Related Experiment Videos
Activating thyrotropin receptor mutations in histologically heterogeneous hyperfunctioning nodules of multinodular
M Tonacchera1, P Vitti, P Agretti
1Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, Università di Pisa, Cisanello, Italy.
Thyroid : Official Journal of the American Thyroid Association
|August 26, 1998
Summary
Activating thyrotropin receptor (TSHr) mutations were found in both adenomatous and hyperplastic nodules of a patient with multinodular goiter. These gain-of-function mutations drive thyroid nodule hyperfunction.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Activating thyrotropin (TSH) receptor mutations are known in toxic adenomas and hot nodules.
- Multinodular goiter is characterized by functional heterogeneity of thyroid follicles.
- TSH receptor mutations lead to constitutive receptor activation and thyroid autonomy.
Observation:
- A patient with a large multinodular goiter presented with normal thyroid hormone levels and suppressed TSH.
- Thyroid scintigraphy revealed two hyperfunctioning nodules in the left lobe.
- Histological examination showed one nodule as a thyroid adenoma and the other as a hyperplastic nodule.
Findings:
- Both the adenomatous and hyperplastic nodules harbored distinct gain-of-function mutations in the TSH receptor gene (T632I and I486M).
- These mutations indicate constitutive activation of the TSH receptor, leading to hyperfunction.
- This is the first report demonstrating TSHr mutations in both adenomatous and hyperplastic nodules within the same multinodular goiter.
Implications:
- Gain-of-function TSHr mutations are a common mechanism in hyperfunctioning thyroid nodules, regardless of histological type.
- This finding expands the understanding of molecular drivers in multinodular goiter pathogenesis.
- Identifies TSHr mutations as key factors in thyroid autonomy within multinodular goiter.