Graves' disease overview: Difference between revisions
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==Historical Perspective== | ==Historical Perspective== | ||
Graves disease owes its name to the Irish doctor Randy Danny Graves, | 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 == | == 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|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, 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. | ||
==Causes== | ==Causes== | ||
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. | 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== | ==Differential Diagnosis== | ||
The table below summarizes the list of differential diagnosis for Graves' disease. | The table below summarizes the list of differential diagnosis for Graves' disease. | ||
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==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
Graves’ disease is the most common cause of [[hyperthyroidism]]. | Graves’ disease is the most common cause of [[hyperthyroidism]]. | ||
===Incidence=== | ===Incidence=== | ||
*Grave's disease annual incidence is about 20 to 50 cases per 100,000 persons. | *Grave's disease annual incidence is about 20 to 50 cases per 100,000 persons. | ||
===Prevalence=== | ===Prevalence=== | ||
The prevalence of Graves’ disease in the 1970s is estimated to be 0.4% in the United States. | |||
===Age=== | ===Age=== | ||
The incidence peaks between 30 and 50 years of age, but people can be affected at any age. | |||
===Race=== | ===Race=== | ||
Graves' disease is more common in Caucasians than in Asians. | |||
===Sex=== | ===Sex=== | ||
Graves' disease is more common among women than men. The lifetime risk is 3% for women and 0.5% for men. | |||
==Risk factors== | ==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 == | == 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, 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. | |||
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== | ==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 | 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. | |||
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]] | * Detectable [[TSH]] receptor antibodies (TRAbs) in the [[serum]] | ||
* Evidence of ophthalmopathy and/or dermopathy | * Evidence of ophthalmopathy and/or dermopathy | ||
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==Symptoms== | ==Symptoms== | ||
Some of the most typical symptoms of Graves' Disease are the following: | 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, [[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]]. | [[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]]. | ||
== Physical Examination == | == Physical Examination == | ||
Signs include [[tachycardia]], stare, eyelid lag, [[proptosis]], [[goiter]], resting [[tremor]], [[hyperreflexia]], and warm, moist, and smooth skin. | Signs include [[tachycardia]], stare, eyelid lag, [[proptosis]], [[goiter]], resting [[tremor]], [[hyperreflexia]], and warm, moist, and smooth skin. | ||
== Laboratory Findings == | == Laboratory Findings == | ||
The laboratory findings for Graves' disease | The laboratory findings for Graves' disease show elevated levels of serum [[thyroxine]] (T4), [[triiodothyronine]] (T3) and undetectable serum [[TSH|TSH.]] | ||
==Hyperthyroidism Therapy== | ==Hyperthyroidism Therapy== | ||
===Medical Therapy=== | ===Medical Therapy=== | ||
In a small proportion of patients, spontaneous remission occurs. | 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. | ||
[[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=== | ===Antithyroid Drugs=== | ||
[[Methimazole]], [[carbimazole]] and [[propylthiouracil]] are the available anti thyroid 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]] 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. | |||
===Radioactive Iodine=== | ===Radioactive Iodine=== | ||
[[Iodine-131|Radioactive iodine]] therapy offers relief from symptoms of [[hyperthyroidism]] within weeks. | [[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. | ||
[[Radioiodine]] is not associated with an increased risk of [[cancer]]. | |||
It can provoke or worsen ophthalmopathy. | |||
==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. | 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 == | == 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]]. | |||
==References== | ==References== | ||
Latest revision as of 21:32, 28 August 2017
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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.