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| {{Infobox_Disease
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| | Name = Graves disease
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| | Image = Graves' disease 6.jpg
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| | Caption = A gross photograph of a thyroid from a case of nodular goiter. <br> <small> [http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology] </small>
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| | DiseasesDB =
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| | ICD10 = {{ICD10|E|05|0|e|00}}
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| | ICD9 = {{ICD9|242.0}}
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| | ICDO =
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| | OMIM = 275000
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| | MedlinePlus = 000358
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| | MeshID = D006111
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| }}
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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' | | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
| {{Graves' disease}} | | {{Graves' disease}} |
| [[Image:pretibial myxedema (Grave's Disease).jpg|thumb|200px|Pretibial myxedema (Grave's Disease)]]
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| {{CMG}} | | {{CMG}},{{AE}}{{MehdiP}} |
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| {{SK}} Basedow disease; Basedow's disease; Graves-Basedow disease. | | {{SK}} Basedow disease; Basedow's disease; Graves-Basedow disease. |
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| ==[[Graves' disease natural history, complications and prognosis|Natural History, Complications and Prognosis]]== | | ==[[Graves' disease natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| [[Image:Basedow-vor-nach-RIT.jpg|thumb|]]
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| == Diagnosis == | | == Diagnosis == |
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| [[Graves' disease history and symptoms|History and Symptoms]] | [[Graves' disease physical examination|Physical Examination]] | [[Graves' disease laboratory findings|Laboratory Findings]] | [[Graves' disease electrocardiogram|Electrocardiogram]] | [[Graves' disease x ray|X Ray]] | [[Graves' disease CT|CT]] | [[Graves' disease MRI|MRI]] | [[Graves' disease echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Graves' disease other imaging findings|Other Imaging Findings]] | [[Graves' disease other diagnostic studies|Other Diagnostic Studies]] | | [[Graves' disease diagnostic approach|Diagnostic Approach]] | [[Graves' disease history and symptoms|History and Symptoms]] | [[Graves' disease physical examination|Physical Examination]] | [[Graves' disease laboratory findings|Laboratory Findings]] | [[Graves' disease electrocardiogram|Electrocardiogram]] | [[Graves' disease x ray|X Ray]] | [[Graves' disease CT|CT]] | [[Graves' disease MRI|MRI]] | [[Graves' disease echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Graves' disease other imaging findings|Other Imaging Findings]] | [[Graves' disease other diagnostic studies|Other Diagnostic Studies]] |
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| == Treatment == | | == Treatment == |
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| [[Graves' disease medical therapy|Medical Therapy]] | [[Graves' disease surgery|Surgery]] | [[Graves' disease primary prevention|Primary Prevention]] | [[Graves' disease secondary prevention|Secondary Prevention]] | [[Graves' disease cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Graves' disease future or investigational therapies|Future or Investigational Therapies]] | | [[Graves' disease hyperthyroidism medical therapy|Hyperthyroidism Medical Therapy]] | [[Graves' disease ophtalmopathy medical therapy|Ophtalmopathy Medical therapy]] | [[Graves' disease dermopathy medical therapy|Dermopathy Medical Therapy]] | [[Graves' disease surgery|Surgery]] | [[Graves' disease cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Graves' disease future or investigational therapies|Future or Investigational Therapies]] |
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| == Case Studies == | | == Case Studies == |
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| [[Graves' disease case study one|Case #1]] | | [[Graves' disease case study one|Case #1]] |
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| Graves' disease may present clinically with one of the following characteristic signs:
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| *[[Goitre|goiter]] (an enlarged thyroid gland, sometimes detectable as a swelling in the neck)
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| *[[exophthalmos]] (protuberance of one or both eyes)
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| *a non-pitting [[edema]] with thickening of the skin, described as "peau d'orange" or "orange peel", usually found on the lower extremities
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| *fatigue, weight loss with increased appetite, and other symptoms of [[hyperthyroidism]]
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| The two signs that are truly ''diagnostic'' of Graves' disease (i.e. not seen in other hyperthyroid conditions) are exophthalmos and nonpitting edema. Goiter, which is caused by an enlarged thyroid gland, can be present with other forms of hyperthyroidism, although Graves' disease is the most common cause. A large goiter is visible to the naked eye, but a smaller goiter may not be clinically detectable, though [[X-ray]]s or [[ultrasound]] can assist in detecting it.
