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Cold nodule

A cold nodule, also referred to as a hypofunctioning thyroid nodule, is an area within the thyroid gland that shows reduced uptake of radiotracer during a nuclear medicine scan. This condition is often discovered during routine physical examinations and can signify various underlying issues. While the majority of cold nodules are benign—such as cysts or inflammatory nodules—there is a small risk, approximately 5 to 15 percent, that they may be malignant. Risk factors for developing a cold nodule align closely with those for thyroid cancer, including past radiation exposure and family history of thyroid disease.

Symptoms typically include an enlarged thyroid gland or a palpable lump, and certain physical characteristics can suggest malignancy. Diagnosis often involves ultrasound and fine-needle aspiration biopsy to assess the nature of the nodule. If malignancy is confirmed, surgical removal may be necessary. Treatment options have expanded in recent years to include techniques like microwave ablation. Overall, while the prognosis for benign cold nodules is excellent, malignant cases require careful evaluation based on stage and type of cancer.

Full Article

DEFINITION: A cold or hypofunctioning nodule is a focal area of decreased uptake of radiotracer on a thyroid nuclear medicine scan that may correlate with a thyroid nodule felt on a routine physical examination of the thyroid gland.

Risk factors: The risk factors for a cold nodule are the same as those for thyroid cancer, including previous radiation to the neck area as therapy for acne or for enlarged tonsillar tissue, a family history of thyroid cancer, and exposure to radioiodine in childhood.

Etiology and the disease process: About 80 to 90 percent of solitary thyroid nodules are hypofunctioning and thus exhibit decreased radiotracer uptake, resulting in a cold nodule. Although malignant thyroid tumors do not concentrate radioisotopes well and can therefore manifest as cold thyroid nodules, only about 5 to 15 percent of cold thyroid nodules are malignant, according to the National Institutes of Health. The remainder are typically cysts, inflammatory nodules of either Hashimoto's or de Quervain’s thyroiditis, hemorrhagic benign nodules, or degenerative nodules.

Incidence: A six-year study of patients with cold thyroid nodules in and around Catania, Italy, published by Antonino Belfiore et al. in 1989, found an annual incidence among the general population of the surrounding area of 5.2 cold nodules per 100,000 young people and 55.9 per 100,000 adults. The overall lifetime risk of developing a palpable cold nodule is between 5 and 10 percent. However, up to 65 percent of people showed thyroid nodules on ultrasound. Malignant cold nodules were most common in adults under thirty or over sixty. Women were more likely to present with cold nodules, but men were more likely to have malignant cold nodules. 

Symptoms: Symptoms include enlargement of the thyroid gland or a palpable lump or nodule within the gland. Physical findings suggestive of a malignant nodule in the thyroid include lymphadenopathy in the neck, size of the nodule, fixation to adjacent structures, or tracheal deviation.

Screening and diagnosis: A cold nodule on a nuclear medicine scan may be composed of solid material, cystic material, or a combination of both. Ultrasound is not especially useful for differentiating benign from malignant nodules of the thyroid unless multiple tiny echogenic foci are seen throughout the nodule, suggestive of microcalcifications. However, it is useful in guiding fine-needle aspiration of the nodule. Neither computed tomography (CT) nor magnetic resonance imaging (MRI) helps distinguish benign from malignant thyroid nodules, unless there is cervical adenopathy or local invasion. Molecular testing can help determine if a nodule is benign or malignant. 

Treatment and therapy: A nodule biopsy is usually recommended, using fine-needle aspiration under ultrasound guidance to obtain tissue for pathologic evaluation. If the pathology from the biopsy shows malignant cells, then surgical removal of the nodule is warranted. In the 2020s, microwave ablation and high-intensity focused ultrasound are treatments used to reduce the size or eliminate cold nodules. Sonographically guided percutaneous ethanol injection was also being investigated for its efficacy. 

