Graves Disease Clinical Presentation
- Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: Romesh Khardori, MD, PhD, FACP more...
Because Graves disease is an autoimmune disorder that also affects other organ systems, taking a careful patient history is essential to establishing the diagnosis.
In some cases, the history might suggest a triggering factor such as trauma to the thyroid, including surgery of the thyroid gland, percutaneous injection of ethanol, and infarction of a thyroid adenoma. Other factors might include interferon (eg, interferon beta-1b) or interleukin (IL-4) therapy.
Patients usually present with symptoms typical of thyrotoxicosis. Hyperthyroidism is characterized by both increased sympathetic and decreased vagal modulation. Tachycardia and palpitation are very common symptoms.
Not all patients present with such classic features. In fact, a subset of patients with euthyroid Graves disease is described.
In elderly individuals, fewer symptoms are apparent to the patient. Clues may include unexplained weight loss, hyperhidrosis, or rapid heart beat.
Young adults of Southeast Asian descent may complain of sudden paralysis thought to be related to thyrotoxic periodic paralysis. There is an association of polymorphisms of the calcium channel alpha1-subunit gene with thyrotoxic periodic paralysis. One third of patients with thyrotoxic hypokalemic periodic paralysis were found to have mutations in the inwardly rectifying potassium channel (Kir2.6).
The symptoms of Graves disease, organized by systems, are as follows:
General - Fatigue, general weakness
Dermatologic - Warm, moist, fine skin; sweating; fine hair; onycholysis; vitiligo; alopecia; pretibial myxedema
Neuromuscular - Tremors, proximal muscle weakness, easy fatigability, periodic paralysis in persons of susceptible ethnic groups
Skeletal - Back pain, increased risk for fractures
Cardiovascular - Palpitations, dyspnea on exertion, chest pain, edema
Respiratory - Dyspnea
Gastrointestinal - Increased bowel motility with increased frequency of bowel movements
Ophthalmologic - Tearing, gritty sensation in the eye, photophobia, eye pain, protruding eye, diplopia, visual loss
Renal - Polyuria, polydipsia
Hematologic - Easy bruising
Metabolic - Heat intolerance, weight loss despite increase or similar appetite, worsening diabetes control
Endocrine/reproductive - Irregular menstrual periods, decreased menstrual volume, secondary amenorrhea, gynecomastia, impotence
Psychiatric - Restlessness, anxiety, irritability, insomnia
Most of the physical findings are related to thyrotoxicosis.
Physical findings that are unique to Graves disease but not associated with other causes of hyperthyroidism include ophthalmopathy and dermopathy. Myxedematous changes of the skin (usually in the pretibial areas) are described as resembling an orange peel in color and texture. Onycholysis can be seen usually in the fourth and fifth fingernails.
The presence of a diffusely enlarged thyroid gland, thyrotoxic signs and symptoms, together with evidence of ophthalmopathy or dermopathy, can establish the diagnosis.
Common physical findings, organized by anatomic regions, are as follows:
General - Increased basal metabolic rate, weight loss despite increase or similar appetite
Skin - Warm, most, fine skin; increased sweating; fine hair; vitiligo; alopecia; pretibial myxedema
Head, eyes, ears, nose, and throat - Chemosis, conjunctival irritation, widening of the palpebral fissures, lid lag, lid retraction, proptosis, impairment of extraocular motion, visual loss in severe optic nerve involvement, periorbital edema
Neck - Upon careful examination, the thyroid gland generally is diffusely enlarged and smooth; a well-delineated pyramidal lobe may be appreciated upon careful palpation; thyroid bruits and, rarely, thrills may be appreciated; thyroid nodules may be palpable.
