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Low-iodine diet (LID) is a crucial preparation for radioactive iodine (RAI) treatment or scan in thyroid cancer. The aim of this study is to analyze the influence of thyroid stimulating hormone (TSH) stimulation protocols and other clinical factors on LID adequacy. Thyroid cancer patients who underwent LID for RAI scan or treatment were retrospectively analyzed. Patients were guided to have LID for 2 weeks before RAI administration and urine iodine/creatinine ratio (UICR, μg/g Cr) was measured. TSH stimulation was conducted using either thyroid hormone withdrawal (THW) or recombinant human TSH (rhTSH) injection. Adequacy of LID was classified by UICR as 'excellent (< 50)', 'adequate (50-100)', 'inadequate (101-250)' and 'poor (> 250)'. A total of 1715 UICR measurements from 1054 patients were analyzed. UICR was significantly higher in case of rhTSH use than THW (72.4 ± 48.1 vs. 29.9 ± 45.8 μg/g Cr, P < 0.001). In patients who underwent LID twice using both TSH stimulation protocols alternately, UICR was higher in case of rhTSH than THW regardless of the order of method. Among clinical factors, female, old-age, and the first LID were significant factors to show higher UICR. Although the adequacy of LID was 'adequate' or 'excellent' in most patients, multivariate analysis demonstrated that THW method, male, young age, and prior LID-experience were significant determinants for achieving 'excellent' adequacy of LID. In conclusion, UICR was higher and the proportion of 'excellent' LID adequacy was lower with rhTSH than with THW. UICR was higher also in women, old-age, and LID-naïve patients. Further researches are required to suggest effective methods to reduce body iodine pool in case of rhTSH use and to validate the efficacy of such methods on outcomes of RAI treatment., Competing Interests: The authors have declared that no competing interests exist.

Context: Following total thyroidectomy and radioactive iodine (RAI) ablation, serum thyroglobulin levels should be undetectable to assure that patients are excellent responders and at very low risk of recurrence., Objective: To assess the utility of stimulated (sTg) and non-stimulated (nsTg) thyroglobulin levels in prediction of patients outcomes with differentiated thyroid cancer (DTC) following total thyroidectomy and RAI ablation., Method: A prospective observational study conducted at a University Hospital in Saudi Arabia. Patients diagnosed with differentiated thyroid cancer and were post total thyroidectomy and RAI ablation. Thyroglobulin levels (nsTg and sTg) were estimated 3-6 months post-RAI. Patients with nsTg <2 ng/ml were stratified based on their levels and were followed-up for 5 years and clinical responses were measured., Results: Of 196 patients, nsTg levels were <0.1 ng/ml in 122 (62%) patients and 0.1-2.0 ng/ml in 74 (38%). Of 122 patients with nsTg <0.1 ng/ml, 120 (98%) had sTg levels <1 ng/ml, with no structural or functional disease. sTg levels >1 occurred in 26 (35%) of patients with nsTg 0.1-2.0 ng/ml, 11 (15%) had structural incomplete response. None of the patients with sTg levels <1 ng/ml developed structural or functional disease over the follow-up period., Conclusion: Suppressed thyroglobulin (nsTg < 0.1 ng/ml) indicates a very low risk of recurrence that does not require stimulation. Stimulated thyroglobulin is beneficial with nsTg 0.1-2 ng/ml for re-classifying patients and estimating their risk for incomplete responses over a 7 years follow-up period., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jammah, Masood, Akkielah, Alhaddad, Alhaddad, Alharbi, Alguwaihes and Alzahrani.)