Prognosis, prevention, and outcomes: If the nodule is benign, the prognosis is excellent. If the nodule is found to contain cancerous cells, then the prognosis depends on the stage and type of thyroid cancer found at surgery.


Bibliography

AlSaedi, Aram H., et al. "Approach to Thyroid Nodules: Diagnosis and Treatment." Cureus, vol. 16, no. 1, 2024, doi.org/10.7759/cureus.52232. Accessed 18 Oct. 2025.

Alzahrani, Hassan A. "Malignancy in a Solitary Thyroid Nodule: A Retrospective Histopathological Evaluation." International Journal of General Medicine, vol. 17, 2024, pp. 135-140. Dovepress, doi.org/10.2147/IJGM.S445734. Accessed 18 Oct. 2025.

Belfiore, A., et al. “Cancer Risk in Patients with Cold Thyroid Nodules: Relevance of Iodine Intake, Sex, Age, and Multinodularity.” The American Journal of Medicine, vol. 93, no. 4, 1992, pp. 363-9, doi:10.1016/0002-9343(92)90164-7. Accessed 18 Oct. 2025.

Belfiore, Antonino, et al. "High Frequency of Cancer in Cold Thyroid Nodules Occurring at Young Age." Acta Endocrinologica, vol. 121, no. 2, 1989, pp. 197–202.

Braunstein, Glenn D., and Wendy Sacks. "Thyroid Nodules." Thyroid Cancer. Ed. Braunstein. Springer, 2012, pp. 45–61.

Elisei, Rossella, and Eleonora Molinaro. "Single Thyroid Nodule." Thyroid Diseases. Ed. Fabrizio Monaco. CRC, 2012, pp. 111–32.

Gharib, Hossein, et al. "American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules." Endocrine Practice, vol. 16, no. 1, 2010, pp. 1–43.

Kini, Sudha R. Thyroid Cytopathology: A Text and Atlas. Lippincott, 2008.

Latrofa, Francesco, and Paolo Vitti. "Diffuse and Nodular Goiter." Thyroid Diseases. Ed. Fabrizio Monaco. CRC, 2012, pp. 9–48.

Wahl, Richard L. "Thyroid Radionuclide Uptake and Imaging Studies." Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text. Ed. Lewis E. Braverman and David S. Cooper. 10th ed., Lippincott, 2013, pp. 257–78.

Wartofsky, Leonard. "Thyroid Nodules." Thyroid Cancer: A Guide for Patients. Ed. Douglas Van Nostrand, et al. 2nd ed., Keystone, 2010, pp. 39–56.

Full Article

DEFINITION: A cold or hypofunctioning nodule is a focal area of decreased uptake of radiotracer on a thyroid nuclear medicine scan that may correlate with a thyroid nodule felt on a routine physical examination of the thyroid gland.

Risk factors: The risk factors for a cold nodule are the same as those for thyroid cancer, including previous radiation to the neck area as therapy for acne or for enlarged tonsillar tissue, a family history of thyroid cancer, and exposure to radioiodine in childhood.

Etiology and the disease process: About 80 to 90 percent of solitary thyroid nodules are hypofunctioning and thus exhibit decreased radiotracer uptake, resulting in a cold nodule. Although malignant thyroid tumors do not concentrate radioisotopes well and can therefore manifest as cold thyroid nodules, only about 5 to 15 percent of cold thyroid nodules are malignant, according to the National Institutes of Health. The remainder are typically cysts, inflammatory nodules of either Hashimoto's or de Quervain’s thyroiditis, hemorrhagic benign nodules, or degenerative nodules.

Incidence: A six-year study of patients with cold thyroid nodules in and around Catania, Italy, published by Antonino Belfiore et al. in 1989, found an annual incidence among the general population of the surrounding area of 5.2 cold nodules per 100,000 young people and 55.9 per 100,000 adults. The overall lifetime risk of developing a palpable cold nodule is between 5 and 10 percent. However, up to 65 percent of people showed thyroid nodules on ultrasound. Malignant cold nodules were most common in adults under thirty or over sixty. Women were more likely to present with cold nodules, but men were more likely to have malignant cold nodules. 