Chest - Gynecomastia, tachypnea, tachycardia, murmur, hyperdynamic precordium, S3, S4 heart sounds, ectopic beats, irregular heart rate and rhythm
Abdomen - Hyperactive bowel sound
Extremities - Edema, acropachy, onycholysis
Neurologic - Hand tremor (fine and usually bilateral), hyperactive deep tendon reflexes
Musculoskeletal - Kyphosis, lordosis, loss of height, proximal muscle weakness, hypokalemic periodic paralysis in persons of susceptible ethnic groups
Psychiatric - Restlessness, anxiety, irritability, insomnia, depression
Ophthalmopathy is a hallmark of Graves disease. Approximately 25-30% of patients with Graves disease have clinical evidence of Graves ophthalmopathy. Progression from mild to moderate/severe ophthalmopathy occurs in about 3% of cases. Thyrotropin receptor is highly expressed in the fat and connective tissue of patients with Graves ophthalmopathy. Measuring diplopia fields, eyelid fissures, range of extraocular muscles, visual acuity, and proptosis provides quantitative assessment to follow the course of ophthalmopathy. Signs of corneal or conjunctival irritation include conjunctival injection and chemosis. A complete ophthalmologic examination, including retinal examination and slit-lamp examination by an ophthalmologist, is indicated if the patient is symptomatic.
Although thyroid nodule(s) may be present, excluding multinodular toxic goiter (especially in older patients) as the cause of thyrotoxicosis is essential. The approach to treatment may be different. Excluding thyroid neoplasia is also important in these patients because reports have indicated that differentiated thyroid cancer is probably more common in patients with Graves disease and may also have a more aggressive course in these patients.
Similarly, mortality has been reported to be increased in patients with Graves disease and differentiated thyroid carcinoma compared with euthyroid control patients with differentiated thyroid carcinoma. Graves disease patients had also higher mortality rates compared with general population, with a particular increase in mortality due to cardiovascular and lung disorders, while hyperthyroid patients had increased mortality secondary to toxic nodules had increased mortality associated with malignancies.
Graves disease is autoimmune in etiology, and the immune mechanisms involved may be one of the following:
Expression of a viral antigen (self-antigen) or a previously hidden antigen
The specificity crossover between different cell antigens with an infectious agent or a superantigen
Alteration of the T cell repertoire, idiotypic antibodies becoming pathogenic antibodies
New expression of HLA class II antigens on thyroid epithelial cells (eg, HLA-DR antigen)
The autoimmune process in Graves disease is influenced by a combination of environmental and genetic factors.
Several autoimmune thyroid disease susceptibility genes have been identified: CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22. Some of these susceptibility genes are specific to either Graves disease or Hashimoto thyroiditis, while others confer susceptibility to both conditions. HLA-DRB1 and HLA-DQB1 also appear to be associated with Graves disease susceptibility. Genetic factors contribute approximately 20-30% of overall disease susceptibility.
Cytotoxic T lymphocyte-associated molecule-4 (CTLA4) is a major thyroid autoantibody susceptibility gene, [29, 30] and it is a negative regulator of T-cell activation and may play an important role in the pathogenesis of Graves disease. The G allele of exon1 +49 A/G single nucleotide polymorphism (SNP) of the CTLA4 gene influences higher TPOAb and TgAb production in patients who are newly diagnosed with Graves disease.  This SNP of the CTLA4 gene can also predict recurrence of Graves disease after cessation of thionamide treatment. 
There is an association of a C/T SNP in the Kozak sequence of CD40 with Graves disease. [3, 32]
The association of SNPs in PTPN22 varies among autoimmune diseases individually or as part of a haplotype, and the mechanisms by which PTPN22 confers susceptibility to Graves disease may differ from other autoimmune diseases. 
Alleles of intron 7 of the thyrotropin receptor gene ( TSHR) have also been shown to contribute to susceptibility to Graves disease.
Inhibitory antibodies directed against insulinlike growth factor receptor-1 (IGFR-1) were seen in 14% of patients with Graves orbitopathy, but there was no activation of IGFR-1 in association with these antibodies. 
Environmental factors associated with susceptibility are largely unproven. Other factors include infection, iodide intake, stress, female sex, steroids, and toxins. Smoking has been implicated in the worsening of Graves ophthalmopathy.
