Graves' disease overview: Difference between revisions

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Latest revision as of 21:32, 28 August 2017

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]

Historical Perspective

Graves disease owes its name to the Irish doctor Randy Danny Graves, who described a case of goiter with exophthalmos in 1835. However, the German Karl Adolph von Basedow independently reported the same constellation of symptoms in 1840. As a result, on the European Continent the term Basedow's disease is more common than Graves' disease.

Pathophysiology

Genetic factors, anti thyrotropin receptor antibodies, T cells, B cells and thyroid epithelial cells, are involved in the main pathologic mechanism of Graves' disease. Genetic factors play a role as an initiating factor, and genes encoding for Thyroglobulin, Thyrotropin receptor, HLA-DRβ-Arg74, protein tyrosine phosphatase nonreceptor type 22 (PTPN22), Cytotoxic T-lymphocyte–associated antigen 4 (CTLA4), CD25, CD40, have all been implicated. Graves' disease is an autoimmune disorder, in which the body produces antibodies to the receptor for thyroid-stimulating hormone (TSH). These are IgG1 subclass of antibodies.

Causes

Graves' disease may be caused by either genetic factors, autoimmune antibodies against thyrotropin receptors, T cells and B cells auto activation and infectious agents.

Differential Diagnosis

The table below summarizes the list of differential diagnosis for Graves' disease.

Cause of thyrotoxicosis	TSH receptor Antibodies	Thyroid US	Color flow Doppler	Radioactive iodine uptake/Scan	Other features
Graves' disease	Present	Hypoechoic pattern	↑	↑	Ophthalmopathy, dermopathy, acropachy
Toxic nodular goiter	Absent	Multiple nodules	-	Hot nodules at thyroid scan	-
Toxic adenoma	Absent	Single nodule	-	Hot nodule	-
Subacute thyroiditis	Absent	Heterogeneous hypoechoic areas	Reduced/absent flow	↓	Neck pain-fever and elevated inflammatory index
Painless thyroiditis	Absent	Hypoechoic pattern	Reduced/absent flow	↓	-
Amiodarone induced thyroiditis-Type 1	Absent	Diffuse or nodular goiter	↓/Normal/↑	↓ but higher than in Type 2	High urinary iodine
Amiodarone induced thyroiditis-Type 2	Absent	Normal	Absent	↓/absent	High urinary iodine
Central hyperthyroidism	Absent	Diffuse or nodular goiter	Normal/↑	↑	Inappropriately normal or high TSH
Trophoblastic disease	Absent	Diffuse or nodular goiter	Normal/↑	↑	-
Factitious thyrotoxicosis	Absent	Variable	Reduced/absent flow	↓	↓ serum thyroglobulin
Struma ovarii	Absent	Variable	Reduced/absent flow	↓	Abdominal RAIU

Epidemiology and Demographics

Graves’ disease is the most common cause of hyperthyroidism.

Incidence

Grave's disease annual incidence is about 20 to 50 cases per 100,000 persons.

Prevalence

The prevalence of Graves’ disease in the 1970s is estimated to be 0.4% in the United States.

Age

The incidence peaks between 30 and 50 years of age, but people can be affected at any age.

Race

Graves' disease is more common in Caucasians than in Asians.

Sex

Graves' disease is more common among women than men. The lifetime risk is 3% for women and 0.5% for men.

Risk factors

The most potent risk factor in the development of Graves' disease is genetic susceptibility. Other risk factors include infections, stress, and smoking.

Natural History, Complications and Prognosis

If left untreated it may lead to serious complications such as thyroid storm, life-threatening arrhythmias, orbitopathies, weight loss and even osteoporosis. Cardiac complications are the most important complications of Graves' disease because they are life threatening. Heart failure and atrial fibrillation are the most common cardiac complications. Thyroid dermopathy, presenting as pretibial myxedema and acropachy is another complication. When compared with people older than 60 years with a healthy thyroid, those who are hyperthyroid have three times the risk of atrial fibrillation. Thyroid associated ophthalmopathy must be evaluated in every patient with Graves' disease. Thyroid crisis is another life-threatening complication of Graves' disease. Prognosis is varied and depends on the severity of the disease and adequacy of treatment. However, it is considered good.

Diagnosis

In the presence of relative clinical symptoms and signs for hyperthyroidism, a diagnostic approach must be taken to address accurate diagnosis and start the management Presence of at least one of the following findings in a hyperthyroid patient is definitive for Graves' disease.

