Sesti Franz, Feola Tiziana, Dolce Pasquale, Guarnotta Valentina, Veresani Alessandro, Guadagno Elia, Bottiglieri Filomena, Tarsitano Maria Grazia, Isidori Andrea M, Colao Annamaria, Faggiano Antongiulio, Giannetta Elisa
Eur Thyroid J. 2025 May 29;14(3). doi: 10.1530/ETJ-24-0347. Print 2025 Jun 1.
Early diagnosis of medullary thyroid cancer (MTC) when basal calcitonin (CT) levels are <100 pg/mL remains a clinical challenge. The calcium stimulation test is a unique tool for stimulating CT. However, standardized and sex-specific cutoff values are lacking. Therefore, this study aimed to investigate whether the calcium stimulation test for CT is adequate for diagnosing MTC in both sexes and to identify sex-specific cutoff values.
This was an individual patient data (IPD) meta-analysis. A literature search was performed using Scopus, PubMed, and Web of Science until September, 2024, to identify articles on the calcium stimulation test for diagnosing MTC.
A total of five studies involving 243 patients (148 females and 95 males) who underwent total thyroidectomy were included in this study. Before surgery, all patients underwent the calcium stimulation test with calcium gluconate (25 mg/kg) for CT assessed by chemiluminescence assay. In females, a global threshold of 162 pg/mL was identified, with a pooled sensitivity of 0.90 (95% confidence interval (95% CI): 0.79-0.97) and specificity of 0.66 (95% CI: 0.56-0.75). The pooled area under the curve (AUC) was 0.87 (95% CI: 0.76-0.97). In males, a global threshold of 562 pg/mL was identified, with a pooled sensitivity of 0.79 (95% CI: 0.60-0.92) and specificity of 0.89 (95% CI: 0.79-0.96). The pooled AUC was 0.94 (95% CI: 0.90-0.99).
The calcium stimulation test for CT for the diagnosis of MTC showed better performance in males than in females, with a suggested cutoff value of 562 pg/mL in males.
The management of indeterminate calcitonin (CT) values is still challenging in the early diagnosis of MTC, lacking general recommendations, which can help clinicians in these cases. This is the first IPD meta-analysis that underscores the sex-based disparity in the diagnostic accuracy of the calcium stimulation test for CT in suspected MTC cases, showing better performance in diagnosing MTC in male versus female patients, with a cutoff value of 562 pg/mL in male subjects. In the context of the limited literature, this paper provides added value for the clinical endocrine practitioner, suggesting the use of the calcium stimulation test in highly selected cases with indeterminate CT values (10-100 pg/mL) with a sex-oriented and personalized approach.
当基础降钙素（CT）水平<100 pg/mL时，甲状腺髓样癌（MTC）的早期诊断仍是一项临床挑战。钙刺激试验是刺激CT的一种独特工具。然而，目前缺乏标准化的、针对性别的临界值。因此，本研究旨在调查CT的钙刺激试验是否适用于两性MTC的诊断，并确定针对性别的临界值。
这是一项个体患者数据（IPD）荟萃分析。使用Scopus、PubMed和Web of Science进行文献检索，直至2024年9月，以识别关于用于诊断MTC的钙刺激试验的文章。
本研究共纳入5项研究，涉及243例接受全甲状腺切除术的患者（148例女性和95例男性）。术前，所有患者均接受了葡萄糖酸钙（25 mg/kg）的钙刺激试验，通过化学发光法测定CT。在女性中，确定的总体临界值为162 pg/mL，合并灵敏度为0.90（95%置信区间（95%CI）：0.79 - 0.97），特异性为0.66（95%CI：0.56 - 0.75）。曲线下面积（AUC）合并值为0.87（95%CI：0.76 - 0.97）。在男性中，确定的总体临界值为562 pg/mL，合并灵敏度为0.79（95%CI：0.60 - 0.92），特异性为0.89（95%CI：0.79 - 0.96）。合并AUC为0.94（95%CI：0.90 - 0.99）。
用于诊断MTC的CT钙刺激试验在男性中的表现优于女性，建议男性的临界值为562 pg/mL。
在MTC的早期诊断中，不确定降钙素（CT）值的处理仍然具有挑战性，缺乏通用建议，这有助于临床医生处理这些情况。这是第一项IPD荟萃分析，强调了在疑似MTC病例中CT钙刺激试验诊断准确性的性别差异，表明在诊断MTC方面男性患者优于女性患者，男性受试者的临界值为562 pg/mL。在现有文献有限的情况下，本文为临床内分泌医生提供了附加价值，建议在高度选择的CT值不确定（10 - 100 pg/mL）的病例中采用针对性别和个性化的方法使用钙刺激试验。
