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Natural History of Benign Solid and Cystic Thyroid Nodules

Erik K. Alexander, MD; Shelley Hurwitz, PhD; Jenny P. Heering, BA; Carol B. Benson, MD; Mary C. Frates, MD; Peter M. Doubilet, MD, PhD; Edmund S. Cibas, MD; P Reed Larsen, MD; and Ellen Marqusee, MD
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From Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Acknowledgments: The authors thank Dr. Robert Utiger for his helpful review of and comments on this article.

Grant Support: By training grants from the National Institutes of Health (DK-07529 and HL-07609); research grant from The Endocrine Fellows Foundation; Thyroid Center of Excellence grant from Knoll Pharmaceuticals; and grants from Biostatistical Consulting Service, Center for Clinical Investigation, Brigham and Women's Hospital.

Requests for Single Reprints: Erik K. Alexander, MD, Endocrine Division, Brigham and Women's Hospital, 221 Longwood Avenue, 2nd Floor, Boston, MA 02115; e-mail, ekalexander@partners.org.

Current Author Addresses: Drs. Alexander, Hurwitz, Benson, Frates, Doubilet, Cibas, Larsen, and Marqusee and Ms. Heering: Endocrine Division, Brigham and Women's Hospital, 221 Longwood Avenue, 2nd Floor, Boston, MA 02115.

Author Contributions: Conception and design: E.K. Alexander, P.R. Larsen, and E. Marqusee.

Analysis and interpretation of the data: E.K. Alexander, S. Hurwitz, J.P. Heering, P.R. Larsen, and E. Marqusee.

Drafting of the article: E.K. Alexander, S. Hurwitz, J.P. Heering, E.S. Cibas, P.R. Larsen, and E. Marqusee.

Critical revision of the article for important intellectual content: S. Hur-witz, J.P. Heering, C.B. Benson, M.C. Frates, P.M. Doubilet, E.S. Ci-bas, P.R. Larsen, and E. Marqusee.

Final approval of the article: E.K. Alexander, S. Hurwitz, M.C. Frates, P.R. Larsen and E. Marqusee.

Provision of study materials or patients: P.R. Larsen and E. Marqusee.

Statistical expertise: S. Hurwitz.

Obtaining of funding: P.R. Larsen.

Administrative, technical, or logistic support: J.P. Heering, C.B. Benson, P.M. Doubilet, E.S. Cibas, P.R. Larsen, and E. Marqusee.

Collection and assembly of data: E.K. Alexander, J.P. Heering, C.B. Benson, M.C. Frates, P.M. Doubilet, and E. Marqusee.

Ann Intern Med. 2003;138(4):315-318. doi:10.7326/0003-4819-138-4-200302180-00010
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Background: Thyroid nodules are common and most often benign. The natural history of benign thyroid nodules, however, is unclear.

Objective: To determine the natural history of cytologically benign thyroid nodules using ultrasonography.

Design: Retrospective case series.

Setting: Single tertiary care clinic.

Participants: All patients referred to the Brigham and Women's Hospital Thyroid Nodule Clinic, Boston, Massachusetts, who had benign cytologic results on ultrasonography-guided fine-needle aspiration of a thyroid nodule between 1995 and 2000 and returned for a requested follow-up examination 1 month to 5 years later.

Measurements: Nodule dimensions were measured at both visits, and growth was defined as an increase in calculated volume of 15% or greater. These results were correlated with the time between examinations, age, sex, baseline serum thyroid-stimulating hormone concentration, and cystic content of each nodule.

Results: Nodule volume increased over time (P < 0.001). The estimated proportion of nodules with an increase in volume of 15% or greater after 5 years was 89%. Nodules with greater cystic content were less likely to grow than solid nodules (P = 0.01). Seventy-four of the 330 nodules were reaspirated on the second visit. Despite an average increase in volume of 69%, only 1 of 74 reaspirated nodules was malignant.

Conclusion: Most solid, benign thyroid nodules grow. Therefore, an increase in nodule volume alone is not a reliable predictor of malignancy.


Grahic Jump Location
Appendix Figure. Overview of patients and thyroid nodules included in analysis of nodule growth. FNA fine-needle aspiration.
Grahic Jump Location




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Summary for Patients

Are Thyroid Nodules that Grow Cancerous?

The summary below is from the full report titled “Natural History of Benign Solid and Cystic Thyroid Nodules.” It is in the 18 February 2003 issue of Annals of Internal Medicine (volume 138, pages 315-318). The authors are EK Alexander, S Hurwitz, JP Heering, CB Benson, MC Frates, PM Doubilet, ES Cibas, PR Larsen, and E Marqusee.


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