Hyperthyroid Disorders

Lesson 4: Causes of Hyperthyroidism

Hereditary Hyperthyroidism and Genetic Mutations

Hereditary hyperthyroidism and a similar condition of hyperthyroidism caused by a somatic mutation to the TSH receptor are two distinct genetic disorders frequently confused with Graves’ disease. Resistance to thyroid hormone or RTH is another genetic disorder that may be confused with Graves’ disease. Studies show that many patients diagnosed with Graves’ disease actually have one of these other disorders. Because Graves’ disease causes more than 70 percent of all cases of hyperthyroidism, some practitioners diagnose disorders of hyperthyroidism as being related to Graves’ disease without performing all the necessary tests.

The primary difference between the genetic hyperthyroid disorders and Graves’ disease is that these genetic disorders are not autoimmune. Tests for thyroid antibodies will be negative. Unfortunately, many doctors diagnose hyperthyroidism as being Graves’ disease without ever running antibody tests to confirm the diagnosis.

To complicate matters, patients with hyperthyroidism who are treated with radioiodine ablation frequently later develop Graves’ disease since radioiodine is a trigger for autoimmune thyroid disease. Radioiodine stimulates immune system cells to produce TSH receptor antibodies. Therefore, it’s impossible to tell if patients treated with radioiodine had Graves’ disease before or after radioiodine ablation although genetic tests can be performed to tell if the patient has a genetic defect responsible for the development of hyperthyroidism.

The hereditary hyperthyroid disorders, like Graves’ disease, will cause an increased RAI-uptake test when they result in hyperthyroidism, and the scan will show an even or diffuse distribution of radioiodine. These genetic disorders can cause a painless goiter and symptoms of thyrotoxicosis. Transmission of hereditary hyperthyroidism appears to be autosomal dominant. Somatic mutations to the TSH receptor involve a mutation of one amino acid in the TSH receptor found on thyroid cells. Over time, this mutation can lead to thyroid adenomas.

Resistance to thyroid hormone is a syndrome of reduced resistance of target tissues to thyroid hormone. RTH can cause both hypothyroidism and hyperthyroidism. In hyperthyroid patients, levels of circulating FT4 and FT3 are high and TSH is usually normal or it may remain high. Point mutations have been identified in subjects from more than 150 different families, and with one exception, RTH is caused by mutations in the thyroid hormone receptor gene.

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