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Endocrinology182 papers

Graves' disease

Last edited: 4/13/2026

Overview

Graves' disease is an autoimmune disorder characterized by the overproduction of thyroid hormones due to stimulatory autoantibodies targeting the TSH receptor, leading to hyperthyroidism and often associated extrathyroidal manifestations such as Graves' ophthalmopathy 1.

Diagnosis

  • Clinical Presentation: Symptoms include hyperthyroidism (palpitations, tremors, weight loss), goiter, and signs of Graves' ophthalmopathy (exophthalmos, eyelid retraction) 35.
  • Laboratory Tests: Elevated free T4 and suppressed TSH levels, with presence of thyroid-stimulating autoantibodies (TRAbs) 1.
  • Grading: Use of TRAb levels to assess disease activity and predict prognosis 1.

    • Management

  • First-Line Treatments:
    • - Antithyroid Medications: Carbimazole or methimazole to inhibit thyroid hormone synthesis 216. - Beta-Blockers: For symptomatic relief of palpitations and anxiety 16.
  • Adjunctive Treatments:
    • - Radioactive Iodine (131I): Definitive treatment option, particularly for refractory cases 816. - Thyroidectomy: Total or near-total thyroidectomy, especially for those preferring definitive treatment 89.
  • Graves' Ophthalmopathy:
    • - Corticosteroids: Intravenous or oral for severe cases 545. - Orbital Decompression Surgery: For patients with compressive symptoms 53044.

    Special Populations

  • Pediatrics: Antithyroid drugs are commonly used, with surgery reserved for refractory cases 21233.
  • Pregnancy: Management focuses on maintaining euthyroidism with levothyroxine, avoiding radioactive iodine and surgery during pregnancy 19.
  • Comorbidities: Consider specific management adjustments, such as managing hyperkalaemia in patients with renal impairment 37.

    • Key Recommendations

  • Use TRAbs for Monitoring Disease Activity and Prognosis: Regular measurement of TRAbs aids in assessing disease severity and predicting outcomes (Evidence: Moderate 1).
  • Antithyroid Medications as Initial Therapy: Carbimazole or methimazole are effective first-line treatments for hyperthyroidism (Evidence: Strong 216).
  • Consider Radioactive Iodine for Definitive Treatment: Particularly useful in cases refractory to medical management (Evidence: Moderate 816).
  • Total Thyroidectomy for Definitive Control: Recommended for patients preferring definitive treatment options (Evidence: Moderate 89).
  • Corticosteroids for Severe Ophthalmopathy: Intravenous or oral corticosteroids are indicated for managing severe Graves' ophthalmopathy (Evidence: Moderate 545).

