Recombinant Human Thyrotropin Research Articles

Development of Graves' Ophthalmopathy after Radioactive Iodine Ablation Using Recombinant Human Thyrotropin for Incidentally Discovered Papillary Thyroid Carcinoma

Development of Graves' Ophthalmopathy after Radioactive Iodine Ablation Using Recombinant Human Thyrotropin for Incidentally Discovered Papillary Thyroid Carcinoma

Risk factors associated with high thyroglobulin level following radioactive iodine ablation, measured 12 months after treatment for papillary thyroid carcinoma.

PurposeThe measurement of serum thyroglobulin (Tg) of papillary thyroid carcinoma patients, 12 months after total thyroidectomy and radioactive iodine (RAI) ablation following thyroxine hormone withdrawal (T4-off Tg) or recombinant human thyroid-stimulating hormone stimulation (rhTSH-Tg), is standard method for monitoring disease status. The aim of this study was to find predictive factors for detectable T4-off Tg during follow-up.MethodsA retrospective review was conducted of 329 patients who underwent total thyroidectomy and RAI ablation between October 2008 and August 2012. Subjects were assigned to high (>1 ng/mL, n = 53) and low (≤1 ng/mL, n = 276) groups, based on T4-off Tg measured 12 months postoperatively. Demographic and clinicopathological characteristics at diagnosis and follow-up were compared between the 2 groups.ResultsThe low and high T4-off Tg groups differed with respect to tumor size, preoperative Tg, ablative Tg, cervical lymph node metastasis, thyroglobulinemia out of proportion to results of diagnostic whole body scan, and American Thyroid Association 3-level stratification and restratification. Multivariate analysis confirmed that ablative Tg > 1.0 ng/mL (odds ratio [OR], 10.801; P = 0.001), more than 5 cervical lymph node metastasis (OR, 6.491; P = 0.003), and thyroglobulinemia out of proportion (OR, 9.221; P = 0.000) were risk factors.ConclusionAblative Tg >1.0 ng/mL, more than 5 cervical lymph node metastasis, and thyroglobulinemia out of proportion were independent factors for T4-off Tg >1 ng/mL 12 months postoperative. In low-risk patients without these risk factors, the possible omission of Tg measurements could be considered during follow-up.

Recombinant human thyrotropin stimulation prior to 131I therapy in toxic multinodular goiter with low radioactive iodine uptake

AimStimulation with recombinant human thyrotropin (rhTSH) increases thyroid radioiodine uptake, and is an aid to 131I therapy in non-toxic multinodular goiter (MNG). However, there are not many studies using rhTSH prior to 131I in toxic multinodular goiter to improve hyperthyroidism and compressive symptoms. Materials and methodsA prospective study was conducted on patients with MNG and hyperthyroidism. Patients were recruited consecutively and divided into group I, stimulated with 0.3mg of rhTSH before radioiodine therapy, and a control group or group II, without stimulation. Thyroid function, radioiodine thyroid uptake, thyroid weight, and compressive symptoms were measured, and patients were followed-up for 9 months. ResultsGroup I consisted of 16 patients (14 women), with a mean age 69.7 years, and group II with 16 patients (12 women), with a mean age 70.7 years. After stimulation with 0.3mg rhTSH in group I, 131I uptake (RAIU) at 24h increased by 78.4%, and the estimated absorbed dose by 89.3%. In group II, the estimated absorbed dose was lower than group I after stimulation with rhTSH (29.8Gy vs. 56.4Gy; P=0.001).At 9 months of follow-up, hyperthyroidism was controlled in 87.5% of patients in group I, and 56.2% in group II (P=0.049). The mean reduction in thyroid weight was higher in group I than in group II (39.3% vs. 26.9%; P=0.017), with a tendency toward subjective improvement of compressive symptoms in group I, although non-significant. Only 2 patients described tachycardias after rhTSH administration, which were resolved with beta-blockers. ConclusionStimulation with 0.3mg of recombinant human thyrotropin prior to radioiodine therapy achieves a reduction in thyroid weight and functional improvement in patients with hyperthyroidism and multinodular goiter with low uptake, and with no need for hospital admission.

