Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence.

A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer.

This review focuses on recent advances in the structure-function relationships of thyroid-stimulating hormone (TSH) and its receptor. TSH is a member of the glycoprotein hormone family constituting a subset of the cystine-knot growth factor superfamily. TSH is produced by the pituitary thyrotrophs and released to the circulation in a pulsatile manner. It stimulates thyroid functions using specific membrane TSH receptor (TSHR) that belongs to the superfamily of G protein-coupled receptors (GPCRs). New insights into the structure-function relationships of TSH permitted better understanding of the role of specific protein and carbohydrate domains in the synthesis, bioactivity, and clearance of this hormone. Recent progress in studies on TSHR as well as studies on the other GPCRs provided new clues regarding the molecular mechanisms of receptor activation. Such advances are a result of extensive site-directed mutagenesis, peptide and antibody approaches, detailed sequence analyses, and molecular modeling as well as studies on naturally occurring gain- and loss-of-function mutations. This review integrates expanding information on TSH and TSHR structure-function relationships and summarizes current concepts on ligand-dependent and -independent TSHR activation. Special emphasis has been placed on TSH domains involved in receptor recognition, constitutive activity of TSHR, new insights into the evolution of TSH bioactivity, and the development of high-affinity TSH analogs. Such structural, physiological, pathophysiological, evolutionary, and therapeutic implications of TSH-TSHR structure-function studies are frequently discussed in relation to concomitant progress made in studies on gonadotropins and their receptors.

https://www.physiology.org/doi/pdf/10.1152/physrev.00031.2001

Thyroid-Stimulating Hormone and Thyroid-Stimulating Hormone Receptor Structure-Function Relationships

Summary
objective To investigate to what extent thyroid remnant ablation and withdrawal from thyroxine are required to achieve sufficient accuracy of serum thyroglobulin (Tg) measurements as an indicator of tumour recurrence in the follow-up of patients with differentiated thyroid carcinoma.

design and methods  We conducted a meta-analysis of the literature from 1975 to 2003 on serum Tg measurements in the follow-up of differentiated thyroid carcinoma. In a computer-based search, we initially found 915 articles that were finally narrowed down to 120. These 120 papers were subjected to strict in/and exclusion criteria, leaving 46 articles (totalling 9094 patients). Data from these articles were extracted in a structured fashion and were grouped according to initial therapy, TSH status, Tg assay method and definition of a ‘gold standard’. Original 2 × 2 tables were pooled by summary receiver operating characteristic curve analysis (sROCa), best estimates of sensitivity and specificity being obtained by the combination of sROCa and Mantel–Haenszel odds ratios.

results  Despite considerable differences between series in laboratory and clinical methodology, we consistently found higher specificity for Tg measurements after thyroid remnant ablation than after surgery alone. Highest pooled sensitivity 0·961 ± 0·013 (SE) was found for immunometric assay (IMA) after thyroid remnant ablation and thyroid hormone withdrawal, at a specificity of 0·947 ± 0·007. Pooled sensitivity decreased significantly if ablated patients were tested while on thyroid hormone (0·778 ± 0·023, at a specificity of 0·977 ± 0·005). Significantly decreased pooled specificity was found in patients who did not undergo remnant ablation (sensitivity 0·972 ± 0·023, at a specificity of 0·759 ± 0·028). If recombinant human TSH (rhTSH) stimulation was used as a substitute for thyroxine withdrawal, sensitivity remained high (0·925 ± 0·018) while specificity decreased to 0·880 ± 0·013. In all analyses, specificity of Tg would decrease when unspecified activity in the thyroid region at scintigraphy was considered benign, whereas sensitivity decreased when such activity was considered malignant.

conclusion  This study confirms that the best accuracy of Tg-guided follow-up in patients treated for differentiated thyroid carcinoma is obtained if treatment includes remnant ablation, and Tg testing is performed while off thyroxine.