The aim of the study was to evaluate the clinical impact of pre-ablation rhTSH-stimulated fluorine-18 fluorodeoxyglucose (F-18 FDG) PET/CT in addition to post-therapeutic whole body radioiodine scanning in patients with intermediate to high risk differentiated thyroid carcinoma (DTC). This was a retrospective single center study including 73 patients with thyroid cancer (44 females, mean age 43.2±16.2 years, 62% papillary, 31% follicular, 7% poorly differentiated). All patients underwent ablative radioiodine treatment (mean activity: 3661±673 MBq I-131) using rhTSH after thyroidectomy and lymph node (LN) dissection (01/2013-10/2016) and TSH-stimulated F-18 FDG PET/CT (4 MBq/kg body weight, low dose CT). Post-treatment I-131 whole body scan (I-131 WBS) was obtained 9 days afterwards in planar technique and in case of equivocal or abnormal findings using SPECT/CT. Thirty-one patients (42%) showed F-18 FDG avid lesions, 14 patients showed more FDG than iodine positive lesions and 5 patients more iodine positive lesions in I-131 WBS, respectively. Fifty-three patients showed identical F-18 FDG PET/CT and I-131 WBS. The initial treatment plan was changed from follow-up to therapy (surgery, systemic therapy using tyrosine-kinase inhibition) in 11 patients (15%) on the basis of F-18 FDG PET/CT imaging. Six of these 11 patients had papillary thyroid cancer. Three patients with histologically proven LN metastases had stimulated thyroglobulin-levels<2.0 ng/ml. Our study demonstrated a clinical benefit of pre-ablation rhTSH-stimulated F-18 FDG PET/CT imaging in about 20% of patients with intermediate to high risk DTC, leading to change in patient management in 15%., Competing Interests: The authors declare that they have no conflict of interest., (Eigentümer und Copyright ©Georg Thieme Verlag KG 2020.)

The use of recombinant human thyrotropin (rhTSH) testing in the diagnosis and therapy of differentiated thyroid cancer (DTC) has been adopted over the last two decades as an alternative to the classical thyroid hormone withdrawal avoiding the threat of hypothyroidism. Serum thyroglobulin (Tg) measurement is crucial for monitoring DTC patients over time. Until about a decade ago, optimal sensitivity of Tg assays for the detection of smaller disease foci required Tg measurement after thyrotropin (TSH) stimulation, carried out following thyroid hormone withdrawal or rhTSH administration. In very recent years, significant improvements in assay technology have resulted in highly sensitive Tg (hsTg) assays, sufficiently sensitive to obviate the need for rhTSH stimulation in most DTC patients. The aim of this paper is to review and discuss, via a 'pros and cons' approach, the current clinical role of rhTSH to stimulate radioiodine (RAI) uptake for treatment and/or imaging purposes and to increase the clinical sensitivity of Tg measurement for monitoring DTC patients when high-sensitive Tg assays are available.

We report a 72-years-old male patient with extensive differentiated thyroid cancer (DTC), who required a tracheostomy and gastrostomy. Considering his clinical condition, risk of aspiration and management of the ostomies, radioiodine (131I) was administered intravenously, using recombinant human thyrotropin (rhTSH) and levothyroxine. The procedure was successful, both clinically and in terms of radioprotection.

Objective: The aim of this study was to assess I-131 biokinetics in thyroid cancer and remnant tissue in patients with differentiated thyroid cancer using whole-body scan (WBS) and SPECT images acquired after I-131 therapy. The influence of thyroid stimulating hormone (TSH) stimulation method on the kinetics was also evaluated., Methods: A total of 57 patients who received I-131 therapy (2.96-7.4 GBq) were retrospectively included. TSH stimulation was achieved by recombinant human thyrotropin (rhTSH) or by thyroid hormone withdrawal (THW). Each patient received three sequential WBSs on days 1, 2, and 4 (or 5) after I-131 administration. All lesions were classified either as thyroid remnant (ThyR) or as metastatic lymph nodes (mLN) after considering the SPECT/CT images acquired during the last WBS. The lesion-based retention rate and absorbed dose of ThyR and mLN were calculated using a commercial dosimetric toolkit combined with the OLINDA software., Results: The retention rate and the effective half-time of mLN were lower than that of ThyR (p < 0.001, p = 0.003). In addition, the retention rate and the effective half-time of ThyR in the rhTSH group were higher than those in the THW group (p < 0.001, p < 0.001). The differences in the retention rate and the effective half-time of mLN were not statistically significant between the THW group and rhTSH group (p = 0.549, p = 0.571)., Conclusions: Radioiodine therapy using rhTSH delivered an at least similar radiation dose to target lesions compared to using THW in thyroid remnants and metastatic lymph nodes.