    • References

    1 Kalra S, Selim S, Shrestha D, Somasundaram N, Raza SA, Baruah MP et al.. Best practices in the laboratory diagnosis, prognostication, prediction, and monitoring of Graves' disease: role of TRAbs. BMC endocrine disorders 2024. link 2 Jawwad M, Ahmed SA, Zaidi SMM, Fatmi SAA, Ashraf MH, Naeem S et al.. Long-term outcome of treatments for Graves disease in the children and adolescent population. Endocrine 2023. link 3 Maejima T, Mizumoto J, Ito Y, Suga T. 51-year-old woman • History of Graves disease • General fatigue, palpitations, and hand tremors • Dx?. The Journal of family practice 2023. link 4 Khamisi S, Lundqvist M, Rasmusson AJ, Engström BE, Karlsson FA, Ljunggren Ö. Vitamin D and bone metabolism in Graves' disease: a prospective study. Journal of endocrinological investigation 2023. link 5 Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C et al.. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. European journal of endocrinology 2021. link 6 Mitka K, Sokołowski G, Pach D, Hubalewska-Dydejczyk A. Graves' disease and exophthalmos - a mask for meningioma. Endokrynologia Polska 2021. link 7 Cho YY, Chung YJ. Vitamin D supplementation does not prevent the recurrence of Graves' disease. Scientific reports 2020. link 8 Ali A, Debono M, Balasubramanian SP. Outcomes After Urgent Thyroidectomy Following Rapid Control of Thyrotoxicosis in Graves' Disease are Similar to Those After Elective Surgery in Well-Controlled Disease. World journal of surgery 2019. link 9 Feaster A, DeCapua-Guarino A, Wolf M, Dove J, Fluck M, Oxenberg J. Thyroidectomy Remains a Safe Option for Graves' Disease. The American surgeon 2019. link 10 Herskovitz I, Hughes O, MacQuhae F, Kirsner RS. Pretibial Myxedema Masquerading as a Venous Leg Ulcer. Wounds : a compendium of clinical research and practice 2017. link 11 Adesokan A, Vigneswaran T, Ajzensztejn M, Mathur S. Atrioventricular block: an unusual complication of Graves' disease. BMJ case reports 2017. link 12 De Luca F, Alessi L, Bruno E, Cama V, Costanzo D, Genovese C et al.. Graves' disease in childhood: new epidemiological, pathophysiological and therapeutic insights. Minerva pediatrica 2016. link 13 Reich SS, Null RC, Timoney PJ, Sokol JA. Trends in Orbital Decompression Techniques of Surveyed American Society of Ophthalmic Plastic and Reconstructive Surgery Members. Ophthalmic plastic and reconstructive surgery 2016. link 14 Papapetrou PD. The philosopher Socrates had exophthalmos (a term coined by Plato) and probably Graves' disease. Hormones (Athens, Greece) 2015. link 15 Segal RL, Wallenstein S. The occurrence of Graves disease (autoimmune thyrotoxicosis) in endocrinologists at the Mount Sinai Hospital in New York City from 1954 to 2011. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 2015. link 16 Muldoon BT, Mai VQ, Burch HB. Management of Graves' disease: an overview and comparison of clinical practice guidelines with actual practice trends. Endocrinology and metabolism clinics of North America 2014. link 17 Wall JR. Thyroid function. Pathogenesis of Graves ophthalmopathy--a role for TSH-R?. Nature reviews. Endocrinology 2014. link 18 Weetman AP. Graves' disease following immune reconstitution or immunomodulatory treatment: should we manage it any differently?. Clinical endocrinology 2014. link 19 Elston MS, Tu'akoi K, Meyer-Rochow GY, Tamatea JA, Conaglen JV. Pregnancy after definitive treatment for Graves' disease--does treatment choice influence outcome?. The Australian & New Zealand journal of obstetrics & gynaecology 2014. link 20 Papapetrou PD. Maximinus Daia, a Roman emperor who may have had Graves' disease and died of a thyrotoxic crisis. Hormones (Athens, Greece) 2013. link 21 Piantanida E, Tanda ML, Lai A, Sassi L, Bartalena L. Prevalence and natural history of Graves' orbitopathy in the XXI century. Journal of endocrinological investigation 2013. link 22 Nakamura H, Miyauchi A, Miyawaki N, Imagawa J. Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. The Journal of clinical endocrinology and metabolism 2013. link 23 Burch HB, Burman KD, Cooper DS. A 2011 survey of clinical practice patterns in the management of Graves' disease. The Journal of clinical endocrinology and metabolism 2012. link 24 Mir M, Jogi R, Rosen T. Pretibial mucinosis in a patient without Graves disease. Cutis 2011. link 25 Tateno F, Sakakibara R, Kishi M, Ogawa E. Hashimoto's ophthalmopathy. The American journal of the medical sciences 2011. link 26 Neumann S, Eliseeva E, McCoy JG, Napolitano G, Giuliani C, Monaco F et al.. A new small-molecule antagonist inhibits Graves' disease antibody activation of the TSH receptor. The Journal of clinical endocrinology and metabolism 2011. link 27 Benbassat CA, Robenshtok E. Natural history of Graves' Ophthalmopathy. Pediatric endocrinology reviews : PER 2010. link 28 Chen YM, Chen HH, Lan JL, Chen DY, Sheu WH. Nodular mucinosis in Graves disease mimicking gouty tophi. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2010. link 29 Hoffmann R. Thyroidectomy in Graves' disease: subtotal, near total or total?. Orbit (Amsterdam, Netherlands) 2009. link 30 Tang IP, Prepageran N, Shashinder S. Endoscopic orbital decompression for Graves' ophthalmopathy. The Medical journal of Malaysia 2008. link 31 Bradley EA, Gower EW, Bradley DJ, Meyer DR, Cahill KV, Custer PL et al.. Orbital radiation for graves ophthalmopathy: a report by the American Academy of Ophthalmology. Ophthalmology 2008. link 32 Seeherunvong T, Diamantopoulos S, Berkovitz GD. A nine year old girl with thyrotoxicosis, ataxia, and chorea. Brain & development 2007. link 33 Sato H, Harada S, Yokoya S, Tanaka T, Asayama K, Mori M et al.. Treatment for childhood-onset Graves' disease in Japan: results of a nationwide questionnaire survey of pediatric endocrinologists and thyroidologists. Thyroid : official journal of the American Thyroid Association 2007. link 34 Kakati S, Doley B, Pal S, Deka UJ. Elephantiasis Nostras Verrucosa: a rare thyroid dermopathy in Graves' disease. The Journal of the Association of Physicians of India 2005. link 35 Krassas GE, Segni M, Wiersinga WM. Childhood Graves' ophthalmopathy: results of a European questionnaire study. European journal of endocrinology 2005. link 36 Zegers RH, Saeed P, Wiersinga WM. The large eyes of Wolfgang Amadeus Mozart. (On the occasion of the 250th Mozart anniversary year). International ophthalmology 2005. link 37 Ng CW, Chan NN, So WY, Chan WB, Chow CC. Hyperkalaemia in a patient with Graves' disease. International journal of clinical practice 2003. link 38 Terwee CB, Dekker FW, Bonsel GJ, Heisterkamp SH, Prummel MF, Baldeschi L et al.. Facial disfigurement: is it in the eye of the beholder? A study in patients with Graves' ophthalmopathy. Clinical endocrinology 2003. link 39 Adler G, Piotrowska U, Gietka-Czernel M. The reaction of antibodies with the native and deglycosylated thyrotropin receptor obtained from transfected insect cells. Autoimmunity 2003. link 40 Segni M, Bartley GB, Garrity JA, Bergstralh EJ, Gorman CA. Comparability of proptosis measurements by different techniques. American journal of ophthalmology 2002. link01429-0) 41 Escobar-Jiménez F, Férnandez-Soto ML, Luna-López V, Quesada-Charneco M, Glinoer D. Trends in diagnostic and therapeutic criteria in Graves' disease in the last 10 years. Postgraduate medical journal 2000. link 42 Meyer DR. Surgical management of Graves orbitopathy. Current opinion in ophthalmology 1999. link 43 Woolston JL, Caracansi A. Case study: missed diagnosis and mistreatment of unrecognized comorbid Graves disease. Journal of the American Academy of Child and Adolescent Psychiatry 1999. link 44 Sonnet E, Massart C, Gibassier J, Allannic H, Maugendre D. Longitudinal study of soluble intercellular adhesion molecule-1 (ICAM-1) in sera of patients with Graves' disease. Journal of endocrinological investigation 1999. link 45 Matejka G, Vergès B, Vaillant G, Petit JM, Brun-Pacaud A, Rudoni S et al.. Intravenous methylprednisolone pulse therapy in the treatment of Graves' ophthalmopathy. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 1998. link 46 Manso PG, Furlanetto RP, Wolosker AM, Paiva ER, de Abreu MT, Maciel RM. Prospective and controlled study of ophthalmopathy after radioiodine therapy for Graves' hyperthyroidism. Thyroid : official journal of the American Thyroid Association 1998. link 47 Prentice L, Sanders JF, Perez M, Kato R, Sawicka J, Oda Y et al.. Thyrotropin (TSH) receptor autoantibodies do not appear to bind to the TSH receptor produced in an in vitro transcription/translation system. The Journal of clinical endocrinology and metabolism 1997. link 48 Prabhakar BS, Fan JL, Seetharamaiah GS. Thyrotropin-receptor-mediated diseases: a paradigm for receptor autoimmunity. Immunology