Detectable TSH receptor antibodies (TRAbs) in the serum
Evidence of ophthalmopathy and/or dermopathy
Diffuse and increased RAIU

Symptoms

Some of the most typical symptoms of Graves' Disease are the following:

Palpitations, tremor (usually fine shaking eg. hands), excessive sweating, heat intolerance, increased appetite, unexplained weight loss despite increased appetite, shortness of breath, muscle weakness (especially in the large muscles of the arms and legs) and degeneration, insomnia, increased energy, fatigue, mental impairment, memory lapses, diminished attention, decreased concentration, nervousness, agitation, irritability, restlessness, erratic behavior, emotional lability, gynecomastia, goiter (enlarged thyroid gland), double vision, eye pain, irritation, or the feeling of grit or sand in the eyes, swelling or redness of the eyes or eyelids/eyelid retraction, sensitivity to light, decrease in menstrual periods (oligomenorrhea), amenorrhea, infertility/recurrent miscarriage, hair loss, a non-pitting edema with thickening of the skin, described as peau d'orange or orange peel, usually found on the lower extremities, smooth, velvety skin, increased bowel movements or diarrhea.

Physical Examination

Signs include tachycardia, stare, eyelid lag, proptosis, goiter, resting tremor, hyperreflexia, and warm, moist, and smooth skin.

Laboratory Findings

The laboratory findings for Graves' disease show elevated levels of serum thyroxine (T4), triiodothyronine (T3) and undetectable serum TSH.

Hyperthyroidism Therapy

Medical Therapy

In a small proportion of patients, spontaneous remission occurs. Smoking cessation is one of the mainstay of treatment. Antithyroid drugs are the first line treatment in Europe. Ablation therapy either by thyroidectomy or radioactive iodine is more accepted in North America.

Antithyroid Drugs

Methimazole, carbimazole and propylthiouracil are the available anti thyroid drugs. Methimazole is preferred for initial therapy in both Europe and North America because of its favorable side-effect profile. Durable remission occurs in 40 to 50% of patients which is defined as euthyroidism for at least 12 months following 1-2 years of treatment. Patients may be switched from one drug to another when necessitated by minor side effects. Monitoring by means of liver function tests and white-cell counts before and during antithyroid drug therapy is advocated by some experts but is not currently supported by consensus opinion.

Radioactive Iodine

Radioactive iodine therapy offers relief from symptoms of hyperthyroidism within weeks. Radioiodine is not associated with an increased risk of cancer. It can provoke or worsen ophthalmopathy.

Ophthalmopathy

Treatment for ophthalmopathy depends on the phase and severity of the disease. It ranges from enhancement of tear film quality and maintenance of ocular surface moisture for the mild disease to intravenously administered pulse glucocorticoid therapy for severe and sight-threatening disease.

Surgery

The patients' thyroid hormone must be normalized before surgery to minimize the risk of surgery. Surgery is recommended for some patients including patients with large goiters, women wishing to become pregnant shortly after treatment and patients who want to avoid exposure to antithyroid drugs or radioiodine.

