Malignant Thyroid Nodules Less Common But More Aggressive With Age

Erik K. Alexander, MD FACP Chief, Thyroid Section, Division of Endocrinology Brigham & Women's Hospital Associate Professor of Medicine, Harvard Medical School

Dr. Erik Alexander Interview with:
Dr. Erik K. Alexander, MD FACP
Chief, Thyroid Section, Division of Endocrinology
Brigham & Women’s Hospital
Associate Professor of Medicine, Harvard Medical School

Medical Research: What is the background for this study? What are the main findings?

Dr. Alexander: Thyroid nodular disease has become an increasingly common medical illness, with prevalence reported to range between 26-67% in the adult.  Though advancing age is known to influence the formation of thyroid nodules, their precise relationship remains unclear.  Furthermore, it is uncertain whether age influences the risk that any thyroid nodule may prove cancerous.  Thus we conducted a study to determine the impact of patient age on nodule formation, the number of thyroid nodules, and risk of thyroid malignancy.

Medical Research:  What are the main findings?

Dr. Alexander: Our study is a prospective cohort analysis of consecutive adults who presented for evaluation of nodular disease from 1995-2011 at Brigham and Women’s Hospital, Boston, MA.  6,391 patients underwent thyroid ultrasound and fine needle aspiration that resulted in 12,115 thyroid nodules ≥1 cm.  Patients were stratified into six age groups and compared using sonographic, cytologic, and histologic endpoints.
We found that the prevalence of thyroid nodular disease increases with advancing age.  The mean number of nodules at presentation increased from 1.5 in the youngest cohort (ages 20–30) to 2.2 in the oldest cohort (>70 years).  In contrast, the risk for malignancy in a newly identified nodule declined with advancing age.  Thyroid cancer incidence per patient was 22.9% in the youngest cohort, but 12.6% in the oldest cohort.  Despite a lower likelihood of malignancy, identified cancers in older patients demonstrated a more aggressive cancer subtype.  While nearly all malignancies in younger patients were well-differentiated, older patients were more likely to have higher risk papillary thyroid cancer variants, poorly differentiated cancer, or anaplastic carcinoma.

Medical Research: What should clinicians and patients take away from your report?

Dr. Alexander: These data provide insight into the clinical paradox that confronts physicians managing this common illness.  Clinicians should be aware that advancing age clearly increases the risk of thyroid nodule formation though decreases the risk such identified nodules will be malignant.  Nonetheless, when thyroid cancer is detected in older individuals, a higher risk histological phenotype is more likely.  Given a cancer risk >20% in young adults with substantial longevity ahead, it is arguable that nearly all clinically relevant thyroid nodules (especially if solid) should be evaluated with ultrasound guided fine needle aspiration in this population.  In contrast, one potential strategy for older adults may include ultrasound evaluation with sonographic risk stratification, thereafter pursuing further evaluation for nodules identified with higher sonographic risk features.  Importantly, older patients with nodular disease must be informed that higher-risk thyroid cancer is nonetheless possible, and continued monitoring of any nodularity is therefore necessary.

With higher risk for thyroid malignancy in younger patients but more aggressive cancer variant in older populations, patient of any age should be encouraged to seek medical care and evaluation when thyroid nodules are detected.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Alexander: Why more thyroid nodules form but are less likely to be malignant with advancing age remains unclear.  Oncogenic mutations have been shown to be causative for the majority of thyroid carcinoma.  Though unproven, mutations are similarly believed to be responsible for benign nodular formation and growth.  Understanding which genetic mutations associate with benign versus malignant disease, while also better defining a potential multi-hit hypothesis or the impact of separate epigenetic factors, will be important areas for future research.

Future studies are needed to develop a multi-variable diagnostic algorithm that include patient age in addition to nodule size, sonographic characteristics, and other historical risk factors to better assess thyroid malignancy risk, as we seek to optimize individualized care for affected patients.


J Clin Endocrinol Metab. 2015 Dec;100(12):4434-40. doi: 10.1210/jc.2015-3100. Epub 2015 Oct 14.

The Influence of Patient Age on Thyroid Nodule Formation, Multinodularity, and Thyroid Cancer Risk.

Kwong N1, Medici M1, Angell TE1, Liu X1, Marqusee E1, Cibas ES1, Krane JF1, Barletta JA1, Kim MI1, Larsen PR1, Alexander EK1.

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<span class=”Z3988″ title=”ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&;bpr3.tags=Medicine%2CHealth%2CCancer%2C+Endocrinology”>Erik K. Alexander, MD FACP (2015). Malignant Thyroid Nodules Less Common But More Aggressive With Age <span style=”font-style: italic;”></span></span>


Last Updated on December 14, 2015 by Marie Benz MD FAAD