Salivary dysfunction and sialadenitis are well known complications of radioiodine treatment for thyroid cancer. The parotid gland is more frequently affected and the salivary gland injury is dose related. The symptoms may develop shortly after therapeutic Iodine 131(I-131) administration or months later and progress with time. The development of unilateral parotiditis following a low dose, diagnostic I-131 scan performed following Thyrogen stimulation in a patient without prior history of sialadenitis is rare in our experience, and has not been reported in the medical literature.

Background: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I therapy., Methods: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2 ± 9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 mL; range 31.9-242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated (131)I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively., Results: At six months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH group, and 53 ± 18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal (131)I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH group (13.4 ± 23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of the study was favorable., Conclusions: When used as adjuvant to (131)I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤ 0.03 mg, indicating that the lower threshold for efficacy is around this level.

Background and Purpose: We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of recombinant human thyrotropin (rhTSH) and thyroid hormone withdrawal (THW) on thyrotropin stimulation prior to remnant ablation of differentiated thyroid cancer (DTC)., Material and Methods: A comprehensive search was conducted for articles discussing rhTSH and THW prior to December 2012. After applying the inclusion criteria, all the available data were summarized to analyze the efficacy of rhTSH and THW for stimulating TSH., Results: Seven RCTs that involved a total of 1535 patients, were included in the analysis. The ablation rates of the rhTSH group and the THW group were not significantly different (RR=0.97, 95% CI: 0.94-1.01, p=0.1). Patients in the rhTSH group had a better quality of life (QoL) than those in the THW group on the day of ablation (RR=3.92, 95% CI: 3.44-5.40, p<0.00001). However, there was no difference in the QoL 3 months after ablation (RR=-0.9, 95% CI: -2.20-0.39, p=0.17). Additionally, there were no significant differences in serum thyroglobulin (Tg) levels measured just before radioiodine remnant ablation (preablation thyroglobulin levels) (RR=-0.14, 95% CI: -0.73-0.45, p=0.65), or in days of hospital isolation (RR=-10.51, 95% CI: -32.79-11.73, p=0.35) CONCLUSIONS: Our findings indicate that the administration of rhTSH had resulted in an ablation rate similar to that of THW for DTC patients, but rhTSH provided a better QoL at the time of ablation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Context: Thyroglobulin (Tg) levels measured at the time of remnant ablation after thyroid hormone withdrawal (THW) were shown to have prognostic value in predicting disease-free status., Objectives: Our objectives were to determine whether stimulated Tg levels, measured at the time of remnant ablation performed under recombinant human TSH (rhTSH) stimulation, has value in predicting absence of detectable disease 1 year after radioiodine therapy and to compare the results obtained with this approach with a cohort of patients submitted to ablation after THW., Design: This was a prospective observational study., Setting and Patients: The study included 293 consecutive patients treated for a differentiated thyroid carcinoma with no initial evidence of distant metastasis. All patients were submitted to a total or near-total thyroidectomy, followed by ablation either under rhTSH (n = 151) or endogenous TSH stimulation (n = 142). Patients with positive Tg antibodies were excluded., Main Outcome Measures: The predictive value of Tg at ablation was assessed by receiver operating characteristic curve analysis., Results: In the rhTSH group, 96 patients (73.3%) were considered disease-free at 1 year. Stimulated Tg at ablation after rhTSH was found to be an independent prognostic indicator of disease persistence 12 months later. The highest-accuracy cutoff value for absence of detectable disease was defined as 7.2 ng/mL, with a negative predictive value of 90%. In the THW group, Tg at ablation also proved to have independent predictive value. Using the same threshold (7.2 ng/mL), the negative predictive value of Tg was 95% in the THW group., Conclusions: When rhTSH was used, stimulated Tg at ablation had independent predictive value for disease-free status 1 year later. A low stimulated Tg at rhTSH-aided ablation may be considered a favorable prognosis factor.

