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Hyperthyroidism in Children Treated with Long Term Medical Therapy: Twenty-Five Percent Remission Every Two Years*
Abstract
We use an antithyroid drug for the treatment of hyperthyroidism due to Graves' disease in children and adolescents for as long as the patients are willing to comply and/or tolerate the drug. In more than 60 patients treated since 1961, the remission rate was 25% in the first 2 yr. This report looks at these same patients again, followed for an additional 5 yr. Survival analysis methods applied to the follow-up data on 63 children confirm our original statistical findings and suggest a continuing remission rate of 25% every 2.1 +/- 0.4 (+/- SE) yr regardless of the duration of previous therapy. The median time to remission was 4.3 +/- 1.5 yr, and 75% of patients are predicted to be in remission in 10.9 +/- 2.3 yr. Of 36 patients who went into remission, defined by their being euthyroid for 1 yr after cessation of therapy, 1 relapsed, and 2 developed spontaneous hypothyroidism; the remainder are euthyroid 1-11.7 yr after therapy was discontinued. Of 14 who switched from medical therapy, 2 of 7 treated surgically and 4 of 7 treated with 131I are hypothyroid. Only 1 patient had a significant adverse reaction to both methimazole and propylthiouracil. While medical therapy may have some direct effect on the autoimmune response in hyperthyroidism, its role in affecting the time to ultimate remission is unknown. These data, however, describe the course of children so treated and allow us to present therapeutic options initially or during treatment based on statistically derived probabilities of outcome.
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“Although two decades ago it was suggested that 25% of children with GD go into remission with every 2 years of continued treatment (341), other studies of larger cohorts of pediatric patients with GD treated with ATDs for extended periods have not revealed similar remission rates (333,339,342).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [341]
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Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938
“Although two decades ago it was suggested that 25% of children with GD go into remission with every 2 years of continued treatment (341), other studies of larger cohorts of pediatric patients with GD treated with ATDs for extended periods have not revealed similar remission rates (333,339,342).”
BackgroundBahn, R. S., Burch, H. B., Cooper, D. S., Garber, J. R., Greenlee, M. C., Klein, I., Laurberg, P., McDougall, I. R., Montori, V. M., Rivkees, S. A., et al. (2011) · Endocrine Practice · doi:10.4158/ep.17.3.456 · Cited by 1,098
“Although two decades ago it was suggested that 25% of children with GD go into remission with every 2 years of continued treatment (220), other studies of larger cohorts of pediatric patients with GD treated with ATDs for extended periods have not revealed similar remission rates (213,216,221).”
BackgroundThe American Thyroid Association and American Association of Clinical Endocrinologists Taskforce on Hyperthyroidism and Other Causes of Thyrotoxicosis, Bahn, R. S., Burch, H. B., Cooper, D. S., Garber, J. R., Greenlee, M. C., Klein, I., Laurberg, P., McDougall, I. R., Montori, V. M., et al. (2011) · Thyroid · doi:10.1089/thy.2010.0417 · Cited by 898
“Although two decades ago it was suggested that 25% of children with GD go into remission with every 2 years of continued treatment (220), other studies of larger cohorts of pediatric patients with GD treated with ATDs for extended periods have not revealed similar remission rates (213,216,221).”
BackgroundLaurberg, P., Wallin, G., Tallstedt, L., Abraham-Nordling, M., Lundell, G., & Tørring, O. (2008) · European Journal of Endocrinology · doi:10.1530/eje-07-0450 · Cited by 428
The Management of Hyperthyroidism
Wood, A. J. J., & Franklyn, J. A. (1994) · New England Journal of Medicine · doi:10.1056/nejm199406163302407 · Cited by 302
The Management of Graves' Disease in Children, with Special Emphasis on Radioiodine Treatment
Rivkees, S. A., Sklar, C. A., & Freemark, M. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.11.5239 · Cited by 207
Dissimilar Hepatotoxicity Profiles of Propylthiouracil and Methimazole in Children
Rivkees, S. A., & Szarfman, A. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2546 · Cited by 177
Kaguelidou, F., Alberti, C., Castanet, M., Guitteny, M.-A., Czernichow, P., & Léger, J. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0842 · Cited by 173
“Pubertal (Tanner 2–4) 58 (38) Postpubertal (Tanner 5) 31 (20) Personal history of autoimmunity and susceptibility factors 22 (14) 154”
BackgroundResultThyrotoxicosis in Prepubertal Children Compared with Pubertal and Postpubertal Patients
Lazar, L., Kalter-Leibovici, O., Pertzelan, A., Weintrob, N., Josefsberg, Z., & Phillip, M. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.10.6922 · Cited by 162
“(7), which reported a remission rate of 25% every 2 yr in children and adolescents, regardless of age.”
