Abstract
Since the introduction of radioiodine (RAI) for treatment of well-differentiated thyroid cancer (DTC) more than 50 years ago, prolonged periods of hypothyroidism were routinely used as part of the treatment regimen. Recombinant human TSH (rhTSH) was introduced in the 1990s as a tool to elevate the serum TSH without the need for thyroid hormone withdrawal and symptomatic hypothyroidism. After being initially approved as a diagnostic tool for use in RAI scanning and stimulated thyroglobulin testing, rhTSH was approved as an adjunct to RAI remnant ablation in patients without distant metastases in Europe in 2005 and in the US in 2007. Following successful use of rhTSH for diagnostic purposes, it has been extensively studied for use with therapeutic doses of RAI in the setting of RAI remnant ablation and is now an integral part of DCT therapy. The use of rhTSH in clinical practice in the last decade was coupled with the growing interest in an individualized, risk-stratified approach to the management of patients with DCT. While traditional treatment for DTC included surgery and RAI therapy for all patients, many more recent studies demonstrated the value of selective use of RAI only in patients who will probably benefit from treatment. This manuscript reviews the evolving role of rhTSH in the current risk adapted climate of thyroid cancer management with particular emphasis on the use of rhTSH as an aid to RAI therapy.
Similar content being viewed by others
References
Schroeder PR, Haugen BR, Pacini F, Reiners C, Schlumberger M, Sherman SI, Cooper DS, Schuff KG, Braverman LE, Skarulis MC, Davies TF, Mazzaferri EL, Daniels GH, Ross DS, Luster M, Samuels MH, Weintraub BD, Ridgway EC, Ladenson PW (2006) 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. J Clin Endocrinol Metab 91:878–884
Lee J, Yun MJ, Nam KH, Chung WY, Soh EY, Park CS (2010) Quality of life and effectiveness comparisons of thyroxine withdrawal, triiodothyronine withdrawal, and recombinant thyroid-stimulating hormone administration for low-dose radioiodine remnant ablation of differentiated thyroid carcinoma. Thyroid: Off J Am Thyroid Assoc 20:173–179
Mazzaferri EL (2007) Management of low-risk differentiated thyroid cancer. Endocr Pract: Off J Am Coll Endocrinol Am Assoc Clin Endocrinol 13:498–512
Tuttle RM, Rondeau G, Lee NY (2011) A risk-adapted approach to the use of radioactive iodine and external beam radiation in the treatment of well-differentiated thyroid cancer. Cancer Control: J Moffitt Cancer Cent 18:89–95
Hanscheid H, Lassmann M, Luster M, Thomas SR, Pacini F, Ceccarelli C, Ladenson PW, Wahl RL, Schlumberger M, Ricard M, Driedger A, Kloos RT, Sherman SI, Haugen BR, Carriere V, Corone C, Reiners C (2006) Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer: procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal. J Nucl Med: Off Publ, Soc Nucl Med 47:648–654
de Keizer B, Hoekstra A, Konijnenberg MW, de Vos F, Lambert B, van Rijk PP, Lips CJ, de Klerk JM (2004) Bone marrow dosimetry and safety of high 131I activities given after recombinant human thyroid-stimulating hormone to treat metastatic differentiated thyroid cancer. J Nucl Med: Off Publ, Soc Nucl Med 45:1549–1554
Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid: Off J Am Thyroid Assoc 19:1167–1214
Durante C, Filetti S (2011) Management of papillary thyroid cancer patients in absence of postoperative radioiodine remnant ablation: Tailoring Follow-up by neck sonography. The J Clin Endocrinol Metab
Torlontano M, Attard M, Crocetti U, Tumino S, Bruno R, Costante G, D’Azzo G, Meringolo D, Ferretti E, Sacco R, Arturi F, Filetti S (2004) Follow-up of low risk patients with papillary thyroid cancer: role of neck ultrasonography in detecting lymph node metastases. J Clin Endocrinol Metab 89:3402–3407