Graves disease has been associated with a variety of infectious agents such as Yersinia enterocolitica and Borrelia burgdorferi. Homologies have been shown between proteins of these organisms and thyroid autoantigens. [35, 36]
Stress can be a factor for thyroid autoimmunity. Acute stress-induced immunosuppression may be followed by immune system hyperactivity, which could precipitate autoimmune thyroid disease. This may occur during the postpartum period, in which Graves disease may occur 3-9 months after delivery. Estrogen may influence the immune system, particularly the B-cell repertoire. Both T- and B-cell function are diminished during pregnancy, and the rebound from this immunosuppression is thought to contribute to the development of postpartum thyroid syndrome.
Interferon beta-1b and interleukin-4, when used therapeutically, may cause Graves disease.
Trauma to the thyroid has also been reported to be associated with Graves disease. This may include surgery of the thyroid gland, percutaneous injection of ethanol, and infarction of a thyroid adenoma.
Ellis H. Robert Graves: 1796-1852. Br J Hosp Med (Lond). 2006 Jun. 67(6):313. [Medline].
Cruz AA, Akaishi PM, Vargas MA, de Paula SA. Association between thyroid autoimmune dysfunction and non-thyroid autoimmune diseases. Ophthal Plast Reconstr Surg. 2007 Mar-Apr. 23(2):104-8. [Medline].
Jacobson EM, Tomer Y. The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: back to the future. J Autoimmun. 2007 Mar-May. 28(2-3):85-98. [Medline].
Iwama S, Ikezaki A, Kikuoka N, et al. Association of HLA-DR, -DQ genotype and CTLA-4 gene polymorphism with Graves' disease in Japanese children. Horm Res. 2005. 63(2):55-60. [Medline].
Chu X, Pan CM, Zhao SX, et al. A genome-wide association study identifies two new risk loci for Graves' disease. Nat Genet. 2011 Aug 14. 43(9):897-901. [Medline].
Douglas RS, Afifiyan NF, Hwang CJ, et al. Increased generation of fibrocytes in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab. 2010 Jan. 95(1):430-8. [Medline]. [Full Text].
Chu X, Pan CM, Zhao SX, Liang J, Gao GQ, Zhang XM, et al. A genome-wide association study identifies two new risk loci for Graves' disease. Nat Genet. 2011 Aug 14. 43(9):897-901. [Medline].
Furszyfer J, Kurland LT, McConahey WM, Elveback LR. Graves' disease in Olmsted County, Minnesota, 1935 through 1967. Mayo Clin Proc. 1970 Sep. 45(9):636-44. [Medline].
Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1977 Dec. 7(6):481-93. [Medline].
Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995 Jul. 43(1):55-68. [Medline].
Riis AL, Jørgensen JO, Gjedde S, et al. Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown. Am J Physiol Endocrinol Metab. 2005 Jun. 288(6):E1067-73. [Medline].
Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006 Dec. 35(4):663-86, vii. [Medline].
Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993 Jun. 22(2):263-77. [Medline].
Park SE, Cho MA, Kim SH, Rhee Y, Kang ES, Ahn CW. The adaptation and relationship of FGF-23 to changes in mineral metabolism in Graves' disease. Clin Endocrinol (Oxf). 2007 Jun. 66(6):854-8. [Medline].
Uchida T, Takeno K, Goto M, et al. Superior thyroid artery mean peak systolic velocity for the diagnosis of thyrotoxicosis in Japanese patients. Endocr J. 2010 Mar 6. [Medline]. [Full Text].
Bunevicius R, Prange AJ Jr. Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options. CNS Drugs. 2006. 20(11):897-909. [Medline].
Vogel A, Elberling TV, Hørding M, Dock J, Rasmussen AK, Feldt-Rasmussen U. Affective symptoms and cognitive functions in the acute phase of Graves' thyrotoxicosis. Psychoneuroendocrinology. 2007 Jan. 32(1):36-43. [Medline].
Schwartz KM, Fatourechi V, Ahmed DD, Pond GR. Dermopathy of Graves' disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab. 2002 Feb. 87(2):438-46. [Medline].