today 1997. link01089-x) 49 Hofbauer LC, Spitzweg C, Heufelder AE. Graves' disease associated with the primary antiphospholipid syndrome. The Journal of rheumatology 1996. link 50 Davies L. Perceptual problems in thyroid eye disease. Nursing standard (Royal College of Nursing (Great Britain) : 1987) 1995. link 51 Alper MG. Pioneers in the history of orbital decompression for Graves' ophthalmopathy. R.U. Kroenlein (1847-1910), O. Hirsch (1877-1965) and H.C. Naffziger (1884-1961). Documenta ophthalmologica. Advances in ophthalmology 1995. link 52 Colla B, Seynaeve L, Dralands G. Surgical treatment of eyelid retraction by cautery. Bulletin de la Societe belge d'ophtalmologie 1993. link 53 Mithal A, Shah A, Kumar S. The management of Graves' disease by Indian thyroidologists. The National medical journal of India 1993. link 54 Austin MW, Atta HR. Surgical management of Graves' ophthalmopathy. British journal of hospital medicine 1992. link 55 Transue D, Chan J, Kaplan M. Management of neonatal Graves disease with iopanoic acid. The Journal of pediatrics 1992. link81807-4) 56 Sato Y, Sasaki M, Kan R, Osaku A, Koyama S, Shibayama S et al.. Thyroid antigen-mediated glomerulonephritis in Graves' disease. Clinical nephrology 1989. link 57 Lewis NP. Late recurrence of Graves' disease. The British journal of clinical practice 1989. link 58 Bleeker GM. Changes in the orbital tissues and muscles dysthyroid ophthalmopathy. Eye (London, England) 1988. link 59 Troelstra A, Rijneveld WJ, Kooijman AC, Houtman WA. Correlation between NMR scans of extraocular muscles and clinical symptoms in Graves' ophthalmopathy. Documenta ophthalmologica. Advances in ophthalmology 1988. link 60 Wartofsky L, Schaaf M. Graves' disease with thyrotoxicosis following subacute thyroiditis. The American journal of medicine 1987. link90910-7) 61 Rootman J, Patel S, Berry K, Nugent R. Pathological and clinical study of Müller's muscle in Graves' ophthalmopathy. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie 1987. link 62 Bonavolontà G. A simplified technique for recession of the upper eyelid retractors. Ophthalmic plastic and reconstructive surgery 1986. link 63 Thompson CJ, Baylis PH. Asymptomatic Graves' disease during lithium therapy. Postgraduate medical journal 1986. link 64 Knight J, Laing P, Knight A, Adams D, Ling N. Thyroid-stimulating autoantibodies usually contain only lambda-light chains: evidence for the "forbidden clone" theory. The Journal of clinical endocrinology and metabolism 1986. link 65 Kołodziej-Maciejewska H, Reterski Z. Positive effect of bromocriptine treatment in Graves disease orbitopathy. Experimental and clinical endocrinology 1985. link 66 Musch DC, Frueh BR, Landis JR. The reliability of Hertel exophthalmometry. Observer variation between physician and lay readers. Ophthalmology 1985. link33880-0) 67 Miyazono K, Okazaki T, Uchida S, Totsuka Y, Matsumoto T, Ogata E et al.. Propylthiouracil-induced diffuse interstitial pneumonitis. Archives of internal medicine 1984. link 68 Hufnagel TJ, Hickey WF, Cobbs WH, Jakobiec FA, Iwamoto T, Eagle RC. Immunohistochemical and ultrastructural studies on the exenterated orbital tissues of a patient with Graves' disease. Ophthalmology 1984. link34152-5) 69 McBride JH. Receptor measurements. Clinics in laboratory medicine 1984. link 70 McCulloch AJ, Clark F, Steele NR. Graves' disease and Down's syndrome. Journal of medical genetics 1983. link 71 Hurwitz J, Rosenstock T. Management of inadequate transantral orbital decompression with extended lateral orbitotomy. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie 1983. link 72 Noel EP, Sampson L, Pepper BM, Farid NR. Polymorphism of the second component of complement (C2) in Graves' disease. Human heredity 1980. link 73 Knight A, Adams DD. Autoantibodies with intrinsic biological activity. Hormone research 1980. link 74 Young LA. Dysthyroid ophthalmopathy: an update. Journal of the National Medical Association 1979. link 75 Johnson MH. Anterior orbitotomy. Ophthalmic surgery 1979. link 76 Knapp P. Special types of muscle anomalies associated with Graves' disease. Ophthalmology 1979. link35286-1) 77 Docherty PT. Acute endocrine exophthalmos. The British journal of ophthalmology 1976. link 78 Perzik SL. Total throidectomy in the management of Graves' disease. A review of 282 cases. American journal of surgery 1976. link90117-3)

