The risk of distant metastasis is rare when thyroidectomy is performed before lymph node involvement occurs in patients with medullary thyroid cancer (MTC), according to a retrospective study published in the Journal of Clinical Endocrinology and Metabolism.

The researchers found that lymph node metastasis was the greatest predictor of distant metastasis in sporadic MTC and hereditary MTC, regardless of mutational risk.

Hereditary and sporadic MTC have a propensity for metastases, but few studies have evaluated associated risk factors. The aim of this study was to characterize risk factors for distant metastasis in MTC.

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This retrospective study included 1115 consecutive patients with hereditary or sporadic MTC who underwent thyroidectomy from 1994 to 2020. Distant metastases were identified by ultrasonography, CT, or MRI.

The mean age at thyroidectomy depended on mutational risk in patients with hereditary MTC and ranged from 12.2 years to 49.8 years. The mean age at thyroidectomy in patients with sporadic MTC was 52.1 years. Age at thyroidectomy or mutational risk was not associated with tumor size.

Lymph node metastasis was significantly associated with primary tumor size in a multivariate analysis, with the largest tumor size (<60 mm) associated with the greatest risk (odds ratio [OR], 7.2; 95% CI, 2.4-21.4; P <.001), compared with the smallest tumor size (≤20 mm).

Lymph node metastasis was the greatest predictor of distant metastasis, resulting in an OR of 12.4 (95% CI, 4.9-31.2; P <.001).

Primary tumor size was also significantly associated with distant metastasis, with the largest tumor size (<60 mm) having an OR of 7.8 (95% CI, 3.1-19.9; P <.001), compared with the smallest tumor size (≤20 mm).

“Distant metastases are exceptional in node-negative MTC, both in patients with hereditary MTC, irrespective of mutation risk, and patients with sporadic MTC,” the authors concluded. “This finding is of extraordinary relevance, debunking the myth of greater tumor ‘aggressiveness’ of hereditary MTC in carriers of mutations falling into the American Thyroid Association (ATA) highest and high-risk categories.”

Based on this finding, the authors proposed classifying hereditary MTC not by risk but by tumor onset — extremely early, very early, early, and delayed onset.


Machens A, Lorenz K, Weber F, Dralle H. Exceptionality of distant metastases in node-negative hereditary and sporadic medullary thyroid cancer: lessons learned. J Clin Endocrinol Metab. Published online March 31, 2021. doi:10.1210/clinem/dgab214