The DOI matches its Crossref record.
Malignant and Benign Neoplasms of the Thyroid in Patients Treated for Hyperthyroidism: A Report of the Cooperative Thyrotoxicosis Therapy Follow-up Study
Abstract
Data concerning the occurrence of malignant and benign thyroid neoplasms in patients treated for hyperthyroidism have been collected at 26 medical centers in the Cooperative Thyrotoxicosis Therapy Follow-up Study. There was 98.8% follow-up in 36,050 patients treated for hyperthyroidism between 1946 and 1968. The analysis is based on 34,684 patients treated by 131I, thyroidectomy, antithyroid drugs, X-irradiation or various combinations of these therapeutic measures. Cases were classified as: Graves' disease without palpable nodules, Graves' disease with palpable nodules, toxic adenoma(s) or unclassified types. The interval of time for the occurrence of a neoplasm (identified by removal) was classified as occurring either at the time of or within 1 year of initial therapy or at sometime greater than 1 yr following therapy. There were 86 malignant thyroid neoplasms found among 34,684 patients. Of those few malignant neoplasms found in Graves' disease, many were of the occult variety, the clinical potential of which is unknown. There were 9 malignant thyroid neoplasms found within 1 yr of treatment in 21,714 patients treated by 131I, 50 in 11,732 patients treated by thyroidectomy, and none in 1,238 patients treated with antithyroid drugs. After an interval of more than 1 yr there were 19 malignant thyroid neoplasms following 131I, 4 following thyroidectomy, and 4 following antithyroid therapy in these respective populations. If the occurrence of 19 malignant lesions found 1 yr or more after 131I is viewed from the standpoint of the incidental malignant lesions found in patients treated primarily by thyroidectomy, the risk from 131I is not significant. There were five anaplastic carcinomas found more than 1 yr following 131I therapy and one fibrosarcoma following thyroidectomy plus 131I therapy. The anaplastic neoplasms occurred within 5 yr of therapy and in patients with an average age of 69.4 yr. No anaplastic lesions were found within 1 yr of any treatment. There were four deaths from malignant thyroid neoplasms among 11,732 patients treated by thyroidectomy, six deaths from malignant neoplasms in 21,704 patients treated with 131I, and no deaths from malignant lesions in 1,238 patients treated more than 1 yr with antithyroid drugs. The occurrence of thyroid adenomas is higher when 131I therapy is used for treatment in the first two decades of life than when used in older individuals.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The goal of RAI therapy for GD is to induce hypothyroidism, rather than euthyroidism, because lower administered activities of RAI result in residual, partially irradiated thyroid tissue that is at increased risk for thyroid neoplasm development (351).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [351]
Citations
Cited by
Sorted by citations
Items 301–392 of 392
Alaoui, N. I., & Raïs, N. B. (2011) · Médecine Nucléaire · doi:10.1016/j.mednuc.2011.06.011 · Cited by 1
Viljanen, E. E., Virtanen, L., Kalfeřt, D., et al. (2025) · Acta Cytologica · doi:10.1159/000548613 · Cited by 1
Momo, H. D., Haymart, M. R., Shi, X., & Mondul, A. M. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag058 · Cited by 2
Autoimmunthyreopathien bei Kindern und Jugendlichen
Dörr, H. G., & Dötsch, J. (2008) · Monatsschrift Kinderheilkunde · doi:10.1007/s00112-008-1739-2 · Cited by 1
Thyroid Disruptors: How They Act and How We React
Elena, N. M., Silva, A. C. D. N., Bueno, R., Marcello, M. A., Leite, L. L., Cristina, E., & Sterian, L. A. (2011) · InTech eBooks · doi:10.5772/20904 · Cited by 1
Are there any Perspectives for Radioiodine Treatment in Patients with Hyperthyroidism in Russia?
