Endocrinol Metab > Volume 28(2); 2013 > Article
Kim: Natural Course of Benign Thyroid Nodules
Thyroid nodules are very common and are observed during ultrasonography (US) in 50% of the adult population. Although most thyroid nodules are benign, some nodules have malignant potential. Therefore, the ultimate goal is to diagnose biologically significant cancers, while exposing the fewest number of patients with benign disease to unnecessary diagnostic testing and thyroid surgery. In initial evaluation, current guidelines (American Association of Clinical Endocrinologists, American Thyroid Association [ATA], and National Cancer Institute) recommend fine needle aspiration (FNA) in indicated nodule to rule out malignancy [1]. After an FNA result is determined to be benign, serial US follow-up is recommended at 6 to 18 month intervals in order to minimize missed malignancy [1]. Through serial US, we can detect the size changes or shape changes of nodules. If significant interval growth is identified, repeat FNA is recommended in current guidelines [1]. An expert group suggests that the discordance between US appearance and cytology is indication for repeat FNA [2]. If nodule size remains stable, the guidelines recommend that FNA-proven benign thyroid nodules be followed-up by US every 3 to 5 years, with no endpoint specified [3].
Thyroid nodules diagnosed as benign require follow-up because of a low but not negligible false-negative rate with FNA [3]. Selective repeated FNA has been suggested in cases of size increment, suspicious imaging features or clinical suspicion. Malignancy is believed to produce more prominent growth than a benign nodule, although benign nodules can also grow with time [4-6]. Thus, nodule growth is not in and of itself pathognomonic of malignancy. Also, nodules that appear benign on US can transform to show suspiciously malignant US features on follow-up US [7]. Thus, it is very important to know the benign course of FNA-proven benign thyroid nodules, which may avoid an unnecessary repeat FNA. Little is known about the natural history of benign thyroid nodules.
In this issue, Lim et al. [8] reported that FNA-proven benign thyroid nodules can experience changed US features or volume in the natural. During follow-up of 202 benign nodules for 21.7±10.7 months, the mean volume change was +0.16±1.71 mL (range, -6.9 to +8.4), and the percentage of volume change compared with the initial volume was +10.5±54.3% (range, -98.5 to +378.6). The frequent US changes were cystic component change (7.4%), change of margin (6.9%) and change of calcification pattern (6.0%). The margin change from well-defined smooth to ill-defined was the most frequent margin change (n=8, 4.0%). The new appearance of macrocalcification was the most frequent among the changes of calcification pattern (n=9, 4.5%). The echogenicity and the ratio of the anteroposterior to transverse dimensions were nearly unchanged morphological findings. Among them, the proportion of nodules with newly developed US changes suggesting malignancy was less than 5%. When using the ATA recommendation as criteria for nodule growth, 19 nodules (9.4%) were increased, 167 (82.7%) were unchanged, and 16 (7.9%) decreased in volume. One patient was diagnosed with thyroid cancer and had a nodule that changed to suspicious for malignancy.
Unfortunately, Lim et al. [8] was conducted in a tertiary referral center where patients with a typical benign nodule may not be referred. Only a few patients underwent thyroid resection in this study. As a result, diagnosing a benign nodule was based on FNA results, which have a 5% false-negative rate. In spite of these limitations, this study is meaningful to clinicians because most thyroid nodules are benign and are observed via US. According to these results, the authors suggest that frequent follow-up US is needed for cases with suspicious US findings because of low malignancy detection rate. This is consistent with findings of another report [9].
Further studies are needed to demonstrate the most important marker in predicting malignancy during follow-up and when clinicians can cease long-term routine follow-up of an FNA-proven benign nodule.

NOTES

No potential conflict of interest relevant to this article was reported.

REFERENCES

1. Paschke R, Hegedus L, Alexander E, Valcavi R, Papini E, Gharib H. Thyroid nodule guidelines: agreement, disagreement and need for future research. Nat Rev Endocrinol 2011;7:354-361.
[CROSSREF]  [PUBMED]  [PDF]
2. Moon WJ, Baek JH, Jung SL, Kim DW, Kim EK, Kim JY, Kwak JY, Lee JH, Lee YH, Na DG, Park JS, Park SW. Korean Society of Thyroid Radiology (KSThR). Korean Society of Radiology. Ultrasonography and the ultrasound-based management of thyroid nodules: consensus statement and recommendations. Korean J Radiol 2011;12:1-14.
[CROSSREF]  [PUBMED]  [PMC] 
3. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-1214.
[CROSSREF]  [PUBMED] 
4. Alexander EK, Hurwitz S, Heering JP, Benson CB, Frates MC, Doubilet PM, Cibas ES, Larsen PR, Marqusee E. Natural history of benign solid and cystic thyroid nodules. Ann Intern Med 2003;138:315-318.
[CROSSREF] 
5. Erdogan MF, Gursoy A, Erdogan G. Natural course of benign thyroid nodules in a moderately iodine-deficient area. Clin Endocrinol (Oxf) 2006;65:767-771.
[CROSSREF]  [PUBMED] 
6. Quadbeck B, Pruellage J, Roggenbuck U, Hirche H, Janssen OE, Mann K, Hoermann R. Long-term follow-up of thyroid nodule growth. Exp Clin Endocrinol Diabetes 2002;110:348-354.
[CROSSREF]  [PUBMED] 
7. Sohn YM, Kim EK, Moon HJ, Kim SJ, Kwak JY. Suspiciously malignant findings on ultrasound after fine needle aspiration biopsy in a thyroid nodule with initially benign ultrasound and cytologic result: to repeat or to follow-up. Clin Imaging 2011;35:470-475.
[CROSSREF] 
8. Lim DJ, Kim JY, Baek KH, Kim MK, Park WC, Lee JM, Kang MI, Cha BY. Natural course of cytologically benign thyroid nodules: observation of ultrasonographic changes. Endocrinol Metab 2013;28:110-118.
[CROSSREF] 
9. Lee S, Skelton TS, Zheng F, Schwartz KA, Perrier ND, Lee JE, Bassett RL, Ahmed S, Krishnamurthy S, Busaidy NL, Grubbs EG. The biopsy-proven benign thyroid nodule: is long-term follow-up necessary? J Am Coll Surg Epub 2013 May 6. DOI: http://dx.doi.org/10.1016/j.jamcollsurg.2013.03.014.
[CROSSREF] 


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