Differences in Brain Glucose Metabolism During Preparation for 131I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin.

In preparation for 131I ablation, temporary withdrawal of thyroid hormone is commonly used in patients with thyroid cancer after total thyroidectomy. The current study aimed to investigate brain glucose metabolism and its relationships with mood or cognitive function in these patients using 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG-PET). A total of 40 consecutive adult patients with thyroid carcinoma who had undergone total thyroidectomy were recruited for this cross-sectional study. At the time of assessment, 20 patients were hypothyroid after two weeks of thyroid hormone withdrawal, while 20 received thyroid hormone replacement therapy and were euthyroid. All participants underwent brain 18F-FDG-PET scans and completed mood questionnaires and cognitive tests. Multivariate spatial covariance analysis and univariate voxel-wise analysis were applied for the image data. The hypothyroid patients were more anxious and depressed than the euthyroid participants. The multivariate covariance analysis showed increases in glucose metabolism primarily in the bilateral insula and surrounding areas and concomitant decreases in the parieto-occipital regions in the hypothyroid group. The level of thyrotropin was positively associated with the individual expression of the covariance pattern. The decreased 18F-FDG uptake in the right cuneus cluster from the univariate analysis was correlated with the increased thyrotropin level and greater depressive symptoms in the hypothyroid group. These results suggest that temporary hypothyroidism, even for a short period, may induce impairment in glucose metabolism and related affective symptoms.

Cost-effectiveness profile, organizational implications and patient preferences on the use of exogenous TSH therapy (Thyrogen®) vs. THW in thyroid residue ablation in Italy

BACKGROUND: Radioiodine ablation is an adjuvant procedure used to treat patients with differentiated thyroid cancer. For ablation to be successful, patients must have elevated levels of thyroid stimulating hormone (TSH). This can be achieved by withholding thyroid hormone therapy (endogenous stimulation), or by administration of recombinant human thyroid stimulating hormone (rhTSH; Thyrogen®; exogenous stimulation) to patients in the euthyroid state.AIM: To compare the estimated health benefits, cost and cost-effectiveness of TSH stimulation with and without Thyrogen® in the Italian setting.METHODS: A cost-utility analysis was undertaken to assess the impact of exogenous vs. endogenous TSH stimulation before radioiodine remnant ablation of patients with newly diagnosed, well-differentiated papillary or follicular thyroid cancer who have undergone total or near-total thyroidectomy. A Markov model was developed to simulate treatment costs and health outcomes associated with exogenous and endogenous stimulation in four distinct health states: pre-ablation, ablation, post-ablation, and well/recovery. Treatment was stratified by patients who receive high- and low-activity (30-100 mCi, respectively) in the ablation state. The Italian National Health System perspective was adopted in the base case scenario while the impact of indirect costs was explored in a sensitivity analysis. Costs and quality-adjusted life years (QALY) specific to each health state were estimated, summarized and converted into a corresponding incremental cost-effectiveness ratio (ICER).RESULTS: We calculated a cost-effectiveness ratio of 18,357.18 €/QALY gained whereas the inclusion of indirect cost and accident cost produced reductions of the ICER to € 14,609.51 and € 15,515.26 per QALY, respectively. Finally, all results in the sensitivity analysis are below the lower bound of national and international cost- effective threshold.CONCLUSION: Thyrogen® represents a cost-effective option for patients with differentiated thyroid cancer who underwent total or near-total thyroidectomy in Italy. Our findings are consistent with other cost-utility analyses.

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

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. 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. 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. 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.