References

Template:WH Template:WS

@@ Line 4: / Line 4: @@
 ==Historical Perspective==
-Graves disease owes its name to the Irish doctor Randy Danny Graves,<ref>{{WhoNamedIt|doctor|695|Robert James Graves}}</ref> who described a case of goiter with exophthalmos in 1835. However, the German [[Karl Adolph von Basedow]] independently reported the same constellation of symptoms in 1840. As a result, on the European Continent the term Basedow's disease is more common than Graves' disease.<ref name="WNI">{{WhoNamedIt|synd|1517|Basedow's syndrome or disease}} - the history and naming of the disease</ref><ref>{{eMedicine|med|917|Goiter, Diffuse Toxic}}</ref>
+Graves disease owes its name to the Irish doctor Randy Danny Graves, who described a case of [[goiter]] with [[exophthalmos]] in 1835. However, the German [[Karl Adolph von Basedow]] independently reported the same constellation of symptoms in 1840. As a result, on the European Continent the term [[Basedow disease|Basedow's disease]] is more common than Graves' disease.
 == Pathophysiology ==
-Genetic factors, anti [[thyrotropin receptor]] antibodies, [[T cells]], [[B cells]] and thyroid epithelial cells involvement are the main pathologic features of Graves' disease.
+Genetic factors, anti [[thyrotropin receptor]] antibodies, [[T cells]], [[B cells]] and thyroid [[epithelial cells]], are involved in the main pathologic mechanism of Graves' disease. Genetic factors play a role as an initiating factor, and genes encoding for [[Thyroglobulin]], [[Thyrotropin receptor]], [[HLA|HLA-DRβ-Arg74]], protein tyrosine phosphatase nonreceptor type 22 (PTPN22), [[CTLA-4|Cytotoxic T-lymphocyte–associated antigen 4]] (CTLA4), [[CD25]], [[CD40]], have all been implicated. Graves' disease is an [[autoimmunity|autoimmune]] disorder, in which the body produces [[antibodies]] to the receptor for [[thyroid-stimulating hormone]] (TSH). These are [[IgG|IgG1]] subclass of antibodies.
-Genetic factors have role as initiating factor include [[Thyroglobulin]], [[Thyrotropin receptor]], [[HLA|HLA-DRβ-Arg74]], The protein tyrosine phosphatase nonreceptor type 22 (PTPN22), [[CTLA-4|Cytotoxic T-lymphocyte–associated antigen 4]] (CTLA4), [[CD25]], [[CD40]].<br>
-Graves' disease is an [[autoimmunity|autoimmune]] disorder, in which the body produces antibodies to the receptor for [[thyroid-stimulating hormone]] (TSH). These are [[IgG|IgG1]] subclass of antibodies.<ref name="pmid2168443">{{cite journal |vauthors=Weetman AP, Yateman ME, Ealey PA, Black CM, Reimer CB, Williams RC, Shine B, Marshall NJ |title=Thyroid-stimulating antibody activity between different immunoglobulin G subclasses |journal=J. Clin. Invest. |volume=86 |issue=3 |pages=723–7 |year=1990 |pmid=2168443 |pmc=296786 |doi=10.1172/JCI114768 |url=}}</ref>
 ==Causes==
-Graves' disease may be caused by either genetic factors, autoimmune antibodies against thyrotropin receptors, T cells and B cells auto activation and infectious agents.<ref name="pmid24460189">{{cite journal |vauthors=Tomer Y |title=Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics |journal=Annu Rev Pathol |volume=9 |issue= |pages=147–56 |year=2014 |pmid=24460189 |pmc=4128637 |doi=10.1146/annurev-pathol-012513-104713 |url=}}</ref><ref name="pmid26459776">{{cite journal |vauthors=Limbach M, Saare M, Tserel L, Kisand K, Eglit T, Sauer S, Axelsson T, Syvänen AC, Metspalu A, Milani L, Peterson P |title=Epigenetic profiling in CD4+ and CD8+ T cells from Graves' disease patients reveals changes in genes associated with T cell receptor signaling |journal=J. Autoimmun. |volume=67 |issue= |pages=46–56 |year=2016 |pmid=26459776 |doi=10.1016/j.jaut.2015.09.006 |url=}}</ref><ref name="pmid2168443">{{cite journal |vauthors=Weetman AP, Yateman ME, Ealey PA, Black CM, Reimer CB, Williams RC, Shine B, Marshall NJ |title=Thyroid-stimulating antibody activity between different immunoglobulin G subclasses |journal=J. Clin. Invest. |volume=86 |issue=3 |pages=723–7 |year=1990 |pmid=2168443 |pmc=296786 |doi=10.1172/JCI114768 |url=}}</ref>
+Graves' disease may be caused by either genetic factors, autoimmune [[antibodies]] against [[Thyrotropin receptor|thyrotropin receptors]], [[T cells]] and [[B cells]] auto activation and infectious agents.
 ==Differential Diagnosis==