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| Another sign of Graves' disease is [[hyperthyroidism]], i.e. over-production of the [[thyroid hormone|thyroid hormones]] T3 and T4. Although, [[hypothyroidism]] has also been associated and may be the causating factor in some patients. Hyperthyroidism can be confirmed by measuring elevated blood levels levels of free (unbound) T3 and T4. Other useful laboratory measurements include [[thyroid-stimulating hormone]] (TSH, low in Graves' disease due to negative feedback from the elevated T3 and T4), and protein-bound [[iodine]] (elevated). Thyroid-stimulating antibodies may also be detected [[serology|serologically]].
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| Definitive diagnosis requires a [[biopsy]].
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| ===Other Graves' Disease Symptoms===
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| Some of the most typical symptoms of Graves' Disease are the following:
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| * [[Palpitations]]
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| * [[Tachycardia]] (rapid heart rate: 100-120 beats per minute, or higher)
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| * [[Arrhythmia]] (irregular heart beat)
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| * Raised blood pressure ([[Hypertension]])
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| * [[Tremor]] (usually fine shaking eg. hands)
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| * [[Excessive sweating]]
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| * Heat intolerance
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| * Increased appetite
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| * Unexplained [[weight loss]] despite increased appetite
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| * [[Shortness of breath]]
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| * Muscle [[weakness]] (especially in the large muscles of the arms and legs) and degeneration
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| * Diminished/Changed sex drive
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| * [[Insomnia]] (inability to get enough sleep)
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| * Increased energy
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| * [[Fatigue]]
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| * Mental impairment, memory lapses, diminished attention span
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| * Decreased concentration
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| * Nervousness, agitation
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| * Irritability
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| * Restlessness
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| * Erratic behavior
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| * Emotional lability
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| * Brittle nails
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| * Abnormal [[breast enlargement]] (men)
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| * [[Goiter]] (enlarged thyroid gland)
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| * [[Protruding eyeballs]] (Graves' disease only)
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| * [[Double vision]]
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| * Eye pain, irritation, or the feeling of grit or sand in the eyes
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| * Swelling or redness of eyes or eyelids/eyelid retraction
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| * Sensitivity to light
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| * Decrease in menstrual periods ([[oligomenorrhea]]), Irregular and scant menstrual flow ([[Amenorrhea]])
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| * Difficulty conceiving/infertility/recurrent miscarriage
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| * [[Hair loss]]
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| * Itchy skin, hives
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| * Chronic sinus infections
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| * Lumpy, reddish skin of the lower legs ([[pretibial myxedema]])
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| * Smooth, velvety skin
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| * Increased bowel movements or [[Diarrhea]]
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| ==Diganostic Studies==
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| :*'''High RAIU:''' de novo T4 synthesis
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| ::*Toxic adenoma
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| ::*Toxic multinodular goiter
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| ::*TSH-producing pituitary tumor
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| ::*Hcg-secreting tumor
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| ::*Hyperemesis gravidarum
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| :*'''Low RAIU:''' released or exogenous T4
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| ::*Thyroiditis - painful, painless, post-partum
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| ::*Amiodarone toxicity
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| ::*Factitious hyperthyroidism
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| ::*Struma ovarii (rare)
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| ::*Metastatic thyroid CA (ridiculously rare)
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| :*Thyroid-stimulating antibodies bind and stimulate the TSH receptor
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| :*Anti-TSHR ABs are 80-95% sensitive, 80-90% specific for Graves’
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| ==Treatment==
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| Medical treatment of Graves' disease includes antithyroid drugs, radioactive [[iodine]] and [[thyroidectomy]] (surgical excision of the gland).
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| Treatment of the hyperthyroidism of Graves disease may be with medications such as carbimazole, methimazole or [[propylthiouracil]] (PTU), which reduce the production of [[thyroid hormone]], or with [[radioiodine|radioactive iodine]]. Surgical removal of the thyroid is another option, but still requires preoperative treatment with methimazole or PTU. This is done to render the patient "euthyroid" (i.e. normothyroid) before the surgery since operating on a frankly hyperthyroid patient is dangerous. Therapy with radioactive iodine (I-131) is the most common treatment in the United States. Thyroid blocking drugs and/or surgical thyroid removal is used more often than radioactive iodine as definitive treatment in Europe, Japan, and most of the rest of the world.