Boelaert K, Newby PR, Simmonds MJ, et al. Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med. 2010 Feb. 123(2):183.e1-9. [Medline].
Tun NN, Beckett G, Zammitt NN, Strachan MW, Seckl JR, Gibb FW. Thyrotropin Receptor Antibody Levels at Diagnosis and After Thionamide Course Predict Graves' Disease Relapse. Thyroid. 2016 Jul 6. [Medline].
Rabon S, Burton AM, White PC. Graves' Disease in Children: Long Term Outcomes of Medical Therapy. Clin Endocrinol (Oxf). 2016 May 12. [Medline].
Chen JL, Chiu HW, Tseng YJ, Chu WC. Hyperthyroidism is characterized by both increased sympathetic and decreased vagal modulation of heart rate: evidence from spectral analysis of heart rate variability. Clin Endocrinol (Oxf). 2006 Jun. 64(6):611-6. [Medline].
Kung AW. Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge. J Clin Endocrinol Metab. 2006 Jul. 91(7):2490-5. [Medline].
Ryan DP, da Silva MR, Soong TW, et al. Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis. Cell. 2010 Jan 8. 140(1):88-98. [Medline]. [Full Text].
Tanda ML, Piantanida E, Liparulo L, Veronesi G, Lai A, Sassi L, et al. Prevalence and Natural History of Graves' Orbitopathy in a Large Series of Patients with Newly Diagnosed Graves' Hyperthyroidism Seen at a Single Center. J Clin Endocrinol Metab. 2013 Feb 13. [Medline].
Chung JO, Cho DH, Chung DJ, et al. Ultrasonographic features of papillary thyroid carcinoma in patients with Graves' disease. Korean J Intern Med. 2010 Mar. 25(1):71-6. [Medline]. [Full Text].
Pellegriti G, Mannarino C, Russo M, Terranova R, Marturano I, Vigneri R. Increased Mortality in Patients with Differentiated Thyroid Cancer Associated With Graves' Disease. J Clin Endocrinol Metab. 2013 Jan 24. [Medline].
Brandt F, Thvilum M, Almind D, Christensen K, Green A, Hegedus L, et al. Graves´ disease and toxic nodular goiter are both associated with increased mortality but differ with respect to the cause of death. A Danish population-based register study. Thyroid. 2012 Dec 20. [Medline].
Zaletel K, Krhin B, Gaberscek S, Pirnat E, Hojker S. The influence of the exon 1 polymorphism of the cytotoxic T lymphocyte antigen 4 gene on thyroid antibody production in patients with newly diagnosed Graves' disease. Thyroid. 2002 May. 12(5):373-6. [Medline].
Zaletel K, Krhin B, Gaberscek S, Hojker S. Thyroid autoantibody production is influenced by exon 1 and promoter CTLA-4 polymorphisms in patients with Hashimoto's thyroiditis. Int J Immunogenet. 2006 Apr. 33(2):87-91. [Medline].
Wang PW, Chen IY, Liu RT, Hsieh CJ, Hsi E, Juo SH. Cytotoxic T lymphocyte-associated molecule-4 gene polymorphism and hyperthyroid Graves' disease relapse after antithyroid drug withdrawal: a follow-up study. J Clin Endocrinol Metab. 2007 Jul. 92(7):2513-8. [Medline].
Ban Y, Tozaki T, Taniyama M, Tomita M, Ban Y. Association of a C/T single-nucleotide polymorphism in the 5' untranslated region of the CD40 gene with Graves' disease in Japanese. Thyroid. 2006 May. 16(5):443-6. [Medline].
Heward JM, Brand OJ, Barrett JC, Carr-Smith JD, Franklyn JA, Gough SC. Association of PTPN22 haplotypes with Graves' disease. J Clin Endocrinol Metab. 2007 Feb. 92(2):685-90. [Medline].
Minich WB, Dehina N, Welsink T, Schwiebert C, Morgenthaler NG, Köhrle J. Autoantibodies to the IGF1 Receptor in Graves' Orbitopathy. J Clin Endocrinol Metab. 2013 Feb. 98(2):752-60. [Medline].
