Endocrinol Metab.  2013 Jun;28(2):110-118. 10.3803/EnM.2013.28.2.110.

Natural Course of Cytologically Benign Thyroid Nodules: Observation of Ultrasonographic Changes

• Lim DJ
• Kim JY
• Baek KH
• Kim MK
• Park WC
• Lee JM
• Kang MI
• Cha BY

• KMID: 1973809
• DOI: http://doi.org/10.3803/EnM.2013.28.2.110

Abstract

BACKGROUND
The natural course of cytologically benign thyroid nodules remains unclear. The aim of this study was to evaluate whether ultrasonographic (US) changes are associated with changes in nodule volume during follow-up.
METHODS
We retrospectively reviewed over 4 years of clinical records of patients with benign thyroid nodules as confirmed by fine needle aspiration (FNA). In total, 186 patients with 202 benign thyroid nodules were included for study. We assessed for changes in nodule volume and examined the cystic portion of the nodule as well as four US features (echogenicity, margin, calcification pattern, and shape).
RESULTS
During follow-up (mean, 21.7+/-10.7 months) and using 50% as a cutoff value, nodule volumes increased in 11.8%, exhibited no change in 79.9%, and decreased in 8.3% of patients. Proportion of nodules demonstrating at least one US change was 20.8% (42/202). The most common US changes (in descending order of frequency) were cystic change, margin change, and calcification pattern change. Nodule shape and echogenicity rarely changed. Increased nodule volume was not significantly associated with any US features or with the number of FNAs but was associated with younger age at time of diagnosis.
CONCLUSION
Although a portion of thyroid nodules confirmed as benign showed US changes or volume changes during the follow-up period, these findings may only represent the natural course of benign nodules. Frequent follow-up with US might be needed for only a small number of cases with suspicious US findings.

Keyword

Thyroid nodule; Neoplasms; Ultrasonography; Growth; Tumor burden

MeSH Terms

Biopsy, Fine-Needle
Follow-Up Studies
Humans
Retrospective Studies
Thyroid Gland
Thyroid Nodule
Tumor Burden

Figure

• 

  Fig. 1 (A) Transverse ultrasonography (US) image from a 46-year-old woman showing an ill-defined, ovoid to round shaped, and isoechoic nodule. (B) After 3 years, follow-up US image shows an increased nodule size with an increased cystic portion. (C) Longitudinal US image from a 46-year-old woman exhibiting an ill-defined, ovoid to round shaped, and isoechoic nodule. (D) After 3 years, follow-up US demonstrates newly developed macrocalcification (arrow) within a nodule. (E) Transverse US image from a 53-year-old woman revealing an ill-defined, ovoid to round shaped, and isoechoic nodule (arrow). (F) After 1 year, follow-up US showed that the nodule changed to an ill-defined, taller than wide shaped, and hypoechoic nodule (arrow).

Reference

1. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med. 1993. 328:553–559.

2. Kuma K, Matsuzuka F, Yokozawa T, Miyauchi A, Sugawara M. Fate of untreated benign thyroid nodules: results of long-term follow-up. World J Surg. 1994. 18:495–498.

3. 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.

4. 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.

5. 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.

6. Gharib H, Papini E, Valcavi R, Baskin HJ, Crescenzi A, Dottorini ME, Duick DS, Guglielmi R, Hamilton CR Jr, Zeiger MA, Zini M. AACE/AME Task Force on Thyroid Nodules. American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract. 2006. 12:63–102.

7. Tae HJ, Lim DJ, Baek KH, Park WC, Lee YS, Choi JE, Lee JM, Kang MI, Cha BY, Son HY, Lee KW, Kang SK. Diagnostic value of ultrasonography to distinguish between benign and malignant lesions in the management of thyroid nodules. Thyroid. 2007. 17:461–466.

8. Kim JY, Jung SL, Kim BS, Ahn KJ, Hahn ST. An analysis of the ultrasound findings of false negative cases for an initial ultrasound-guided fine needle aspiration biopsy (FNAB). J Korean Radiol Soc. 2007. 57:213–218.

9. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Sherman SI, Tuttle RM;. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006. 16:109–142.

10. Brander AE, Viikinkoski VP, Nickels JI, Kivisaari LM. Importance of thyroid abnormalities detected at US screening: a 5-year follow-up. Radiology. 2000. 215:801–806.

11. Knudsen N, Perrild H, Christiansen E, Rasmussen S, Dige-Petersen H, Jorgensen T. Thyroid structure and size and two-year follow-up of solitary cold thyroid nodules in an unselected population with borderline iodine deficiency. Eur J Endocrinol. 2000. 142:224–230.

12. Gordon DL, Flisak M, Fisher SG. Changes in thyroid nodule volume caused by fine-needle aspiration: a factor complicating the interpretation of the effect of thyrotropin suppression on nodule size. J Clin Endocrinol Metab. 1999. 84:4566–4569.

13. Kuma K, Matsuzuka F, Kobayashi A, Hirai K, Morita S, Miyauchi A, Katayama S, Sugawara M. Outcome of long standing solitary thyroid nodules. World J Surg. 1992. 16:583–587.

14. Frates MC, Benson CB, Charboneau JW, Cibas ES, Clark OH, Coleman BG, Cronan JJ, Doubilet PM, Evans DB, Goellner JR, Hay ID, Hertzberg BS, Intenzo CM, Jeffrey RB, Langer JE, Larsen PR, Mandel SJ, Middleton WD, Reading CC, Sherman SI, Tessler FN. Society of Radiologists in Ultrasound. Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Radiology. 2005. 237:794–800.

15. Kim EK, Park CS, Chung WY, Oh KK, Kim DI, Lee JT, Yoo HS. New sonographic criteria for recommending fine-needle aspiration biopsy of nonpalpable solid nodules of the thyroid. AJR Am J Roentgenol. 2002. 178:687–691.

16. Papini E, Guglielmi R, Bianchini A, Crescenzi A, Taccogna S, Nardi F, Panunzi C, Rinaldi R, Toscano V, Pacella CM. Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features. J Clin Endocrinol Metab. 2002. 87:1941–1946.

17. Cappelli C, Castellano M, Pirola I, Gandossi E, De Martino E, Cumetti D, Agosti B, Rosei EA. Thyroid nodule shape suggests malignancy. Eur J Endocrinol. 2006. 155:27–31.

18. Khoo ML, Asa SL, Witterick IJ, Freeman JL. Thyroid calcification and its association with thyroid carcinoma. Head Neck. 2002. 24:651–655.

19. Takashima S, Fukuda H, Nomura N, Kishimoto H, Kim T, Kobayashi T. Thyroid nodules: re-evaluation with ultrasound. J Clin Ultrasound. 1995. 23:179–184.

20. Costante G, Crocetti U, Schifino E, Ludovico O, Capula C, Nicotera M, Arturi F, Filetti S. Slow growth of benign thyroid nodules after menopause: no need for long-term thyroxine suppressive therapy in post-menopausal women. J Endocrinol Invest. 2004. 27:31–36.