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Graves disease, susceptibility to, 1(GRD)

MedGen UID:
341307
Concept ID:
C1848795
Finding
Synonym: GRD
 
Monarch Initiative: MONDO:0100489
OMIM®: 275000

Definition

Graves disease (GRD) is an autoimmune disorder in which antibodies to the thyrotropin receptor (TSHR; 603372) result in constitutive activation of the receptor and increased levels of thyroid hormone. Wilkin (1990) reviewed endocrine disorders of hormone excess and hormone deficiency resulting from receptor autoimmunity. Genetic Heterogeneity of Graves Disease Susceptibility to Graves disease-1 (GRD1) has been mapped to chromosome 14q31. Other susceptibility loci for Graves disease include GRD2 (603388) on chromosome 20q13, GRDX1 (300351) on Xp11, and GRDX2 (see 300351) on Xq21.33-q22. Graves disease has also been mapped to several loci that confer susceptibility to autoimmune thyroid diseases, including Hashimoto thyroiditis (HT; 140300): AITD1 (608173) on 6p11; AITD2 (608174) on 5q31-q33; AITD3 (608175) on 8q24; AITD4 (608176) on 10q, and AITD5 (601941) on 18q21. [from OMIM]

Additional description

From MedlinePlus Genetics
Graves' disease is a condition that affects the function of the thyroid, which is a butterfly-shaped gland in the lower neck. The thyroid makes hormones that help regulate a wide variety of critical body functions. For example, thyroid hormones influence growth and development, body temperature, heart rate, menstrual cycles, and weight. In people with Graves' disease, the thyroid is overactive and makes more hormones than the body needs. The condition usually appears in mid-adulthood, although it may occur at any age.

Excess thyroid hormones can cause a variety of signs and symptoms. These include nervousness or anxiety, extreme tiredness (fatigue), a rapid and irregular heartbeat, hand tremors, frequent bowel movements or diarrhea, increased sweating and difficulty tolerating hot conditions, trouble sleeping, and weight loss in spite of an increased appetite. Affected women may have menstrual irregularities, such as an unusually light menstrual flow and infrequent periods. Some people with Graves' disease develop an enlargement of the thyroid called a goiter. Depending on its size, the enlarged thyroid can cause the neck to look swollen and may interfere with breathing and swallowing.

Between 25 and 50 percent of people with Graves' disease have eye abnormalities, which are known as Graves' ophthalmopathy. These eye problems can include swelling and inflammation, redness, dryness, puffy eyelids, and a gritty sensation like having sand or dirt in the eyes. Some people develop bulging of the eyes caused by inflammation of tissues behind the eyeball and "pulling back" (retraction) of the eyelids. Rarely, affected individuals have more serious eye problems, such as pain, double vision, and pinching (compression) of the optic nerve connecting the eye and the brain, which can cause vision loss.

A small percentage of people with Graves' disease develop a skin abnormality called pretibial myxedema or Graves' dermopathy. This abnormality causes the skin on the front of the lower legs and the tops of the feet to become thick, lumpy, and red. It is not usually painful.  https://medlineplus.gov/genetics/condition/graves-disease

Clinical features

From HPO
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Weight loss
MedGen UID:
853198
Concept ID:
C1262477
Finding
Reduction of total body weight.
Abnormal abdomen morphology
MedGen UID:
866551
Concept ID:
C4020869
Anatomical Abnormality
A structural abnormality of the abdomen ('belly'), that is, the part of the body between the pelvis and the thorax.
Polyphagia
MedGen UID:
9369
Concept ID:
C0020505
Finding
A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Pretibial myxedema
MedGen UID:
450990
Concept ID:
C0033103
Disease or Syndrome
A diffuse, non-pitting edema and thickening of the skin usually on the anterior aspect of the lower legs spreading to the dorsum of the feet.
Onycholysis
MedGen UID:
39324
Concept ID:
C0085661
Disease or Syndrome
Detachment of the nail from the nail bed.
Goiter
MedGen UID:
42270
Concept ID:
C0018021
Disease or Syndrome
An enlargement of the thyroid gland.
Graves disease
MedGen UID:
6677
Concept ID:
C0018213
Disease or Syndrome
An autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones (a serious metabolic imbalance known as hyperthyroidism and thyrotoxicosis). This is caused by autoantibodies to the TSH-receptor (TSHR-Ab) that activate that TSH-receptor (TSHR), thereby stimulating thyroid hormone synthesis and secretion, and thyroid growth (causing a diffusely enlarged goiter). The resulting state of hyperthyroidism can cause a dramatic constellation of neuropsychological and physical signs and symptoms, which can severely compromise the patients.
Decreased thyroid-stimulating hormone level
MedGen UID:
717708
Concept ID:
C1295607
Finding
Reduced amount of the thyroid-stimulating hormone (TSH), which is produced by the anterior pituitary gland and stimulates the function of the thyroid gland.
Increased circulating free T3
MedGen UID:
867466
Concept ID:
C4021843
Finding
An elevated concentration of free 3,3',5-triiodo-L-thyronine in the blood circulation.
Increased circulating free T4 concentration
MedGen UID:
1771990
Concept ID:
C5421591
Finding
An elevated concentration of free thyroxine (fT4) in the blood circulation.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

