Diagnostic Challenges of Medullary Thyroid Carcinoma

Oncology. 2021;99(7):422-432. doi: 10.1159/000515373. Epub 2021 Apr 20.


Background: Medullary thyroid carcinoma (MTC) comprises 1-2% of all thyroid cancers, yet 15% of all thyroid cancer-related deaths. While up to 20% of cases may be predicted due to autosomal dominant germline mutations, 80% of cases are sporadic. However, due to non-specific presenting symptoms and diagnostic imaging, prompt diagnosis and treatment has remained elusive. This article will further investigate the limitations of MTC diagnosis and look into future areas for diagnostic improvement.

Methods: Relevant articles were identified using a systematic PubMed and Google Scholar search.

Results: Prophylactic total thyroidectomy for the 20% of MTC cases that are present in autosomal dominant disorder provides definitive treatment. Serum calcitonin (Ctn) screening has several technical limitations due to population variability and laboratory assay interference, but advances in laboratory technology and combined use with fine needle aspiration increase its sensitivity. Other serum assays such as carcinoembryonic antigen and procalcitonin have limited applicability. Thyroid ultrasound remains the gold standard for the initial diagnostic planning, with limited application for CT, MRI, and PET imaging.

Conclusion: With complete surgical resection the only definitive treatment, early MTC diagnosis has presented an elusive challenge, mainly due to its relative rarity and difficulty in finding an economic screening strategy. Careful family history combined with fine needle aspiration with serum Ctn analysis can improve diagnostic sensitivity and specificity to greater than 95%.

Keywords: Calcitonin; Diagnostic challenges; Imaging; Medullary thyroid cancer.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / blood
  • Biopsy, Fine-Needle
  • Calcitonin / blood*
  • Carcinoma, Neuroendocrine / blood*
  • Carcinoma, Neuroendocrine / diagnostic imaging*
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Neuroendocrine / surgery
  • Female
  • Genetic Testing / methods*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Positron Emission Tomography Computed Tomography / methods*
  • Sensitivity and Specificity
  • Thyroid Neoplasms / blood*
  • Thyroid Neoplasms / diagnostic imaging*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / surgery
  • Thyroidectomy / methods
  • Ultrasonography / methods


  • Biomarkers, Tumor
  • Calcitonin

Supplementary concepts

  • Thyroid cancer, medullary