Diagnostic Value of Preoperative Serum Calcitonin Levels in Medullary Thyroid Carcinoma

  • Clin Thyroidol 2022;34:85–88.
  • Background:
    • Thyroid cancers represent approximately 1% of all new cancer diagnoses each year
    • Thyroid cancers are divided into:
      • Papillary carcinomas, follicular carcinomas, medullary thyroid carcinomas (MTCs), anaplastic carcinomas, primary thyroid lymphomas, and primary thyroid sarcomas
    • In the United States, MTCs represent 1% to 2% of all thyroid malignancies, with a slight preponderance in women
    • MTC originates from parafollicular calcitonin-producing cells (C- cells)
    • Approximately 75% to 80% of cases are sporadic:
      • While hereditary forms such as multiple endocrine neoplasia (MEN) type 2A or 2B account for almost 20% to 25% of cases
    • The 10-year survival rates of MTC are estimated at 81% to 89%
    • Calcitonin is a specific tumor marker for MTC:
      • Although the routine use of serum calcitonin measurements for the preoperative assessment of thyroid nodules is still controversial, according to current guidelines
    • The aim of this study was to assess serum calcitonin cutoff levels in patients undergoing surgery for benign and malignant thyroid disease in Germany and Austria
    • A second goal was to assess the potential correlations between serum calcitonin levels and size of the resected MTCs, the presences of lymph node metastases, and the time to biochemical normalization
  • Methods:
    • The cohort was obtained from the German DGAV/StuDoQ registry, which is a prospective, multi-center database that includes data on the surgical treatment of benign and malignant thyroid disease, as well as hyperparathyroidism
    • All patients with thyroid surgery documented in the registry between March 2017 and September 2020 were included
    • Data regarding subject demographics, preoperative and postoperative serum calcitonin levels, the diagnosis of C-cell hyperplasia or MTC, surgical procedures, histopathology, and biochemical cure rates were recorded
    • C-cell hyperplasia was defined as the presence of > 50 microscopically calcitonin-positive cells in at least one low-power field and considered to be a benign thyroid pathology
    • Biochemical recovery of MTC was defined by serum calcitonin levels below 10 pg/ml postoperatively (timepoint unspecified)
    • The study also assessed sex-specific calcitonin cutoff levels
    • The tumor size and the presence of lymph node metastases predicting biochemical recovery of calcitonin levels were analyzed by univariate and multivariate logistic regression
  • Results:
    • Total thyroidectomy was performed in 93% of the patients
    • MTC was diagnosed in 1.2%, and the mean (±SD) tumor diameter was 14.7±12.43 mm (range, 1–80)
    • Histopathology of MTCs revealed that 173 ± 48.4% were pT1a, 100±28.0% pT1b, 65±18.2% pT2, 17±4.8% pT3, and 2±0.6% pT4
    • Preoperative calcitonin screening was available in 92.4% of the data set
    • Of the 29,054 patients without C-cell hyperplasia or MTC:
      • The median preoperative calcitonin level was 2.0 pg/ml, and calcitonin levels were marginally higher in those with coexisting renal hyperparathyroidism than in those without
    • In the 206 patients with C-cell hyperplasia:
      • The median calcitonin level was 16.1 pg/ml (range, 1–183.3)
    • There were 330 patients with MTC:
      • In whom the median calcitonin level was 168.0 pg/ml, with men having higher calcitonin levels than women
      • Both female and male patients with C-cell hyperplasia or MTC:
        • Demonstrated significantly higher calcitonin levels than those with benign thyroid disease
    • Using receiver operating characteristic (ROC) analysis:
      • The serum calcitonin thresholds for predicting MTC were 7.9 pg/ml in women and 15 pg/ml in men (P<0.001)
      • The tumor size of MTC was positively correlated with median calcitonin levels:
        • Tumor diameters of 6 to 10 mm had a median calcitonin level of 81 pg/ml (range, 10.6–2000), tumors with diameters between 3 and 5 mm 31 pg/ml (range, 1–5890), and tumors smaller than 3 mm 13 pg/ml (range, 0-187.8)
      • Single lymph node metastases were detected at a median calcitonin level of 256 pg/ml (range, 23–2740), which increased to 3012 pg/ml (range, 825–4410) in patients with more than 21 metastatic lymph nodes
      • The median calcitonin level in those with metastatic MTC was 7025 pg/ml (range, 1538–85,800)
      • In 71.4% of patients with MTC, biochemical normalization of serum calcitonin levels was achieved after thyroid surgery:
        • With higher rates seen in those with hereditary MTCs than in those with sporadic forms
      • Overall, biochemical cure was achieved in:
        • 90% of pT1a tumors, 66.7% of pT1b tumors, 48.7% of pT2 tumors, and 25% of pT3 tumors, but calcitonin normalization was not significantly correlated with tumor size
  • Conclusions:
    • Preoperative serum calcitonin levels of > 7.9 pg/ml in women and >15 pg/ml in men should be regularly monitored and considered for the diagnosis of MTC, particularly in patients with increasing serum calcitonin levels or sonographically suspicious thyroid nodules
  • It is well established that the early diagnosis and surgical treatment of MTC significantly improve the outcomes of this disease
  • The routine measurement of serum calcitonin in patients with thyroid nodules is still controversial in the United States; the latest guidelines from the American Thyroid Asso-ciation do not recommend it as a routine screening test
  • In contrast, several European countries have implemented the preoperative measurement of serum calcitonin to improve the diagnosis of MTC
  • During the beginning of the COVID-19 pandemic, restrictions for outpatient procedures were implemented across institutions in the United States
  • In the Phoenix Veteran Administration Hospital, they implemented a protocol for thyroid nodules that included serum calcitonin as a surrogate marker for the potential diagnosis of MTC
  • Recommendations are emergent fine-needle aspiration (FNA) in patients with serum calcitonin levels >10 pg/ml
  • In patients with calcitonin levels > 100 pg/ml, thyroid surgery was recommended
  • The strengths of this study include its large sample size, multicenter cohort, and long follow-up (mean duration, 3.5 years)
  • In addition, the establishment of a sex-specific serum calcitonin cutoff is useful for clinicians
  • However, limitations include the use of different calcitonin assays among the various centers and missing data regarding the use of proton-pump inhibitors, renal function, and liver cirrhosis, all of which may falsely increase calcitonin levels
  • In summary, the evidence provided by this study suggests that routine serum calcitonin screening in patients with thyroid nodules allows earlier diagnosis and improves the prognosis of MTC, particularly in those with smaller tumor sizes and less lymph node involvement
  • Although the cost-effectiveness of such a strategy is an important factor, the practice should be considered in our thyroid clinics across the United States

#Arrangoiz #ThyroidSurgeon #ThyroidExpert #CancerSurgeon #HeadandNeckSurgeon #MedullaryThyroidCancer #MTC #EndocrineSurgery #Miami #Mexico #MountSinaiMedicalCenter

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