-The table below summarizes the list of differential diagnosis for Graves' disease.<ref name="pmid2258582">{{cite journal |vauthors=Lambert M, Unger J, De Nayer P, Brohet C, Gangji D |title=Amiodarone-induced thyrotoxicosis suggestive of thyroid damage |journal=J. Endocrinol. Invest. |volume=13 |issue=6 |pages=527–30 |year=1990 |pmid=2258582 |doi= |url=}}</ref><ref name="pmid24282820">{{cite journal |vauthors=Ahmadieh H, Salti I |title=Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment |journal=Biomed Res Int |volume=2013 |issue= |pages=725410 |year=2013 |pmid=24282820 |pmc=3824811 |doi=10.1155/2013/725410 |url=}}</ref><ref name="pmid8351956">{{cite journal |vauthors=Vialettes B, Guillerand MA, Viens P, Stoppa AM, Baume D, Sauvan R, Pasquier J, San Marco M, Olive D, Maraninchi D |title=Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies |journal=Acta Endocrinol. |volume=129 |issue=1 |pages=31–8 |year=1993 |pmid=8351956 |doi= |url=}}</ref><ref name="pmid23067331">{{cite journal |vauthors=Jha S, Waghdhare S, Reddi R, Bhattacharya P |title=Thyroid storm due to inappropriate administration of a compounded thyroid hormone preparation successfully treated with plasmapheresis |journal=Thyroid |volume=22 |issue=12 |pages=1283–6 |year=2012 |pmid=23067331 |doi=10.1089/thy.2011.0353 |url=}}</ref><ref name="pmid2666114">{{cite journal |vauthors=Cohen JH, Ingbar SH, Braverman LE |title=Thyrotoxicosis due to ingestion of excess thyroid hormone |journal=Endocr. Rev. |volume=10 |issue=2 |pages=113–24 |year=1989 |pmid=2666114 |doi=10.1210/edrv-10-2-113 |url=}}</ref>
+The table below summarizes the list of differential diagnosis for Graves' disease.
+{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
-{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
+! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Cause of thyrotoxicosis}}
-! style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1  | {{fontcolor|#FFFFFF|Cause of thyrotoxicosis}}
+! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|TSH receptor Antibodies}}
-! style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1  | {{fontcolor|#FFFFFF|TSH receptor Antibodies}}
+! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Thyroid US}}
-! style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1  | {{fontcolor|#FFFFFF|Thyroid US}}
+! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Color flow Doppler}}
-! style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1  | {{fontcolor|#FFFFFF|Color flow Doppler}}
+! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Radioactive iodine uptake/Scan}}
-! style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1  | {{fontcolor|#FFFFFF|Radioactive iodine uptake/Scan}}
+! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Other features}}
-! style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1  | {{fontcolor|#FFFFFF|Other features}}
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Graves' disease}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Graves' disease}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Present
 | style="padding: 5px 5px; background: #F5F5F5;" | Hypoechoic pattern
@@ Line 34: / Line 30: @@
 | style="padding: 5px 5px; background: #F5F5F5;" | Ophthalmopathy, dermopathy, acropachy
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Toxic nodular goiter}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Toxic nodular goiter}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Absent
 | style="padding: 5px 5px; background: #F5F5F5;" | Multiple nodules
@@ Line 41: / Line 37: @@
 | style="padding: 5px 5px; background: #F5F5F5;" | -
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Toxic adenoma}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Toxic adenoma}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Absent
 | style="padding: 5px 5px; background: #F5F5F5;" | Single nodule
@@ Line 48: / Line 44: @@
 | style="padding: 5px 5px; background: #F5F5F5;" | -
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Subacute thyroiditis}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Subacute thyroiditis}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Absent
 | style="padding: 5px 5px; background: #F5F5F5;" | Heterogeneous hypoechoic areas
 | style="padding: 5px 5px; background: #F5F5F5;" | Reduced/absent flow
 | style="padding: 5px 5px; background: #F5F5F5;" | ↓
-| style="padding: 5px 5px; background: #F5F5F5;" | Neck pain-fever and<br> elevated inflammatory index
+| style="padding: 5px 5px; background: #F5F5F5;" | Neck pain-fever and<br>elevated inflammatory index
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Painless thyroiditis}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Painless thyroiditis}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Absent
 | style="padding: 5px 5px; background: #F5F5F5;" | Hypoechoic pattern
@@ Line 62: / Line 58: @@
 | style="padding: 5px 5px; background: #F5F5F5;" | -
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Amiodarone induced thyroiditis-Type 1}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Amiodarone induced thyroiditis-Type 1}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Absent