Benvenga S, Guarneri F, Vaccaro M, et al. Homologies between proteins of Borrelia burgdorferi and thyroid autoantigens. Thyroid. 2004. 14:964-6. [Medline].
Gangi E, Kapatral V, El-Azami El-Idrissi M, et al. Characterization of a recombinant Yersinia enterocolitica lipoprotein; implications for its role in autoimmune response against thyrotropin receptor. Autoimmunity. 2004 Sep-Nov. 37(6-7):515-20. [Medline].
Al-Muqbel KM, Tashtoush RM. Patterns of thyroid radioiodine uptake: Jordanian experience. J Nucl Med Technol. 2010 Mar. 38(1):32-6. [Medline].
De Bellis A, Sansone D, Coronella C, et al. Serum antibodies to collagen XIII: a further good marker of active Graves' ophthalmopathy. Clin Endocrinol (Oxf). 2005 Jan. 62(1):24-9. [Medline].
Cappelli C, Pirola I, De Martino E, Agosti B, Delbarba A, Castellano M. The role of imaging in Graves' disease: A cost-effectiveness analysis. Eur J Radiol. 2007 Apr 23. [Medline].
Markovic V, Eterovic D. Thyroid echogenicity predicts outcome of radioiodine therapy in patients with graves' disease. J Clin Endocrinol Metab. 2007 Sep. 92(9):3547-52. [Medline].
Kubota S, Ohye H, Yano G, Nishihara E, Kudo T, Ito M. Two-day thionamide withdrawal prior to radioiodine uptake sufficiently increases uptake and does not exacerbate hyperthyroidism compared to 7-day withdrawal in Graves' disease. Endocr J. 2006 Oct. 53(5):603-7. [Medline].
Bonnema SJ, Bennedbaek FN, Veje A, et al. Propylthiouracil before 131I therapy of hyperthyroid diseases: effect on cure rate evaluated by a randomized clinical trial. J Clin Endocrinol Metab. 2004. 89:4439-44. [Medline].
Read CH Jr, Tansey MJ, Menda Y. A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves' patients. J Clin Endocrinol Metab. 2004 Sep. 89(9):4229-33. [Medline].
Ceccarelli C, Canale D, Battisti P, Caglieresi C, Moschini C, Fiore E. Testicular function after 131I therapy for hyperthyroidism. Clin Endocrinol (Oxf). 2006 Oct. 65(4):446-52. [Medline].
Rivkees SA, Dinauer C. An optimal treatment for pediatric Graves' disease is radioiodine. J Clin Endocrinol Metab. 2007 Mar. 92(3):797-800. [Medline].
Chen YK, Lin CL, Chang YJ, Cheng FT, Peng CL, Sung FC. Cancer risk in patients with Graves' disease: A nationwide cohort study. Thyroid. 2013 Feb 19. [Medline].
Ye X, Liu J, Wang Y, Bin L, Wang J. Increased serum VEGF and b-FGF in Graves' ophthalmopathy. Graefes Arch Clin Exp Ophthalmol. 2014 Oct. 252 (10):1639-44. [Medline].
Stein JD, Childers D, Gupta S, Talwar N, Nan B, Lee BJ, et al. Risk factors for developing thyroid-associated ophthalmopathy among individuals with Graves disease. JAMA Ophthalmol. 2015 Mar. 133 (3):290-6. [Medline].
Watanabe N, Noh JY, Kozaki A, Iwaku K, Sekiya K, Kosuga Y, et al. Radioiodine-Associated Exacerbation of Graves' Orbitopathy in the Japanese Population: Randomized Prospective Study. J Clin Endocrinol Metab. 2015 Jul. 100 (7):2700-8. [Medline].
Shiber S, Stiebel-Kalish H, Shimon I, Grossman A, Robenshtok E. Glucocorticoid regimens for prevention of Graves' ophthalmopathy progression following radioiodine treatment: systematic review and meta-analysis. Thyroid. 2014 Oct. 24 (10):1515-23. [Medline].
