Thyrogen (Thyrotropin Alfa)

Number: 0515

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

Policy

Scope of Policy

This Clinical Policy Bulletin addresses Thyrogen (thyrotropin alfa) for commercial medical plans. 

  1. Medical Necessity

    Aetna considers Thyrogen (thyrotropin alfa) medically necessary for the following indications:

    1. As an adjunctive diagnostic tool for thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of members with well-differentiated thyroid carcinoma who have previously undergone thyroidectomy; or
    2. As an adjunct to facilitate radioiodine ablation of thyroid tissue remnants in members who have undergone a near-total or total thyroidectomy for well-differentiated thyroid cancer; or 
    3. As an adjunct to facilitate radioiodine ablation therapy for non-toxic multi-nodular goiter.

  2. Dosing Recommendations

    Thyrogen is available for injection as: 0.9 mg of thyrotropin alfa as a lyophilized powder in a single-dose vial.

    Thyrogen should be used by physicians knowledgeable in the management of persons with thyroid cancer. A two-injection regimen is recommended. Thyrogen 0.9 mg is administered intramuscularly, followed by a second 0.9 mg intramuscular injection 24 hours later.

    Source: Genzyme, 2023

  3. Experimental, Investigational, or Unproven

    Aetna considers thyrotropin alfa experimental, investigational, or unproven for all other indications (e.g., for individuals with differentiated thyroid cancer who have suppressed serum thyroglobulin [less than 0.1 ng/ml]) because of insufficient evidence of effectiveness.

Table:

CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Other CPT codes related to the CPB:
60240 Thyroidectomy, total or complete
78012 Thyroid uptake, single or multiple quantitative measurement(s) (including stimulation, suppression, or discharge, when performed)
78013 Thyroid imaging (including vascular flow, when performed);
78014     with single or multiple uptake(s) quantitative measurement(s) (including stimulation, suppression, or discharge, when performed)
78015 - 78018 Thyroid carcinoma metastases imaging
+ 78020 Thyroid carcinoma metastases uptake (List separately in addition to code for primary procedure)
79005 Radiopharmaceutical therapy, by oral administration
80418 Combined rapid anterior pituitary evaluation panel
80438 Thyrotropin releasing hormone (TRH) stimulation panel; one hour
80439     two hour
84432 Thyroglobulin
84443 Thyroid stimulating hormone (TSH)
86800 Thyroglobulin antibody
96372 Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular

HCPCS codes covered if selection criteria are met:
J3240 Injection, thyrotropin alpha, 0.9 mg, provided in 1.1 mg vial

Other HCPCS codes related to the CPB:
A9517 Iodine i-131 sodium iodide capsule(s), therapeutic, per millicurie

ICD-10 codes covered if selection criteria are met:
C73 Malignant neoplasm of thyroid gland [except for suppressed serum thyroglobulin (less than 0.1 ng/ml)]
E04.2 Nontoxic multinodular goiter [adjunct to radioiodine ablation]
Z85.850 Personal history of malignant neoplasm of thyroid

Background

U.S. Food and Drug Administration (FDA)-Approved Indications

Thyrogen is indicated for:

  • Adjunctive Diagnostic Tool for Well-Differentiated Thyroid Cancer: Use as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer who have previously undergone thyroidectomy.

    Limitations of Use

    • Thyrogen-stimulated Tg levels are generally lower than, and do not correlate with Tg levels after thyroid hormone withdrawal.
    • Even when Thyrogen-Tg testing is performed in combination with radioiodine imaging, there remains a risk of missing a diagnosis of thyroid cancer or underestimating the extent of the disease.
    • Anti-Tg Antibodies may confound the Tg assay and render Tg levels uninterpretable.

  • Adjunct for Thyroid Remnant Ablation in Well-Differentiated Thyroid Cancer:Use as an adjunctive treatment for radioiodine ablation of thyroid tissue remnants in patients who have undergone a near-total or total thyroidectomy for well-differentiated thyroid cancer and who do not have evidence of distant metastatic thyroid cancer.