Is a second recombinant human thyrotropin stimulation test useful? The value of postsurgical undetectable stimulated thyroglobulin level at the time of remnant ablation on clinical outcome

The management of patients with differentiated thyroid cancer (DTC) has changed in recent years, and monitoring depends on the risk of persistent/recurrent disease. The objective was to assess the prognostic value of a single stimulated thyroglobulin (Tg) measured at the time of the first radioiodine therapy (Stim-Tg1), and the utility of a second stimulated Tg measurement performed 6-12months later (Stim-Tg2). We also examined the role of neck ultrasound (US) in the early diagnosis of recurrence. This was a retrospective observational cohort study conducted in a tertiary referral hospital. Of 213 evaluated patients with DTC, 169 were finally included. Measurement of Stim-Tg1, Stim-Tg2 and neck US. Stim-Tg1 was undetectable in 71 of 169 patients (42%). All of them (71/71) continued to have negative Stim-Tg2. Seventy of 71 had an excellent response to the first treatment. Sixty-eight of 71 had no evidence of disease after an average follow-up of 7·2years. In patients with detectable Stim-Tg1 (98/169; 58%), Stim-Tg2 became negative in 40. The negative predictive value (NPV) of Stim-Tg1 was 0·96. The optimal Stim-Tg1 cut-off level for identifying persistence was 3·65ng/ml. Recurrence was detected in 14 patients. Neck US was useful for identifying local recurrence (13/14; 92·85%). Stim-Tg1 is a reliable marker with a high NPV. A second stimulation test should be avoided in patients with negative Stim-Tg1. In patients with biochemical persistence, Stim-Tg2 is useful for confirming/ruling out final status. Neck US plays a valuable role in the early diagnosis of recurrence.

Long-Term Outcomes of Patients with Papillary Thyroid Cancer Undergoing Remnant Ablation with 30 milliCuries Radioiodine.

The study considered the long-term outcome of patients with papillary thyroid carcinoma treated with 30 mCi radioiodine. The aims of this study were to define and compare the remission rates of papillary thyroid carcinoma ablated with 30 mCi (131)I prepared by either thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH; Thyrogen(®)), and to identify variables predictive of a favorable prognosis. An observational study was conducted at an academic medical center and a comparative summary of six studies is presented. Three hundred and seventy patients (THW group, n = 203; rhTSH group, n = 167) were recruited from a prospectively managed registry. The mean follow-up was 9.3 years (range 5.1-15.8 years) in the THW group and 7.1 years (range 5.0-9.7 years) in the rhTSH group. The primary endpoint was the long-term remission rates (no evidence of disease) in the THW group compared with the rhTH group. The response at 12-18 months after 30 mCi remnant ablation was excellent in 79.3% and 76.0% of patients in the THW group and the rhTSH group, respectively (p > 0.05). The long-term remission rates also did not significantly differ between both groups at 95.6% and 97.0%. Although the surveillance period for the THW group exceeded that of the rhTSH group, no significant difference in recurrence-free survival was discerned by the Kaplan-Meier curves. In a multivariate analysis, an excellent response to therapy at 12-18 months correlated significantly with long-term remission rates in the THW group (p = 0.031, odds ratio [OR] = 2.6 [confidence interval (CI) 1.1-6.0]), the rhTSH group (p = 0.03, OR = 5.3 [CI 1.2-23.8]), and the pooled groups (p = 0.001, OR = 3.43 [CI 1.63-7.2]). The pre-ablation thyroglobulin level significantly correlated with remission rates only in the THW group (p = 0.035, OR = 5.5 [CI 1.1-27.1]). The response to remnant ablation with 30 mCi radioiodine is often excellent, and the long-term remission rates can be expected to be high, independent of the method of delivery (i.e., THW or rhTSH).

Usefulness of Day 5 sampling in thyroid cancer patients for radioactive iodine therapy with recombinant human thyrotropin

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Radioiodine therapy under rhTSH for follicular thyroid carcinoma with sellar metastasis and non-rising TSH

