Use Of Recombinant Human Thyrotropin Research Articles

Analysis of Radiometry on Patients Undergoing Radioactive Iodine Therapy.

The treatment for differentiated thyroid cancer consists of thyroidectomy followed by radioactive iodine therapy (RIT), in which the patient remains in isolation until the dose rate of the radioactive iodine reduces to a certain limit. The present research intends to estimate the length of stay of patients who undergo RIT, with radiometry analysis performed throughout the patient's admission. Methods: Information such as age, sex, weight, height, prescribed activity, volume of liquids ingested, and the use of recombinant human thyrotropin was gathered from 204 patients with differentiated thyroid cancer who underwent RIT. During the admission, the dose rate was periodically measured. The data served as variables for a multiple regression, in which the coefficients (the term coefficient in this paper is related to the multiplicative factor of each considered variable used in Eqs. 1-4) and significance of each were verified as a function of the dose rate. Results: The results showed that length of stay, administered activity, volume of liquids ingested, use of recombinant human thyrotropin, and patient weight impacted significantly on the dose rate. The average effective half-life of the 131I, considering all patients, was 12.61 ± 3.28 h, and the average time for their radiologic release was 15.23 ± 5.50 h. On the basis of the results, it was possible to develop a tool to estimate a patient's length of stay and effective half-life. Conclusion: The results can contribute to optimization of the radiologic protection of patients who undergo RIT, as well as allow better logistics regarding their admission, which can lead to more appropriate accommodation for the patient and a better use of resources.

Current and Future Perspectives in Thyroid Carcinoma Treatment

Thyroid nodules are a common clinical problem and evaluation with neck and thyroid ultrasound and fine-needle aspiration biopsy are the most accurate methods for evaluating and identifying those that require surgical resection. The surgical treatment of differentiated thyroid carcinoma is the most common and recommended approach. Postoperative131I remnant ablation is used to eliminate the postsurgical thyroid remnant and may facilitate the early detection of recurrence. The conclusion of two important recent studies is that the use of recombinant human thyrotropin and low131I dose, 30 mCi, for postoperative ablation may be sufficient for the management of low-risk thyroid cancer. Recently, multitargeted kinase inhibitors have emerged as promising treatments for metastatic differentiated thyroid cancers based on mutation detection in samples from thyroid cancer. Motesanib, sorafenib, vandetanib, sunitinib, lenvatinib, imatinib, and cabozantinib are multikinase inhibitors that have the ability of inhibiting the rearranged during transection (RET) and vascular endothelial growth factor receptor (VEGFR), and other kinases, and have been used in advanced differentiated thyroid carcinoma. By contrast, axitinib and pazopanib seem to act only as anti-angiogenic agents. Anaplastic thyroid carcinoma is often advanced and metastatic at diagnosis. Patients with localized disease not amenable to surgical resection can be treated with adjuvant chemoradiotherapy.

Potential Use of Recombinant Human Thyrotropin in the Treatment of Distant Metastases in Patients with Differentiated Thyroid Cancer

In order to effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum TSH levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The goal of this review is to present current data on the relative efficacy and side effects profile of rhTSH-aided versus THW-aided RAI therapy for the treatment of patients with distant metastases of DTC. We have searched the PubMed database for articles including the keywords "rhTSH", "thyroid cancer", and "distant metastases" published between January 1, 1996 and January 7, 2012. As references, we used clinical case series, case reports, review articles, and practical guidelines. Exogenous stimulation of TSH is associated with better quality of life because it obviates signs and symptoms of hypothyroidism resulting from endogenous TSH stimulation. The rate of neurological complications after rhTSH and THW-aided RAI therapy for brain and spine metastases is similar. The rate of leukopenia, thrombocytopenia, xerostomia, and pulmonary fibrosis is similar after preparation for RAI treatment with rhTSH and THW. There is currently a controversy regarding RAI uptake in metastatic lesions after preparation with rhTSH versus THW, with some studies suggesting equal and some superior uptake after preparation with THW. Analysis of available retrospective studies comparing survival rates, progression free survival, and biochemical and structural response to a dosimetrically-determined dose of RAI shows similar efficacy after preparation for therapy with rhTSH and THW. The rhTSH stimulation is not presently approved by the FDA as a method of preparation for adjunctive therapy with RAI in patients with metastatic DTC. Data on rhTSH compassionate use suggest that rhTSH stimulation is as equally effective as THW as a method of preparation for dosimetry-based RAI treatment in patients with RAI-avid metastatic DTC.

