An autoimmune disease resulting in nonsuppressible overproduction of thyroid hormone characterized by hyperthyroidism, goiter, and exophthalmos. There is often a family history of both Graves disease and autoimmune thyroiditis.
Basedow Disease; Begbie Disease; Diffuse Thyrotoxic Goiter; Flajani Disease; Flajani-Basedow Syndrome; Graves-Basedow Disease; Marsh Disease; Parry Disease.
First reported 800 years ago by the Persian physician Sayyid Ismail Al-Jurjani (in Thesaurus of the Shah of Khwarazm); Robert James Graves (1797-1853) was an Irish physician who described the disease including exophthalmos in 1835. The German physician Karl Adolph von Basedow (1799-1854) described the disease in 1840.
Autoimmune disease involving thyroidal and orbital tissue resulting in a goiter with thyrotoxicosis and ophthalmic abnormalities.
1% of the population suffers from Graves disease, with a female predominance (female-to-male ratio 4:1). Peak onset is in the third and fourth decades of life; only 5% of cases arise in childhood and adolescence. It is extremely rare in neonates (1:50,000 live births).
Etiology is unknown, but there is a genetic predisposition to the disease. Both autosomal dominant and autosomal recessive inheritance have been suggested. May be multifactorial.
Production of thyroid-stimulating IgG immunoglobulins (TSI), which are antibodies to the thyroid stimulating hormone (TSH)-receptors of the thyroid follicular cell. TSI activate TSH receptors, which induces the intracellular production of cyclic AMP via adenylate cyclase, leading to excessive thyroid hormone secretion. In approximately 40% of cases, lymphocytic infiltration and deposition of glucosaminoglycans into the exterior eye muscles leads to Basedow ophthalmopathy. In neonates, the most common source of TSI is active transplacental transfer of IgG immunoglobulin from mothers with Graves disease and is therefore self-limited (4-8 weeks) and resolves with the disappearance of these TSI from the neonatal serum. Secondary to pituitary suppression of TSH production by the elevated levels of TSI, a transient period of hypothyroidism may follow.
Clinical features; biochemical (high circulating levels of T4 and T3, low serum TSH, presence of TSI); imaging studies (diffuse and increased 123I uptake).
Antenatal: Intrauterine growth retardation, fetal tachycardia, premature birth, and intrauterine death.
Neonatal: Arrhythmias, systemic and pulmonary hypertension, heart failure, hepatosplenomegaly, prolonged neonatal jaundice, flushing, fever, diaphoresis, diarrhea, vomiting, failure to thrive (with sometimes profound weight loss), goiter that may cause airway obstruction, and eye signs (lid lag, exophthalmos, and stare).
Childhood: Marked weight loss despite enormous appetite, enlarged thyroid gland with bruit, tachycardia, hypertension, high output cardiac failure, tremors, nervousness, sweating, heat intolerance, diarrhea, hyperactivity, fatigue, behavior disturbances, poor concentration, hyperreflexia, and ophthalmic manifestations that are less severe than in adults; pretibial myxedema is rare in children.