Thereafter constitutively activating TSH receptor mutations were identified in 20-80% of toxic thyroid nodules and in 3 of 6 toxic multinodular goiters.
Mutations of the TSH receptor (TSHR) or G proteins (gsp) that activate adenylyl cyclase have been identified in autonomously functioning thyroid nodules.
These in vitro and clinical findings suggest that VEGF/VPF is at least partly involved in the accumulation of cyst fluid in thyroid nodules, and that a high VEGF/VPF concentration predicts rapid accumulation of the cyst fluid, possibly necessitating interventional treatment.
We now report a case of MTC in which a RET somatic mutation at codon 918 was detected in fine-needle aspiration specimens obtained from both the thyroid nodule and two enlarged neck lymph nodes but not in peripheral blood.
In conclusion, our findings show for the first time that gain-of-function TSHr mutations are not only present in hyperfunctioning thyroid nodules with the histological features of the true thyroid adenomas, but also in hyperfunctioning hyperplastic nodules contained in the same multinodular goiter.
Clonality was studied in thyroid nodules using the polymerase chain reaction (PCR) assay in the X-linked human androgen receptor (HUMARA) gene by random X chromosome inactivation in women.
In contrast, hTERT gene expression was detected in only 5 (28%) of 18 benign thyroid nodules, including 2 of 7 follicular adenomas and 3 of 11 hyperplastic nodules.
Serum calcitonin screening has recently been found to be a useful supplement to fine-needle aspiration biopsy, ultrasound and radionuclide imaging in the evaluation of thyroid nodules.
Activating mutations affecting important pathway components such as the TSH receptor and Gsalpha occur in the majority of autonomously functioning thyroid nodules.
This is the first evidence that TSH receptor mutations occur in microscopic areas with increased (125)I-labelling in euthyroid goiters and it suggests that TSH receptor mutations in these areas confer the potential to develop into toxic thyroid nodules.