Garbusov, P., & Narkevich, B. Y. (2009) · Clinical and experimental thyroidology · doi:10.14341/ket2009513-7 · Cited by 1
Gundgurthi, A., Dutta, M. K., Garg, M. K., & Pandit, A. (2012) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2012-0008 · Cited by 1
Doherty, P. (1992) · BMJ · doi:10.1136/bmj.305.6862.1159-c · Cited by 1
Simultaneous onset of idiopathic dilated cardiomyopathy in identical middle-aged twins
Sutton, A. G. C., Somasundram, U., & Hall, J. A. (1999) · Postgraduate Medical Journal · doi:10.1136/pgmj.75.881.157 · Cited by 1
Khan, A. A., & Walter, O. (2010) · Molecular pathology library · doi:10.1007/978-1-4419-1707-2_5 · Cited by 1
Bhargav, P. R. K. (2014) · World Journal of Endocrine Surgery · doi:10.5005/jp-journals-10002-1140 · Cited by 1
“Unilobar hyperplasia (ULH) (11) (8)* 7 9 3 5”
InfluentialCarcinogenesis of Specific Sites
Mettler, F. A., & Upton, A. C. (2008) · Elsevier eBooks · doi:10.1016/b978-0-7216-0200-4.10005-8 · Cited by 1
The Use of 131Iodine in the Treatment of Graves’ Disease in Children
Rivkees, S. A., & Dinauer, C. (2009) · Elsevier eBooks · doi:10.1016/b978-0-12-374135-6.00098-4 · Cited by 1
Hyperthyroidism and Thyroiditis
Patel, K. N. (2015) · Springer eBooks · doi:10.1007/978-3-319-13662-2_5 · Cited by 1
Marinò, M., Chiovato, L., & Pinchera, A. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4160-5583-9.00080-0 · Cited by 1
Thyroid Hormone Excess: Graves’ Disease
AGRAWAL, N. K., Prakash, V., & Sharm, M. (2012) · InTech eBooks · doi:10.5772/47864 · Cited by 1
Autonomous Functioning Thyroid Nodule in a 4-year-old Male Child Treated with Radioiodine (I-131)
Khare, A., Bhutani, P., & Chauhan, S. (2013) · World Journal of Nuclear Medicine · doi:10.4103/1450-1147.136695 · Cited by 1
Radioiodine Therapy of Hyperthyroidism
Pepe, G., & Cusato, G. (2018) · Springer eBooks · doi:10.1007/978-3-319-63067-0_3 · Cited by 2
Radiation-Induced Thyroid Disease
Yamashita, S., Pacini, F., & Elisei, R. (2022) · doi:10.1093/med/9780198870197.003.0050 · Cited by 1
Carceller, D. B., Segundo, P. L., Beltrán, P. N., París, A. S., Hernández, P. D. C., Villanueva, M. M., & Olivares, D. A. (2011) · Revista Española de Medicina Nuclear · doi:10.1016/s1578-200x(11)70021-3 · Cited by 1
Management of Graves’ Disease in Children
Rivkees, S. A. (2000) · Endocrine updates · doi:10.1007/978-1-4615-4407-4_13 · Cited by 1
Schneider, A. B., & Ron, E. (1997) · doi:10.1007/978-1-4757-2594-0_13 · Cited by 1
Does radioiodine therapy for hyperthyroidism increase long-term morbidity?