    Limitations of Use

    The effect of THYROGEN on thyroid cancer recurrence greater than 5 years post-remnant ablation has not been evaluated.

Surgery is the cornerstone of management of patients with differentiated thyroid cancer.  As an adjunct to this treatment, some high-risk patients may need to undergo radioactive iodine treatment, further destroying normal thyroid tissue.  All patients with tumors arising from follicular epithelium require thyroid stimulating hormone (TSH) suppression since differentiated thyroid cancers contain membrane receptors responsive to TSH.  Long-term thyroid hormone supplements are used to maintain metabolism in patients who have had partial or total thyroidectomy and/or radioactive iodine treatment and to suppress endogenous levels of TSH.

Management of patients with a history of thyroid carcinoma requires continuing evaluation to monitor cancer recurrence and metastatic disease by periodic physical examinations, thyroglobulin levels, radioiodine scans, and assurance of appropriate TSH suppression.  A high level of TSH in a patient's bloodstream is necessary to achieve optimal sensitivity of serum thyroglobulin testing and in order for radioiodine imaging to detect remnant thyroid tissue or metastatic disease.  In order to accomplish this, patients must stop taking their hormone supplements for two to six weeks prior to testing.  This thyroid hormone withdrawal causes patients to experience symptoms of hypothyroidism – fatigue, weight gain, constipation, mental dullness, lethargy, depression, and other adverse reactions.

On December 1, 1998, the Food and Drug Administration (FDA) granted marketing approval for Thyrogen (thyrotropin alfa) for use as "an adjunctive diagnostic tool for serum thyroglobulin testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer."  Thyrogen, a recombinant form of TSH, provides an external source of TSH and allows thyroid cancer patients to avoid hormone withdrawal and its debilitating effects while undergoing diagnostic testing.

The FDA made its decision based on review of 2 phase III clinical trials, which were conducted on 358 patients with well-differentiated thyroid cancer to compare 48-hour radioiodine whole body scans obtained after Thyrogen to whole body scans after thyroid hormone withdrawal.  One of these trials also compared thyroglobulin levels obtained after Thyrogen to those on thyroid hormone suppression therapy, and to those after thyroid hormone withdrawal.  Across the 2 clinical studies, Thyrogen was shown to significantly enhance the sensitivity of thyroglobulin testing in patients maintained on thyroid hormone therapy.  The combination of a Thyrogen-stimulated scan and a serum thyroglobulin test did detect all patients with metastatic disease, although not as sensitive as combination testing performed after patients were withdrawn from thyroid hormone supplements.  The Thyrogen-stimulated scan failed to detect remnant and/or cancer localized to the thyroid bed in 16% (20/124) of patients in whom it was detected by a scan after thyroid hormone withdrawal.  In addition, the Thyrogen scan failed to detect metastatic disease in 24% (9/38) of patients in whom it was detected by a scan after thyroid hormone withdrawal.  Based on these studies, it can be concluded that even when Thyrogen-stimulated thyroglobulin testing is performed in combination with radioiodine imaging, there remains a meaningful risk of missing a diagnosis of thyroid cancer or of under-estimating the extent of disease.

Recombinant human thyrotropin has also been demonstrated to be useful to facilitate radioiodine ablation of remnant thyroid tissue after surgery for differentiated thyroid carcinoma, as an alternative to thyroid hormone withdrawal.  After surgery for differentiated thyroid carcinoma, many patients are treated with radioiodine to ablate remnant thyroid tissue.  This procedure is most commonly performed with the patient in the hypothyroid state to promote endogenous TSH stimulation to optimize radioiodine uptake by remnant thyroid tissue.  However, thyroid hormone withdrawal is associated with hypothyroid symptoms and impaired quality of life.  Pacini et al. (2006) reported the results of a randomized controlled clinical trial to compare recombinant human thyrotropin to prepare patients on thyroid hormone therapy to ablate remnant thyroid tissue with radioiodine, compared with conventional remnant ablation preformed in the hypothyroid state.  The investigators found comparable remnant ablation rates by administering recombinant human thryrotropin or by withholding thyroid hormone.  Successful thyroid remnant ablation was achieved by 23 of 24 patients (96%) treated with recombinant human thyrotropin, compared to 18 of 21 (86%) patients treated in the hypothyroid state (p = 0.23).  These investigators reported that subjects treated with recombinant human thyrotropin had a significantly higher quality of life during treatment than subjects treated in the hypothyroid state.  They reported that subjects treated with recombinant human thyrotropin also had a significantly lower radiation exposure to the blood than patients treated in the hypothyroid state.