BackgroundResultCooper, D. (2003) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2003-030185 · Cited by 142
Léger, J., Gelwane, G., Kaguelidou, F., Benmerad, M., Alberti, C., & the French Childhood Graves' Disease Study Group (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1944 · Cited by 144
“09 Remission 15 (68) 53 (40) Definitive treatment 3 (14) 42 (32) Still on ATD treatment 2 (9) 12 (9) Lost to follow-up 2 (9) 25 (19)”
BackgroundResultInfluentialRemission of Graves’ disease during anti-thyroid drug therapy. Time to reconsider the mechanism?
Laurberg, P. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02295 · Cited by 139
SHULMAN, D. I., MUHAR, I., JORGENSEN, E. V., DIAMOND, F. B., BERCU, B. B., & ROOT, A. W. (1997) · Thyroid · doi:10.1089/thy.1997.7.755 · Cited by 134
“Overall, the remission rate after medical therapy of our PUB group (30% treated a mean of 2.8 years achieved at least a 1-year remission) is comparable to the experience of Lippe et al. (8) who reported a remission rate (euthyroid 1 year off therapy) of 25% for every 2 years of therapy.”
InfluentialGlaser, N. S., Styne, D. M., & for the Organization of Pediatric Endocrinologists of Northern California Collaborative Graves’ Disease Study Group (2008) · Pediatrics · doi:10.1542/peds.2007-1535 · Cited by 125
Antithyroid drugs and Graves' disease — prospective randomized assessment of long‐term treatment
Maugendre, D., Gatel, A., Campion, L., Massart, C., Guilhem, I., LORCY, Y., Lescouarc’h, J., Herry, J. Y., & Allannic, H. (1999) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1999.00629.x · Cited by 116
“In a retrospective analysis, Lippe et al. (1987) demontrated that remission rate in 63 children and adolescents treated with ATD (treatment duration range: 0·4– 12·4 years) increased by an additional 25% every two years.”
BackgroundLong-Term Antithyroid Drug Treatment: A Systematic Review and Meta-Analysis
Azizi, F., & Malboosbaf, R. (2017) · Thyroid · doi:10.1089/thy.2016.0652 · Cited by 114
Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use
Rivkees, S. A., & Mattison, D. R. (2009) · International Journal of Pediatric Endocrinology · doi:10.1155/2009/132041 · Cited by 135
“, 1987 [59] 63 1 1.”
Ohye, H., Minagawa, A., Noh, J. Y., Mukasa, K., Kunii, Y., Watanabe, N., Matsumoto, M., Suzuki, M., Yoshihara, A., Ito, K., et al. (2014) · Thyroid® · doi:10.1089/thy.2012.0612 · Cited by 106
“On the other hand, some studies have shown that remission rates increase over multiple years of treatment with ATD in children (2,4,17), and it remains uncertain whether the approach to the treatment of GD in adults described above is suitable in pediatric populations (26).”
Predictors of Early Remission of Hyperthyroidism in Children1
Glaser, N. S., & Styne, D. M. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.6.3986 · Cited by 115
ANTITHYROID DRUGS FOR THE TREATMENT OF HYPERTHYROIDISM CAUSED BY GRAVES' DISEASE
Cooper, D. S. (1998) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70308-x · Cited by 101
Zimmerman, D., & Lteif, A. N. (1998) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70302-9 · Cited by 121
Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use
Rivkees, S., & Mattison, D. (2009) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2009-132041 · Cited by 90
Hyperthyroidism in Childhood: Causes, when and how to treat
Léger, J., & Carel, J. (2012) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.854 · Cited by 83
“Previous studies had their limitations but evaluated age, goiter size, decrease in body mass index and severity of biochemical hyperthyroidism at onset, TRAb levels at onset and at the end of treatment, and duration of medical treatment as predictive markers of GD relapse during childhood (23,27,33,34,35,36,37).”