Burman, K. D. (2008) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0780 · Cited by 1
“Patients with hyperthyroidism should be counseled that radioiodine is generally safe and effective”
BackgroundRadioiodine Therapy for Hyperthyroidism and Risk of Malignancy
Sheppard, M. C. (1990) · Elsevier eBooks · doi:10.1016/b978-0-08-037496-3.50016-3 · Cited by 1
A Review of Risks of Internal Irradiation of the Thyroid Gland – in Utero, Neonatally, Adults
Walinder, G. (1990) · Elsevier eBooks · doi:10.1016/b978-0-08-037496-3.50015-1 · Cited by 1
Volpe, R. J. (1990) · Elsevier eBooks · doi:10.1016/b978-0-7216-2190-6.50017-0 · Cited by 1
Weigel, R. J. (2001) · Springer eBooks · doi:10.1007/978-3-642-57282-1_39 · Cited by 1
Schneider, A. B., & Ron, E. (2003) · Humana Press eBooks · doi:10.1007/978-1-59259-352-1_12 · Cited by 1
Management of the Various Causes of Thyrotoxicosis
Ross, D. S. (2003) · Humana Press eBooks · doi:10.1007/978-1-59259-352-1_9 · Cited by 1
Dietlein, M., & Schmidt, M. C. (2012) · Medical radiology · doi:10.1007/174_2012_673 · Cited by 2
Head and Neck Cancer: A General Overview
Laramore, G. E. (1989) · Medical radiology · doi:10.1007/978-3-642-83501-8_1
Rivkees, S. A. (2015) · Springer eBooks · doi:10.1007/978-1-4939-2534-6_11
131-J-Therapie (a−c) Present Status of Radioiodine Treatment of Hyperthyroidism
Becker, D. V. (1978) · Handbuch der medizinischen Radiologie · doi:10.1007/978-3-642-81170-8_6
Self-citationThyroid Surgery in Paediatric Patients
Rivkees, S. A., Breuer, C. K., & Udelsman, R. (2012) · Wiley eBooks · doi:10.1002/9781118444832.ch4
Surgical Management of Benign Thyroid Disease
Lesnik, D. J., O’Leary, M. A., Noordzij, J. P., & Randolph, G. W. (2010) · doi:10.1002/9781444307641.ch8
Kopp, P. (2000) · Elsevier eBooks · doi:10.1016/b978-012288145-9/50061-9
Thyroid scanning of the patient with history of childhood irradiation.
Nolan, N. G., Koppikar, M. M., & Kotlyarov, E. V. (1981) · PubMed
Radioiodine for hyperthyroidism.
Wheeler, M. H. (1992) · BMJ · doi:10.1136/bmj.305.6862.1160
Radioactivity in the Service of Man
Yalow, R. S. (1981) · BioScience · doi:10.2307/1308174
Carcinoma papilar tiroideo asociado a linfoma. A propósito de tres casos
Bajo, Á. V., Álvarez‐Escolá, C., Vaquero, P. M., et al. (2006) · Endocrinología y Nutrición · doi:10.1016/s1575-0922(06)71149-4
Importância do iodo radiativo no tratamento da doença de graves
Graf, H. (1999) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27301999000200002
Radioiodine for hyperthyroidism: Authors' reply
Franklyn, J. A., & Sheppard, M. C. (1992) · BMJ · doi:10.1136/bmj.305.6862.1160-a
Graves' Hyperthyroidism with Incidental Ossified Nodular Lesion
Lee, M., Wang, C., & Chang, T. (2006) · Journal of Medical Ultrasound · doi:10.1016/s0929-6441(09)60065-5
“The risk of malignant nodular lesions was reported to be 10–15% in patients with Graves’ disease [5,6], i F g.”
BackgroundRadioiodine for hyperthyroidism.
OʼHalloran, D. J., & Shalet, S. M. (1992) · BMJ · doi:10.1136/bmj.305.6862.1160-b
Respuesta al tratamiento de la Enfermedad de Graves-Basedow en pacientes pediátricos
Calagua-Quispe, M. R., Almache, O. N., Boggio, J. F., Villar, C. D. Á., de Lama, R. L., Rojas-Gabulli, M. I., Chávez, E. M., Robles, O. A. E., & Ibárcena, P. M. P. (2014) · Anales de la Facultad de Medicina · doi:10.15381/anales.v75i2.8385
Epidemiologic Studies on the Health Effects of Ionizing Radiation
Goldman, M. (1998) · Springer eBooks · doi:10.1007/978-94-011-5208-2_43
“In 1961 the United States Public Health Service began the Cooperative Thyrotoxicosis Therapy Follow-up Study to investigate the occurrence of benign and malignant neoplasms in 36,050 hyperthyroid patients treated between 1946 and 1964 [16].”
BackgroundLong-term Prognosis of Patients Treated With Radioactive Iodine for Hyperthyroidism
Metso, S. (2007) · Tampere University Institutional Repository (Tampere University)
Malignant Disease after Iodine-131 Therapy
Holm, L., Hall, P. N., & Lundell, G. E. F. (1991) · Springer eBooks · doi:10.1007/978-1-4615-3850-9_31
[A 49-year-old man with irritability, palpitations, hand tremor, weight loss and thyroid nodule].