Bartalena L, Marcocci C, Bogazzi F, et al. Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. N Engl J Med. 1998 Jan 8. 338(2):73-8. [Medline].
Bartalena L, Marcocci C, Bogazzi F, Panicucci M, Lepri A, Pinchera A. Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism. N Engl J Med. 1989 Nov 16. 321(20):1349-52. [Medline].
Bartalena L, Tanda ML, Piantanida E, Lai A, Pinchera A. Relationship between management of hyperthyroidism and course of the ophthalmopathy. J Endocrinol Invest. 2004 Mar. 27(3):288-94. [Medline].
Macchia PE, Bagattini M, Lupoli G, et al. High-dose intravenous corticosteroid therapy for Graves' ophthalmopathy. J Endocrinol Invest. 2001. 24:152-8. [Medline].
Sisti E, Coco B, Menconi F, Leo M, Rocchi R, Latrofa F, et al. Intravenous glucocorticoid therapy for Graves' ophthalmopathy and acute liver damage: an epidemiological study. Eur J Endocrinol. 2015 Mar. 172 (3):269-76. [Medline].
Liao SL, Huang SW. Correlation of retrobulbar volume change with resected orbital fat volume and proptosis reduction after fatty decompression for Graves ophthalmopathy. Am J Ophthalmol. 2011 Mar. 151(3):465-9.e1. [Medline].
Wakelkamp IM, Tan H, Saeed P, et al. Orbital irradiation for Graves' ophthalmopathy: Is it safe? A long-term follow-up study. Ophthalmology. 2004 Aug. 111(8):1557-62. [Medline].
Seals KF, Lee EW, Cagnon CH, Al-Hakim RA, Kee ST. Radiation-Induced Cataractogenesis: A Critical Literature Review for the Interventional Radiologist. Cardiovasc Intervent Radiol. 2015 Sep 24. [Medline].
Rajendram R, Bunce C, Lee RW, Morley AM. Orbital radiotherapy for adult thyroid eye disease. Cochrane Database Syst Rev. 2012 Jul 11. 7:CD007114. [Medline].
Dickinson AJ, Vaidya B, Miller M, Coulthard A, Perros P, Baister E. Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab. 2004 Dec. 89(12):5910-5. [Medline].
Wemeau JL, Caron P, Beckers A, et al. Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study. J Clin Endocrinol Metab. 2005. 90:841-8. [Medline].
Stan MN, Garrity JA, Bradley EA, Woog JJ, Bahn MM, Brennan MD. Randomized, double-blind, placebo-controlled trial of long-acting release octreotide for treatment of Graves' ophthalmopathy. J Clin Endocrinol Metab. 2006 Dec. 91(12):4817-24. [Medline].
Durrani OM, Reuser TQ, Murray PI. Infliximab: a novel treatment for sight-threatening thyroid associated ophthalmopathy. Orbit. 2005 Jun. 24(2):117-9. [Medline].
Salvi M, Vannucchi G, Campi I, Currò N, Dazzi D, Simonetta S. Treatment of Graves' disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study. Eur J Endocrinol. 2007 Jan. 156(1):33-40. [Medline].
Stan MN, Garrity JA, Carranza Leon BG, Prabin T, Bradley EA, Bahn RS. Randomized controlled trial of rituximab in patients with Graves' orbitopathy. J Clin Endocrinol Metab. 2015 Feb. 100 (2):432-41. [Medline].
Salvi M, Vannucchi G, Currò N, Campi I, Covelli D, Dazzi D, et al. Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Graves' orbitopathy: a randomized controlled study. J Clin Endocrinol Metab. 2015 Feb. 100 (2):422-31. [Medline].
Ebner R, Devoto MH, Weil D, et al. Treatment of thyroid associated ophthalmopathy with periocular injections of triamcinolone. Br J Ophthalmol. 2004 Nov. 88(11):1380-6. [Medline]. [Full Text].