Symptoms: Symptoms include enlargement of the thyroid gland or a palpable lump or nodule within the gland. Physical findings suggestive of a malignant nodule in the thyroid include lymphadenopathy in the neck, size of the nodule, fixation to adjacent structures, or tracheal deviation.

Screening and diagnosis: A cold nodule on a nuclear medicine scan may be composed of solid material, cystic material, or a combination of both. Ultrasound is not especially useful for differentiating benign from malignant nodules of the thyroid unless multiple tiny echogenic foci are seen throughout the nodule, suggestive of microcalcifications. However, it is useful in guiding fine-needle aspiration of the nodule. Neither computed tomography (CT) nor magnetic resonance imaging (MRI) helps distinguish benign from malignant thyroid nodules, unless there is cervical adenopathy or local invasion. Molecular testing can help determine if a nodule is benign or malignant. 

Treatment and therapy: A nodule biopsy is usually recommended, using fine-needle aspiration under ultrasound guidance to obtain tissue for pathologic evaluation. If the pathology from the biopsy shows malignant cells, then surgical removal of the nodule is warranted. In the 2020s, microwave ablation and high-intensity focused ultrasound are treatments used to reduce the size or eliminate cold nodules. Sonographically guided percutaneous ethanol injection was also being investigated for its efficacy. 

Prognosis, prevention, and outcomes: If the nodule is benign, the prognosis is excellent. If the nodule is found to contain cancerous cells, then the prognosis depends on the stage and type of thyroid cancer found at surgery.


Bibliography

AlSaedi, Aram H., et al. "Approach to Thyroid Nodules: Diagnosis and Treatment." Cureus, vol. 16, no. 1, 2024, doi.org/10.7759/cureus.52232. Accessed 18 Oct. 2025.

Alzahrani, Hassan A. "Malignancy in a Solitary Thyroid Nodule: A Retrospective Histopathological Evaluation." International Journal of General Medicine, vol. 17, 2024, pp. 135-140. Dovepress, doi.org/10.2147/IJGM.S445734. Accessed 18 Oct. 2025.

Belfiore, A., et al. “Cancer Risk in Patients with Cold Thyroid Nodules: Relevance of Iodine Intake, Sex, Age, and Multinodularity.” The American Journal of Medicine, vol. 93, no. 4, 1992, pp. 363-9, doi:10.1016/0002-9343(92)90164-7. Accessed 18 Oct. 2025.

Belfiore, Antonino, et al. "High Frequency of Cancer in Cold Thyroid Nodules Occurring at Young Age." Acta Endocrinologica, vol. 121, no. 2, 1989, pp. 197–202.

Braunstein, Glenn D., and Wendy Sacks. "Thyroid Nodules." Thyroid Cancer. Ed. Braunstein. Springer, 2012, pp. 45–61.

Elisei, Rossella, and Eleonora Molinaro. "Single Thyroid Nodule." Thyroid Diseases. Ed. Fabrizio Monaco. CRC, 2012, pp. 111–32.

Gharib, Hossein, et al. "American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules." Endocrine Practice, vol. 16, no. 1, 2010, pp. 1–43.

Kini, Sudha R. Thyroid Cytopathology: A Text and Atlas. Lippincott, 2008.

Latrofa, Francesco, and Paolo Vitti. "Diffuse and Nodular Goiter." Thyroid Diseases. Ed. Fabrizio Monaco. CRC, 2012, pp. 9–48.

Wahl, Richard L. "Thyroid Radionuclide Uptake and Imaging Studies." Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text. Ed. Lewis E. Braverman and David S. Cooper. 10th ed., Lippincott, 2013, pp. 257–78.

Wartofsky, Leonard. "Thyroid Nodules." Thyroid Cancer: A Guide for Patients. Ed. Douglas Van Nostrand, et al. 2nd ed., Keystone, 2010, pp. 39–56.

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