Calculation and validation of a plasma calcitonin limit for early detection of medullary thyroid carcinoma in nodular thyroid disease.
BACKGROUND
The early diagnosis of medullary thyroid carcinoma (MTC) is crucial for effective therapy. Elevated plasma calcitonin concentrations (pCT-Cs) are generally a specific and sensitive indicator for C-cell hyperplasia or MTC. The presence of thyroid nodules raises the possibility of MTC. Hence, in endemic goiter regions, there is a need for information regarding the pCT-C values that are indicative of C-cell hyperplasia or MTC. The aim of this study, therefore, was to determine an upper pCT-C to distinguish patients with and without MTC in a collective with nodular thyroid disease, and to give an estimation of the prevalence of MTC in an endemic goiter area.


METHODS
Basal pCT-C was measured in 21,928 patients with thyroid nodules living in central Germany, an area with endemic goiter due to previous iodine deficiency. In 218 subjects with pCT-Cs exceeding 10 ng/L, stimulated pCT-C was additionally determined, as suggested by the German consensus recommendation. A nominal normal range for basal pCT-C was calculated with data from 21,900 subjects without known MTC. The predicted upper limit was then validated using the known diagnoses of 376 patients with pCT-Cs exceeding 10 ng/L, 28 of whom presented with MTC.


RESULTS
For basal pCT-C, calculation of the three-sigma borders after logarithmic transformation revealed upper limits of the nominal normal range of 14.6 ng/L in females and 32.8 ng/L in males, respectively. However, three male patients with small MTCs had basal pCT-Cs between 15 and 33 ng/L. None of the patients with MTC had a basal pCT-C below 15 ng/L or an increase in pCT-C after pentagastrin stimulation that was less than 80 ng/L. In the basal pCT-C range between 15 and 50 ng/L (n = 192; eight with MTC), the positive predictive value for the detection of MTC was 4% in our group. Applying an upper limit for basal pCT-C of 15 ng/L in both sexes, 329 of the total of 21,928 patients exceeded this range. Among these, the final outcome is known in 231 subjects, including all 28 MTCs.


CONCLUSIONS
An upper limit of 15 ng/L instead of 10 ng/L for basal pCT-C is able to detect all MTC and reduce false-positive cases. The prevalence of MTC in nodular thyroid disease in our group was approximately 1.8 per thousand.
Department of Nuclear Medicine, Municipal Hospital, Hanau, Germany. rink@em.uni-frankfurt.de
Thomas
T
Rink
Phuong-Ngan
PN
Truong
Hans-Joachim
HJ
Schroth
Jürgen
J
Diener
Michael
M
Zimny
Frank
F
Grünwald
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002116:Calcitonin / Q000097:blood*; D018276:Carcinoma, Medullary / Q000175:diagnosis* / Q000453:epidemiology; D002648:Child; D005858:Germany / Q000453:epidemiology; D006043:Goiter, Endemic / Q000097:blood; D006801:Humans; D008875:Middle Aged; D015995:Prevalence; D012016:Reference Values; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000453:epidemiology; D016606:Thyroid Nodule / Q000097:blood* / Q000453:epidemiology; D013967:Thyroiditis, Autoimmune / Q000453:epidemiology
D002116:Calcitonin