Endocrine Abstracts

Introduction: Virtually all familial cases of Medullary Thyroid Carcinoma (MTC) have a RET germline mutation. Subjects harboring RET germline mutation without unaware of their condition are defined gene carriers (GC). Thyroid surgery timing is decided upon RET mutation and calcitonin levels (both basal, bCT, and stimulated, sCT). However, bCT and sCT thresholds for planning thyroid surgery have not been established, yet.

Methods: we evaluated 189 GCs by clinical, biochemical (bCT and sCT) and neck US every 6-12 months. Thyroid surgery was planned in case of elevated bCT (i.e., higher than upper limit of normal range) and/or positive stimulation test, or subjects (or parents, if minor) willing. After surgery, all patients were submitted to biochemical analysis (bCT and, if necessary, sCT) and neck ultrasound.

Results: 92/189 GCs were submitted to thyroid surgery after a median time of 6 months (IQR 2-13). MTC foci (73.3% < 1 cm, 15% between 1 and 2 cm, 11.7% > 2 cm) were present in 71 (77.2%) while CCH in 21 (22.8%) subjects. At last clinical evaluation after surgery (median follow-up 85.5, IQR 35.25-147 months), clinical remission was observed in 71 patients (88.6% of microMTC, 66.6% of MTC between 1 and 2 cm, 28.6% of MTC > 2 cm and 100% of CCH patients) while 18 presented disease persistence (11.4% of microMTC, 33.4% of MTC between 1 and 2 cm and 71.4% of MTC > 2 cm): 13 and 5 MTC patients presented biochemical and structural persistence, respectively. Both presurgical bCT (P < 0.001) and sCT (P = 0.009) were higher in not cured patients (median 218 and 1326 pg/ml, respectively) compared to cured ones (20 and 178 pg/ml, respectively). Interestingly, presurgical bCT lower than 28.25 pg/ml significantly identified CCH and MTC who will be cured, with a high specificity (93.3%) and good sensitivity (76.2%). Conversely, values of presurgical bCT higher than 12.60 pg/ml and of presurgical sCT higher than 134.0 pg/ml, correlated with the presence of MTC foci with high sensitivity (95.0% and 94.40%, respectively) and good specificity (75.0% and 61.40%, respectively).

Conclusions: in a large cohort of consecutive GCs who were submitted to thyroid surgery, presurgical bCT <28.25 pg/ml identified, with high specificity and good sensitivity, CCH or small MTC that will be cured with thyroidectomy. When presurgical bCT is >12.6 pg/ml, some cases of MTC may be present but, if the bCT is still <28.25 pg/ml, they also will be safely cured.