Mallick et al. (2012) noted that it is not known whether low-dose radioiodine (1.1 GBq [30 mCi]) is as effective as high-dose radioiodine (3.7 GBq [100 mCi]) for treating patients with differentiated thyroid cancer or whether the effects of radioiodine (especially at a low-dose) are influenced by using either thyrotropin alfa or thyroid hormone withdrawal.  At 29 centers in the United Kingdom, these researchers conducted a randomized non-inferiority trial comparing low-dose and high-dose radioiodine, each in combination with either thyrotropin alfa or thyroid hormone withdrawal before ablation.  Patients (age range of 16 to 80 years) had tumor stage T1 to T3, with possible spread to nearby lymph nodes but without metastasis.  End points were the rate of success of ablation at 6 to 9 months, adverse events, quality of life, and length of hospital stay.  A total of 438 patients underwent randomization; data could be analyzed for 421.  Ablation success rates were 85.0% in the group receiving low-dose radioiodine versus 88.9% in the group receiving the high-dose and 87.1% in the thyrotropin alfa group versus 86.7% in the group undergoing thyroid hormone withdrawal.  All 95% confidence intervals for the differences were within +/- 10 percentage points, indicating non-inferiority.  Similar results were found for low-dose radioiodine plus thyrotropin alfa (84.3%) versus high-dose radioiodine plus thyroid hormone withdrawal (87.6%) or high-dose radioiodine plus thyrotropin alfa (90.2%).  More patients in the high-dose group than in the low-dose group were hospitalized for at least 3 days (36.3% versus 13.0%, p < 0.001).  The proportions of patients with adverse events were 21% in the low-dose group versus 33% in the high-dose group (p = 0.007) and 23% in the thyrotropin alfa group versus 30% in the group undergoing thyroid hormone withdrawal (p = 0.11).  The authors concluded that low-dose radioiodine plus thyrotropin alfa was as effective as high-dose radioiodine, with a lower rate of adverse events.

Rosario et al. (2012) evaluated the effectiveness of recombinant human thyroid stimulating hormone [rhTSH (versus hypothyroidism)] in thyroid ablation with an activity of 1.1 GBq (30 mCi) (131)I.  A total of 102 patients with thyroid cancer who fulfilled the following criteria were studied: submitted to total thyroidectomy with complete tumor resection; tumor less han or equal to 4 cm without extra-thyroid invasion or lymph node metastases; negative anti-thyroglobulin (anti-Tg) antibodies.  Thirty-two patients (group A) received 0.9 mg of rhTSH for 2 consecutive days followed by (131)I administration and 70 patients (group B) were prepared by levothyroxine withdrawal for 4 weeks.  The groups were similar in sex, age, and tumor characteristics.  Ablation was successful (stimulated Tg less than 1 ng/ml and negative diagnostic whole-body scanning and neck ultrasonography 9 to 12 mo after ablation) in 27 patients of group A (84.3%) and in 58 of group B (83%).  Considering patients with Tg greater than 1 ng/ml immediately before (131)I administration, the rates were 72.2% in group A and 75% in group B.  In group A, the ablation rate was similar for patients who discontinued levothyroxine-T4 3 days before (131)I administration and those maintained on hormone therapy.  The mean follow-up was 29.6 months in group A and 55 months in group B.  Stimulated Tg (after rhTSH) was undetectable in 29 patients of group A (90.6%) and in 61 of group B (87%) and 1 patient of group B presented cervical metastases at the last assessment.  The authors concluded that low (131)I activity after rhTSH is effective for remnant ablation in patients who are at low-risk of recurrence.

