Cancer risk in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity

Am J Med. 1992 Oct;93(4):363-9. doi: 10.1016/0002-9343(92)90164-7.


Purpose: We evaluated the frequency of thyroid cancer in patients with cold thyroid nodules in relation to iodine intake, sex, age, and multinodularity in a consecutive series of patients with nodular thyroid diseases.

Patients: In the period from 1980 to 1990, 5,637 patients were studied: 4,176 patients were from an iodine-sufficient area (ISA) and 1,461 from an adjacent iodine-deficient area (IDA). Surgery was performed in 792 patients on the basis of a suspicious or malignant finding at fine-needle aspiration biopsy.

Results: The overall thyroid cancer frequency was 4.6% (259 patients had cancer). Iodine intake affected the cancer rate in patients with cold nodules. The frequency of cancer in patients with cold thyroid nodules was 5.3% in the ISA and 2.7% in the IDA. This difference, however, was significant only in females. Sex had a major influence on the malignant rate of cold nodules; although female patients were more frequently observed (n = 5,028) than male patients (n = 609), the frequency of cancer was significantly lower in female patients with cold nodules (4.2%) than in males (8.2%). Age was an important factor in both sexes. The proportion of nodules that were malignant was smallest in patients of the 4th decade and was greatest in patients younger than 30 years or older than 60 years. Multivariate analysis showed that sex and age interact in determining the cancer risk in patients with thyroid nodules. Finally, the frequency of thyroid cancer in patients with a solitary nodule was not different from the frequency in patients with multiple nodules.

Conclusion: Our study indicates that thyroid cancer risk in a patient with a nodular goiter varies markedly according to iodine intake, sex, and age but not in relation to multinodularity, as assessed by clinical examination. The knowledge of these epidemiologic aspects of thyroid cancer may increase the accuracy of the preoperative selection of patients with cold nodules of the thyroid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Biopsy, Needle
  • Diagnosis, Differential
  • Female
  • Humans
  • Iodine / administration & dosage*
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Prevalence
  • Regression Analysis
  • Retrospective Studies
  • Risk Factors
  • Sex Factors
  • Thyroid Neoplasms / epidemiology*
  • Thyroid Neoplasms / pathology
  • Thyroid Nodule / pathology*


  • Iodine