 | style="padding: 5px 5px; background: #F5F5F5;" | Diffuse or nodular goiter
@@ Line 69: / Line 65: @@
 | style="padding: 5px 5px; background: #F5F5F5;" | High urinary iodine
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Amiodarone induced thyroiditis-Type 2}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Amiodarone induced thyroiditis-Type 2}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Absent
 | style="padding: 5px 5px; background: #F5F5F5;" | Normal
@@ Line 76: / Line 72: @@
 | style="padding: 5px 5px; background: #F5F5F5;" | High urinary iodine
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Central hyperthyroidism}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Central hyperthyroidism}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Absent
 | style="padding: 5px 5px; background: #F5F5F5;" | Diffuse or nodular goiter
 | style="padding: 5px 5px; background: #F5F5F5;" | Normal/↑
 | style="padding: 5px 5px; background: #F5F5F5;" | ↑
-| style="padding: 5px 5px; background: #F5F5F5;" | Inappropriately normal or high TSH
+| style="padding: 5px 5px; background: #F5F5F5;" | Inappropriately normal or high [[TSH]]
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Trophoblastic disease}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Trophoblastic disease}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Absent
 | style="padding: 5px 5px; background: #F5F5F5;" | Diffuse or nodular goiter
@@ Line 90: / Line 86: @@
 | style="padding: 5px 5px; background: #F5F5F5;" | -
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Factitious thyrotoxicosis}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Factitious thyrotoxicosis}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Absent
 | style="padding: 5px 5px; background: #F5F5F5;" | Variable
 | style="padding: 5px 5px; background: #F5F5F5;" | Reduced/absent flow
 | style="padding: 5px 5px; background: #F5F5F5;" | ↓
-| style="padding: 5px 5px; background: #F5F5F5;" | ↓ serum thyroglobulin
+| style="padding: 5px 5px; background: #F5F5F5;" | ↓ serum [[thyroglobulin]]
 |-
-| style="background: #4479BA; padding: 5px 5px;" rowspan=1 colspan=1 |{{fontcolor|#FFFFFF|Struma ovarii}}
+| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Struma ovarii}}
 | style="padding: 5px 5px; background: #F5F5F5;" | Absent
 | style="padding: 5px 5px; background: #F5F5F5;" | Variable
@@ Line 104: / Line 100: @@
 | style="padding: 5px 5px; background: #F5F5F5;" | Abdominal RAIU
 |}
 ==Epidemiology and Demographics==
-Graves’ disease is the most common cause of hyperthyroidism.
+Graves’ disease is the most common cause of [[hyperthyroidism]].
 ===Incidence===
-*It's annual incidence is about 20 to 50 cases per 100,000 persons.<ref name="pmid25591468">{{cite journal |vauthors=Zimmermann MB, Boelaert K |title=Iodine deficiency and thyroid disorders |journal=Lancet Diabetes Endocrinol |volume=3 |issue=4 |pages=286–95 |year=2015 |pmid=25591468 |doi=10.1016/S2213-8587(14)70225-6 |url=}}</ref>
+*Grave's disease annual incidence is about 20 to 50 cases per 100,000 persons.
 ===Prevalence===
-The prevalence of Graves’ disease in 1970s estimated to be 0.4% in the United States.<ref name="pmid5066850">{{cite journal |vauthors=Furszyfer J, Kurland LT, McConahey WM, Woolner LB, Elveback LR |title=Epidemiologic aspects of Hashimoto's thyroiditis and Graves' disease in Rochester, Minnesota (1935-1967), with special reference to temporal trends |journal=Metab. Clin. Exp. |volume=21 |issue=3 |pages=197–204 |year=1972 |pmid=5066850 |doi= |url=}}</ref>
+The prevalence of Graves’ disease in the 1970s is estimated to be 0.4% in the United States.
 ===Age===
-*The incidence peaks between 30 and 50 years of age, but people can be affected at any age.
+The incidence peaks between 30 and 50 years of age, but people can be affected at any age.
 ===Race===
-*Graves' disease is more common in Caucasians than in Asians.<ref name="pmid1563082">{{cite journal |vauthors=Tellez M, Cooper J, Edmonds C |title=Graves' ophthalmopathy in relation to cigarette smoking and ethnic origin |journal=Clin. Endocrinol. (Oxf) |volume=36 |issue=3 |pages=291–4 |year=1992 |pmid=1563082 |doi= |url=}}</ref>
+Graves' disease is more common in Caucasians than in Asians.
 ===Sex===
-*Graves' disease is more common among women than mrn. The lifetime risk is 3% for women and 0.5% for men.<ref name="pmid27797318">{{cite journal |vauthors=Smith TJ, Hegedüs L |title=Graves' Disease |journal=N. Engl. J. Med. |volume=375 |issue=16 |pages=1552–1565 |year=2016 |pmid=27797318 |doi=10.1056/NEJMra1510030 |url=}}</ref>
+Graves' disease is more common among women than men. The lifetime risk is 3% for women and 0.5% for men.
 ==Risk factors==