BackgroundLaurberg, P., Berman, D. C., Andersen, S., & Pedersen, I. B. (2011) · Thyroid · doi:10.1089/thy.2011.0039 · Cited by 87
Controversies in the management of Graves’ disease in children
Rivkees, S. A. (2016) · Journal of Endocrinological Investigation · doi:10.1007/s40618-016-0477-x · Cited by 77
“Of the 63 patients followed on ATDs, 36 (57 %) remitted after an average of 4 years of therapy [16].”
BackgroundInfluentialThyroid disorders in children from birth to adolescence
Bettendorf, M. (2002) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-002-0905-3 · Cited by 77
“propylthiouracil) is associated with side-effects such as rash, granulocytopenia, arthritis and hepatitis, and a disappointing long-term remission rate as low as 30%‐40% even after prolonged therapy [43, 47, 48 ].”
BackgroundGoldstein, S. M., Katowitz, W. R., Moshang, T., & Katowitz, J. A. (2008) · Thyroid · doi:10.1089/thy.2008.0014 · Cited by 75
“Propylthiouracil and methimazole both have been used in children with Graves’ disease (11).”
Graves’ Disease in Childhood: Advances in Management with Antithyroid Drug Therapy
Kaguelidou, F., Carel, J., & Léger, J. (2009) · Hormone Research in Paediatrics · doi:10.1159/000223414 · Cited by 71
Adverse Events Associated with Methimazole Therapy of Graves' Disease in Children
Rivkees, S. A., Stephenson, K., & Dinauer, C. (2010) · International Journal of Pediatric Endocrinology · doi:10.1155/2010/176970 · Cited by 95
“These studies reveal an incidence of minor adverse events between 1% [13] and 15% [12].”
BackgroundGarcía-Mayor, R. V., Páramo, C., Cano, R. L., Méndez, L. F. P., Galofré, J. C., & Andrade, A. (1992) · Journal of Endocrinological Investigation · doi:10.1007/bf03348811 · Cited by 69
Approach to the Pediatric Patient with Graves' Disease: When Is Definitive Therapy Warranted?
Bauer, A. J. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0898 · Cited by 66
“With the watchful-waiting approach, 15–30% of the time a subgroup of pediatric patients will enter remission; however, this may take between 2 and 10 yr to achieve, and 35– 60% of patients may experience a relapse after medications are discontinued (9, 20, 35, 38).”
BackgroundLéger, J., Petit, I., Rodrigue, D., Lambert, A.-S., & Coutant, R. (2018) · Annales d Endocrinologie · doi:10.1016/j.ando.2018.08.001 · Cited by 70
Léger, J., Kaguelidou, F., Alberti, C., & Carel, J. (2013) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2013.08.008 · Cited by 65
Adverse Events Associated with Methimazole Therapy of Graves' Disease in Children
Rivkees, S., Stephenson, K., & Dinauer, C. (2010) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2010-176970 · Cited by 63
Okamura, K., Sato, K., Fujikawa, M., Bandai, S., Ikenoue, H., & Kitazono, T. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-4466 · Cited by 64
Safety of long-term antithyroid drug treatment? A systematic review
Azizi, F., & Malboosbaf, R. (2019) · Journal of Endocrinological Investigation · doi:10.1007/s40618-019-01054-1 · Cited by 64
Pediatric Graves' Disease: Outcome and Treatment
Gruñeiro-Papendicck, L., Chiesa, A. E., Finkielstain, G. P., & Heinrich, J. J. (2003) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2003.16.9.1249 · Cited by 62
“Lippe et al.(5) extended the follow up to 12 years, confirming previous studies, while Lazar et cil.”
ResultGraves Disease in Children: Thyroid-Stimulating Hormone Receptor Antibodies as Remission Markers
Gastaldi, R., Poggi, E., Mussa, A., Weber, G., Vigone, M. C., Salerno, M., Delvecchio, M., Peroni, E., Pistorio, A., & Corrias, A. (2014) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2013.12.047 · Cited by 59
“As regards to childhood and adolescence, previous studies suggest that remission occurs only in 20%-30% of those treated with ATD,(6,8-10,12-14) and less than 25% of patients obtain remission within 2 years of ATD therapy.(2,11,15) The likelihood of remission and its determinants with longterm ATD has been estimated b…”
ResultRelapse following antithyroid drug therapy for Graves’ hyperthyroidism
Laurberg, P., Krejbjerg, A., & Andersen, S. L. (2014) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0000000000000088 · Cited by 60
“This is especially so in subgroups with a high risk, such as children [9,10] and patients with Graves’ orbitopathy [44,45].”