Hay ID, Thompson GB, Grant CS, Bergstralh EJ, Dvorak CE, Gorman CA, Maurer MS, McIver B, Mullan BP, Oberg AL, Powell CC, van Heerden JA, Goellner JR (2002) Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940–1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. World J Surg 26:879–885
Sawka AM, Brierley JD, Tsang RW, Thabane L, Rotstein L, Gafni A, Straus S, Goldstein DP (2008) An updated systematic review and commentary examining the effectiveness of radioactive iodine remnant ablation in well-differentiated thyroid cancer. Endocrinol Metab Clin N Am 37:457–480, x
Jonklaas J, Sarlis NJ, Litofsky D, Ain KB, Bigos ST, Brierley JD, Cooper DS, Haugen BR, Ladenson PW, Magner J, Robbins J, Ross DS, Skarulis M, Maxon HR, Sherman SI (2006) Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid: Off J Am Thyroid Assoc 16:1229–1242
Vaisman F, Shaha A, Fish S, Tuttle R. (2011) Initial therapy with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation is associated with very low rates of structural disease recurrence in properly selected patients with differentiated thyroid cancer. Clin Endocrinol
Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, Brokhin M, Omry G, Fagin JA, Shaha A (2010) Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid: Off J Am Thyroid Assoc 20:1341–1349
Pilli T, Brianzoni E, Capoccetti F, Castagna MG, Fattori S, Poggiu A, Rossi G, Ferretti F, Guarino E, Burroni L, Vattimo A, Cipri C, Pacini F (2007) A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer. J Clin Endocrinol Metab 92:3542–3546
(2011) 81st annual meeting of the American Thyroid Association meeting ABSTRACTS & AGENDA. Thyroid : Off J Am Thyroid Assoc 21:1–111
Chianelli M, Todino V, Graziano FM, Panunzi C, Pace D, Guglielmi R, Signore A, Papini E (2009) Low-activity (2.0 GBq; 54 mCi) radioiodine post-surgical remnant ablation in thyroid cancer: comparison between hormone withdrawal and use of rhTSH in low-risk patients. Eur J Endocrinol/Eur Federation Endocr Soc 160:431–436
Taieb D, Sebag F, Cherenko M, Baumstarck-Barrau K, Fortanier C, Farman-Ara B, De Micco C, Vaillant J, Thomas S, Conte-Devolx B, Loundou A, Auquier P, Henry JF, Mundler O (2009) Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation (RRA) with recombinant human TSH (rhTSH): a randomized controlled study. Clin Endocrinol 71:115–123
Pacini F, Ladenson PW, Schlumberger M, Driedger A, Luster M, Kloos RT, Sherman S, Haugen B, Corone C, Molinaro E, Elisei R, Ceccarelli C, Pinchera A, Wahl RL, Leboulleux S, Ricard M, Yoo J, Busaidy NL, Delpassand E, Hanscheid H, Felbinger R, Lassmann M, Reiners C (2006) Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study. J Clin Endocrinol Metab 91:926–932
Ma C, Xie J, Liu W, Wang G, Zuo S, Wang X, Wu F (2010) Recombinant human thyrotropin (rhTSH) aided radioiodine treatment for residual or metastatic differentiated thyroid cancer. Cochrane database of systematic reviews (Online):CD008302
Tuttle RM, Brokhin M, Omry G, Martorella AJ, Larson SM, Grewal RK, Fleisher M, Robbins RJ (2008) Recombinant human TSH-assisted radioactive iodine remnant ablation achieves short-term clinical recurrence rates similar to those of traditional thyroid hormone withdrawal. J Nucl Med: Off Publ, Soc Nucl Med 49:764–770
Barbaro D, Boni G, Meucci G, Simi U, Lapi P, Orsini P, Pasquini C, Piazza F, Caciagli M, Mariani G (2003) Radioiodine treatment with 30 mCi after recombinant human thyrotropin stimulation in thyroid cancer: effectiveness for postsurgical remnants ablation and possible role of iodine content in L-thyroxine in the outcome of ablation. J Clin Endocrinol Metab 88:4110–4115