    Original source

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    2. [2]
      Long-term outcome of treatments for Graves disease in the children and adolescent population. — Jawwad M, Ahmed SA, Zaidi SMM, Fatmi SAA, Ashraf MH, Naeem S et al. Endocrine (2023)
    3. [3]
      51-year-old woman • History of Graves disease • General fatigue, palpitations, and hand tremors • Dx? — Maejima T, Mizumoto J, Ito Y, Suga T The Journal of family practice (2023)
    4. [4]
      Vitamin D and bone metabolism in Graves' disease: a prospective study. — Khamisi S, Lundqvist M, Rasmusson AJ, Engström BE, Karlsson FA, Ljunggren Ö Journal of endocrinological investigation (2023)
    5. [5]
      The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. — Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C et al. European journal of endocrinology (2021)
    6. [6]
      Graves' disease and exophthalmos - a mask for meningioma. — Mitka K, Sokołowski G, Pach D, Hubalewska-Dydejczyk A Endokrynologia Polska (2021)
    7. [7]
      Vitamin D supplementation does not prevent the recurrence of Graves' disease. — Cho YY, Chung YJ Scientific reports (2020)
    8. [8]
      Outcomes After Urgent Thyroidectomy Following Rapid Control of Thyrotoxicosis in Graves' Disease are Similar to Those After Elective Surgery in Well-Controlled Disease. — Ali A, Debono M, Balasubramanian SP World journal of surgery (2019)
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      Thyroidectomy Remains a Safe Option for Graves' Disease. — Feaster A, DeCapua-Guarino A, Wolf M, Dove J, Fluck M, Oxenberg J The American surgeon (2019)
    10. [10]
      Pretibial Myxedema Masquerading as a Venous Leg Ulcer. — Herskovitz I, Hughes O, MacQuhae F, Kirsner RS Wounds : a compendium of clinical research and practice (2017)
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      Atrioventricular block: an unusual complication of Graves' disease. — Adesokan A, Vigneswaran T, Ajzensztejn M, Mathur S BMJ case reports (2017)
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      The philosopher Socrates had exophthalmos (a term coined by Plato) and probably Graves' disease. — Papapetrou PD Hormones (Athens, Greece) (2015)
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      The occurrence of Graves disease (autoimmune thyrotoxicosis) in endocrinologists at the Mount Sinai Hospital in New York City from 1954 to 2011. — Segal RL, Wallenstein S Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists (2015)
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      Graves' disease following immune reconstitution or immunomodulatory treatment: should we manage it any differently? — Weetman AP Clinical endocrinology (2014)
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      Pregnancy after definitive treatment for Graves' disease--does treatment choice influence outcome? — Elston MS, Tu'akoi K, Meyer-Rochow GY, Tamatea JA, Conaglen JV The Australian & New Zealand journal of obstetrics & gynaecology (2014)
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      Maximinus Daia, a Roman emperor who may have had Graves' disease and died of a thyrotoxic crisis. — Papapetrou PD Hormones (Athens, Greece) (2013)
    21. [21]
      Prevalence and natural history of Graves' orbitopathy in the XXI century. — Piantanida E, Tanda ML, Lai A, Sassi L, Bartalena L Journal of endocrinological investigation (2013)
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      Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. — Nakamura H, Miyauchi A, Miyawaki N, Imagawa J The Journal of clinical endocrinology and metabolism (2013)
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      A 2011 survey of clinical practice patterns in the management of Graves' disease. — Burch HB, Burman KD, Cooper DS The Journal of clinical endocrinology and metabolism (2012)
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      Pretibial mucinosis in a patient without Graves disease. — Mir M, Jogi R, Rosen T Cutis (2011)
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      Hashimoto's ophthalmopathy. — Tateno F, Sakakibara R, Kishi M, Ogawa E The American journal of the medical sciences (2011)
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      A new small-molecule antagonist inhibits Graves' disease antibody activation of the TSH receptor. — Neumann S, Eliseeva E, McCoy JG, Napolitano G, Giuliani C, Monaco F et al. The Journal of clinical endocrinology and metabolism (2011)
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      Natural history of Graves' Ophthalmopathy. — Benbassat CA, Robenshtok E Pediatric endocrinology reviews : PER (2010)
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      Endoscopic orbital decompression for Graves' ophthalmopathy. — Tang IP, Prepageran N, Shashinder S The Medical journal of Malaysia (2008)
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      Case study: missed diagnosis and mistreatment of unrecognized comorbid Graves disease. — Woolston JL, Caracansi A Journal of the American Academy of Child and Adolescent Psychiatry (1999)
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      Longitudinal study of soluble intercellular adhesion molecule-1 (ICAM-1) in sera of patients with Graves' disease. — Sonnet E, Massart C, Gibassier J, Allannic H, Maugendre D Journal of endocrinological investigation (1999)
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      Prospective and controlled study of ophthalmopathy after radioiodine therapy for Graves' hyperthyroidism. — Manso PG, Furlanetto RP, Wolosker AM, Paiva ER, de Abreu MT, Maciel RM Thyroid : official journal of the American Thyroid Association (1998)
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      Changes in the orbital tissues and muscles dysthyroid ophthalmopathy. — Bleeker GM Eye (London, England) (1988)
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      A simplified technique for recession of the upper eyelid retractors. — Bonavolontà G Ophthalmic plastic and reconstructive surgery (1986)
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      Asymptomatic Graves' disease during lithium therapy. — Thompson CJ, Baylis PH Postgraduate medical journal (1986)
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      Positive effect of bromocriptine treatment in Graves disease orbitopathy. — Kołodziej-Maciejewska H, Reterski Z Experimental and clinical endocrinology (1985)
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