between the rhTSH group (low dose, median (131)I: 152 MBq) and the non-rhTSH group (high dose, median (131)I: 419 MBq; 8-oxoGuo: p = 0.66, 8-oxodG: p = 0.71). CONCLUSION: Systemic oxidative stress, as detected by nucleic acids metabolites in the urine, is not increased after thyroid stimulation with 0.1 mg of rhTSH, or after (131)I therapy. Our method cannot quantify the oxidative stress induced locally in the thyroid gland, but the study supports that (131)I therapy of benign nodular goiter carries no or only a minute risk of developing subsequent malignancies. It remains to be explored whether our findings also apply to hyperthyroid disorders.

Age and body composition influence TSH concentrations after administration of rhTSH.

AIM: Previous studies listed body surface area (BSA), lean body mass (LBM), and age as modifying factors on the TSH concentrations after administration of recombinant human thyrotropin (rhTSH). The purpose of this study was to identify the main modifying factors on serum TSH levels and to compare the stimulation via single rhTSH injection after a short thyroid hormone withdrawal (THW) with that of the standard stimulating protocol. PATIENTS, METHODS: 106 patients with differentiated thyroid cancer (DTC) undergoing radioiodine therapy (RIT) after rhTSH administration were obtained through chart review. Two groups were evaluated: Group I was treated with a single rhTSH administration after two weeks of T3 therapy followed by one week of THW. Group II was stimulated according to the international standard protocol via rhTSH injections for two consecutive days. Serum TSH concentrations were documented prior to rhTSH administration (day 1 TSH), one day after (day 3 TSH) and 3-6 days after (mean 4.2 days, day 6 TSH) the last rhTSH injection. The following data was collected: age, gender, weight, height, BMI, LBM, BSA, residual thyroid tissue, CRP, creatinine, GFR, liver enzymes, alkaline phosphatase, cholesterol, and triglycerides. RESULTS: Group I: Age combined with anthropometric factors like BMI (TSH increase and day 6 TSH), BSA (TSH decrease), and gender (day 6 TSH) are the main modifying factors on serum TSH concentrations after rhTSH administration. Group II: Age and lean body mass (LBM) showed a significant impact on day 3 TSH, TSH increase (day 3-day 1), and TSH decrease (day 6-day 3). Day 6 TSH was found to be influenced by GFR (group II). CONCLUSION: Age and anthropometric parameters have significant independent influence on TSH concentrations after rhTSH injection in both groups. Anthropometric parameters (BSA, LBM) and demographic parameters (female gender) show strong influence on TSH concentrations. Further research should be conducted to examine the influence of body compartments on TSH levels through measuring total body water.

New-generation thyroglobulin assay: performance and implications for follow-up of differentiated thyroid carcinoma.

OBJECTIVES: Differentiated thyroid cancer (DTC) requires long-term follow-up by serum thyroglobulin assay and cervical ultrasound, due to the risk of recurrence. Guidelines recommend basal assay under hormone therapy at 3 months, repeated at 6-12 months post-surgery, with or without associated isotopic ablation, after stimulation by recombinant human TSH to improve assay sensitivity. It was hypothesized that a new-generation assay kit with lower limits of detection and quantification would improve the sensitivity of the basal assay, enhance detection of premature recurrence and decrease the rate of false-negatives, thereby avoiding the need for the complementary stimulation test. MATERIAL AND METHODS: A validation study of the second-generation thyroglobulin serum assay was performed in the laboratory of the Lyon Sud Hospital Centre (Lyon, France), with comparison to stimulation test results. Low-concentration serum pools were constituted, including patients followed for stage I to III DTC for whom basal and post-stimulation samples were available in the serum bank. RESULTS: The new assay proved robust and reliable, with good correlation with the technique presently used in the Lyon hospitals. None of the 54 patients showed false-negative results, which was the objective of our choice of threshold, and 5 were false-positive, for thyroglobulin thresholds of 0.1µg/L at baseline and 1.0µg/L post-stimulation. Positive and negative predictive values were 100% and 87.8% respectively. CONCLUSION: These results allow an improvement in the follow-up algorithm for DTC, replacing the stimulation test by the new-generation thyroglobulin assay in post-therapeutic assessment.

How to manage patients with differentiated thyroid cancer and a rising serum thyroglobulin level.

Serum thyroglobulin (sTg) is the marker for monitoring persistence/recurrence of differentiated thyroid cancer, in patients without sTg antibodies. Patients with undetectable basal sTg or peak sTg <2 ng/mL are cured with low risk to recur. Newly detectable level of sTg indicates the recurrence. The significance of increasing sTg in patients treated with emithyroidectomy or total-thyroidectomy but not ablated with radioiodine is undefined. A doubling time <1 year may be a poor prognostic factor, but this is more relevant in cases with high levels of sTg. Because of its sensitivity, neck ultrasound should be performed at any visit, especially when an increased sTg is seen.