Barbaro D, Boni G, Meucci G, Simi U, Lapi P, Orsini P, Pasquini C, Turco A, Mariani G (2006) Recombinant human thyroid-stimulating hormone is effective for radioiodine ablation of post-surgical thyroid remnants. Nucl Med Commun 27:627–632
Pacini F, Molinaro E, Castagna MG, Lippi F, Ceccarelli C, Agate L, Elisei R, Pinchera A (2002) Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal. J Clin Endocrinol Metab 87:4063–4068
Robbins RJ, Larson SM, Sinha N, Shaha A, Divgi C, Pentlow KS, Ghossein R, Tuttle RM (2002) A retrospective review of the effectiveness of recombinant human TSH as a preparation for radioiodine thyroid remnant ablation. J Nucl Med: Off Publ, Soc Nucl Med 43:1482–1488
Tuttle RM, Lopez N, Leboeuf R, Minkowitz SM, Grewal R, Brokhin M, Omry G, Larson S (2010) Radioactive iodine administered for thyroid remnant ablation following recombinant human thyroid stimulating hormone preparation also has an important adjuvant therapy function. Thyroid: Off J Am Thyroid Assoc 20:257–263
Maxon HR 3rd, Smith HS (1990) Radioiodine-131 in the diagnosis and treatment of metastatic well differentiated thyroid cancer. Endocrinol Metab Clin N Am 19:685–718
Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, Ricard M, Lumbroso JD, De Vathaire F, Schlumberger M (2006) Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab 91:2892–2899
Maxon HR 3rd, Englaro EE, Thomas SR, Hertzberg VS, Hinnefeld JD, Chen LS, Smith H, Cummings D, Aden MD (1992) Radioiodine-131 therapy for well-differentiated thyroid cancer–a quantitative radiation dosimetric approach: outcome and validation in 85 patients. J Nucl Med: Off Publ, Soc Nucl Med 33:1132–1136
Wang W, Larson SM, Tuttle RM, Kalaigian H, Kolbert K, Sonenberg M, Robbins RJ (2001) Resistance of [18f]-fluorodeoxyglucose-avid metastatic thyroid cancer lesions to treatment with high-dose radioactive iodine. Thyroid: Off J Am Thyroid Assoc 11:1169–1175
Rudavsky AZ, Freeman LM (1997) Treatment of scan-negative, thyroglobulin-positive metastatic thyroid cancer using radioiodine 131I and recombinant human thyroid stimulating hormone. J Clin Endocrinol Metab 82:11–14
Luster M, Lippi F, Jarzab B, Perros P, Lassmann M, Reiners C, Pacini F (2005) rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review. Endocr-relat Cancer 12:49–64
Robbins RJ, Driedger A, Magner J (2006) Recombinant human thyrotropin-assisted radioiodine therapy for patients with metastatic thyroid cancer who could not elevate endogenous thyrotropin or be withdrawn from thyroxine. Thyroid: Off J Am Thyroid Assoc 16:1121–1130
Driedger AA, Kotowycz N (2004) Two cases of thyroid carcinoma that were not stimulated by recombinant human thyrotropin. J Clin Endocrinol Metab 89:585–590
Taieb D, Jacob T, Zotian E, Mundler O (2004) Lack of efficacy of recombinant human thyrotropin versus thyroid hormone withdrawal for radioiodine therapy imaging in a patient with differentiated thyroid carcinoma lung metastases. Thyroid: Off J Am Thyroid Assoc 14:465–467
Potzi C, Moameni A, Karanikas G, Preitfellner J, Becherer A, Pirich C, Dudczak R (2006) Comparison of iodine uptake in tumour and nontumour tissue under thyroid hormone deprivation and with recombinant human thyrotropin in thyroid cancer patients. Clin Endocrinol 65:519–523
Freudenberg LS, Jentzen W, Petrich T, Fromke C, Marlowe RJ, Heusner T, Brandau W, Knapp WH, Bockisch A (2010) Lesion dose in differentiated thyroid carcinoma metastases after rhTSH or thyroid hormone withdrawal: 124I PET/CT dosimetric comparisons. Eur J Nucl Med Mol Imaging 37:2267–2276
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Robenshtok, E., Tuttle, R.M. Role of Recombinant Human Thyrotropin (rhTSH) in the Treatment of Well-Differentiated Thyroid Cancer. Indian J Surg Oncol 3, 182–189 (2012). https://doi.org/10.1007/s13193-011-0115-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13193-011-0115-1