BackgroundLéger, J., & Carel, J. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-0938 · Cited by 57
Juvenile thyrotoxicosis; can we do better?
Birrell, G. (2004) · Archives of Disease in Childhood · doi:10.1136/adc.2003.035980 · Cited by 56
Diagnosis and management of hyperthyroidism from prenatal life to adolescence
Léger, J., & Carel, J. (2018) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2018.03.014 · Cited by 57
Guidelines for the treatment of childhood-onset Graves’ disease in Japan, 2016
Minamitani, K., Sato, H., Ohye, H., Harada, S., & Arisaka, O. (2017) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.26.29 · Cited by 54
“However, previous reports indicate that a longer duration of minimum dose treatment is associated with a higher remission rate (10, 71, 100, 101).”
BackgroundThe long-term follow-up of patients with thionamide-treated Graves’ hyperthyroidism
Bandai, S., Okamura, K., Fujikawa, M., Sato, K., Ikenoue, H., & Kitazono, T. (2019) · Endocrine Journal · doi:10.1507/endocrj.ej18-0418 · Cited by 51
“Very few studies have evaluated the long-term progno‐ sis of GD in a large number of patients mainly treated by ATD for more than eight years [13, 15, 20-22].”
BackgroundInfluentialThe safety and efficacy of antithyroid drugs
Azizi, F. (2005) · Expert Opinion on Drug Safety · doi:10.1517/14740338.5.1.107 · Cited by 52
“Longer courses of therapy in children are accompanied by more likelihood of remission [58].”
BackgroundThe Treatment of Graves' Disease in Children
Rivkees, S. A. (2006) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2006.19.9.1095 · Cited by 48
Kraiem, Z., & Newfield, R. (2001) · Journal of Pediatric Endocrinology & Metabolism (JPEM) · doi:10.1515/jpem.2001.14.3.229 · Cited by 51
Hyperthyroidism in Children and Adolescents
Zimmerman, D., & Gan-Gaisano, M. (1990) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(16)37011-0 · Cited by 47
Diagnosis and Management of Juvenile Hyperthyroidism in Germany: A Retrospective Multicenter Study
Dötsch, J., Siebler, T., Hauffa, B. P., Doeker, B. M., Andler, W., Bettendorf, M., Heinrich, U., Gohlke, B. C., Albers, N., Willgerodt, H., et al. (2000) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2000.13.7.879 · Cited by 46
Age‐Related Therapeutic Response to Antithyroid Drug in Patients with Hyperthyroid Graves' Disease
Yamada, T., Aizawa, T., Koizumi, Y., et al. (1994) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1994.tb04973.x · Cited by 47
Pediatric Graves’ disease: management in the post-propylthiouracil Era
Rivkees, S. A. (2014) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2014-10 · Cited by 46
“workers estimated that 25% of children go into remission for every two years of treatment [44].”