Salcedo-Gómez, A., González‐Virla, B., López-Tarabay, C., et al. (2007) · PubMed
Management of hyper & hypo thyroid conditions
Locke, W. (1982) · Postgraduate Medicine · doi:10.1080/00325481.1982.11716017
Sporadic Medullary Thyroid Carcinoma in Grave's disease -Report of a case-
Arima, H., Nakajo, A., Kijima, Y., et al. (2015)
ТИРЕОИДЭКТОМИЯ КАК ПАТОГЕННЫЙ ФАКТОР В РАЗВИТИИ РАКА ЩИТОВИДНОЙ ЖЕЛЕЗЫ
Timofeeva, L. A. (2011) · CyberLeninK (CyberLeninka)
Radioactive Iodide Therapy for Graves’ Disease
DeGroot, L. J. (2002) · CRC Press eBooks · doi:10.3109/9780203908983-19
Fantz, C. R., & Gronowski, A. M. (2002) · CRC Press eBooks · doi:10.3109/9780203908983-17
ICloppenborg, P. W. C., Hermus, A. R., & Corstens, F. H. M. (1996)
Hipertiroidizm ile tiroid kanseri birlikteliği Coexistence of hyperthyroidism and thyroid cancer
Ay, E., Kuzu, H., Girgin, S., et al. (2014)
Role of PET/CT in Pediatric Malignancy
Barfett, J. J., Vali, R., & Shammas, A. (2016) · Springer eBooks · doi:10.1007/978-3-319-40070-9_21
The Role of Medical Management for Nodular Hyperthyroidism
Ycaza, A. E. E. D., & Stan, M. N. (2017) · Springer eBooks · doi:10.1007/978-3-319-43618-0_8
Radioiodine Therapy of Benign Thyroid Diseases
Campennì, A., Deandreis, D., Finessi, M., Ruggeri, R. M., & Baldari, S. (2019) · Springer eBooks · doi:10.1007/978-3-030-17494-1_2
Reoperation for Benign Thyroid Disease
Sywak, M. S., Prichard, R. S., & Delbridge, L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-66127-0.00009-0
(2006) · Elsevier eBooks · doi:10.1016/b0-44-451005-2/00975-x
PEERENBOOM, H., KECK, E., Kley, H. K., et al. (1981) · Verhandlungen der Deutschen Gesellschaft für Innere Medizin · doi:10.1007/978-3-642-47092-9_11
Weigel, R. J. (2008) · Springer eBooks · doi:10.1007/978-0-387-68113-9_57
Rudolph, H. (1982) · Springer eBooks · doi:10.1007/978-3-642-88238-8_15
McDougall, I. R. (1978) · World Journal of Surgery · doi:10.1007/bf01561495
tsch, J. D., Rascher, W., & rr, H. G. D. (2003) · Pediatric Drugs · doi:10.2165/00148581-200305020-00003
Rastad, J. (1994) · World Journal of Surgery · doi:10.1007/bf00353755
IODINE AND DRUGS THAT AFFECT THYROID FUNCTION
(2009) · Elsevier eBooks · doi:10.1016/b978-0-444-53271-8.50007-7
(2015) · Elsevier eBooks · doi:10.1016/b978-0-444-53717-1.01386-x
Chassin, J. L. (1984) · Springer eBooks · doi:10.1007/978-1-4757-4172-8_50
Chassin, J. L. (1994) · Springer eBooks · doi:10.1007/978-1-4757-4169-8_96
Bouillon, R. (1977) · Side effects of drugs annual · doi:10.1016/s0378-6080(77)80042-1
Moreno, M. A., Perrier, N. D., & Clark, O. H. (2011) · doi:10.1093/med/9780199235292.003.3198
Köbberling, J., Pickardt, C. R., Becker, W. S., et al. (1990) · Springer eBooks · doi:10.1007/978-3-642-88313-2_9
von Bruchhausen, F., Ebel, S., Hackenthal, E., et al. (1999) · Springer eBooks · doi:10.1007/978-3-642-58388-9_3
Radionuclide Therapy in Benign Thyroid Diseases: Graves’ Disease
Araz, M., & Özkan, E. (2022) · Springer eBooks · doi:10.1007/978-3-030-97220-2_5
A historical look at Cleveland: Its health care institutions and contributions to endocrine surgery
McHenry, C. R. (2022) · Surgery · doi:10.1016/j.surg.2022.09.032