Effect of 1110 MBq Radioiodine in Reducing Thyroid Volume in Multinodular Goiter: A New Protocol

BackgroundThere is no consensus on the optimal treatment of multinodular goiter (MNG), but in the past few years, the use of radioiodine has increased. This study’s objective was to evaluate adjuvant methimazole (MMI) therapy to increase and standardize radioiodine uptake (RAIU) with a fixed therapeutic 131I dose of 1110 MBq (30 mCi).MethodsOur study included 5 women with MNG treated with MMI, 10 - 15 mg/day for 2 to 4 months, prior to the administration of 1110 MBq 131I (30 mCi); none of the patients developed hypothyroidism during MMI therapy and had average basal TSH levels of 0.32 ± 0.39 mIU/L that increased to 2.6 ± 0.9 mIU/L (P = 0.07).ResultsRAIU increased from 25.6 ± 8.7% to 49.2 ± 8.3% (P = 0.003). All patients were followed for 12 months: median thyroid volume (TV) decreased from 77.2 mL (32.9 - 124.2) to 48.8 ml (12.4 - 68.9) with an average decrease of 46.4 ± 14.8% (P = 0.01). All patients developed hypothyroidism during the first 6 months after radioiodine therapy.ConclusionsThis new therapeutic protocol using MMI as adjuvant therapy is effective in increasing RAIU as well as the deleterious effects of 131I, without increasing the required dose, but leading to thyroid volume decreases similar to those reported with the use of recombinant human thyrotropin (rhTSH) or higher radioiodine doses.

Strategies of Radioiodine Ablation in Patients with Low-Risk Thyroid Cancer

BackgroundIt is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care.MethodsIn our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine (131I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor–node–metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin–stimulated thyroglobulin. Comparisons were based on an equivalence framework.ResultsThere were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the 131I doses and between the thyrotropin-stimulation methods.ConclusionsThe use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.)

Current and Future Perspectives in Thyroid Carcinoma Treatment.

Thyroid nodules are a common clinical problem and evaluation with neck and thyroid ultrasound and fine-needle aspiration biopsy are the most accurate methods for evaluating and identifying those that require surgical resection. The surgical treatment of differentiated thyroid carcinoma is the most common and recommended approach. Post-operative 131I remnant ablation is used to eliminate the post-surgical thyroid remnant and may facilitate the early detection of recurrence. The conclusion of two important recent studies is that the use of recombinant human thyrotropin and low 131I dose, 30 mCi, for post-operative ablation may be sufficient for the management of low-risk thyroid cancer. Recently, multi-targeted kinase inhibitors have emerged as promising treatments for metastatic differentiated thyroid cancers based on mutation detection in samples from thyroid cancer. Motesanib, sorafenib, vandetanib, sunitinib, lenvatinib, imatinib and cabozantinib are multi-kinase inhibitors that have the ability of inhibiting the rearranged during transection (RET) and vascular endothelial growth factor receptor (VEGFR), and other kinases, and have been used in advanced differentiated thyroid carcinoma. By contrast, axitinib and pazopanib seem to act only as anti-angiogenic agents. Anaplastic thyroid carinoma is often advanced and metastatic at diagnosis. Patients with localised disease not amenable to surgical resection can be treated with adjuvant chemoradiotherapy.

An outline concerning the potential use of recombinant human thyrotropin for improving radioiodine therapy of multinodular goiter

Radioiodine ((131)I) treatment for nontoxic and toxic multinodular goiter (MNG) is an alternative therapeutic procedure used especially for patients with contraindication for surgery. Several studies have been conducted in recent years assessing the use of recombinant human TSH (rhTSH) in increasing (131)I uptake in MNGs. This procedure also decreases the activity level of the administered (131)I, changes the distribution of (131)I in the thyroid, lowers the absorption dose, and dramatically reduces the volume of the goiter (50-75% of the baseline volume). A major disadvantage, however, is the induction of hypothyroidism in a relatively large number of patients. A transient increase in thyroid volume and tenderness was noted in the first week of treatment. Also a short period (2-4 weeks) of hyperthyroidism was observed in most patients with potential consequences particularly for the elderly. Still, there has been no evidence to date that the adverse effects outweigh the positive results of using rhTSH. The use of rhTSH in benign goiter disease has not yet been approved worldwide, but its positive activity in MNG is remarkable and promising.