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| The development of radioactive iodine (I-131) in the early 1940s at the [[Mallinckrodt General Clinical Research Center]] and its widespread adoption as treatment for Graves' Disease has led to a progressive reduction in the use of surgical thyroidectomy for this problem. In general, RAI therapy is effective, less expensive, and avoids the small but definite risks of surgery. Treatment with antithyroid medications must be given for six months to two years, in order to be effective. Even then, upon cessation of the drugs, the hyperthyroid state may recur. Side effects of the antithyroid medications include a potentially fatal reduction in the level of white blood cells.
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| ===Antithyroid drugs===
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| The main antithyroid drugs are [[methimazole]] (US), [[carbimazole]] (UK) and [[propylthiouracil]]. These drugs block the binding of iodine and coupling of iodotyrosines. The most dangerous side-effect is [[agranulocytosis]] (1/250, more in PTU); this is an idiosyncratic reaction which does not stop on cessation of drug. Others include [[neutropenia|granulocytopenia]] (dose dependent, which improves on cessation of the drug) and [[aplastic anemia]]. Patients on these medications should see a doctor if they develop sore throat or fever. The most common side effects are rash and peripheral neuritis. These drugs also cross the [[placenta]] and are secreted in breast milk.
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| ===Radioiodine===
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| This modality is suitable for most patients, although some prefer to use it mainly for older patients. Indications for [[radioiodine]] are: failed medical therapy or surgery and where medical or surgical therapy are contraindicated.
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| Contraindications to RAI are [[pregnancy]] (absolute), ophthalmopathy (relative- it can aggravate thyroid eye disease), solitary [[thyroid nodule|nodules]]. Disadvantages of this treatment are a high incidence of [[hypothyroidism]] (up to 80%) requiring hormone supplementation. It acts slowly and has a relapse rate that depends on the dose administered.
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| ===Surgery===
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| This modality is suitable for young patients and pregnant patients. Indications are: a large goiter (especially when compressing the [[vertebrate trachea|trachea]]), suspicious nodules or suspected [[cancer]] (to pathologically examine the thyroid) and patients with ophthalmopathy.
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| Both bilateral subtotal thyroidectomy and the Hartley-Dunhill procedure (hemithyroidectomy on 1 side and partial lobectomy on other side) are possible.
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| Advantages are: immediate cure and potential removal of [[carcinoma]]. Its risks are injury of the [[recurrent laryngeal nerve]], [[hypoparathyroidism]] (due to removal of the [[parathyroid gland]]s), [[hematoma]] (which can be life-threatening if it compresses the trachea) and scarring.
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| ===Herbal===
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| For treating Graves disease, along with many other thyroid disorders, one can use the herb bugleweed. This herb has a profound effect on thyroid function and regulation of thyroid hormones.
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| ===Eye disease===
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| Thyroid-associated ophthalmopathy is one of the most typical symptom of Graves Disease. It is known by a variety of terms, the commonest being [[Graves ophthalmopathy]]. Thyroid eye disease is an inflammatory condition which affects the orbital contents including the extraocular muscles and orbital fat. It is almost always associated with Graves' disease but may rarely be seen in Hashimoto's thyroiditis, primary hypothyroidism, or thyroid cancer.
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| The ocular manifestations include soft tissue inflammation, eyelid retraction, proptosis, corneal exposure, and optic nerve compression. The signs and symptoms of the disease are characteristic. These include lid retraction, lid lag, and a delay in the downward excursion of the upper eyelid in down gaze that is specific to thyroid-associated ophthalmopathy.
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| *For mild disease - artificial tears, steroid eyedrops, oral steroids (to reduce chemosis)
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| *For moderate disease - lateral [[tarsorrhaphy]]
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| *For severe disease - orbital decompression or retro-orbital radiation
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| ==Pathological Findings: A Case Example==
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| ===Clinical Summary===
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| An 18-year-old girl presented with complaints of swelling in the neck, weight loss, bulging of the eyes, tremor, decreased heat tolerance, loose stools, and occasional palpitations. Physical examination revealed normal blood pressure, resting tachycardia of 110 beats per minute, mild exophthalmos, eyelid lag, and a diffusely enlarged thyroid gland. Pertinent laboratory findings were thyroxine (T4) level 30.8 mcg/dL, free thyroxine was 2.7 ng/dL, and thyroid stimulating hormone (TSH) was 0.22 mcIU/mL. She was given propylthiouracil until she became nearly euthyroid, at which time a thyroidectomy was done.
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| ===Autopsy Findings===
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| The thyroid gland weighed 45 grams. It was beefy red in color and had a homogeneous fleshy consistency.
