Summary of findings'. 'Summary of findings table.
| Review question | What is the diagnostic accuracy of calcitonin testing in the detection of MTC in people with thyroid nodules? | |||||
| Population | People with thyroid nodular disease found by palpation or ultrasound. | |||||
| Setting | Mostly individuals referred to outpatient clinics. | |||||
| Index test | All serum tests used to determine basal and stimulated calcitonin. | |||||
| Importance | No consensus exists about routine calcitonin testing in the work‐up of people with thyroid nodules. | |||||
| Reference standard | Histopathological examination is considered the optimal reference standard, however this is a problem in people without an elevated calcitonin test, as surgery is performed very rarely. We therefore used an alternative clinical follow‐up for at least three years. | |||||
| Studies | We included all retrospective and prospective cohort studies in which all people with thyroid nodules had undergone determination of basal calcitonin levels (and stimulated calcitonin, if performed). | |||||
| Limitations | There was a poor reported follow‐up of calcitonin‐negative participants. Due to the small numbers of studies only for a few subgroups' summary measures could be calculated | |||||
| Test / subgroup |
Reported Sensitivity/specificity (range) |
Summary measures (95% CI) | No. of participants (studies) | Median prevalence (range) | Implications | Certainty of the evidence and comments |
| Basal calcitonin | ||||||
| Reported cut‐off value (range 4.6 ‐100 pg/mL) |
Sensitivity 83% to 100% Specificity 94% to 100% |
Median specificity: 96.6% Estimated sensitivity: 99.7% (68.8% to 100%) |
72,368 (16) | 0.32% (0% to 0.85%) |
There is a high median specificity across the studies with a high estimated sensitivity. However, due to the different thresholds it is difficult to make general implications | The reported cut‐off value included the cut‐off values of the calcitonin test reported by the different studies (range 4.6 pg/mL to 100 pg/mL). The reported follow‐up of calcitonin‐negative participants was poor, thereby limiting the interpretation of these results |
| Combined basal and stimulated calcitonin | ||||||
| Reported cut‐off value (range basal calcitonin 4.6 pg/mL to 35 pg/mL, range stimulated calcitonin 50 pg/mL to 100 pg/mL) |
Sensitivity 82% to 100% Specificity 99% to 100% |
Median specificity: 99.8% Estimated sensitivity: 98.8% (65.8% to 100%) |
69,702 (13) | 0.31% (0% to 0.85%) |
There is a high median specificity across the studies with a high estimated sensitivity. However due to the different thresholds it is difficult to make general implications | The reported cut‐off value included the cut‐off values of the basal and stimulated calcitonin test reported by the different studies (range basal calcitonin 4.6 pg/mL to 35 pg/mL; range stimulated calcitonin 50 pg/mL to 100 pg/mL) The reported follow‐up of calcitonin negative participants was poor, thereby limiting the interpretation of these results |
| Subgroup analysis | ||||||
| Cut‐off value | ||||||
| 10 pg/mL |
Sensitivity (92% to 100%) Specificity (94% to 99%) |
Sensitivity 100% (99.7% to 100%) Specificity 97.2% (95.9% to 98.6%) |
44,393 (10) | 0.23% (0% to 0.69%) |
With a prevalence of 0.23% in a population of 10,000 nodular thyroid disease patients, 23 people will have a MTC. Of these MTC patients none will be missed using a cut‐off value of 10 pg/mL, while 280 people will have a false‐positive test result | The reported follow‐up of calcitonin‐negative participants was poor, thereby limiting the interpretation of these results |
| Gender (basal calcitonin) | ||||||
| Female |
Sensitivity 96% to 100% Specificity 97% to 100% |
a | 14,858 (6) | 0.25% (0% to 0.51%) |
There is a high reported specificity and sensitivity across the studies. However due to the different thresholds it is difficult to make general implications | The reported cut‐off value included the cut‐off values of the calcitonin test reported by the different studies (range 4.6 pg/mL to 30 pg/mL). The reported follow‐up of calcitonin‐negative participants was poor, thereby limiting the interpretation of these results |
| Male |
Sensitivity 82% to 100% Specificity 92% to 100% |
a | 4339 (6) | 0.49% (0.23% to 1.78%) |
Most studies report a high specificity and sensitivity. However due to the different thresholds it is difficult to make general implications | The reported cut‐off value included the cut‐off values of the calcitonin test reported by the different studies (range 5 pg/mL to30 pg/mL). The reported follow‐up of calcitonin‐negative participants was poor, thereby limiting the interpretation of these results |
aCould not be assessed due to limited number of studies
CI: confidence interval; MTC: medullar thyroid cancer; pg/mL: picograms per millilitre;