Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma.
نویسندگان
چکیده
Toxic multinodular goiter is a cause of nonautoimmune hyperthyroidism and is believed to differ in its nature and pathogenesis from toxic adenoma. Gain-of-function mutations of the TSH receptor gene have been identified as a cause of toxic adenoma. The pathogenesis at the molecular level of hyperfunctioning nodules in toxic multinodular goiter has yet not been reported. Six patients with a single hot nodule within a multinodular goiter and 11 patients with toxic thyroid adenoma were enrolled in our study. At histology five hyperfunctioning nodules in multinodular goiters showed the features of adenomas, and one was identified as a hyperplastic nodule. The entire exon 10 of the TSH receptor gene was directly sequenced after PCR amplification from genomic DNA obtained from surgical specimens. Functional studies of mutated receptors were performed in COS-7 cells. Five out of 6 (83%) hyperfunctioning nodules within toxic multinodular goiters harbored a TSH receptor mutation. A TSH receptor mutation was also evident in the hyperfunctioning nodule that at histology had the features of noncapsulated hyperplastic nodule. Among toxic adenomas, 8 out of 11 (72%) nodules harbored a TSH receptor mutation. All the mutations were heterozygotic and somatic. Nonfunctioning nodules, whether adenomas or hyperplastic nodules present in association with hyperfunctioning nodules in the same multinodular goiters, had no TSH receptor mutation. All the mutations identified had constitutive activity as assessed by cAMP production after expression in COS-7 cells. Hyperfunctioning thyroid nodules in multinodular goiters recognize the same pathogenetic event (TSH receptor mutation) as toxic adenoma. Other mechanisms are implicated in the growth of nonfunctioning thyroid nodules coexistent in the same gland.
منابع مشابه
A somatic mutation in the thyrotropin receptor gene in a patient with an autonomous nodule within a multinodular goiter.
Thyrotropin (TSH) is the prime regulator of thyroid cell growth and function and acts through the thyrotropin receptor (TSHR) located on the surface membrane of thyrocytes. Somatic heterozygous mutations that cause TSHR activation in the absence of TSH have been found in toxic adenomas and in hot nodules of multinodular goiters. Clinically and histologically heterogeneous nodules can share comm...
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Constitutively activating mutations have recently been identified in the thyrotropin receptor (TSHR) of hyperfunctioning thyroid adenomas and familial hyperthyroidism. In the present study, we evaluated the frequency of constitutively activating TSHR mutations in a large series of autonomously functioning thyroid nodules (AFTNs) in Japan. Forty-five AFTNs (38 solitary hyperfunctioning thyroid a...
متن کاملHyperthyroidism
Hyperthyroidism is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormone. The most common cause of this syndrome is Graves' disease, followed by toxic multinodular goitre, and solitary hyperfunctioning nodules. Autoimmune postpartum and subacute thyroiditis, tumors that secrete thyrotropin, and drug-induced thyroid dysfunction, are also important...
متن کاملThyroid Hormone Excess: Graves’ Disease
Thyroid hormone excess due to any cause is state of thyrotoxicosis, whereas hyperthyroidism is a state of thyroid hormone excess due to hyperfunctioning of thyroid gland. The major causes of thyrotoxicosis include Graves’ disease, solitary toxic adenoma, and toxic multinodular goiter. In thyrotoxicosis, free hormone levels are invariably increased. The reverse is not true in that increased free...
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There are two clinical situations in which establishing the diagnosis of a toxic adenoma or toxic multinodular goiter is more difficult. First, the autonomously functioning tissue may be sufficiently diffuse that it is difficult to differentiate a toxic multinodular goiter from Graves' disease by thyroid scintigraphy alone. When it is important to distinguish these disorders, a high serum conce...
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ورودعنوان ژورنال:
- The Journal of clinical endocrinology and metabolism
دوره 83 2 شماره
صفحات -
تاریخ انتشار 1998