Purpose: Fetuin-A is a hepatokine that is linked to lipid metabolism, obesity, insulin resistance, type 2 diabetes and cardiovascular disease. Elevated thyroid-stimulating hormone (TSH) levels are associated with metabolic and cardiovascular disturbances. Our aim was to determine if TSH can regulate fetuin-A levels., Methods: Fetuin-A serum levels were examined in 26 subjects (19 women; previous thyroidectomy and radioactive iodine ablation) undergoing recombinant human TSH (rhTSH) stimulation to screen for thyroid cancer recurrence. Their age was 49±10 years, and body mass index (BMI) was 28±6 (both expressed as mean±SD). The patients received two doses of rhTSH (0.9 mg), administered 24 hours apart on days 1 and 2, without discontinuation of ongoing L-thyroxine therapy. Morning blood samples were obtained on days 1 (prior to the first dose of rhTSH), 3 and 5., Results: The baseline value of fetuin-A (mean±SD) for all participants was 527±186 mg/L. Values of fetuin-A did not change in response to rhTSH administration. The lack of response was not dependent on gender, age, baseline free thyroxine level or BMI., Conclusion: Fetuin-A has been implicated in metabolic and inflammatory conditions, but there have been no reports on whether fetuin-A is influenced by TSH. Within the context of rhTSH administration for surveillance of thyroid cancer recurrence, there was no effect on serum levels of fetuin-A.

Context: In patients with differentiated thyroid carcinoma (DTC) who, after thyroidectomy, are to receive radioiodine therapy or diagnostics, a strong TSH stimulus is necessary. Traditionally, this is induced by thyroid hormone withdrawal (THW) over a period of 4-5weeks; alternatively thyroid hormone replacement therapy is continued and recombinant human thyrotropin (rhTSH) is administered. During the hypothyroid state due to THW, patients often report mood disturbances and physical complaints but also an impairment of performance during attention demanding tasks., Objective: Based on physiological, self-report and performance test data collected from various studies, we proposed the hypothesis that thyroidectomized DTC patients perform significantly worse in cognitive-motor functions that are relevant for driving when in the THW-induced hypothyroid state compared to when thyroid hormone replacement therapy is continued and rhTSH is administered., Methods: We compared 41 DTC patients (age 42.3 (9.4) years; 80.5% female) after 4weeks THW with 41 DTC patients after the application of rhTSH, pairwise matched according to age, gender and educational level, with respect to performance in 4 core tests of the Act-React-Testsystem ART-90, a validated test battery for examining fitness to drive., Results: Contrary to our expectations, no statistically relevant impairment of performance could be confirmed in the THW group in comparison to the rhTSH group for any variable (at adjusted α). At most there is a tendency in the THW group for slowed reaction times in simple-choice reaction tasks; the (standardized) difference to the rhTSH group is however small (d'=0.31). Furthermore, large effects due to THW, as they are suggested by several studies, could be excluded., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Traditionally, during the follow-up and in order to receive 131 I therapy, patients with differentiated thyroid carcinoma (DTC) have to withdraw from using thyroid hormone. The hypothyroidism induced by hormone withdrawal can negatively affect the quality-of-life (QOL) of DTC patients. Without the hormone withdrawal, recombinant human thyroid-stimulating hormone-aided management of DTC patients can effectively obviate the consequences of hypothyroidism. This review will focus on the clinical application of recombinant human thyroid-stimulating hormone (rhTSH) in the management of DTC patients.

