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Report on the Annual Meeting of the European Thyroid Association

Report on the Annual Meeting of the European Thyroid Association

Professor George Kahaly reviews key scientific breakthroughs in calcitonin and medullary thyroid carcinoma (MTC), discussed at the annual meeting of the ETA. This five-day event was a great scientific and medical success, attended by approximately 1500 participants and supported by 25 European sponsors. The meeting presented the latest developments in the field of thyroid research.

This report reports on two key presentations at the ETA meeting that covered calcitonin and MTC.

Serum calcitonin measurement

Two oral communications (from Jürgen Kratzsch, Leipzig, Germany and Furio Pacini Siena, Italy) focused on the measurement of this serum biomarker in people with confirmed or suspected MTC.

Professor Kratzsch presented innovative data on the validation of a sensitive immunoassay that has recently been developed. He reviewed data from four European referral centres, encompassing ~1000 participants, which demonstrated the sensitive and accurate measurement of serum calcitonin in patients with C-cell hyperplasia and MTC.

However, he noted that a selection of benign thyroid and non-thyroidal diseases were also associated with elevated serum calcitonin levels. These were:

  • Patients with neuroendocrine tumours, hypercalcaemia, primary hyperparathyroidism or chronic renal failure
  • Patients on dialysis
  • Patients with autoimmune thyroid diseases, e.g. Hashimotos’ thyroiditis or Graves’ disease
  • Male male patients with euthyroid or toxic thyroid nodules.

Between five and 25% of these patients demonstrated elevated calcitonin values, making this marker a sensitive one but not a specific one.

In addition, over one-third of patients on proton pump inhibitors had markedly elevated serum calcitonin levels.

Reference limits

The novel calcitonin assay is more sensitive and detects serum calcitonin at markedly lower concentrations, compared with other assays and devices. The upper reference limit (97.5 percentile) was defined at 6.4 pg/ml for female and 9.52 pg/ml for male patients, whereas it was 13.3 pg/ml in those with euthyroid thyroid nodules.

Maximal serum calcitonin concentrations of patients with Graves’ disease, autoimmune thyroiditis, toxic goitre and disorders of calcium homeostasis were 19.9, 10.1, 13.3, and 19.1 pg/ml, respectively. Position in the clinical setting

Previous experiments Professor Kratzsch also showed the lower limit of detection and quantitation of this new assay in contrast to various commercial devices. Nevertheless – and from the clinical point of view – the fact that several benign thyroidal and non-glandular disorders significantly enhance the serum calcitonin levels leads to the necessity of performing stimulation tests to either confirm or exclude the presence of medullary thyroid neoplasms.

The stimulation tests indeed clearly differentiate between benign disorders, showing no calcium-induced increase of the serum calcitonin level.

Paediatric reference ranges

A working group led by Professor Furio Pacini, who is also the current president of the ETA, has looked at a large paediatric collective (2006 newborn, children and adolescents aged up to 16 years), aiming to define a normal reference range for serum calcitonin, in this young group.

Serum calcitonin levels in children progressively decrease during the first 3 years of life. Thereafter, serum calcitonin levels are comparable with those of adults. Serum calcitonin was undetectable (<2pg/ml, two-site chemiluminescence immunometric assay, analytical sensitivity 2.0 pg/ml) in 57% of samples, whereas undetectable samples were more frequent, starting from the second year of age.

The mean (standard deviation) serum calcitonin level in children aged <1 year was 9.0 pg/ml (8.8), range 0.7-49 pg/ml. At age 16, the mean serum calcitonin was 1.2 pg/ml (1.3), range 0-5.6 pg/ml. These data may be of help in screening young carriers of the RET mutation.

Molecular profiling

Gene-expression profiles and divergent roles of forkhead family transcription factor paralogues, according to the types of RET mutations found in patients with MTC, were introduced in scientific sessions at the ETA meeting.

Furthermore, molecular profiling undertaken in patients with sporadic MTC by next-generation sequencing – as well as the clinical impact of RET genetic screening in the management of these tumours – emphasized the crucial role of genetic analyses in patients with MTC and their first-degree relatives.

Aggressive MTC has a distinct molecular profile from surgically cured MTC. The role of further mutations e.g. the ERBB2, NRAS and P13KCA gene mutations are being currently evaluated.

All in all, this was an interesting and challenging session at the ETA meeting, which demonstrated the close relationship between phenotype, genotype and serological markers to optimize early diagnosis as well as accurate and timely management of patients with C-cell hyperplasia and MTC.

George J. Kahaly

Professor of Medicine and Endocrinology / Metabolism, Chief of the endocrine outpatient clinic
Dept of Medicine
Gutenberg University Medical Center
Mainz, Germany
Serum calcitonin measurement
Medullary thyroid carcinoma
Calcitonin assay
Paediatric calcitonin levels
Molecular profiling