Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer

Abstract

Men and women differ in thyroidal C-cell mass and calcitonin secretion. This difference may have implications for the definition of calcitonin thresholds to distinguish sporadic C-cell hyperplasia from occult medullary thyroid cancer. This retrospective study examined the hypothesis that gender-specific calcitonin thresholds predict occult medullary thyroid cancer more accurately among patients with increased basal calcitonin levels than unisex thresholds. A total of 100 consecutive patients were evaluated with occult sporadic C-cell disease no larger than 10 mm who were referred for increased basal calcitonin levels and underwent pentagastrin stimulation preoperatively at this institution. Altogether, gender-specific calcitonin thresholds predicted medullary thyroid cancer better than unisex thresholds. At lower (%50 pg/ml basally; %500 pg/ml after stimulation), but not higher, calcitonin serum levels, women revealed medullary thyroid cancer four to eight times more often than men. Most discriminatory between C-cell hyperplasia and medullary thyroid cancer was a basal calcitonin threshold of 15 pg/ml (corrected 20 pg/ml) for women and 80 pg/ml (corrected 100 pg/ml) for men, based on the greatest accuracy at the lowest possible calcitonin level. The respective gender-specific stimulated peak calcitonin thresholds were 80 pg/ml (corrected 100 pg/ml) and 500 pg/ml. Corresponding positive predictive values for medullary thyroid cancer at these calcitonin thresholds were 89 and 90% for women, as opposed to 100% for men. To increase the positive predictive value for women to 100%, the respective calcitonin thresholds would have to be raised to 40 pg/ml (corrected 50 pg/ml) and 250 pg/ml. These findings indicate that gender-specific calcitonin thresholds predict sporadic occult medullary thyroid cancer better than unisex thresholds.

American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules - 2016 Update Appendix

“…In addition, sex, age, weight, increased calcium levels, and the assay itself also affect the calcitonin levels. Cross-reactivity with procalcitonin must be excluded (235 there is no description of tumors >0.5 cm and lymph node metastasis when the basal calcitonin is 30 to 60 pg/mL. A single nonstimulated calcitonin measurement may be considered in the work-up of thyroid nodules with suspicious US or cytologic findings with the above caveats taken into account.…”

Analytical validation of the Liaison Calcitonin_II-Gen (DiaSorin)

“…We evaluated the measurement 23 uncertainty, the accuracy and the β-expectation limits: measurement uncertainty characterizes 24 the dispersion of the values around the true value and β-expectation tolerance limits with 25 β=0.95 are the upper and lower values in-between which each future measurements of the 1 same level has a probability of 95% to be found (10;11). We consider that the method will 2 provide accurate results if the 95% β-expectation tolerance interval at each concentration 3 level is fully included in the acceptance limits that we decided to settle at ±20% (12). 4 We checked the specificity of the assay by using 14 samples from patients treated by 5 complete thyroidectomy and irradiation.…”

Usefulness of preoperative serum calcitonin in patients with nodular thyroid disease without suspicious history or cytology for medullary thyroid carcinoma

“…Whereas sporadic MTC is very unlikely in the presence of basal sCT < 10 pg/mL (9,10), serum concentration > 100 pg/mL has an excellent positive predictive value (PPV) for this tumor in the absence of any apparent cause (e.g., chronic renal failure, use of proton pump inhibitors, other known secretory tumors) (6,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), and stimulation tests are not necessary in these cases. Despite the traditional cutoff value of 100 pg/mL, at least in women, PPV of 100% was reported in many series for basal sCT > 60 pg/mL (6,(8)(9)(10)(12)(13)(14)(17)(18)(19)(20)(21). In agreement with this finding, in the present study, after known causes of hypercalcitoninemia were excluded, none of the 492 patients without MTC had basal sCT > 40 pg/mL.…”

“…Although some studies reported PPV of 100% (8,10,20), many series found a value of only 25% (21), 20% (22), and 0/13 (9) in patients with elevated basal sCT, but < 100 pg/mL, who converted to levels > 100 pg/mL after stimulation. As a consequence, different cutoffs of stimulated sCT have been proposed in the literature (11)(12)(13)15,19), and this value remains undefined.…”