Recombinant human TSH acutely impairs endothelium-dependent vasodilation

We read with interest the review article by Duntas & Biondi dealing with clinical and quality of life consequences induced by short-term hypothyroidism (1). Withdrawal of levothyroxine therapy exacerbates neuropsychiatric symptoms and increases cardiovascular risk, although these effects are usually reversible restoring a condition of stable euthyroidism (1). Shortterm hypothyroidism is associated with cardiac abnormalities, increased peripheral vascular resistance, and endothelium dysfunction. In this setting, the recent use of recombinant human thyrotropin (rhTSH) in the clinical practice of thyroid carcinoma represents a valid alternative to levothyroxine withdrawal. The authors state that rhTSH administration is not accompanied by significant cardiac alterations and induces beneficial effects on the vascular system by increasing circulating nitric oxide (2). In this regard, we have recently assessed the acute effects of TSH on endothelial function in patients monitored for differentiated thyroid carcinoma (DTC) (3). Our data demonstrate that acutely raising serum TSH into the supraphysiological range leads to an acute impairment of endothelium-dependent vasodilation along with a significant increase in blood interleukin (IL)-6, tumour necrosis factor a (TNFa), and lipoperoxide levels. These observations are in keeping with the in vitro evidence of functional TSH receptors in several extra-thyroidal tissues, such as cardiomyocytes (4), aortic endothelium (5), and bone marrow cells (6), in which TSH is able to directly induce IL-6 and TNFa production (7) .T NFa is a pivotal NO-controlling cytokine and may promote the expression of inducible NO synthase, leading to increased oxidative stress (8). This mechanism may explain the increased NO metabolites previously described in patients receiving rhTSH for the follow-up of DTC (2). Therefore, while agreeing with the authors that rhTSH administration is generally safe and able to avoid most signs and symptoms of short-term hypothyroidism, we underline that rhTSH per se may acutely induce low-grade inflammation and endothelial function impairment.

Timing of Iodine-123 Scintigraphy Following Use of Recombinant Human Thyrotropin in Differentiated Thyroid Carcinoma

Timing of Iodine-123 Scintigraphy Following Use of Recombinant Human Thyrotropin in Differentiated Thyroid Carcinoma

Stimulation With 0.3-mg Recombinant Human Thyrotropin Prior to Iodine 131 Therapy to Improve the Size Reduction of Benign Nontoxic Nodular Goiter

Use of recombinant human thyrotropin increases the thyroid radioiodine (iodine 131 [(131)I]) uptake and may have a role in the context of (131)I therapy of benign goiter. In a double-blind, placebo-controlled trial, 57 patients with nodular nontoxic goiter (51 women and 6 men) were randomized to receive either 0.3 mg of recombinant human thyrotropin (n = 28) or placebo (n = 29) 24 hours before (131)I therapy. The (131)I dose was calculated based on thyroid size (measured by ultrasound), thyroid (131)I uptake, and (131)I half-life. The follow-up period was 1 year and included measurements of thyroid size and function and patient satisfaction. Baseline median goiter volume was 51 mL (range, 20-99 mL) in the placebo group and 59 mL (range, 25-92 mL) in the thyrotropin group (P = .75). At 12 months, the mean +/- SEM relative goiter reduction was 46.1% +/- 4.0% in the placebo group and 62.1% +/- 3.0% in the thyrotropin group (P = .002 between groups). The difference was most pronounced among patients with large goiters. Within each group, there was no significant correlation between retained thyroid (131)I dose and goiter reduction. Adverse effects were significantly more frequent in the thyrotropin group (34 vs 12 events; P<.001). Permanent hypothyroidism developed in 3 patients (11%) in the placebo group compared with 16 patients (62%) in the thyrotropin group (P<.001). Patient satisfaction was high and uninfluenced by the use of recombinant human thyrotropin. Stimulation with recombinant human thyrotropin prior to (131)I therapy improves thyroid size reduction by 35%, with a 5-fold higher rate of hypothyroidism. These effects are, at least partially, mediated through mechanisms other than an increase in retained (131)I thyroid dose. Further recombinant human thyrotropin dose-finding studies are warranted before routine use.