Aims: To evaluate the incidence and clinical implications of a positive whole-body I-131 scan but negative stimulated serum Tg/TgAb level following an ablative or diagnostic I-131 dose in patients with well-differentiated thyroid cancer and whether there is a difference in incidence if prepared with thyroid hormone withdrawal compared with rhTSH stimulation., Methods: I-131 scan findings, serum Tg/TgAb levels, TNM stage and method of thyroid tissue stimulation in 193 consecutive patients (138F, 55M) with well-differentiated thyroid cancer undergoing postoperative ablative I-131 therapy and 121 consecutive (94F, 27M) patients undergoing diagnostic I-131 surveillance scans were retrospectively reviewed. Comparisons of proportions were performed using Chi-square tests. Clinical, biochemical and I-131 scan follow-up data were obtained for each patient cohort., Results: 39/193 (20·2%) postablative I-131 and 10/121 (8·3%) diagnostic I-131 patients had negative stimulated serum Tg/TgAb levels but positive I-131 scans for residual thyroid tissue. Nine (4·7%) of the postablative patients had I-131 uptake in the lateral neck suspicious for loco-regional metastatic disease. In the postablative I-131 group, 38/169 (22·5%) prepared with rhTSH compared to 1/24 (4·2%) prepared with thyroid hormone withdrawal were Tg/TgAb negative but I-131 scan positive (P = 0·04). Follow-up of 21/39 postablative I-131 patients with negative Tg/TgAb but positive I-131 scans confirmed a significant proportion of patients (4/21) (19·1%), remained Tg/TgAb negative/I-131 scan positive, some of whom had higher-risk disease at original diagnosis (2/4) (50%)., Conclusions: Our study confirms that in the setting of I-131 ablation therapy or diagnostic I-131 scanning, a significant proportion of patients (20·2% and 8·3%, respectively) have residual benign or malignant thyroid tissue on whole-body scanning despite a negative stimulated serum Tg level. Whether such patients who would otherwise be missed as having residual thyroid tissue on serum Tg testing alone have a worse clinical outcome remains uncertain. Our findings do however suggest performing both stimulated serum Tg/TgAb levels and I-131 scans for the follow-up of patients with higher-risk thyroid cancer may be important. There may also be a slightly higher incidence of this phenomenon in patients prepared with rhTSH rather than by thyroxine withdrawal., (© 2012 Blackwell Publishing Ltd.)

Background: To effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum thyrotropin (TSH) levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The aim of our study was to compare the relative efficacy and side effect profile of rhTSH versus THW preparation for RAI therapy of metastatic DTC., Methods: Fifty-six patients (31 women and 25 men) with RAI-avid distant metastases of DTC treated with either rhTSH-aided (n=15) or THW-aided RAI (n=41) and followed for 72±36.2 months were retrospectively analyzed. The groups were comparable in regard to mean size of target lesions (rhTSH vs. THW 6.4 vs. 4.8 cm, p=0.41), mean baseline thyroglobulin level (6995 vs. 5544 ng/mL, p=0.83), distribution of micronodular and macronodular pulmonary metastases (67% vs. 63%, p=0.54, 13% vs. 15% p=0.64, respectively), osseous (53% vs. 29%, p=0.09), brain (0% vs. 2%, p=0.73), and liver/kidney metastases (13% vs. 2%, p=0.61). Patients in the rhTSH group were older (rhTSH vs. THW mean 62 vs. 49 years, p=0.01), and received lower cumulative RAI dose (256 vs. 416 mCi, p=0.03), which was more frequently based on dosimetric calculations (80% vs. 46%, p=0.024). Responses to treatment were based on RECIST 1.1 criteria., Results: Adjusted by age rates of complete response (CR), stable disease (SD), progressive disease (PD), and progression free survival (PFS) were not different between the groups (rhTSH vs. THW CR hazard ratio [HR] 0.97, 95% CI 0.08-11.42, p=0.982; SD HR 3.22, 95% CI 0.79-13.18, p=0.104, PD HR 0.26, 95% CI 0.52-1.26, p=0.094; PFS HR 0.41, 95% CI 0.14-1.23, p=0.112). The only independent risk factor for nonresponding to treatment and presentation with PD was age (HR 1.06, 95% CI 1.02-1.11, p=0.008). Age was also an independent factor affecting PFS (HR 1.04 for each year, 95% CI 1.02-1.07, p=0.001). Rates of leukopenia, thrombocytopenia, xerostomia, and restrictive pulmonary disease after RAI were not significantly different (rhTSH vs. THW 30% vs. 28%, p=0.61, 10% vs. 0%, p=0.37, 0% vs. 12%, p=0.20, 0% vs. 2%, p=0.73, respectively)., Conclusions: Patients with metastatic DTC prepared with rhTSH achieve comparable benefit of RAI therapy as those treated after THW.

