Thyroid Nodule

  • Markus Eszlinger
  • Laszlo Hegedüs
  • Ralf PaschkeEmail author
Reference work entry
Part of the Endocrinology book series (ENDOCR)


Benign thyroid nodules are highly prevalent in iodine-deficient areas. Histologically, benign thyroid nodules are characterized by morphologic criteria as encapsulated lesions (true adenomas) or adenomatous nodules, which lack a capsule. On functional grounds, nodules are classified as either “cold,” “normal,” or “hot,” depending on whether they show decreased, normal, or increased uptake on scintiscan. Approximately 50–85% of all nodules are “cold,” up to 40% are scintigraphically indifferent and about 10% are “hot,” although the prevalence will vary geographically with the ambient iodine supply and with the clinical setting.

Hot thyroid nodules (autonomously functioning thyroid nodules, AFTNs) are mainly due to mutations which confer a constitutive activation of the cAMP cascade (e.g., TSHR and Gsα mutations) which results in a stimulation of growth and function. In contrast, the molecular etiology of cold thyroid nodules (CTNs) is still largely unknown.

Thyroid autonomy (i.e., AFTNs) is an almost exclusively benign disease, and there is little evidence in the literature to suggest the contrary. In contrast, the differential diagnosis of scintigraphically indifferent and CTNs includes benign follicular adenoma and adenomatous nodules, as well as papillary thyroid carcinoma and its variants and follicular thyroid carcinoma. While fine-needle aspiration cytology is currently the most sensitive and specific tool to select thyroid nodules for surgery after prioritization by assessment of ultrasound malignancy criteria, it is characterized by an inherent limitation, resulting in “indeterminate” cytologies. Molecular tests in the form of “rule out” and “rule in” malignancy tests have been proposed to fill this diagnostic gap.

The most important therapeutic options for hot nodules are radioiodine therapy or surgery and surgery for scintigraphically indifferent and CTNs if symptomatic or associated with increased malignancy risk.


Autonomously functioning thyroid nodules Cold thyroid nodules Mutations Ultrasonography Scintigraphy Fine-needle aspiration cytology Molecular diagnostics Antithyroid drug treatment Surgery Radioiodine therapy Thyroid hormone treatment Percutaneous interventional therapy 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Markus Eszlinger
    • 1
  • Laszlo Hegedüs
    • 2
  • Ralf Paschke
    • 3
    Email author
  1. 1.Department of Oncology and Arnie Charbonneau Cancer Institute, Cumming School of MedicineUniversity of CalgaryCalgaryCanada
  2. 2.Department of Endocrinology and MetabolismOdense University HospitalOdenseDenmark
  3. 3.Section of Endocrinology and Metabolism, Departments of Medicine, Oncology, Biochemistry and Molecular Biology and Arnie Charbonneau Cancer Institute, Cumming School of MedicineUniversity of CalgaryCalgaryCanada

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