BackgroundMethimazole-induced remission rates in pediatric Graves’ disease: a systematic review
van Lieshout, J. M., Mooij, C. F., van Trotsenburg, A. S. P., & Zwaveling‐Soonawala, N. (2021) · European Journal of Endocrinology · doi:10.1530/eje-21-0077 · Cited by 46
Tamai, H., Hayaki, I., Kawai, K., Komaki, G., Matsubayashi, S., Kuma, K., Kumagai, L. F., & Nagataki, S. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.5.7744989 · Cited by 52
Graves' disease in children and adolescents: Response to long‐term treatment
Barrio, R., López-Capapé, M., Martínez-Badás, I., Carrillo, Á., Moreno, J. C., & Alonso, M. (2005) · Acta Paediatrica · doi:10.1080/08035250500252872 · Cited by 42
Long-term Methimazole Therapy in Juvenile Graves’ Disease: A Randomized Trial
Azizi, F., Takyar, M., Madreseh, E., & Amouzegar, A. (2019) · PEDIATRICS · doi:10.1542/peds.2018-3034 · Cited by 44
“Family history, young age, large goiter, severity of biochemical hyperthyroidism, serum TRAb concentration at onset, and the end of treatment have all been considered as predictive factors for relapse of Graves’ disease in children and adolescents.(7,16,27,30,31) Because of the small number of relapses after LT methim…”
BackgroundThyrotoxicosis in children: thirty years' experience
Raza, J., Hindmarsh, P. C., & Brook, C. (1999) · Acta Paediatrica · doi:10.1080/08035259950168405 · Cited by 41
Mashio, Y., Beniko, M., Matsuda, A., et al. (1997) · Endocrine Journal · doi:10.1507/endocrj.44.553 · Cited by 40
Review of the outcome of management of Graves’ disease in children and adolescents
Bergman, P., Auldist, A., & Cameron, F. (2001) · Journal of Paediatrics and Child Health · doi:10.1046/j.1440-1754.2001.00641.x · Cited by 39
Lavard, L., Sehested, A., Jacobsen, B. B., et al. (1999) · Hormone Research in Paediatrics · doi:10.1159/000023312 · Cited by 39
Radioiodine Treatment of Graves’ Disease in Young People
Cheetham, T. D., WRAIGHT, P. R., Hughes, I. A., & Barnes, N. D. (1998) · Hormone Research in Paediatrics · doi:10.1159/000023183 · Cited by 38
“of antithyroid drug treatment affects the incidence of relapse. In children and adolescents a remission rate of 25p after a 2-year course of medical treatment has been reported from the USA [”
ResultPredictors of Early Remission of Hyperthyroidism in Children 384
Glaser, N. S., & Styne, D. M. (1997) · Pediatric Research · doi:10.1203/00006450-199704001-00404 · Cited by 37
The treatment of Graves' disease in children and adolescents
Lee, H. S., & Hwang, J. S. (2014) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2014.19.3.122 · Cited by 36
Mussa, G. C., Corrias, A., SILVESTRO, L., Battan, E., Mostert, M., Mussa, F., & Pellegrino, D. (1999) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.1999.12.4.537 · Cited by 35
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“[8,9] However, these data are still subject to argument.”
BackgroundAzizi, F. (2020) · Thyroid · doi:10.1089/thy.2019.0814 · Cited by 33
“In the last 2 decades, few studies have re-ported high remission rate with long-term ATD treatment (15,16,27,28); one meta-analysis showed that long-term ATD could induce higher remission rates, compared with conventional therapy (39).”
Surgical Treatment of Graves’ Disease in Patients Younger than 18 Years
Søreide, J. A., van Heerden, J. A., Lo, C., Grant, C. S., Zimmerman, D., & Ilstrup, D. M. (1996) · World Journal of Surgery · doi:10.1007/s002689900121 · Cited by 29
Treatment of Graves’ Disease in Children and Adolescents
Grüters, A. (1998) · Hormone Research in Paediatrics · doi:10.1159/000023182 · Cited by 32
“Graves’ disease (GD) is a rare disease in childhood and adolescence with only 1–5p of all patients being children. The incidence of juvenile GD ranges from 0.1 in young children to 3.0 in 100,000 in adolescents. Despite the numerous literature about therapy of GD in adults only a few investigations concerning children…”
BackgroundInfluentialLiu, X., Qiang, W., Liu, X., Liu, L., Liu, S., Gao, A., Gao, S., & Shi, B. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0704 · Cited by 30
Orunesu, E., Bagnasco, M., Salmaso, C., Altrinetti, V., Bernasconi, D., Monte, P. D., Pesce, G., Marugo, M., & Mela, G. S. (2004) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2004.01318.x · Cited by 30
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Kourime, M., McGowan, S., Altowati, M. A., Ahmed, S. F., Stewart, G. A., Williamson, S., Hunter, I., & Donaldson, M. (2017) · Archives of Disease in Childhood · doi:10.1136/archdischild-2017-313454 · Cited by 27
Treatment of Graves' disease: The American way
Levy, E. G. (1997) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(97)80798-7 · Cited by 27
Okawa, E. R., Grant, F. D., & Smith, J. R. (2015) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000000241 · Cited by 25
Management of thyrotoxicosis in children and adolescents: 35 years’ experience in 304 patients
Azizi, F., & Amouzegar, A. (2018) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2017-0394 · Cited by 25
The Surgical Treatment of Graves’ Disease in Children and Adolescents
Chiapponi, C., Stocker, U., Mussack, T., Gallwas, J. K. S., Hallfeldt, K., & Ladurner, R. (2011) · World Journal of Surgery · doi:10.1007/s00268-011-1238-9 · Cited by 24
Radioiodine treatment for pediatric hyperthyroid Grave’s disease
Ma, C., Jiawei, X., Wang, G., Jianbin, L., Liu, W., Driedger, A., Zuo, S., & Zhang, Q. (2009) · European Journal of Pediatrics · doi:10.1007/s00431-009-0992-2 · Cited by 22
Graves’ Disease in Children: An Update
Metwalley, K. A., & Farghaly, H. S. (2023) · Clinical Medicine Insights Endocrinology and Diabetes · doi:10.1177/11795514221150615 · Cited by 29
LAFRANCHI, S. H. (1993) · Current Problems in Pediatrics · doi:10.1016/0045-9380(93)90018-8 · Cited by 22
Long-Term Treatment with Antithyroid Drugs: Efficacy and Safety
Malboosbaf, R., & Azizi, F. (2020) · Intern J Endocrinol Metab · doi:10.5812/ijem.101487 · Cited by 24
“It has been suggested that long-term ATD therapy is effective and safe both in adults (54, 62, 63) and in children and adolescents (42, 63-68).”