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| ===Histopathological Findings===
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| [http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
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| [[Image:Graves' disease 1.jpg|left|thumb|400px|A photograph of the thyroid from this case. Note that the gland is enlarged and is dark red.]]
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| [[Image:Graves' disease 2.jpg|left|thumb|400px|This is a low-power photomicrograph of thyroid tissue from this case. The tissue is very cellular with very little colloid.]]
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| [[Image:Graves' disease 3.jpg|left|thumb|400px|This is a higher-power photomicrograph of thyroid. The tissue is very cellular and there is little colloid.]]
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| [[Image:Graves' disease 4.jpg|left|thumb|400px|This is a high-power photomicrograph of thyroid. Note the cellularity of the tissue with marked infolding of the epithelial tissue.]]
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| [[Image:Graves' disease 5.jpg|left|thumb|400px|This is a high-power photomicrograph of thyroid. Note the papillary projections and the moth-eaten appearance of the colloid. This appearance indicates active absorption of the colloid to form thyroglobulin.]]
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| [[Image:Graves' disease 6.jpg|left|thumb|400px|This is a gross photograph of a thyroid from a case of nodular goiter.]]
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| [[Image:Graves' disease 7.jpg|left|thumb|400px|Closer view of cut surface of the thyroid with nodular goiter. Note the multilobular appearance of the tissue.]]
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| <br clear="left"/>
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| ==Bibliography==
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| {{refbegin|2}}
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| * Sayyid Ismail Al-Jurjani. ''Thesaurus of the Shah of Khwarazm.''
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| * Flajani G. ''Sopra un tumor freddo nell'anterior parte del collo broncocele. (Osservazione LXVII).'' In Collezione d'osservazioni e reflessioni di chirurgia. Rome, Michele A Ripa Presso Lino Contedini, 1802;3:270-273.
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| * Testa AG. ''Delle malattie del cuore, loro cagioni, specie, segni e cura.'' Bologna, 1810. 2nd edition in 3 volumes, Florence, 1823; Milano 1831; German translation, Halle, 1813.
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| * Parry CH. ''Enlargement of the thyroid gland in connection with enlargement or palpitations of the heart.'' Posthumous, in: Collections from the unpublished medical writings of C. H. Parry. London, 1825, pp. 111-129. According to Garrison, Parry first noted the condition in 1786. He briefly reported it in his Elements of Pathology and Therapeutics, 1815. Reprinted in Medical Classics, 1940, 5: 8-30.
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| * Graves RJ. ''New observed affection of the thyroid gland in females''. (Clinical lectures.) London Medical and Surgical Journal (Renshaw), 1835; 7: 516-517. Reprinted in Medical Classics, 1940;5:33-36.
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| * Marsh H. ''Dilatation of the cavities of the heart. Enlargement of the thyroid gland.'' Dublin Journal of Medical and Chemical Science. 1842, 20: 471-474. Abstract.
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| * Von Basedow KA. ''Exophthalmus durch Hypertrophie des Zellgewebes in der Augenhöhle.'' [Casper's] Wochenschrift für die gesammte Heilkunde, Berlin, 1840, 6: 197-204; 220-228. Partial English translation in: Ralph Hermon Major (1884-1970): Classic Descriptions of Disease. Springfield, C. C. Thomas, 1932. 2nd edition, 1939; 3rd edition, 1945.
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| * Von Basedow KA. ''Die Glotzaugen.'' [Casper's] Wochenschrift für die gesammte Heilkunde, Berlin, 1848: 769-777.
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| * Begbie J. ''Anaemia and its consequences; enlargement of the thyroid gland and eyeballs. Anaemia and goitre, are they related?'' Monthly Journal of Medical Science, London, 1849, 9: 496-508.
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| {{refend}}
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| ==References==
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| {{reflist|2}}
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| == See also == | | == See also == |
| * [[Graves ophthalmopathy]] | | * [[Graves ophthalmopathy]] |
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| == External links ==
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| * [http://www.bucksendocrine.com Minimal access thyroid surgery for Graves disease discussed by a UK specialist surgeon]
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| * [http://www.medifocushealth.com/ND004/graves_disease.php MedifocusHealth.com] guidebook on Graves' Disease based on medical literature.
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| * [http://graves.medshelf.org/Main_Page Compilation of basic information and self help strategies for those suffering from Graves' Disease].
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| == Acknowledgements ==
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| The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.
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| {{Endocrine pathology}} | | {{Endocrine pathology}} |