Graves' disease

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Graves disease
A gross photograph of a thyroid from a case of nodular goiter.
Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology
ICD-10 E05.0
ICD-9 242.0
OMIM 275000
MedlinePlus 000358
MeSH D006111

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Graves' disease Microchapters

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Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Graves' disease from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

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History and Symptoms

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Medical Therapy

Hyperthyroidism
Ophtalmopathy
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Case #1

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Basedow disease; Basedow's disease; Graves-Basedow disease.

Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Graves' disease from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies

Treatment

Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

Case Studies

Case #1


Treatment

Medical treatment of Graves' disease includes antithyroid drugs, radioactive iodine and thyroidectomy (surgical excision of the gland).

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 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.

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.

Antithyroid drugs

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 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.

Radioiodine

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.

Contraindications to RAI are pregnancy (absolute), ophthalmopathy (relative- it can aggravate thyroid eye disease), solitary 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.

Surgery

This modality is suitable for young patients and pregnant patients. Indications are: a large goiter (especially when compressing the trachea), suspicious nodules or suspected cancer (to pathologically examine the thyroid) and patients with ophthalmopathy.

Both bilateral subtotal thyroidectomy and the Hartley-Dunhill procedure (hemithyroidectomy on 1 side and partial lobectomy on other side) are possible.

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 glands), hematoma (which can be life-threatening if it compresses the trachea) and scarring.

Herbal

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.

Eye disease

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.

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.

  • For mild disease - artificial tears, steroid eyedrops, oral steroids (to reduce chemosis)
  • For moderate disease - lateral tarsorrhaphy
  • For severe disease - orbital decompression or retro-orbital radiation

Pathological Findings: A Case Example

Clinical Summary

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.

Autopsy Findings

The thyroid gland weighed 45 grams. It was beefy red in color and had a homogeneous fleshy consistency.

Histopathological Findings

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

A photograph of the thyroid from this case. Note that the gland is enlarged and is dark red.


This is a low-power photomicrograph of thyroid tissue from this case. The tissue is very cellular with very little colloid.


This is a higher-power photomicrograph of thyroid. The tissue is very cellular and there is little colloid.


This is a high-power photomicrograph of thyroid. Note the cellularity of the tissue with marked infolding of the epithelial tissue.


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.


This is a gross photograph of a thyroid from a case of nodular goiter.


Closer view of cut surface of the thyroid with nodular goiter. Note the multilobular appearance of the tissue.


Bibliography

  • Sayyid Ismail Al-Jurjani. Thesaurus of the Shah of Khwarazm.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Von Basedow KA. Die Glotzaugen. [Casper's] Wochenschrift für die gesammte Heilkunde, Berlin, 1848: 769-777.
  • 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.

References

See also

External links

Acknowledgements

The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.

de:Basedow-Krankheit it:Morbo di Basedow he:מחלת גרייבס nl:Ziekte van Graves sv:Basedows sjukdom uk:Базедова хвороба


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