Fast et al. (2012) evaluated the long-term outcome of rhTSH-augmented radioiodine ((131)I) therapy for benign multi-nodular non-toxic goiter.  Between 2002 and 2005, a total of 86 patients with a multi-nodular non-toxic goiter were treated with (131)I in 2 randomized, double-blind, placebo-controlled trials.  (131)I-therapy was preceded by 0.3 mg rhTSH (n = 42) or placebo (n = 44).  In 2009, 80 patients completed a follow-up (FU) visit, including determination of thyroid volume, thyroid function, and patient satisfaction by a visual analog scale (VAS).  In both groups, thyroid volume was further reduced from 1 year to final FU (71 months).  The mean goiter volume reductions obtained at 1 year and final FU [59.2 +/- 2.4% (sem) and 69.7 +/- 3.1%, respectively] in the rhTSH group were significantly greater than those obtained in the (131)I-alone group (43.2 +/- 3.7 and 56.2 +/- 3.6%, respectively, p = 0.001 and p = 0.006), corresponding to a gain of 24% at final FU.  At last FU, the mean reduction in compression VAS was significantly greater in patients receiving rhTSH (p = 0.049).  Additional therapy (thyroid surgery or (131)I) was required more often in the placebo group (9 of 44) compared with the rhTSH group (2 of 42) (p = 0.05).  The prevalence of hypothyroidism at 1 year [9 and 43% in the placebo and rhTSH groups, respectively (p < 0.0001)] increased to 16 and 52%, respectively, at final FU (p = 0.001).  The authors concluded that enhanced goiter volume reduction with rhTSH-augmented (131)I therapy improved the long-term reduction in goiter-related symptoms and reduced the need for additional therapy compared with plain (131)I therapy.  They noted that overall patient satisfaction was benefited despite a higher rate of permanent hypothyroidism.

Chindris et al. (2012) noted that surveillance of patients with differentiated thyroid cancer (DTC) is achieved using serum Tg, neck ultrasonography (US), and rhTSH-stimulated Tg (Tg-stim).  These investigators assessed the utility of rhTSH Tg-stim in patients with suppressed Tg (Tg-supp) below 0.1 ng/ml using a sensitive assay.  The secondary aims were to assess the utility of US and to summarize the profile of subsequent Tg-supp measures.  A total of 163 patients (status: after thyroidectomy and radioactive iodine treatment) who had Tg-supp below 0.1 ng/ml and rhTSH Tg-stim within 60 days of each other were included.  After rhTSH stimulation, Tg remained below 0.1 ng/ml in 94 (58%) and increased to 0.1 to 0.5 in 56 (34%), more than 0.5 to 2.0 in 9 (6%), and above 2.0 ng/ml in 4 (2%) patients.  Serial Tg-supp levels were obtained in 138 patients followed over a median of 3.6 years.  Neck US was performed on 153 patients; suspicious examinations had fine-needle aspiration (FNA).  All positive FNA were identified around the time of the initial rhTSH test; 6 of 7 recurrences were detected by US (Tg-stim greater than 2.0 ng/ml in 1, 0.8 in 1 and less than or equal to 0.5 in 4).  One stage IV patient had undetectable Tg-stim.  The authors concluded that in patients with DTC whose T(4)-suppressed serum Tg is below 0.1 ng/ml, long-term monitoring with annual Tg-supp and periodic neck US are adequate to detect recurrences.  In the authors’ experience, rhTSH testing does not change management and is not needed in this group of patients.