Metastasis to the pituitary gland/sella turcica is an uncommon complication of thyroid cancer. Treating this condition is a challenge in the setting of pituitary insufficiency due to this lesion, and recombinant human thyroid-stimulating hormone (rhTSH) stimulation becomes critically essential. We present a rare case of an 82-year-old female patient with follicular carcinoma of the thyroid with metastasis to the sella turcica in addition to multiple skeletal and lung metastases. MRI of the brain showed a hypointense suprasellar lesion on T 1 weighted images. The thyroid-stimulating hormone level remained persistently low even 4 weeks after thyroidectomy. A whole-body pertechnetate scan could not localize any abnormal tracer uptake and radioactive iodine uptake was also persistently low. The patient did not have symptoms related to pituitary involvement but TSH and early morning adrenocorticotrophic hormone levels were low. After thorough discussion with the neurosurgeon and radiotherapist, it was decided to start the patient on high-dose radioiodine treatment. Persistently low TSH level was a concern for starting radioiodine therapy. In view of this clinical context, rhTSH stimulation was used to achieve adequate TSH levels prior to radioiodine therapy. Subsequently, the patient was treated with 3.7 GBq (100 mci) of high-dose radioiodine. A post-therapy scan demonstrated radioiodine concentration in the thyroid bed remnant, multiple skeletal lesions and the sellar region. Thus, the use of rhTSH was critical in the management of this patient. It helped in radioiodine treatment by stimulating radioiodine uptake in the remnant and at the metastatic sites.

Abstract #1167: Prognostic Value of Serum Thyroglobulin Measured in 48 Hours After Second Dose of Recombinant Human Thyrotropin in Surveillance of Welldifferentiated Thyroid Cancer

Abstract #1167: Prognostic Value of Serum Thyroglobulin Measured in 48 Hours After Second Dose of Recombinant Human Thyrotropin in Surveillance of Welldifferentiated Thyroid Cancer

Evaluation of ablation of thyroid remnants with 1850 MBq iodine-131 in 67 patients with thyroid cancer.

Radioiodine remnant ablation (RRA) is used to destroy residual normal thyroid tissue after total thyroidectomy in differentiated thyroid carcinoma (DTC) patients. As 1850-MBq RRA is routinely performed at our facility, we evaluated the outcomes. Sixty-seven DTC patients without macroscopic residual lesions after total thyroidectomy were evaluated. Thyroglobulin (Tg) was measured 2-3 months before RRA with thyroxin administration (pretreatment); just before ablation after a 3-week iodine intake restriction with thyroxin withdrawal (THW) (N.=16) or recombinant human thyroid-stimulating hormone (rhTSH) stimulation (N.=51); and 3 months after RRA, after a 2-week iodine intake restriction and 3-week THW (N.=57) or rhTSH stimulation (N.=10). All patients received 131I (1850 MBq) treatment followed by 131I scintigraphy about 8 days later (8.18±0.91) and 131I scintigraphy (185 MBq) after the dosage 24 hours later 3months after RRA. Initial RRA goal was defined as negatively visible uptake in 131I thyroid bed (VUT) and a Tg level of <2 ng/mL 3 months after RRA. Rest 60 patients whose TSH levels were below 0.5 µIU/mL of all 67 patients were evaluated. Negatively VUT on 3 months after RRA was shown in 56 out of 60 patients (93.3%). Initial RRA goal was achieved in 21 (42.0%) of 50 patients, excluding 3 patients whose Tg levels 3 months after RRA were not measured and 7 patients with anti-Tg antibodies. Pretreatment Tg levels (P=0.0003) was significant predictive factor for Initial RRA goal on multivariate logistic regression analysis. RRA with 1850 MBq is effective by visual diagnosis, about 40% of all intermediate or high-risk DTC patients achieved initial RRA goals by both visual and Tg levels diagnosis.

Cytogenetic and dosimetric effects of 131I in patients with differentiated thyroid carcinoma: comparison between stimulation with rhTSH and thyroid hormone withdrawal treatments

A study directed to the cytogenetic and dosimetric aspects of radionuclides of medical interest is very valuable, both for an accurate evaluation of the dose received by the patients, and consequently of the genetic damage, and for the optimization of therapeutic strategies. Cytogenetic and dosimetric effects of (131)I in lymphocytes of thyroidectomized differentiated thyroid cancer (DTC) patients were evaluated through chromosome aberration (CA) technique: Euthyroid patients submitted to recombinant human thyroid-stimulating hormone (rhTSH) therapy (group A) were compared with hypothyroid patients left without levothyroxine treatment (group B). CA analysis was carried out prior to and 24h, 1week, 1month and 1year after radioiodine administration (4995-7030MBq) in both groups. An activity-response curve of (131)I (0.074-0.740MBq/mL) was elaborated, comparing dicentric chromosomes in vivo and in vitro in order to estimate the absorbed dose through Monte Carlo simulations. In general, radioiodine therapy induced a higher total CA rate in hypothyroid patients as compared to euthyroid patients. The frequencies of dicentrics obtained in DTC patients 24h after treatment were equivalent to those induced in vitro (0.2903±0.1005MBq/mL in group A and 0.2391±0.1019MBq/mL in group B), corresponding to absorbed doses of 0.65±0.23Gy and 0.53±0.23Gy, respectively. The effect on lymphocytes of internal radiation induced by (131)I therapy is minimal when based on the frequencies of CA 1year after the treatment, maintaining a higher quality of life for DTC patients receiving rhTSH-aided therapy.