Professional guidelines

PubMed

Caron P
Endocrine 2022 Dec;78(3):406-417. Epub 2022 Jun 28 doi: 10.1007/s12020-022-03118-4. PMID: 35763241Free PMC Article
Asselta R, Paraboschi EM, Gerussi A, Cordell HJ, Mells GF, Sandford RN, Jones DE, Nakamura M, Ueno K, Hitomi Y, Kawashima M, Nishida N, Tokunaga K, Nagasaki M, Tanaka A, Tang R, Li Z, Shi Y, Liu X, Xiong M, Hirschfield G, Siminovitch KA; Canadian-US PBC Consortium; Italian PBC Genetics Study Group; UK-PBC Consortium; Japan PBC-GWAS Consortium, Carbone M, Cardamone G, Duga S, Gershwin ME, Seldin MF, Invernizzi P
Gastroenterology 2021 Jun;160(7):2483-2495.e26. Epub 2021 Mar 4 doi: 10.1053/j.gastro.2021.02.061. PMID: 33675743Free PMC Article
Tomer Y
Autoimmun Rev 2002 Aug;1(4):198-204. doi: 10.1016/s1568-9972(02)00053-8. PMID: 12848996

Recent clinical studies

Etiology

Antonelli A, Ferrari SM, Ragusa F, Elia G, Paparo SR, Ruffilli I, Patrizio A, Giusti C, Gonnella D, Cristaudo A, Foddis R, Shoenfeld Y, Fallahi P
Best Pract Res Clin Endocrinol Metab 2020 Jan;34(1):101387. Epub 2020 Feb 4 doi: 10.1016/j.beem.2020.101387. PMID: 32107168
Graves DT, Ding Z, Yang Y
Periodontol 2000 2020 Feb;82(1):214-224. doi: 10.1111/prd.12318. PMID: 31850631
Graves DT, Corrêa JD, Silva TA
J Dent Res 2019 Feb;98(2):148-156. Epub 2018 Oct 25 doi: 10.1177/0022034518805739. PMID: 30359170Free PMC Article
Rayman MP
Proc Nutr Soc 2019 Feb;78(1):34-44. Epub 2018 Sep 13 doi: 10.1017/S0029665118001192. PMID: 30208979
Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P
Autoimmun Rev 2015 Feb;14(2):174-80. Epub 2014 Oct 25 doi: 10.1016/j.autrev.2014.10.016. PMID: 25461470

Diagnosis

Kemp SA, Collier DA, Datir RP, Ferreira IATM, Gayed S, Jahun A, Hosmillo M, Rees-Spear C, Mlcochova P, Lumb IU, Roberts DJ, Chandra A, Temperton N; CITIID-NIHR BioResource COVID-19 Collaboration; COVID-19 Genomics UK (COG-UK) Consortium, Sharrocks K, Blane E, Modis Y, Leigh KE, Briggs JAG, van Gils MJ, Smith KGC, Bradley JR, Smith C, Doffinger R, Ceron-Gutierrez L, Barcenas-Morales G, Pollock DD, Goldstein RA, Smielewska A, Skittrall JP, Gouliouris T, Goodfellow IG, Gkrania-Klotsas E, Illingworth CJR, McCoy LE, Gupta RK
Nature 2021 Apr;592(7853):277-282. Epub 2021 Feb 5 doi: 10.1038/s41586-021-03291-y. PMID: 33545711Free PMC Article
Song RH, Wang B, Yao QM, Li Q, Jia X, Zhang JA
Front Immunol 2019;10:2349. Epub 2019 Oct 1 doi: 10.3389/fimmu.2019.02349. PMID: 31681268Free PMC Article
Minelli R, Gaiani F, Kayali S, Di Mario F, Fornaroli F, Leandro G, Nouvenne A, Vincenzi F, De' Angelis GL
Acta Biomed 2018 Dec 17;89(9-S):11-16. doi: 10.23750/abm.v89i9-S.7872. PMID: 30561390Free PMC Article
Kahaly GJ, Frommer L, Schuppan D
Nutrients 2018 Jun 25;10(7) doi: 10.3390/nu10070814. PMID: 29941778Free PMC Article
Ruggeri RM, Giuffrida G, Campennì A
Minerva Endocrinol 2018 Sep;43(3):305-322. Epub 2017 Oct 9 doi: 10.23736/S0391-1977.17.02757-2. PMID: 28990742