BackgroundCury, A. N., Meira, V. T., Monte, O., Marone, M. M. S., Scalissi, N. M., Kochi, C., Calliari, L. E., & Longui, C. A. (2012) · Endocrine Connections · doi:10.1530/ec-12-0049 · Cited by 21
Lavard, L., Perrild, H., Jacobsen, B. B., et al. (2000) · Autoimmunity · doi:10.3109/08916930008994089 · Cited by 20
Treatment of juvenile Graves' disease and its ophthalmic complication: the 'European way'
Krassas, G. E. (2004) · European Journal of Endocrinology · doi:10.1530/eje.0.1500407 · Cited by 19
“Vaidya et al. (18) 17 5 0 1 3 8 Barnes et al. (17) 16 14 6 8 1 NR Shiroozu et al. (97) 5 5 0 1.5 1.5 0 Buckingham et al. (94) 7 32 14 7.5 9 6 Hamburger (73) 9 17 6 8 3 5 Lippe et al. ( 95 ) 2 NR 2 NR NR NR Gorton et al. (96) 13 11 4 7 2 11”
InfluentialLong-term outcomes of graves disease in children treated with anti-thyroid drugs
Chiang, Y.-T., Ting, W., Huang, C., Huang, S.-K., Chan, C.-I., Cheng, B.-W., Lin, C., Wu, Y., Hung, C.-M., Li, H., et al. (2020) · Pediatrics & Neonatology · doi:10.1016/j.pedneo.2019.12.009 · Cited by 18
Behavioral assessment of children and adolescents with Graves’ disease: A prospective study
Hamed, S. A., Attiah, F. A., Abdulhamid, S. K., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0248937 · Cited by 18
“7 mg/kg/day which was subsequently titrated to maintain normal thyroid hormone levels based on the results of serum thyroid hormone testing during follow-ups [11].”
MethodAn update on the pharmacological management of hyperthyroidism due to Graves’ disease
Bartalena, L., Tanda, M. L., Bogazzi, F., Piantanida, E., Lai, A., & Martino, E. (2005) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.6.6.851 · Cited by 17
“One study showed that > 75% of children and adolescents treated with thionamides for > 11 years remained in remission [42].”
BackgroundManagement of Thyrotoxicosis in Children and Adolescents: A Turkish Multi-center Experience
Esen, İ., Bayramoğlu, E., Yıldız, M., Aydın, M., Özturan, E. K., Aycan, Z., Bolu, S., Önal, H., Kör, Y., Ökdemir, D., et al. (2019) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.galenos.2018.2018.0210 · Cited by 17
“These studies have reported that ethnicity, age, pubertal status, BMI (SDS), goiter volume, initial severity (higher fT4 concentration and TRAb levels) and presence of other autoimmune conditions are prognostic factors (14,15,16,31).”
