Long- versus short-interval follow-up of cytologically benign thyroid nodules: a prospective cohort study

Abstract

BackgroundThyroid nodules are common, and most are benign. Given the risk of false-negative cytology (i.e. malignancy), follow-up is recommended after 1–2 years, though this recommendation is based solely on expert opinion. Sonographic appearance may assist with planning, but is limited by large inter-observer variability. We therefore compared the safety and efficacy of long- versus short-interval follow-up after a benign initial aspiration, regardless of sonographic appearance.MethodsThis study evaluated all patients referred to the Brigham and Women’s Hospital Thyroid Nodule Clinic, between 1999 and 2010, with a cytologically benign nodule >1 cm and who had returned for follow-up sonographic evaluation. Despite standard clinical recommendations, variation in patient compliance resulted in variable follow-up intervals from time of initial aspiration to the first repeat evaluation. Main outcome measures included nodule growth, repeat fine needle aspiration (FNA), thyroidectomy, malignancy, and disease-specific mortality.ResultsWe evaluated 1,254 patients with 1,819 cytologically benign nodules, with a median time to first follow-up of 1.4 years (range, 0.5–14.1 years). The longer the follow-up interval, the more nodules grew and the more repeat FNAs were performed (P <0.001). The most clinical meaningful endpoints of malignancy or mortality, however, did not differ between the various follow-up intervals. The risk of a thyroidectomy (usually because of compressive symptoms) increased when time to first follow-up exceeded >3 years (4.9 % vs. 1.2 %, P = 0.0001), though no difference in malignancy risk was identified (0.2–0.8 %, P = 0.77). No (0 %) thyroid cancer-specific deaths were identified in either cohort.ConclusionsWhile expert opinion currently recommends repeat evaluation of a cytologically benign nodule at 1–2 years, these are the first data to demonstrate that this interval can be safely extended to 3 years without increased mortality or patient harm. Nodule growth can be expected, though detection of malignancies is unchanged. While replication of these data in large prospective multicenter studies is needed, this extension in follow-up interval would reduce unnecessary visits and medical interventions for millions of affected patients worldwide, leading to healthcare savings.Please see related commentary article: http://dx.doi.org/10.1186/s12916-016-0559-9 and research article: http://dx.doi.org/10.1186/s12916-015-0419-z.

TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower 131i uptake in metastases

“…RAS mutations also play an important role in thyroid tumorigenesis. Recent advances in understanding the clinical utility of the RAS mutation indicate that it rather correlates with less aggressive tumor behavior and good prognosis, Therefore, RAS mutation‐positive differentiated thyroid cancer can be treated more conservatively . Furthermore, RAS mutation‐positive, but cytologically benign, thyroid nodules can be followed on the long term without surgical intervention.…”

“…On the other hand, the RAS mutation occurs mostly in the follicular variant of PTC and is also found in follicular thyroid adenoma. Based on recent studies, this mutation is associated with a rather good prognosis .…”

Cervical ultrasound assessment of thyroid nodules at risk of malignancy: single-center experience

“…The American Thyroid Association recommends FNAB evaluation even for highly suspicious nodules on cervical ultrasound examination, to properly assess patients and help in the decision-making process, avoiding for selected patients © C I C E d i z i o n i I n t e r n a z i o n a l i surgical treatment and its subsequent morbidity and financial burden (7). In a single center study, Medici et al (11) proposed that after an initial benign cytology patients could be reevaluated through FNAB after an interval of three years, without affecting patient safety or increasing mortality, implying a lowering of associated medical costs (11). FNAB represents a cheap, easy to perform, minimally invasive, with little risk method of investigation that should allow for a better evaluation of thyroid nodules.…”

Ultrasound of Thyroid Nodules

“…Since the vast majority of thyroid nodules are neither investigated via FNAB nor surgically removed, sonographic follow-up is the usual clinical practice. Depending on the risk stratification, recommendations for a control interval range from 3 months to 6, 12 months up to 24 months [97,98]. Scientific evidence for these recommendations is very limited.…”

“…It makes sense to have an interval for conspicuous nodules that are not subjected to further diagnostics at the time of the examination, of at least 6 months, otherwise usually 12 -24 months. Recent studies indicate that a control interval of 36 months may be sufficient if the cytology was benign [98]. In the elderly, due to the very low risk, extending the interval or even terminating sonographic follow-up can be considered [9,99].…”