Therapy

Kemp SA, Collier DA, Datir RP, Ferreira IATM, Gayed S, Jahun A, Hosmillo M, Rees-Spear C, Mlcochova P, Lumb IU, Roberts DJ, Chandra A, Temperton N; CITIID-NIHR BioResource COVID-19 Collaboration; COVID-19 Genomics UK (COG-UK) Consortium, Sharrocks K, Blane E, Modis Y, Leigh KE, Briggs JAG, van Gils MJ, Smith KGC, Bradley JR, Smith C, Doffinger R, Ceron-Gutierrez L, Barcenas-Morales G, Pollock DD, Goldstein RA, Smielewska A, Skittrall JP, Gouliouris T, Goodfellow IG, Gkrania-Klotsas E, Illingworth CJR, McCoy LE, Gupta RK
Nature 2021 Apr;592(7853):277-282. Epub 2021 Feb 5 doi: 10.1038/s41586-021-03291-y. PMID: 33545711Free PMC Article
Davies TF, Andersen S, Latif R, Nagayama Y, Barbesino G, Brito M, Eckstein AK, Stagnaro-Green A, Kahaly GJ
Nat Rev Dis Primers 2020 Jul 2;6(1):52. doi: 10.1038/s41572-020-0184-y. PMID: 32616746
Rayman MP
Proc Nutr Soc 2019 Feb;78(1):34-44. Epub 2018 Sep 13 doi: 10.1017/S0029665118001192. PMID: 30208979
Kahaly GJ, Frommer L, Schuppan D
Nutrients 2018 Jun 25;10(7) doi: 10.3390/nu10070814. PMID: 29941778Free PMC Article
Wang N, Hammarström L
Curr Opin Allergy Clin Immunol 2012 Dec;12(6):602-8. doi: 10.1097/ACI.0b013e3283594219. PMID: 23026772

Prognosis

Kuhlmann T, Moccia M, Coetzee T, Cohen JA, Correale J, Graves J, Marrie RA, Montalban X, Yong VW, Thompson AJ, Reich DS; International Advisory Committee on Clinical Trials in Multiple Sclerosis
Lancet Neurol 2023 Jan;22(1):78-88. Epub 2022 Nov 18 doi: 10.1016/S1474-4422(22)00289-7. PMID: 36410373Free PMC Article
Zhang Y, Liu J, Wang C, Liu J, Lu W
Front Immunol 2021;12:672346. Epub 2021 Apr 26 doi: 10.3389/fimmu.2021.672346. PMID: 33981318Free PMC Article
Asselta R, Paraboschi EM, Gerussi A, Cordell HJ, Mells GF, Sandford RN, Jones DE, Nakamura M, Ueno K, Hitomi Y, Kawashima M, Nishida N, Tokunaga K, Nagasaki M, Tanaka A, Tang R, Li Z, Shi Y, Liu X, Xiong M, Hirschfield G, Siminovitch KA; Canadian-US PBC Consortium; Italian PBC Genetics Study Group; UK-PBC Consortium; Japan PBC-GWAS Consortium, Carbone M, Cardamone G, Duga S, Gershwin ME, Seldin MF, Invernizzi P
Gastroenterology 2021 Jun;160(7):2483-2495.e26. Epub 2021 Mar 4 doi: 10.1053/j.gastro.2021.02.061. PMID: 33675743Free PMC Article
Kemp SA, Collier DA, Datir RP, Ferreira IATM, Gayed S, Jahun A, Hosmillo M, Rees-Spear C, Mlcochova P, Lumb IU, Roberts DJ, Chandra A, Temperton N; CITIID-NIHR BioResource COVID-19 Collaboration; COVID-19 Genomics UK (COG-UK) Consortium, Sharrocks K, Blane E, Modis Y, Leigh KE, Briggs JAG, van Gils MJ, Smith KGC, Bradley JR, Smith C, Doffinger R, Ceron-Gutierrez L, Barcenas-Morales G, Pollock DD, Goldstein RA, Smielewska A, Skittrall JP, Gouliouris T, Goodfellow IG, Gkrania-Klotsas E, Illingworth CJR, McCoy LE, Gupta RK
Nature 2021 Apr;592(7853):277-282. Epub 2021 Feb 5 doi: 10.1038/s41586-021-03291-y. PMID: 33545711Free PMC Article
Shukla SK, Singh G, Ahmad S, Pant P
Microb Pathog 2018 Mar;116:279-288. Epub 2018 Jan 8 doi: 10.1016/j.micpath.2018.01.004. PMID: 29325864