BackgroundBayramoğlu, E., Elmaoğulları, S., Sağsak, E., & Aycan, Z. (2019) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2018-0495 · Cited by 17
Abdi, H., Amouzegar, A., & Azizi, F. (2019) · PubMed Central · doi:10.22037/ijpr.2020.112892.14005 · Cited by 33
Clinical Course of Pediatric and Adolescent Graves' Disease Treated with Radioactive Iodine
Pinto, T. E., Cummings, E. A., Barnes, D., & Salisbury, S. R. (2007) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2007.20.9.973 · Cited by 16
Maladie de basedow chez l'enfant: aspects cliniques et évolutifs
Boiko, J., Léger, J., Raux-Demay, M. C., Cabrol, S., Bouc, Y. L., & Czernichow, P. (1998) · Archives de Pédiatrie · doi:10.1016/s0929-693x(98)80052-3 · Cited by 17
Okamura, K., Bandai, S., Fujikawa, M., Sato, K., Ikenoue, H., & Kitazono, T. (2020) · Intern J Endocrinol Metab · doi:10.5812/ijem.101139 · Cited by 16
“Namely, the patients are advised to continue ATD treatment until GD is no longer present, regardless of the time taken to achieve this end (13, 17, 26-29); however, the issue with this approach is that it is difficult to tell when patients have achieved remission.”
BackgroundAntithyroid drug therapy of Graves’ hyperthyroidism: realistic goals and focus on evidence
Laurberg, P., Andersen, S., & Karmisholt, J. (2006) · Expert Review of Endocrinology & Metabolism · doi:10.1586/17446651.1.1.91 · Cited by 17
Anti-thyroid drugs in pediatric Graves′ disease
John, M., Sundrarajan, R., & Gomadam, S. (2015) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.152766 · Cited by 17
“Lippe et al. [14] MMI and PTU 1.6% Arthritic reaction ( n =1) Lazar et al. 2000 [22] PTU and MMI 35% Major in 5% patients and minor in 30% patients.”
InfluentialThyrotoxicosis in children: treatment and outcome.
Jaruratanasirikul, S., Leethanaporn, K., & Sriplung, H. (2006) · PubMed · Cited by 14
Propylthiouracil-Induced Hepatic Failure and Encephalopathy in a Child
Kirkland, J. L. (1990) · DICP · doi:10.1177/106002809002400505 · Cited by 14
Treatment of hyperthyroidism in young people
Cheetham, T. D., Hughes, I. A., Barnes, N. D., & Wraight, E. P. (1998) · Archives of Disease in Childhood · doi:10.1136/adc.78.3.207 · Cited by 13
“The remission rate of children in the USA is reported to be 25% after each of repeated two year courses of medical treatment,”
BackgroundWang, S.-Y., Wang, C., Tien, K., Chang, C., & Liu, T. (2019) · The Kaohsiung Journal of Medical Sciences · doi:10.1002/kjm2.12167 · Cited by 12
McCormack, S. E., Mitchell, D. M., Woo, M., Levitsky, L. L., Ross, D. S., & Misra, M. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03565.x · Cited by 13
Santos, T. J. D., Martos‐Moreno, G. Á., Muñoz-Calvo, M. T., Pozo, J., Rodríguez‐Artalejo, F., & Argente, J. (2018) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2018-0132 · Cited by 11
Thyrotoxicosis in children: thirty years’experience
Raza, J., Hindmarsh, P., & Brook, C. (1999) · Acta Paediatrica · doi:10.1111/j.1651-2227.1999.tb00185.x · Cited by 11
“The presenting signs and symptoms were in keeping with those reported in the literature (4, 9, 17).”
BackgroundResult
Metadata
- Authors
- LIPPE, B. M., LANDAW, E. M., & KAPLAN, S. A.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1987-06
- Volume
- 64
- Issue
- 6
- Pages
- 1241-1245
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1992904825
- Cited by
- 192
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 15 · 2018: 9 · 2017: 5 · 2016: 3 · 2015: 7 · 2014: 12 · 2013: 3 · 2012: 7
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01am025744-06)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Ophthalmology › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- pediatric hyperthyroidism, Graves' disease, antithyroid drug therapy, long-term medical therapy, remission rate, time to remission, hypothyroidism, relapse, methimazole, propylthiouracil, adverse drug reactions, survival analysis, treatment outcome prediction
- MeSH terms
- Child, Female, Graves Disease, Humans, Hyperthyroidism, Male, Methimazole, Propylthiouracil, Statistics as Topic, Time Factors
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