Challenges and strategies on radioiodine treatment for differentiated thyroid carcinoma.

Radioiodine ((131)I) is considered an effective and low-risk therapeutic radionuclide for differentiated thyroid carcinoma (DTC); however, dilemmas exist in the optimization of indications, pre-treatment thyroid stimulating hormone (TSH) stimulation, dose decision, as well as in the treatment of (131)I-refractory disease. Refined strategies on (131)I treatment for DTC based on late evidence and novel insights are greatly needed. The indications of (131)I ablation continue to be refined with a better understanding of the risks and benefits. For pre-treatment TSH stimulation, recombinant human thyrotropin presents a better choice as it improves the quality of life, but is indicated only for ablation of the thyroid remnant and follow-up. Decreased doses of (131)I seem to be more appropriate in patients without gross residual disease or metastases, but maximal doses are suggested in patients with advanced disease. Imaging procedures contributing to decision-making for patients with advanced DTC also continue to be modified. As for the (131)I-refractory disease, there is a trend to increase (131)I uptake and retention by using additional therapeutic agents like kinase inhibitors with encouraging results.

Recombinant human thyrotropin-stimulated thyroglobulin level at the time of radioactive iodine ablation is an independent prognostic marker of differentiated thyroid carcinoma in the setting of prophylactic central neck dissection.

We investigated the value of the stimulated thyroglobulin (Tg) level at the time of recombinant human thyrotropin (rhTSH)-aided remnant ablation for predicting disease status 1year later in patients with DTC who underwent total thyroidectomy with central neck dissection (CND). This was a prospective observational study of 253 consecutive patients with DTC who underwent rhTSH-aided RAI ablation after total thyroidectomy and prophylactic CND. Patients with evidence of initial distant metastasis or positive Tg antibodies were excluded. We compared rhTSH-stimulated Tg level at RAI ablation according to the disease status at 1year and evaluated optimal cut-off value of rhTSH-stimulated Tg. Binary logistic regression analysis was performed to investigate the independent predictive factors for disease status 1year after ablation. Among study participants, 228 (90·1%) were considered disease free at 1year after remnant ablation. Patients with persistent or recurrent disease were more likely to be aged ≥45years, and to have N1b stage, TNM stage III or IV, and higher rhTSH-stimulated Tg level at RAI ablation. The optimal cut-off of rhTSH-stimulated Tg for predicting persistent or recurrent disease was 1·79ng/ml, with a negative predictive value of 99·5%. A serum rhTSH-stimulated Tg level ≥1·79 at the time of ablation was independently associated with persistent or recurrent disease 1year later. N1b stage tended to be associated with persistent or recurrent disease. A low stimulated serum Tg level at rhTSH-aided RAI ablation may be a favourable prognostic marker in the setting of prophylactic CND.

Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter.