Pak and colleagues (2014) evaluated the effectiveness of rhTSH versus thyroid hormone withdrawal (THW) prior to radioiodine remnant ablation (RRA) in thyroid cancer.  A systematic search of MEDLINE, EMBASE, the Cochrane Library, and SCOPUS was performed.  Randomized controlled trials that compared ablation success between rhTSH and THW at 6 to 12 months following RRA were included in this study.  A total of 6 trials with 1,660 patients were included.  When ablation success was defined as a Tg cut-off of 1 ng/ml (risk ratio [RR], 0.99; 95% confidence interval [CI]: 0.96 to 1.03) or a Tg cut-off of 1 ng/ml plus imaging modality (RR 0.97; CI: 0.90 to 1.05), the results of rhTSH and THW were similar.  There were no significant differences when ablation success was defined as a Tg cut-off of 2 ng/ml (RR 1.03; CI: 0.95 to 1.11) or a Tg cut-off of 2 ng/ml plus imaging modality (RR 1.02; CI: 0.95 to 1.09).  When a negative (131)I-whole body scan was used solely as the definition of ablation success, the effects of rhTSH and THW were not significantly different (RR 0.97; CI: 0.93 to 1.02).  The authors concluded that the ablation success rates were comparable when RRA is prepared by either rhTSH or THW.

Radioactive iodine therapy with iodine-131 ablation of post-surgical thyroid gland remnant could be prepared by recombinant human thyrotropin (rhTSH) stimulation or thyroid hormone withdrawal. American Thyroid Association prefers rhTSH stimulation over thyroid hormone withdrawal (strong recommendation, high certainty evidence) based on multiple randomized controlled trials and meta-analyses consistently demonstrate no significant difference in ablation success between the two approaches while highlighting worse health-related quality of life in patients undergoing thyroid hormone withdrawal due to hypothyroid symptoms (Ringel, et al., 2025). The National Comprehensive Cancer Network (NCCN) clinical practice guidelines for thyroid carcinoma does not express preference between the 2 methods for radioactive iodine ablation though for thyroglobulin testing, the guideline places preference of rhTSH over thyroid hormone withdrawal. The guidance was based on data showing the all cases of metastatic carcinoma were detected with the use of rhTSH in combination with whole body iodine-131 imaging and serum thyroglobulin measurements while having less adverse events from hypothyroid symptoms than the thyroid hormone withdrawal approach (NCCN, 2026).

Recombinant Human Thyroid Stimulating Hormone as Adjunct to Facilitate Radioiodine Therapy for Nontoxic Multinodular Goiter

In a Cochrane systematic review, Huo et al. (2021) reviewed randomized controlled clinical trials evaluating recombinant human thyrotropin–aided radioiodine treatment compared with radioiodine alone for non‑toxic multinodular goitre. The review included six randomized controlled trials with a total of 321 participants, of whom 197 received rhTSH‑aided radioiodine and 124 received radioiodine alone, with follow‑up durations ranging from 12 to 36 months. Participants were adults with non‑toxic multinodular goitre with women represented the majority of participants across studies. The review assessed health‑related quality of life, hypothyroidism, adverse events, thyroid volume reduction, all‑cause mortality, and costs. RhTSH‑aided radioiodine increased the incidence of hypothyroidism compared with radioiodine alone, with hypothyroidism reported in 64 of 197 participants (32.5%) versus 15 of 124 participants (12.1%), corresponding to a risk ratio of 2.53 (95% CI, 1.52 to 4.20; 6 studies; 321 participants). Adverse events occurred in 118 of 197 participants (59.9%) in the rhTSH‑aided group and 60 of 124 participants (48.4%) in the radioiodine‑only group, with a random‑effects risk ratio of 1.24 (95% CI, 0.94 to 1.63; 6 studies; 321 participants). Thyroid volume reduction was greater with rhTSH‑aided radioiodine, with a mean difference of 11.9% (95% CI, 4.4% to 19.4%; 6 studies; 268 participants); moderate-certainty evidence. The authors concluded that rhTSH‑aided radioiodine treatment probably increased the risk of hypothyroidism while probably resulting in a greater reduction in thyroid volume compared with radioiodine alone.

