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
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 to 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
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.
Thyroid function must be well
controlled prior to anesthesia to avoid thyrotoxic crisis, which can be
triggered by any form of stress including surgery, but also by iodine-based
contrast agents. Baseline therapy consists of antithyroid drugs, such as
methimazole, carbimazole, and propylthiouracil. ...