Radioiodine therapy (RIT) in patients with large nontoxic multinodular goiter (MNG) recently becomes more common method in comparison to surgery (especially in elderly patients and with contraindications because of severe chronic diseases other systems). Repeatedly low thyroid radioactive iodine uptake (RAIU) decreases effectiveness of RIT or makes it impossible. The recombinant human thyrotropin can increase RAIU and improve the results of RIT. was to assess the influence of a single very low dose (0.03 mg) of rhTSH on RAIU and thyroid function in euthyroid (MNG-EU) and subclinical hyperthyroid (MNG-SC) patients with a large multinodular goiter. 40 patients (14 male, 26 female, age 57-80 yr) with large non-toxic MNG over 80 grams and with baseline RAIU < 40% were included into the double-blind randomized study and divided into two groups: rhTSH-group and control group. First group received the single intramuscular injection of 0.03 mg rhTSH and the second received placebo. The RAIU were measured 24 and 48 hours after the rhTSH and then all the patients were administered therapeutic doses of I-131. TSH and free thyroxine levels were measured at 1st and 2nd day after the injection of rhTSH and later, at 4 and 8 weeks after the RIT. The mean RAIU increased significantly from 30.44 ± 7.4% to 77.22 ± 8.7% (p < 0.001). There were no statistically significant differences in RAIU between euthyroid (MNG-EU) and subclinically hyperthyroid (MNG-SC) patients. The peak of serum TSH was noticed 24 hours after rhTSH injection and in MNG-EU patients it has remained within normal range, similarly as fT4. In the MNG-SC group the administration of rhTSH resulted in a significant increase in the TSH values after 24 hours, whose mean level slightly exceeded the upper limit of the normal range with normalization at 48 hours. 8 weeks after the RIT, the TSH and fT4 levels did not exceed the normal range and did not differ in a statistically significant way. Even the single very low dose of rhTSH increases the values of RAIU in significant way, in euthyroid and subclinically hyperthyroid patients. The administration of rhTSH is well-tolerated. Neoadjuvant administration of a low dose (0.03 mg) of rhTSH before I-131 seems to be an optimal method of management which may increase the effectiveness of RIT and decrease the exposure of the patients to absorbed doses of ionizing radiation.

Assessment of the Role of Different Imaging Modalities with Emphasis on Fdg Pet/Ct in the Management of Well Differentiated Thyroid Cancer (WDTC).

Positron emission tomography/computed tomography is suggested to have a role in detection of iodine negative recurrence in well differentiated thyroid cancer. The aim of this study is to identify role of different imaging modalities in the management of well differentiated thyroid cancer. We reviewed 900 well differentiated thyroid cancer patients after post-thyroidectomy who underwent recombinant human thyroid stimulating hormone stimulated Sodium Iodide I 131 imaging. Out of 900 patients, 74 had positron emission tomography/computed tomography. Multivariate analysis was performed by controlling positron emission tomography/computed tomography, Sodium Iodide I 131 scan, neck ultrasonography, age, sex, primary tumor size, stage, histology, thyroglobulin. Patients were grouped according to results of Sodium Iodide I 131 scan and positron emission tomography/computed tomography. Positron emission tomography/computed tomography was positive in 23 of 74 patients. The sensitivity for positron emission tomography was 11/11(100%), the specificity was 51/63 (81.0%), the positive predictive value was 11/23 (47.8%), and the negative predictive value was 51/51 (100%). The sensitivity for the neck ultrasonography was 4/8 (50%), the specificity was 53/60 (88.3%), positive predictive value was 4/11 (36.4%), and negative predictive value was 53/57 (93.0%). 50% of patients who had Sodium Iodide I 131 negative scan and positive positron emission tomography/computed tomography had a change in management. Thirty-six percent with positive neck ultrasonography had a change in management. Out of 11 recurrences, 6 had distant metastatic disease, and 5/11 had regional nodal disease. Neck ultrasonography showed nodal metastasis in 4/5 (80%). Positron emission tomography/computed tomography altered management in the presence of a high thyroglobulin level and a negative Sodium Iodide I 131 scan. Neck ultrasonography should be the first line of imaging with rising thyroglobulin levels. Positron emission tomography/computed tomography should be considered for cases with high thyroglobulin levels and normal neck ultrasonography to look for distant metastatic disease.