Recombinant Human Thyroid Stimulating Hormone for the Treatment of Benign Thyroid Nodules

Bountouris et al. (2023) stated that the nature of thyroid nodules is heterogenous.  Most of them are benign and, in the absence of pressure symptoms of adjunct structures, no treatment is needed.  These investigators examined the acute effects of a low dose of rhTSH on the volume of benign thyroid nodules.  They studied 27 nodules (14 isoechoic and 13 hypoechoic) in 15 (11 women and 4 men; mean age of 51.0 ± 15.9 years) consecutive patients with 1 to 3 well-separated asymptomatic benign thyroid nodules.  All subjects were euthyroid, with negative thyroid antibodies, and none received levothyroxine.  The total thyroid volume and thyroid nodule volume were sonographically determined by 2 independent examiners before, 48 hours and 6 months post intra-muscular (IM) administration of 0.3-mg rhTSH, and the mean values of the 2 examiners' measurements were used; thyroid function tests were obtained at the same time-points.  The mean volume of isoechoic nodules increased by 57.3%, of hypoechoic nodules by 46.6% and of the surrounding thyroid parenchyma by 70.4% 48 hours post-rhTSH; mean volumes had returned to baseline levels 6 months later.  A large variance in the volume change responses was observed.  The relative change in nodule volume (defined as the% change in nodule volume divided by the% change in the surrounding parenchyma) from baseline to 48 hours was significantly higher in isoechoic versus hypoechoic nodules (p < 0.05).  The authors concluded that a single-dose of 0.3-mg rhTSH transiently increased the volume of benign thyroid nodules.  The increase was more pronounced in isoechoic nodules and had a great variability.  These researchers stated that these findings could be useful in the management of benign thyroid nodules, by helping in understanding which nodules would be more responsive to TSH suppression therapy.

Effect of Recombinant Human Thyroid Stimulating Hormone on Long-Term Salivary Gland Dysfunction in Thyroid Cancer Patients Treated with Radioactive Iodine

Sunavala-Dossabhoy and Petti (2023) noted that adjuvant radioactive iodine (RAI) is administered to thyroid cancer patients following thyroidectomy for remnant tissue ablation and metastatic disease management.  Patients are prepared with THW or rhTSH.  Long-term salivary gland dysfunction (LT-SGD) is a common, dosage-dependent, RAI adverse effect.  Although rhTSH preparation appeared to reduce LT-SGD, this effect could be due to lower RAI activity generally used in rhTSH-prepared patients.  In a meta-analysis, these investigators examined the effect of preparation type on LT-SGD development.  They carried out a literature search (PubMed, Medline, EmBase, Cochrane, Web of Science, LILACS, Google Scholar) 4 times (January to November 2022) and studies reporting LT-SGD incidence 1 year or more after RAI in patients prepared with rhTSH/THW were identified.  The LT-SGD RR was estimated with various models considered for sensitivity analysis (fixed-effect, random-effects, study-quality adjusted, publication-bias adjusted, individual-patient-data meta-analysis adjusted for RAI).  Subgroup analysis according to RAI activity (less than 3.7/3.7 or higher GBq) also was performed.  Literature search resulted in 5 studies (321 rhTSH, 632 THW patients).  The pooled RRs according to various models were 0.65 (95% CI: 0.49 to 0.86; fixed-effect); 0.62 (95% CI: 0.38 to 1.02; random-effects); 0.72 (95% CI: 0.54 to 0.96; quality adjusted); 0.76 (95% CI: 0.58 to 0.99; publication-bias adjusted); 0.0.80 (95% CI: 0.55 to 1.14; individual-patient-data meta-analysis).  The pooled RRs stratified for RAI activity were 0.26 (95% CI: 0.05 to 1.30) for less than 3.7 GBq; 0.75 (95% CI: 0.57 to 0.98) for 3.7or higher GBq.  The number of patients needed to be prepared with rhTSH to prevent 1 case of LT-SGD ranged between 7 and 37.  The authors concluded that there is moderate-quality scientific evidence that rhTSH preparation may consistently protect salivary gland function.

