Can Thyroid Nodule Localization Predict Thyroid Cancer?
Stefan Amisten, Senior Medical Writer, Touch Medical Media, UK
Jeremy Betts, Account Director and Advisory Editor, Touch Medical Media, UK
-Insights into a Recently Released Study Revealing Thyroid Nodule Location's Predictive Value for Malignancy, presented at AACE, Boston, US, 18 May 2018

Thyroid nodules are discrete lesions within the thyroid gland that are radiologically distinct from the surrounding thyroid parenchyma.1 Thyroid nodules are common in the general population and are discovered through ultrasound imaging in 20–76% of the adult population,2–4 and through surgery and autopsy in 50–65% of all adults.5

The estimated lifetime probability for developing a thyroid nodule is approximately 10%. Women are four times likely than men to develop thyroid nodules and the frequency increases with age and low iodine intake.2,4 Thyroid nodules may disrupt normal endocrine function or cause pressure symptoms, but mainly receive clinical attention due to their malignant potential.6–10

Thyroid ultrasound allows for the identification of candidates for fine-needle aspiration (FNA) biopsy sampling. Cytological analysis of FNA biopsies is the safest and most cost-effective diagnostic tool available for the clinical evaluation of malignancy in thyroid nodules,11,12 and is often used in combination with genetic and immunohistochemical analysis and serum markers such as serum thyroid-stimulating hormone (TSH) and calcitonin. 10

A risk-stratifying approach based on medical history, ultrasound characteristics, and nodule size is currently used to evaluate if FNA sampling should be pursued. FNA is a simple, reliable, inexpensive, and generally safe diagnostic procedure, with the most frequently reported adverse events being post-FNA local pain and minor hematomas.10 However, FNA is a surgical procedure, and rare serious adverse events such as recurrent laryngeal nerve palsy, vasovagal reactions, needle track seeding of papillary carcinoma, nodule volume alterations, and post-aspiration thyrotoxicosis have been reported.13 The reported malignancy prevalence in biopsy-evaluated thyroid nodules ranges from 4.0–6.5%, which means that 93.5–96.0% of all biopsied thyroid nodules are non-malignant. Moreover, thyroid nodule malignancy does not appear to be dependent on nodule size.6,9 Improved methods for identifying thyroid nodules that are more likely to be malignant would reduce the need for unnecessary FNA biopsy sampling and surgical resection of non-malignant thyroid nodules.

At the 27th American Association of Clinical Endocrinologists (AACE) meeting, which was held in Boston, MA, May 16–20, 2018, Dr Fan Zhang, MD, a resident in the Department of Internal Medicine at Brookdale University Hospital and Medical Center in Brooklyn, NY, presented a study demonstrating how thyroid nodules located in the upper pole of the thyroid gland are more likely to be cancerous than thyroid nodules located in the lower pole.14

Dr Zhang’s group performed a retrospective study on the ultrasound characteristics of thyroid nodules from 188 patients who had had FNA from July 2016 to June 2017 and analyzed the laterality (left versus isthmus versus right), polarity (upper versus middle versus lower), microcalcifications, and multi-nodularity of the biopsied nodules.

“We found that the thyroid nodules were evenly distributed between the left and right lobes (50.5% versus 47.3%), with only 2.1% located in the isthmus” Dr Zhang explains. “Moreover, 79.3% of the nodules were in the lower pole of the thyroid gland as compared to 9.6% in the upper pole, and 6.9% were in the middle pole. Multiple nodules were found in 39.9% of the examined patients”.

“We also found a higher frequency of malignancy among nodules located in the upper pole of the gland (22.2%) compared to the lower (4.7%) and middle (14.3%) poles. After adjusting for number of thyroid nodules, patient age, gender, BMI, and laterality using a multiple logistic regression model, we were able to confirm an association between nodule location and malignancy, with malignancy in upper pole nodules four times higher than nodules in other locations.”

“Due to the high prevalence of thyroid nodules in the general population, accurate assessment to avoid unnecessary biopsies and overtreatment is needed” Dr Zhang explains. “This study demonstrates that nodules located in the upper pole present a higher malignancy risk factor and, therefore, the location of thyroid nodules may need to be included in ultrasound classification guidelines to enhance the predictive value of malignancy, diagnostic accuracy and reliability as an indicator to perform FNA.”

Dr Zhang’s study is the first of its kind to demonstrate an association between thyroid nodule location and the likelihood of thyroid nodule malignancy. These very promising findings warrant further studies, with the aim of generating additional data to support the inclusion of evaluation of thyroid nodule location in clinical guidelines on how to select thyroid nodules most suitable for FNA biopsy. Increased accuracy in the identification of potentially malignant thyroid nodules is clearly needed, as more than 90% of all thyroid nodules currently biopsied appear to be non-cancerous.


1. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1–133.
2. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med. 1993;328:553–9.
3. Ezzat S, Sarti DA, Cain DR, Braunstein GD. Thyroid incidentalomas. Prevalence by palpation and ultrasonography. Arch Intern Med. 1994;154:1838–40.
4. Tan GH, Gharib H . Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med. 1997;126:226–31.
5. Mortensen JD, Woolner LB, Bennett WA. Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab. 1955;15:1270–80.
6. Hegedüs L. Clinical practice. The thyroid nodule. N Engl J Med. 2004;351:1764–71.
7. Werk EE Jr, Vernon BM, Gonzalez JJ, et al. Cancer in thyroid nodules. A community hospital survey. Arch Intern Med. 1984;144:474–6.
8. Belfiore A, Giuffrida D, La Rosa GL, et al. High frequency of cancer in cold thyroid nodules occurring at young age. Acta Endocrinol (Copenh). 1989;121:197–202.
9. Lin JD, Chao TC, Huang BY, et al. Thyroid cancer in the thyroid nodules evaluated by ultrasonography and fine-needle aspiration cytology. Thyroid. 2005;15:708–17.
10. Popoveniuc G, Jonklaas J. Thyroid nodules. Med Clin North Am. 2012;96:329–49.
11. Castro MR, Gharib H. Thyroid fine-needle aspiration biopsy: progress, practice, and pitfalls. Endocr Pract. 2003;9:128–36.
12. Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med. 1993;118:282–9.
13. Polyzos SA, Anastasilakis AD. Clinical complications following thyroid fine-needle biopsy: a systematic review. Clin Endocrinol (Oxf). 2009;71:157–65.
14. Zhang F, et al. Thyroid nodule location on ultrasonography as a predictor of malignancy. Late-breaking abstract #1204. AACE 2018, Boston, MA, USA