-The most potent risk factor in the development of Graves' disease is genetic susceptibility. Other risk factors include infections, stress and smoking.
+The most potent risk factor in the development of Graves' disease is genetic susceptibility. Other risk factors include infections, stress, and smoking.
 == Natural History, Complications and Prognosis ==
-*If left untreated it may lead to serious complications such as, thyroid storm, life threatening arrhythmias, orbitopathies, weight loss and even osteoporosis.
+If left untreated it may lead to serious complications such as [[thyroid storm]], life-threatening [[arrhythmias]], orbitopathies, [[weight loss]] and even [[osteoporosis]].
-*Cardiac complications are the most important complications of Graves' disease because they are life threatening. [[Heart failure]] and [[atrial fibrillation]] are the most common cardiac complications. Thyroid dermopathy, presents as pretibial [[myxedema]] and acropachy is another complication.<ref name="pmid24766932">{{cite journal |vauthors=Devereaux D, Tewelde SZ |title=Hyperthyroidism and thyrotoxicosis |journal=Emerg. Med. Clin. North Am. |volume=32 |issue=2 |pages=277–92 |year=2014 |pmid=24766932 |doi=10.1016/j.emc.2013.12.001 |url=}}</ref>
+Cardiac complications are the most important complications of Graves' disease because they are life threatening. [[Heart failure]] and [[atrial fibrillation]] are the most common cardiac complications. Thyroid dermopathy, presenting as pretibial [[myxedema]] and acropachy is another complication. When compared with people older than 60 years with a healthy thyroid, those who are hyperthyroid have three times the risk of atrial fibrillation. Thyroid associated ophthalmopathy must be evaluated in every patient with Graves' disease. Thyroid crisis is another life-threatening complication of Graves' disease. Prognosis is varied and depends on the severity of the disease and adequacy of treatment. However, it is considered good.
-*When compared with people older than 60 years with a healthy thyroid, those who are hyperthyroid have three times the risk of atrial fibrillation.<ref name="pmid7935681">{{cite journal |vauthors=Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, Bacharach P, Wilson PW, Benjamin EJ, D'Agostino RB |title=Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons |journal=N. Engl. J. Med. |volume=331 |issue=19 |pages=1249–52 |year=1994 |pmid=7935681 |doi=10.1056/NEJM199411103311901 |url=}}</ref><ref name="pmid27811932">{{cite journal |vauthors=Jabbar A, Pingitore A, Pearce SH, Zaman A, Iervasi G, Razvi S |title=Thyroid hormones and cardiovascular disease |journal=Nat Rev Cardiol |volume=14 |issue=1 |pages=39–55 |year=2017 |pmid=27811932 |doi=10.1038/nrcardio.2016.174 |url=}}</ref>
-Thyroid associated ophtalmopathy must be evaluated in every patient with Graves' disease.<ref name="pmid24766932">{{cite journal |vauthors=Devereaux D, Tewelde SZ |title=Hyperthyroidism and thyrotoxicosis |journal=Emerg. Med. Clin. North Am. |volume=32 |issue=2 |pages=277–92 |year=2014 |pmid=24766932 |doi=10.1016/j.emc.2013.12.001 |url=}}</ref>
-Thyroid crisis is another life threatening complication of Graves' disease.
 ==Diagnosis==
-In the presence of relative clinical symptoms and signs for hyperthyroidism, a diagnostic approach must be taken to address accurate diagnosis and start the management.<ref name="pmid22776786">{{cite journal |vauthors=Tozzoli R, Bagnasco M, Giavarina D, Bizzaro N |title=TSH receptor autoantibody immunoassay in patients with Graves' disease: improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis |journal=Autoimmun Rev |volume=12 |issue=2 |pages=107–13 |year=2012 |pmid=22776786 |doi=10.1016/j.autrev.2012.07.003 |url=}}</ref><ref name="pmid">{{cite journal |vauthors=Pedersen IB, Knudsen N, Perrild H, Ovesen L, Laurberg P |title=TSH-receptor antibody measurement for differentiation of hyperthyroidism into Graves' disease and multinodular toxic goitre: a comparison of two competitive binding assays |journal=Clin. Endocrinol. (Oxf) |volume=55 |issue=3 |pages=381–90 |year=2001 |pmid= |doi= |url=}}</ref><ref>{{Cite journal
+In the presence of relative clinical symptoms and signs for [[hyperthyroidism]], a diagnostic approach must be taken to address accurate diagnosis and start the management
- | author = [[Terry J. Smith]] & [[Laszlo Hegedus]]
+Presence of at least one of the following findings in a hyperthyroid patient is definitive for Graves' disease.
- | title = Graves' Disease
+* Detectable [[TSH]] receptor antibodies (TRAbs) in the [[serum]]
- | journal = [[The New England journal of medicine]]
- | volume = 375
- | issue = 16
- | pages = 1552–1565
- | year = 2016
- | month = October