Follicular thyroid cancer with thyroid hormone secreting metastases is an extremely rare condition, with only a few cases reported world-wide. We here present the case of a 64-year-old female patient affected by follicular thyroid cancer with extensive thyroid hormone secreting metastases leading to TSH-suppression. We have also summarized the relevant diagnostic and therapeutic approaches and describe, for the first time, the effects of rhTSH-application in this rare tumor entity. In this patient, we found that rhTSH increased ¹³¹I-uptake into the thyroid hormone secreting metastases and prolonged the effective half-life of ¹³¹I. These effects of rhTSH should be considered when fixed activities of ¹³¹I are prescribed., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

The incidence of thyroid cancer has increased exponentially around the world (mostly papillary thyroid carcinoma). This growth may reflect the combined effects of increased screening practices, together with changes in risk factors for thyroid cancer. In spite of this, disease specific mortality remained stable in the last three decades. Due to the fact that patients with papillary thyroid carcinoma often have a very good prognosis, with high survival in the long term follow-up compared with other types of carcinomas, there has been no need to change the standard treatment. The mainstays of thyroid cancer treatment are surgery (total or near-total thyroidectomy) with or without the additional administration of radioiodine (131I). These approaches are now in the center of discussion in all global forums. The current trend is to ensure the most effective and less harmful treatment and the most important issue at this point is to individualize patients according to tumor stage and risk of recurrence, to define which patients will benefit of more aggressive therapy and who could be handled with a more conservative approach.

Background: The use of recombinant human TSH (rhTSH) is indicated to evaluate thyroid carcinoma patients. In recent years, some authors have reported that rhTSH could serve as a dynamic test of thyroid reserve. The aim of the present study was to determine whether or not rhTSH can predict the evolution from subclinical hypothyroidism (SH) to overt hypothyroidism., Materials and Methods: Twenty-one women who met the diagnostic criteria of SH were enrolled. All patients received a single dose of rhTSH (0.1 mg). Basal blood samples for TSH, free T4 (fT4), thyroglobulin (Tg), and anti-thyoperoxidase and anti-Tg antibodies were obtained before and 1 day after rhTSH administration. All patients were followed for 2 yr, and blood samples were obtained every 6 months., Results: Twenty-four hours after rhTSH administration, the TSH level increased to >20 mU/l in 14 patients; the serum peak TSH levels remained <10 mU/l in only 5 patients. On follow-up, 7 women (33%) required L-T4 replacement therapy for overt hypothyroidism or a persistent TSH level >10 mlU/l. None of the parameters analyzed differed significantly between patients who developed overt hypothyroidism from those who had persistent SH., Conclusions: The response of thyroid function tests to a single low dose of rhTSH is not useful in identifying those patients with SH who will develop overt hypothyroidism over a 2-yr period.