Effect of Storage of Reconstituted Recombinant Human Thyroid‐Stimulating Hormone (rhTSH) on Thyroid‐Stimulating Hormone (TSH) Response Testing in Euthyroid Dogs

Bovine thyrotropin (bTSH) stimulation testing has long been considered the gold standard for diagnosis of canine hypothyroidism. Unfortunately, bTSH is no longer commercially available. Recently, the use of recombinant human thyrotropin (rhTSH) to perform thyroid‐stimulating hormone (TSH) stimulation testing in dogs was described. The cost of an rhTSH vial (1.1 mg) limits the practical use of this product. The study reported here was performed to determine the effects of storing rhTSH on the post‐TSH increase of serum total (TT4) and free (FT4) thyroxine concentrations during TSH stimulation testing in 12 euthyroid Beagles in a crossover trial. Three TSH tests with recombinant human thyrotropin (rhTSH; 91.5 μg IV) were performed on each dog during 3 different periods: 1 with freshly reconstituted rhTSH (fresh); 1 with rhTSH, reconstituted and stored at 4°C for 4 weeks (refrigerated); and 1 with rhTSH, reconstituted and frozen at‐20°C for 8 weeks (frozen). Blood samples for determination of TT4 and FT4 concentrations were collected before and 4 and 6 hours after rhTSH administration. There was no significant difference in TT4 or FT4 concentration after stimulation with fresh, refrigerated, and frozen rhTSH. Furthermore, there was no significant difference between TT4 or FT4 serum concentration observed 4 and 6 hours after rhTSH administration. In conclusion, reconstituted rhTSH can be stored at 4°C for 4 weeks and at‐20°C for 8 weeks without loss of biological activity, allowing clinicians to perform more TSH response tests per vial.

Differentiated thyroid cancer: comparison of therapeutic iodine 131 biological elimination after discontinuation of levothyroxine versus administration of recombinant human thyrotropin

The biological elimination of therapeutic 131I in patients with differentiated thyroid cancer (DTC), post total or near-total thyroidectomy, was compared after withholding levothyroxine suppression against administration of recombinant human thyrotropin without stopping levothyroxine. In 163 patients (group G1) levothyroxine was withheld before 131I therapy: in 138 patients the tumor was limited to the thyroid bed (group G1.1) and in 25 patients metastases were present (group G1.2). A second group of patients (G2; n = 28) received 131I therapy after administration of recombinant human thyrotropin without stopping levothyroxine. Mean retained 131I activity (as a percentage of the administered dose) was 5%-29% (group G1.1), 20%-43% (group G1.2) and 1%-17% (group G2). The effective half-life of 131I was 0.59-0.69 days (group G1.1), 0.87-1.22 days (group G1.2) and 0.38-0.44 days (group G2). In conclusion, the use of recombinant human thyrotropin to prepare patients with thyroid cancer for therapy with 131I shortens its effective half-life and reduces its retained activity compared to preparation with discontinuation of levothyroxine suppression.

Effect of Storage of Reconstituted Recombinant Human Thyroid-Stimulating Hormone (rhTSH) on Thyroid-Stimulating Hormone (TSH) Response Testing in Euthyroid Dogs