- | doi = 10.1056/NEJMra1510030
- | pmid = 27797318
-}}</ref>
-Presence of at least one of the following findings in a hyperthyroid patient is definitive for Graves' disease.<ref>{{cite book | last = Shoenfeld | first = Yehuda | title = Diagnostic criteria in autoimmune diseases | publisher = Humana | location = Place of publication not identified | year = 2014 | isbn = 978-1627038584 }}</ref>
-* Detectable TSH receptor antibodies (TRAbs) in the serum
 * Evidence of ophthalmopathy and/or dermopathy
 * Diffuse and increased RAIU
 ==Symptoms==
-Some of the most typical symptoms of Graves' Disease are the following:<ref>{{Cite journal
+Some of the most typical symptoms of Graves' Disease are the following:
- | author = [[Terry J. Smith]] & [[Laszlo Hegedus]]
- | title = Graves' Disease
+[[Palpitations]], [[tremor]] (usually fine shaking eg. hands), [[excessive sweating]], heat intolerance, increased [[appetite]], unexplained [[weight loss]] despite increased appetite, [[shortness of breath]], muscle [[weakness]] (especially in the large muscles of the arms and legs) and degeneration, [[insomnia]], increased energy, [[fatigue]], mental impairment, memory lapses, diminished attention, decreased concentration, [[nervousness]], [[agitation]], [[irritability]], [[restlessness]], erratic behavior, [[emotional lability]], [[gynecomastia]], [[goiter]] (enlarged thyroid gland), [[double vision]], [[eye pain]], [[irritation]], or the feeling of grit or sand in the eyes, swelling or redness of the eyes or [[eyelids]]/eyelid retraction, [[Photophobia|sensitivity to light]], decrease in menstrual periods ([[oligomenorrhea]]), [[amenorrhea]], [[infertility]]/recurrent [[miscarriage]], [[hair loss]], a non-pitting [[edema]] with thickening of the skin, described as [[Peau d'orange|'''peau d'orange''']] or '''orange peel''', usually found on the lower extremities, smooth, velvety skin, increased bowel movements or [[diarrhea]].
- | journal = [[The New England journal of medicine]]
- | volume = 375
- | issue = 16
- | pages = 1552–1565
- | year = 2016
- | month = October
- | doi = 10.1056/NEJMra1510030
- | pmid = 27797318
-}}</ref><br>
-[[Palpitations]], [[tremor]] (usually fine shaking eg. hands), [[excessive sweating]], heat intolerance, increased appetite, unexplained [[weight loss]] despite increased appetite, [[shortness of breath]], muscle [[weakness]] (especially in the large muscles of the arms and legs) and degeneration, [[insomnia]], increased energy, [[fatigue]], mental impairment, memory lapses, diminished attention span, decreased concentration, nervousness, agitation, irritability, restlessness, erratic behavior, emotional lability, [[gynecomastia]], [[goiter]] (enlarged thyroid gland), [[double vision]], eye pain, irritation, or the feeling of grit or sand in the eyes, swelling or redness of eyes or eyelids/eyelid retraction, sensitivity to light, decrease in menstrual periods ([[oligomenorrhea]]), [[amenorrhea]], infertility/recurrent miscarriage, [[hair loss]], a non-pitting [[edema]] with thickening of the skin, described as "peau d'orange" or "orange peel", usually found on the lower extremities, smooth, velvety skin, increased bowel movements or [[diarrhea]].
 == Physical Examination ==
-*Signs include tachycardia, stare, eyelid lag, proptosis, goiter, resting tremor, hyperreflexia, and warm, moist, and smooth skin. <ref>{{Cite journal
+Signs include [[tachycardia]], stare, eyelid lag, [[proptosis]], [[goiter]], resting [[tremor]], [[hyperreflexia]], and warm, moist, and smooth skin.
- | author = [[Terry J. Smith]] & [[Laszlo Hegedus]]
- | title = Graves' Disease
- | journal = [[The New England journal of medicine]]
- | volume = 375
- | issue = 16
- | pages = 1552–1565
- | year = 2016
- | month = October
- | doi = 10.1056/NEJMra1510030
- | pmid = 27797318
-}}</ref>
 == Laboratory Findings ==
-The laboratory findings for Graves' disease are:
+The laboratory findings for Graves' disease show elevated levels of serum [[thyroxine]] (T4), [[triiodothyronine]] (T3) and undetectable serum [[TSH|TSH.]]
-*Elevated levels of serum thyroxine (T4) and triiodothyronine (T3)
-*Undetectable serum TSH.
 ==Hyperthyroidism Therapy==
-===Genreral aspects===
-*In a small proportion of patients, spontaneous remission occurs.
+===Medical Therapy===
-*Smoking cessation is one of the main stays of treatment.
+In a small proportion of patients, spontaneous remission occurs. [[Smoking cessation]] is one of the mainstay of treatment. Antithyroid drugs are the first line treatment in Europe. Ablation therapy either by [[thyroidectomy]] or [[radioactive iodine]] is more accepted in North America.
-*Antithyroid drugs are the first line treatment in Europe.