Diagnostic value of serum thyroglobulin measurements in the follow-up of differentiated thyroid carcinoma, a structured meta-analysis

Context: Thyroid carcinoma requires lifelong monitoring with serum thyroglobulin, radioactive iodine whole body scanning, and other imaging modalities. Levothyroxine (l-T4) withdrawal for thyroglobulin measurement and whole body scanning increases these tests’ sensitivities but causes hypothyroidism. Recombinant human TSH (rhTSH) enables testing without l-T4 withdrawal. Objective: Our objective was to examine the impact of short-term hypothyroidism on the health-related quality of life (HRQOL) of patients after rhTSH vs. l-T4 withdrawal. Design, Setting, and Patients: In this multicenter study, the SF-36 Health Survey was administered to 228 patients at three time points: on l-T4, after rhTSH, and after l-T4 withdrawal. Interventions: Interventions included administration of rhTSH on l-T4 and withdrawal from thyroid hormone. Main Outcome Measures: Mean SF-36 scores were compared during the two interventions and with the U.S. general population and patients with heart failure, depression, and migraine head...

A Comparison of Short-Term Changes in Health-Related Quality of Life in Thyroid Carcinoma Patients Undergoing Diagnostic Evaluation with Recombinant Human Thyrotropin Compared with Thyroid Hormone Withdrawal

Current treatment strategies for pediatric patients with nonmedullary, well-differentiated thyroid carcinoma (WDTC) are derived from single-institution clinical cohorts, reports of extensive person...

Current Controversies in the Management of Pediatric Patients with Well-Differentiated Nonmedullary Thyroid Cancer: A Review

Current diagnostic studies [radioiodine uptake and serum thyroglobulin (Tg) levels] for residual or metastatic thyroid tissue in patients with differentiated thyroid carcinoma require a hypothyroid status necessary for adequate endogenous TSH stimulation. However, almost all patients have symptoms of clinical hypothyroidism during this period. As shown in the present study, recombinant human TSH (rhTSH) allows stimulation of 131I uptake and Tg release from residual thyroid tissue in euthyroid patients. To assess safety, dosage, and preliminary efficacy, comparison was made of the stimulation of 131I uptake and Tg release after rhTSH administration and after T3 withdrawal in 19 patients after a recent thyroidectomy for differentiated thyroid carcinoma. Various doses (10-40 U) of rhTSH were injected im for 1-3 days in patients receiving suppressive doses of T3. Twenty-four hours after the last dose of rhTSH, 1-2 mCi 131I were administered, followed by a neck and whole body scan 48 h later. After discontinuing T3 for a median period of 19 days (range, 15-28), endogenous serum TSH levels were markedly elevated, and the patients were given a second dose of 131I and rescanned 48 h later. The injections of rhTSH were tolerated well. No major adverse effects were reported; nausea was reported in 3 (16%) and vomiting in 1 of the patients treated with high doses. The quality of life, as measured by two psychometric scales, was far better during rhTSH treatment than after T3 withdrawal. The peak levels of serum TSH (mean +/- SD) after a single dose of 10, 20, or 30 U were 127 +/- 19, 309 +/- 156, and 510 +/- 156 mU/L, respectively, and occurred 2-8 h after injection. Twenty-four hours after the injection, TSH levels decreased to 83 +/- 31, 173 +/- 73, and 463 +/- 148 mU/L in these treatment groups, respectively. The quality of the thyroid scans and the number of sites of abnormal 131I uptake were similar after rhTSH treatment and in the hypothyroid scans in 12 (63%) patients. Two additional sites of uptake in the chest and one in the thyroid bed, not visible on the hypothyroid scans, were identified in 3 (16%) patients after rhTSH. In 1 patient a focus of uptake was better visualized after rhTSH than after withdrawal. In 3 (16%) other patients, 1 lesion in the chest and 2 in the neck were seen only after T3 withdrawal.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnostic Use of Recombinant Human Thyrotropin in Patients with Thyroid Carcinoma (Phase I/II Study)*

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Diagnostic Use of Recombinant Human Thyrotropin in Patients with Thyroid Carcinoma (Phase I/II Study)*