Bovine thyrotropin (bTSH) stimulation testing has long been considered the gold standard for diagnosis of canine hypothyroidism. Unfortunately, bTSH is no longer commercially available. Recently, the use of recombinant human thyrotropin (rhTSH) to perform thyroid-stimulating hormone (TSH) stimulation testing in dogs was described. The cost of an rhTSH vial (1.1 mg) limits the practical use of this product. The study reported here was performed to determine the effects of storing rhTSH on the post-TSH increase of serum total (TT4) and free (FT4) thyroxine concentrations during TSH stimulation testing in 12 euthyroid Beagles in a crossover trial. Three TSH tests with recombinant human thyrotropin (rhTSH; 91.5 microg IV) were performed on each dog during 3 different periods: 1 with freshly reconstituted rhTSH (fresh); 1 with rhTSH, reconstituted and stored at 4 degrees C for 4 weeks (refrigerated); and 1 with rhTSH, reconstituted and frozen at -20 degrees C for 8 weeks (frozen). Blood samples for determination of TT4 and FT4 concentrations were collected before and 4 and 6 hours after rhTSH administration. There was no significant difference in TT4 or FT4 concentration after stimulation with fresh, refrigerated, and frozen rhTSH. Furthermore, there was no significant difference between TT4 or FT4 serum concentration observed 4 and 6 hours after rhTSH administration. In conclusion, reconstituted rhTSH can be stored at 4 degrees C for 4 weeks and at -20 degrees C for 8 weeks without loss of biological activity, allowing clinicians to perform more TSH response tests per vial.

Changing Concepts in the Management of Differentiated Thyroid Cancer

The management of patients with differentiated thyroid cancer has changed significantly over the last few decades. Mortality has decreased as the result of earlier detection, refined surgical approaches, subsequent radioiodine ablation, and the development of more sensitive methods for detecting and monitoring disease recurrence. The latter has been facilitated by serum thyroglobulin measurements, the use of recombinant human thyrotropin, and the use of 18F-deoxyglucose/positron emission tomography in selected instances where radioiodine imaging fails to locate known or suspected recurrent or metastatic disease.

Successful use of recombinant human thyrotropin in the therapy of pediatric well-differentiated thyroid cancer

Recombinant human TSH (rhTSH) is increasingly employed in stimulating radioiodine (131I) uptake in adults with well-differentiated thyroid cancer (WDTC) for diagnostic scanning, and preliminary evidence suggests that it may have a role in radioactive iodine therapy as well. However, the safety and efficacy of rhTSH in children have not been determined. We report a case of a 13-yr-old boy presenting with metastatic papillary thyroid cancer. After total thyroidectomy, his serum thyroglobulin (Tg) was 302 ng/ml (3.7-49.3) with negative antibodies. A diagnostic whole body scan (WBS) demonstrated multiple foci of uptake in the neck, thyroid bed and chest. His serum TSH only increased to 14.2 microU/ml (0.3-4.7) upon thyroid hormone withdrawal. Therefore, the patient was given 0.9 mg rhTSH every 24 h for two consecutive days and treated with 102 mCi 131I 24 h after the last rhTSH injection. Six months later, the patient was again conditioned with rhTSH and treated with an additional 150 mCi 131I. This treatment effectively reduced his tumor load with his most recent (10 months after the second ablation) serum Tg measuring 19.3 ng/ml. This case highlights the safety and effectiveness of rhTSH stimulated radioablation in pediatric WDTC, and proposes to invite controlled studies to further investigate pediatric rhTSH use, particularly in patients in whom thyroid hormone withdrawal is not a viable option.

The use of recombinant human thyrotropin (Thyrogen) in the diagnosis and treatment of thyroid cancer

The introduction of human recombinant thyrotropin (rhTSH/Thyrogen) into the diagnosis of thyroid cancer has substantially ameliorated the patient's quality of life through the avoidance of debilitating hypothyroidism. With the aim of updating the use of Thyrogen, we report 7 cases which were treated with Thyrogen for diagnostic or therapeutic purposes. All 7 patients were thyroidectomised and radioiodine ablated and all had detectable [> 1 ng/ml] basal serum thyroglobulin (b-Tg) levels. Thyrogen stimulation resulted in a rise of Tg (s-Tg) in all patients. Five patients had negative whole body scanning (WBS) and no clinical or radiological signs of disease. Two patients with a b-Tg value of 5 ng/ml and 11 ng/ml, respectively showed a s-Tg of 17 ng/ml and 84 ng/ml, respectively, whereas WBS was negative. Both of these patients received 100 mCi (3700 MBq) 131I. Owo patients had a positive Tg and positive WBS with skull, lung and hepatic metastases and received 150 131I after preparation with Thyrogen. Six months later one of these patients was free of disease and the other will be evaluated during the coming months. In conclusion, Thyrogen emerges as a reliable and safe agent for the diagnosis of thyroid cancer. Furthermore, it appears that Thyrogen could be used in the treatment of metastases as an alternative to thyroid hormone withdrawal.