-*Ablation therapy either by thyroidectomy or radioactive iodine is more accepted in North America.
 ===Antithyroid Drugs===
+[[Methimazole]], [[carbimazole]]  and [[propylthiouracil]] are the available anti thyroid drugs. [[Methimazole]] is preferred for initial therapy in both Europe and North America because of its favorable side-effect profile. Durable remission occurs in 40 to 50% of patients which is defined as euthyroidism for at least 12 months following 1-2 years of treatment. Patients may be switched from one drug to another when necessitated by minor side effects. Monitoring by means of [[liver function tests]] and [[White blood cells|white-cell]] counts before and during antithyroid drug therapy is advocated by some experts but is not currently supported by consensus opinion.
-*[[Methimazole]], [[carbimazole]]  and [[propylthiouracil]] are the available anti thyroid drugs.
+===Radioactive Iodine===
-*Methimazole is preferred for initial therapy in both Europe and North America because of its favorable side-effect profile.<ref name="pmid23043191">{{cite journal |vauthors=Burch HB, Burman KD, Cooper DS |title=A 2011 survey of clinical practice patterns in the management of Graves' disease |journal=J. Clin. Endocrinol. Metab. |volume=97 |issue=12 |pages=4549–58 |year=2012 |pmid=23043191 |doi=10.1210/jc.2012-2802 |url=}}</ref><ref name="pmid25581877">{{cite journal |vauthors=Bartalena L, Burch HB, Burman KD, Kahaly GJ |title=A 2013 European survey of clinical practice patterns in the management of Graves' disease |journal=Clin. Endocrinol. (Oxf) |volume=84 |issue=1 |pages=115–20 |year=2016 |pmid=25581877 |doi=10.1111/cen.12688 |url=}}</ref>
+[[Iodine-131|Radioactive iodine]] therapy offers relief from symptoms of [[hyperthyroidism]] within weeks. [[Radioiodine]] is not associated with an increased risk of [[cancer]]. It can provoke or worsen ophthalmopathy.
-*Durable remission occurs in 40 to 50% of patients which is defined as euthroidism for at least 12 months following 1-2 years of treatment.
-*Patients may be switched from one drug to another when necessitated by minor side effects.
-*Monitoring by means of liver-function tests and white-cell counts before and during antithyroid drug therapy is advocated by some experts but is not currently supported by consensus opinion.
-===Radioactive Iodine===
+==Ophthalmopathy==
-*[[Iodine-131|Radioactive iodine]] therapy offers relief from symptoms of hyperthyroidism within weeks.
+Treatment for ophthalmopathy depends on the phase and severity of the disease. It ranges from enhancement of tear film quality and maintenance of ocular surface moisture for the mild disease to intravenously administered pulse [[glucocorticoid]] therapy for severe and sight-threatening disease.
-*Radioiodine is not associated with an increased risk of cancer.<ref name="pmid9686552">{{cite journal |vauthors=Ron E, Doody MM, Becker DV, Brill AB, Curtis RE, Goldman MB, Harris BS, Hoffman DA, McConahey WM, Maxon HR, Preston-Martin S, Warshauer ME, Wong FL, Boice JD |title=Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group |journal=JAMA |volume=280 |issue=4 |pages=347–55 |year=1998 |pmid=9686552 |doi= |url=}}</ref>
-*It can provoke or worsen ophthalmopathy.<ref name="pmid19264688">{{cite journal |vauthors=Bartalena L, Tanda ML |title=Clinical practice. Graves' ophthalmopathy |journal=N. Engl. J. Med. |volume=360 |issue=10 |pages=994–1001 |year=2009 |pmid=19264688 |doi=10.1056/NEJMcp0806317 |url=}}</ref>
-==Ophtalmopathy==
-Treatment for ophthalmopathy depends on the phase and severity of the disease. It is ranged from enhancement of tear-film quality and maintenance of ocular surface moisture for mild disease to intravenously administered pulse glucocorticoid therapy for severe and sight threatening disease.
 == Surgery ==
-*The patients' thyroid hormone must be normalized before surgery to minimize the risk of surgery.
+The patients' thyroid hormone must be normalized before surgery to minimize the risk of surgery. Surgery is recommended for some patients including patients with large [[Goiter|goiters]], women wishing to become pregnant shortly after treatment and patients who want to avoid exposure to antithyroid drugs or [[radioiodine]].
-*Surgery is recommended for some patients including,<ref name="pmid21700562">{{cite journal |vauthors=Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN |title=Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists |journal=Endocr Pract |volume=17 |issue=3 |pages=456–520 |year=2011 |pmid=21700562 |doi= |url=}}</ref>
-#Patients with large goiters
-#Women wishing to become pregnant shortly after treatment
-#Patients who want to avoid exposure to antithyroid drugs or radioiodine.
 ==References==