Finamor FE, Martins JR, Nakanami D, Paiva ER, Manso PG, Furlanetto RP. Pentoxifylline (PTX)--an alternative treatment in Graves' ophthalmopathy (inactive phase): assessment by a disease specific quality of life questionnaire and by exophthalmometry in a prospective randomized trial. Eur J Ophthalmol. 2004 Jul-Aug. 14(4):277-83. [Medline].
Grodski S, Stalberg P, Robinson BG, Delbridge LW. Surgery versus Radioiodine Therapy as Definitive Management for Graves' Disease: The Role of Patient Preference. Thyroid. 2007 Feb. 17(2):157-60. [Medline].
Genovese BM, Noureldine SI, Gleeson EM, Tufano RP, Kandil E. What is the best definitive treatment for graves' disease? A systematic review of the existing literature. Ann Surg Oncol. 2013 Feb. 20(2):660-7. [Medline].
Pradeep PV, Agarwal A, Baxi M, Agarwal G, Gupta SK, Mishra SK. Safety and efficacy of surgical management of hyperthyroidism: 15-year experience from a tertiary care center in a developing country. World J Surg. 2007 Feb. 31(2):306-12; discussion 313. [Medline].
Panzer C, Beazley R, Braverman L. Rapid preoperative preparation for severe hyperthyroid Graves' disease. J Clin Endocrinol Metab. 2004 May. 89(5):2142-4. [Medline].
Erbil Y, Ozluk Y, Giris M, Salmaslioglu A, Issever H, Barbaros U. Effect of lugol solution on thyroid gland blood flow and microvessel density in the patients with Graves' disease. J Clin Endocrinol Metab. 2007 Jun. 92(6):2182-9. [Medline].
Alsuhaibani AH, Carter KD, Policeni B, Nerad JA. Effect of orbital bony decompression for Graves' orbitopathy on the volume of extraocular muscles. Br J Ophthalmol. 2011 Sep. 95(9):1255-8. [Medline].
Hiraiwa T, Ito M, Imagawa A, et al. High diagnostic value of a radioiodine uptake test with and without iodine restriction in Graves' disease and silent thyroiditis. Thyroid. 2004 Jul. 14(7):531-5. [Medline].
Anagnostis P, Adamidou F, Polyzos SA, Katergari S, Karathanasi E, Zouli C, et al. Predictors of long-term remission in patients with Graves' disease: a single center experience. Endocrine. 2013 Feb 11. [Medline].
Sato H, Sasaki N, Minamitani K, Minagawa M, Kazukawa I, Sugihara S, et al. Higher dose of methimazole causes frequent adverse effects in the management of Graves' disease in children and adolescents. J Pediatr Endocrinol Metab. 2012. 25(9-10):863-7. [Medline].
Rivkees SA, Stephenson K, Dinauer C. Adverse events associated with methimazole therapy of Graves' disease in children. Int J Pediatr Endocrinol. 2010. 2010:176970. [Medline]. [Full Text].
Mohlin E, Filipsson Nyström H, Eliasson M. Long-term prognosis after medical treatment of Graves' disease in a northern Swedish population 2000-2010. Eur J Endocrinol. 2014 Mar. 170 (3):419-27. [Medline].
Liu X, Shi B, Li H. Valuable predictive features of relapse of Graves' disease after antithyroid drug treatment. Ann Endocrinol (Paris). 2015 Oct 26. [Medline].
Villagelin D, Romaldini JH, Santos RB, Milkos AB, Ward LS. Outcomes in Relapsed Graves' Disease Patients Following Radioiodine or Prolonged Low Dose of Methimazole Treatment. Thyroid. 2015 Oct 20. [Medline].
Salvi M, Campi I. Medical Treatment of Graves' Orbitopathy. Horm Metab Res. 2015 Sep. 47 (10):779-88. [Medline].
Prasek K, Płazińska MT, Krolicki L. Diagnosis and treatment of Graves' disease with particular emphasis on appropriate techniques in nuclear medicine. General state of knowledge. Nucl Med Rev Cent East Eur. 2015. 18 (2):110-6. [Medline].