Compassionate Use of Recombinant Human Thyrotropin to Facilitate Radioiodine Therapy: Case Report and Review of Literature

To describe the use of recombinant human thyrotropin (thyroid-stimulating hormone) (rhTSH) to assist in radioiodine therapy in a patient with thyroid carcinoma who was unable to produce sufficient endogenous thyrotropin when hypothyroid and to review the related literature. The study patient underwent formal dosimetric analysis and received radioiodine in conjunction with rhTSH. Follow-up scanning studies were performed. We found good localization of radioiodine on the posttherapy scans after administration of (131)I while the patient continued to receive thyroxine replacement after two intramuscularly administered injections of rhTSH. Some of his metastatic lesions disappeared and his serum thyroglobulin level decreased after the first rhTSH-assisted dose of (131)I was administered. His blood radioiodine clearance rate was unexpectedly more rapid in the hypothyroid state than when he was euthyroid (taking thyroxine) after administration of rhTSH. His whole-body clearance rate was more delayed when he was hypothyroid. Swelling of some of the metastatic thyroid cancer lesions developed when the patient was hypothyroid and after rhTSH was administered, the latter being much more rapid in onset. Therapeutic doses of radioiodine can be delivered with the assistance of rhTSH administration while patients continue to take suppressive doses of thyroxine. Metastatic thyroid carcinoma lesions can swell rapidly after administration of rhTSH. The commercially available form of rhTSH is approved only for diagnostic use. Its safety and efficacy in assisting radioiodine therapy have not been fully determined.

Use of Recombinant Human Thyrotropin before Radioiodine Therapy in Patients with Advanced Differentiated Thyroid Carcinoma

Use of Recombinant Human Thyrotropin before Radioiodine Therapy in Patients with Advanced Differentiated Thyroid Carcinoma

The use of recombinant human thyrotropin (rhTSH) in the management of differentiated thyroid cancer.

The use of recombinant human thyrotropin (rhTSH) in the management of differentiated thyroid cancer.

The use of recombinant human thyrotropin produced by Chinese hamster ovary cells for the preparation of immunoassay reagents.

Recombinant human TSH (rec-hTSH; Thyrogen, lot M-17073) obtained from transformed Chinese hamster ovary cells was tested for both radioiodination and preparation of a secondary standard used in RIA and immunoradiometric assay (IRMA) for routine clinical investigation. Results were compared to those obtained with high quality pituitary TSH (pit-hTSH; Dr. P. Torjesen, Oslo, Norway; and NIDDK, Rockville, MD), traditionally used in these assays. After extensive characterization and testing, it was found that [125I]rec-hTSH matched all binding and chromatographic criteria usually obtained with [125I]pit-hTSH, including Stokes' radius, labeling, and storage stability, and did not introduce any significant bias when used in the measurement of unknown serum samples. A preparation of rec-hTSH was calibrated against a local secondary standard as well as against two well known international reference preparations (NIDDK hTSH RP-1 and WHO International Reference Preparation 80/558) by IRMA and RIA. In the RIA, NIDDK anti-hTSH-3 polyclonal antibody was used, whereas in the IRMA, two commercial preparations were used: a monoclonal antibody as the detecting antibody, and a polyclonal antibody as the capture antibody. In both assays, the recombinant standard preparation yielded good fit displacement curves, showing significant parallelism compared to pit-hTSH and therefore allowing an unbiased measurement of unknown serum samples. The specific activity of the rec-hTSH preparation calibrated against the WHO International Reference Preparation was 7.7 IU/mg protein when measured by IRMA and 7.1 IU/mg when measured by RIA. In conclusion, these results indicate for the first time that rec-hTSH can fully replace pit-hTSH as both standard and tracer in diagnostic in vitro systems such as RIA and IRMA, suggesting that other recombinant glycosylated hormones might also serve for immunoassay reagent preparation.