Clinical prediction guides

Kuhlmann T, Moccia M, Coetzee T, Cohen JA, Correale J, Graves J, Marrie RA, Montalban X, Yong VW, Thompson AJ, Reich DS; International Advisory Committee on Clinical Trials in Multiple Sclerosis
Lancet Neurol 2023 Jan;22(1):78-88. Epub 2022 Nov 18 doi: 10.1016/S1474-4422(22)00289-7. PMID: 36410373Free PMC Article
Asselta R, Paraboschi EM, Gerussi A, Cordell HJ, Mells GF, Sandford RN, Jones DE, Nakamura M, Ueno K, Hitomi Y, Kawashima M, Nishida N, Tokunaga K, Nagasaki M, Tanaka A, Tang R, Li Z, Shi Y, Liu X, Xiong M, Hirschfield G, Siminovitch KA; Canadian-US PBC Consortium; Italian PBC Genetics Study Group; UK-PBC Consortium; Japan PBC-GWAS Consortium, Carbone M, Cardamone G, Duga S, Gershwin ME, Seldin MF, Invernizzi P
Gastroenterology 2021 Jun;160(7):2483-2495.e26. Epub 2021 Mar 4 doi: 10.1053/j.gastro.2021.02.061. PMID: 33675743Free PMC Article
Hu Z, Li W, Li M, Wei H, Hu Z, Chen Y, Luo A, Li W
BMC Med Genomics 2021 Feb 10;14(1):46. doi: 10.1186/s12920-020-00865-z. PMID: 33568133Free PMC Article
Kemp SA, Collier DA, Datir RP, Ferreira IATM, Gayed S, Jahun A, Hosmillo M, Rees-Spear C, Mlcochova P, Lumb IU, Roberts DJ, Chandra A, Temperton N; CITIID-NIHR BioResource COVID-19 Collaboration; COVID-19 Genomics UK (COG-UK) Consortium, Sharrocks K, Blane E, Modis Y, Leigh KE, Briggs JAG, van Gils MJ, Smith KGC, Bradley JR, Smith C, Doffinger R, Ceron-Gutierrez L, Barcenas-Morales G, Pollock DD, Goldstein RA, Smielewska A, Skittrall JP, Gouliouris T, Goodfellow IG, Gkrania-Klotsas E, Illingworth CJR, McCoy LE, Gupta RK
Nature 2021 Apr;592(7853):277-282. Epub 2021 Feb 5 doi: 10.1038/s41586-021-03291-y. PMID: 33545711Free PMC Article
Rayman MP
Proc Nutr Soc 2019 Feb;78(1):34-44. Epub 2018 Sep 13 doi: 10.1017/S0029665118001192. PMID: 30208979

Recent systematic reviews

Wang J, Chen Z, Carru C, Capobianco G, Sedda S, Li Z
BMC Endocr Disord 2023 Sep 12;23(1):194. doi: 10.1186/s12902-023-01450-y. PMID: 37700292Free PMC Article
Song RH, Wang B, Yao QM, Li Q, Jia X, Zhang JA
Front Immunol 2019;10:2349. Epub 2019 Oct 1 doi: 10.3389/fimmu.2019.02349. PMID: 31681268Free PMC Article
Tu Y, Fan G, Zeng T, Cai X, Kong W
Biosci Rep 2018 Apr 27;38(2) Epub 2018 Mar 21 doi: 10.1042/BSR20180143. PMID: 29440561Free PMC Article
Imani D, Rezaei R, Razi B, Alizadeh S, Mahmoudi M
Acta Med Iran 2017 Nov;55(11):665-671. PMID: 29307154
Wong KH, Rong SS, Chong KK, Young AL, Pang CP, Chen LJ
Sci Rep 2015 Nov 18;5:16672. doi: 10.1038/srep16672. PMID: 26578206Free PMC Article

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