Comparison of Recombinant Human Thyroid-Stimulating Hormone and Thyroid Hormone Withdrawal for 131-I Therapy in Patients with Intermediate- to High-Risk Thyroid Cancer

In a systematic review and meta-analysis, Park et al. (2024) examined the effectiveness and advantages associated with the use of rhTSH for RAI therapy in patients with intermediate- to high-risk differentiated thyroid cancer.  These investigators searched Medline, Embase, and Cochrane data-bases to identify relevant studies examining clinical outcomes of rhTSH compared with THW in patients with intermediate- to high-risk differentiated thyroid cancer published between January 2012 and June 2023.  Meta-analyses were carried out to evaluate the success rate of RRA in patients with intermediate- to high-risk and determine the disease control rate (DCR) among patients with distant metastases, evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.  A total of 13 studies involving 1,858 patients were included in the meta-analysis.  Pooled analyses showed significantly higher overall RRA success rate in the rhTSH group compared with the THW group, with a RR of 1.12 (95% CI: 1.01 to 1.25).  However, in the subgroup analysis of high-risk patients, pooled analyses revealed no significant differences in RRA success rate between the rhTSH group compared with the THW group with a pooled RR of 1.05 (95% CI: 0.88 to 1.24).  In patients with distant metastases, there were no significant differences in the DCR between groups, with a pooled RR of 1.06 (95% CI: 0.78 to 1.44).  The authors concluded that rhTSH for RAI therapy was a practical option for RAI therapy in patients with intermediate- to high-risk thyroid cancer, including those with distant metastases.

Medium- and Long-Term Recurrence after Radioiodine Therapy for Differentiated Thyroid Carcinoma with Recombinant Human Thyrotropin

Yao et al. (2024) noted that RAI is often used in the treatment of DTCs; however, its long-term effectiveness and the risk of tumor recurrence remain unclear.  In particular, the comparison between rhTSH and THW in terms of medium- and long-term recurrence rate in DTC patients has not been fully elucidated.  These investigators conducted a systematic search to identify studies comparing medium- and long-term outcomes (longer than 2 years) based on treatment with either rhTSH or THW.  A total of 10 studies, consisting of 6 RCTs and 4 retrospective studies with a total of 2,833 patients, were included in the analysis.  There was no significant difference in the medium- and long-term recurrence rates between the rhTSH group and the THW group.  This was also the case in subgroup analyses of only RCTs or only retrospective studies.  The structural incomplete response (SIR) rate was slightly higher in the rhTSH group; however, a subgroup analysis of RCTs alone revealed no significant difference in SIR between the 2 groups.  The authors concluded that rhTSH was comparable to THW in achieving successful ablation of residual disease and maintaining low recurrence rates.  Moreover, these researchers stated that further RCTs are needed to examine if rhTSH would increase the risk of SIR.

References

The above policy is based on the following references:

  1. Bahena-García A, Saldívar C, Siller P, et al. Recombinant human TSH in pediatric thyroid cancer. Rev Med Inst Mex Seguro Soc. 2011;49(6):665-667.
  2. Bartenstein P, Calabuig EC, Maini CL, et al. High-risk patients with differentiated thyroid cancer T4 primary tumors achieve remnant ablation equally well using rhTSH or thyroid hormone withdrawal. Thyroid. 2014;24(3):480-487.
  3. Basaria M, Graf H, Cooper DS. The use of recombinant thyrotropin in the follow-up of patients with differentiated thyroid cancer.  Am J Med.  2002;112(9):721-725.
  4. Bauer DC.  Review: Sensitive thyrotropin testing in unselected inpatients has low diagnostic accuracy.  Evidence Based Med.  2000;5(1):29. 
  5. Bombardieri E, Seregni E, Villano C, et al. Recombinant human thyrotropin (rhTSH) in the follow-up and treatment of patients with thyroid cancer. Tumori. 2003;89(5):533-536.
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  7. Bountouris P, Markantes GK, Mamali I, et al. Benign thyroid nodules respond to a single administration of 0.3mg recombinant human thyrotropin with highly variable volume increase. Front Endocrinol (Lausanne). 2023;13:1066379.
  8. British Thyroid Association, Royal College of Physicians.  Guidelines for the management of thyroid cancer in adults.  London, UK: Royal College of Physicians; March 2002.
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