Natural History of Benign Solid and Cystic Thyroid Nodules

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

    Abstract

    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.

    Article and Author Information

    • 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{at}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.

    Summary for Patients

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