Outcome and Evaluation of the Patient Thyroidectomy with Hyperthyroidism: A Case-Control Study
Rashid, M. H. U., Haque, M. M., Islam, M. S., Rahim, H. M. A., Tasrif, S. M., & Bhuiya, M. M. M. (2023) · Medicine Today · doi:10.3329/medtoday.v35i1.64939
Overall Conclusions and Recommendations
(1990) · Elsevier eBooks · doi:10.1016/b978-0-08-037496-3.50023-0
Second Primary Malignancy after Radioiodine Treatment of Thyroid Disease: Current Status
Lee, J., Hong, C. M., & Ha, J. (2023) · International Journal of Thyroidology · doi:10.11106/ijt.2023.16.1.101
Villanova, M., di Filippo, L., Bolamperti, F. M., Rodella, C. A., Castellino, L., & Giubbini, R. (2024) · Clinical and Translational Imaging · doi:10.1007/s40336-024-00643-2
“However, the possible risk of increased thyroid and non-thyroidal cancer incidence and mortality after the use of RAI for hyperthyroidism has been evaluated in multiple studies [2–10] reporting conflicting results, mainly due to their retrospective nature and heterogeneous population evaluated.”
Nuclear Medicine in the Diagnosis and Management of Thyroid Nodules and Cancer
Nguyen, N. C., Chekuri, S., & Öz, O. K. (2024) · Springer eBooks · doi:10.1007/978-3-031-65288-2_6
Kloos, R. T., & Mazzaferri, E. L. (2002) · Humana Press eBooks · doi:10.1007/978-1-59259-277-7_6
(2000) · Time to knit · doi:10.1016/s1155-1941(15)50472-1
Radioiodine Treatment for Hyperthyroid Graves’ Disease
Jiang, Y., & Ma, C. (2025) · IntechOpen eBooks · doi:10.5772/intechopen.1007146
Does Radioactive Iodine Therapy for Graves' Disease Increase the Risk of Thyroid Cancer?
Srethbhakd, A., Gild, M. L., & Tsang, V. (2025) · Clinical Thyroidology · doi:10.1089/ct.2025;37.222-225
Genetic Aspects of Endocrine Neoplasia
Schimke, R. N. (1982) · Cancer treatment and research · doi:10.1007/978-94-009-7615-3_5
Ambekar, A. N., Sonwane, A. C., Kandula, S. G. N. S. V., et al. (2026) · Thyroid Research and Practice · doi:10.4103/trp.trp_18_25
Sakashita, T., Onuma, K., Sugasawa, A., et al. (2026) · Frontiers in Veterinary Science · doi:10.3389/fvets.2026.1897774
Metadata
- Authors
- DOBYNS, B. M., SHELINE, G. E., WORKMAN, J. B., TOMPKINS, E. A., McCONAHEY, W. M., & BECKER, D. V.
- Affiliations
- MetroHealth (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1974-06
- Volume
- 38
- Issue
- 6
- Pages
- 976-998
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2047788194
- Cited by
- 391
- References
- 0
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 10 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 12 · 2014: 7 · 2013: 10 · 2012: 5
- FWCI
- 10.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- thyroid cancer, hyperthyroidism, Graves' disease, radioiodine therapy, iodine-131, thyroidectomy, antithyroid drugs, anaplastic carcinoma, fibrosarcoma, thyroid nodules, occult thyroid cancer, radiation-induced cancer, long-term follow-up, thyroid cancer mortality
- MeSH terms
- Adenoma, Follow-Up Studies, Graves Disease, Humans, Hyperthyroidism, Iodine Radioisotopes, Antithyroid Agents, Thyroid Neoplasms, Thyroidectomy, Time Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
