Benign thyroid nodules with RAS mutation grow faster.

CONTEXT: The management of a benign thyroid nodule includes follow-up until its size requires a surgical or alternative treatment. To date, it is difficult or impossible to predict the size changes of a benign nodule in a given patient because no specific growth parameters exist. RAS mutations have been described in thyroid adenomas and hyperplastic benign nodules. OBJECTIVE: The aim of this study was to establish whether the volume changes of benign nodules are associated with the presence of RAS mutation. PATIENTS AND METHODS: Genomic DNA obtained by fine-needle aspiration of 78 thyroid nodules with benign cytology was analysed by pyrosequencing for the presence of NRAS(61) and KRAS(13) mutations. Ultrasonographic features were obtained. The volume of nodules at baseline and their changes after a mean follow-up of 25 months were evaluated according to the presence of RAS mutation. RESULTS: A RAS mutation was found in 24 thyroid aspirates (30·8%, 8 NRAS(61) and 16 KRAS(13) ). RAS mutation was not associated with ultrasonographic features, but was significantly associated with a larger size at baseline (P = 0·017). After a 25-month mean follow-up, RAS mutation-positive nodules displayed faster growth (RAS mutation-positive vs RAS mutation-negative % annual growth 27·6% ±32·2% vs 1·0% ±17·0%, P < 0·001). CONCLUSIONS: Benign thyroid nodules bearing RAS mutation grow more rapidly than those with wild-type RAS. Searching for RAS mutations in thyroid nodules with benign cytology might be useful to the clinician in choosing a more appropriate and timely surgical management.

Evolution of benign thyroid nodules under levothyroxine non-suppressive therapy.

BACKGROUND: Non-suppressive or partially suppressive L-T4 treatment demonstrated to be effective in reducing the volume of the nodules. However, studies with long follow-up are lacking and significant controversy exists regarding the efficacy of non-suppressive L-T4 treatment in benign nodular goiter. AIM: The goal of this study was to determine the evolution of thyroid nodules in subjects treated with a non-suppressive levothyroxine (L-T4) dose, compared to untreated subjects. DESIGN AND PATIENTS: We followed for a period of 1-9 years the thyroid nodule size in 356 female patients in the age range 19-45 at study entry, of which 201 untreated (Group 0) and 165 treated with a non-suppressive L-T4 dose (Group L-T4). MEASUREMENTS: We determined the volume of thyroid nodules by ultrasonography. RESULTS: The initial mean nodule volume in Group 0 and Group L-T4 was 3.91 ± 6.87 and 4.01 ± 7.35 mL, respectively. Nodule volume increase was inversely correlated to the initial volume. The final volume was slightly higher in untreated than in L-T4 treated subjects (5.37 ± 8.49 and 4.39 ± 6.72 mL). In both groups, the mean of annual fold increase of nodule volume was inversely correlated with the follow-up duration (P < 0.0046), indicating a slower growth as time advances. In the subjects treated with L-T4, the mean annual increase of nodule volume was significantly minor compared to untreated subjects. Concomitant nodules in ten multinodular goiters exhibited totally independent evolution, demonstrating that intranodular factors are more important for the nodule behavior than extra nodular factors. CONCLUSIONS: Our study demonstrates that the growth of benign thyroid nodules is inversely correlated to their size, benign nodules naturally growth slowly as time advances, and that a chronic treatment with L-T4 at a non-TSH-suppressive dose significantly reduces their growth.

[Diagnostic value of BRAFV600E and RET/PTC oncogenes in thyroid nodule aspirates]. / Valore diagnostico degli oncogeni BRAFV600E e RET/PTC nei noduli tiroidei.

Fine-needle aspiration cytology (FNC) is the primary means to distinguish benign form malignant nodules. Aim of this study is to evaluate the diagnostic value of BRAF(V600E) and RET/PTC oncogenes in a large cohort of thyroid nodules with inconclusive FNC. We searched for BRAF(V600E) and RET/PTC in 299 thyroid nodule aspirates then removed by surgery. RET/PTC demonstrated a poor specificity. The search for BRAF(V600E) demonstrated to be useful in 25 cases, identifying a PTC in 2 false negative, 2 inadequate, 11 indeterminate and 10 suspicious FNC. Detection of BRAF(V600E) revealed to be a useful tool to refine inconclusive cytology.

Detection of RAS mutation by pyrosequencing in thyroid cytology samples.

INTRODUCTION: Fine-needle aspiration cytology (FNAC) is the primary means to distinguish benign from malignant thyroid nodules. However, adjunctive diagnostic tests are needed as 20-40% of FNAC are inconclusive. RAS mutations have been described in differentiated thyroid cancer and they could be used as tumor markers. However, their prevalence varies widely among studies, probably as a result of the detection methods used. We investigated whether the pyrosequencing method can be applied to detect NRAS and KRAS mutations in thyroid aspirates. PATIENTS AND METHODS: A total of 37 thyroid aspirates, including benign hyperplastic nodules (HBN, N = 16) and follicular thyroid carcinomas (FTC, N = 21) were analyzed for the presence of NRAS(61) and KRAS(13) mutations. RESULTS: A RAS mutation was found in 31% and 62% of BN and FTC respectively. Most samples displayed a percentage of mutated alleles lower than 50% (median = 30.8% and 15.3% in FTC and HBN respectively), a result compatible with the presence of extra-nodular cells contaminating the FNA or with the subclonal nature of both types of thyroid nodules. DISCUSSION: Pyrosequencing is a reliable assay to detect RAS mutations in fine-needle thyroid aspirates. CONCLUSIONS: The low specificity and sensitivity limit the power of this test to distinguish between FTC and benign nodules in inconclusive FNACs.