Comparison of Thyroglobulin Measurements Using Three Different Immunoassay Kits: A BRAMHS Tg-Plus RIA Kit, a BRAMHS hTg Sensitive Kryptor Kit, and a Beckman Coulter ACCESS Immunoassay Kit

BackgroundSecond-generation thyroglobulin immunometric assays (Tg-IMAs) have been developed with improved sensitivity. Our aim was to compare the diagnostic value of Tg-IMA measurements using a Kryptor (BRAHMS AG) kit (Tg-K) and an ACCESS (Beckman Coulter) kit (Tg-A) with that of the first-generation Tg measurement using a Tg-plus (BRAHMS AG) kit (Tg+).MethodsWe enrolled 82 differentiated thyroid cancer patients who underwent total thyroidectomy with radioactive iodine remnant ablation and who underwent diagnostic whole body scan using recombinant human thyroid stimulating hormone (rhTSH). The Tg+, Tg-K, and Tg-A were measured before rhTSH administration during levothyroxine treatment (suppressed Tg) from the same sample. Serum Tg+ was measured after rhTSH stimulation (stimulated Tg).ResultsSuppressed Tg+ was more significantly correlated with suppressed Tg-K (R2=0.919, P<0.001) than with suppressed Tg-A (R2=0.536, P<0.001). The optimal cut-off values of suppressed Tg+, Tg-K, and Tg-A for predicting stimulated Tg+ of 1 ng/mL were 0.3, 0.2, and 0.2 ng/mL, respectively. The sensitivity, specificity, and accuracy of suppressed Tg+ were 67%, 100%, and 90%, respectively; those of suppressed Tg-K were 83%, 90%, and 88%; those of suppressed Tg-A were 96%, 82%, and 87%, respectively. The positive predictive and negative predictive values of Tg+ were 100% and 87%, respectively; those of Tg-K were 79% and 92%; and those of Tg-A were 73% and 98%.ConclusionWe could not clearly demonstrate which kit had better diagnostic performance after comparison of first-generation Tg measurements with Tg-IMA measurements. Also, there were kit-to-kit variations between Tg-IMA kits. Suppressed Tg measured by Tg-IMA was insufficient to completely substitute for a stimulated Tg measurement.

Changes in radioiodine therapy for thyroid disorders

Radioiodine therapy for benign and malignant thyroid diseases was introduced about 70 years ago, however, there is still a lack of consensus regarding indications, doses and procedure. This review covers treatment results in immunogenic hyperthyroidism including the problem of orbitopathy. Radioiodine therapy for toxic and non-toxic multinodular goiter is also discussed with striking possibility of enhanching the radioiodine uptake. In this respect the recombinant human thyrotropin should be mentioned. Thyroid cancer treatment protocol has changed, too, due to ineffectivity in low-risk patients. More attention is needed to the carcinogenecity of radioiodine. The numerous problems mentioned above require large and well-designed prospective trials to resolve the fundamental questions. The author emphasizes that radioiodine dose should be administered in doses as low as reasonably achievable.

Effects of Thyroid Hormone Withdrawal and Recombinant Human Thyrotropin on Glomerular Filtration Rate During Radioiodine Therapy for Well-Differentiated Thyroid Cancer.

Renal function is related to thyroid hormonal status, and glomerular filtration rate (GFR) seems to be impaired in patients with hypothyroidism. The aim of this work was to evaluate quantitatively the effect of hypothyroidism on GFR using a (51)Cr-EDTA radioisotope assay. Twenty-eight patients without known renal disease or dysfunction who had been referred for radioiodine therapy (RIT) after total thyroidectomy were enrolled in this study and divided into two groups. Group A underwent thyroid hormone withdrawal (THW) resulting in hypothyroidism, while group B underwent recombinant human thyrotropin (rhTSH) stimulation and hence remained euthyroid. GFR was assessed by (51)Cr-EDTA before and after THW or rhTSH. No clinical differences were observed between the two groups. The mean ± SD GFRs were 94 ± 19 mL/min/1.73 m(2) before THW and 76 ± 16 mL/min/1.73 m(2) after THW for group A (p = 0.009), and 91 ± 18 mL/min/1.73 m(2) before rhTSH and 93 ± 15 mL/min/1.73 m(2) after rhTSH for group B (p = 0.613). The percent decrease in GFR during hypothyroidism is approximately 18-22%. GFR decreases in patients with normal kidney function during THW for RIT, and rhTSH preserves GFR in these patients. This GFR impairment following thyroidectomy is related to hypothyroidism due to a significant reduction in thyroid hormone levels and is not due to a rise in the TSH level.