Evidence map›Paper›PMID 40334050›Full record

SynthesisEuropean thyroid journal2025

Role of the calcium stimulation test in diagnosing medullary thyroid cancer: is it adequate to achieve a diagnosis in both sexes? An individual patient data meta-analysis.

Franz Sesti, Tiziana Feola, Pasquale Dolce, Valentina Guarnotta, Alessandro Veresani, Elia Guadagno, Filomena Bottiglieri, Maria Grazia Tarsitano, Andrea M Isidori, Annamaria Colao and 3 more

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in European thyroid journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Franz SestiDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.ORCID https://orcid.org/0000-0003-3850-627X
Tiziana FeolaDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.ORCID https://orcid.org/0000-0003-1066-0064
Pasquale DolceDepartment of Translational Medical Science, Federico II University of Naples, Naples, Italy.
Valentina GuarnottaDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Section of Endocrinology, University of Palermo, Palermo, Italy.
Alessandro VeresaniEndocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy.
Elia GuadagnoDepartment of Neurosciences, Reproductive Sciences and Dentistry, Gynecology Unit, Federico II University Hospital of Naples, Naples, Italy.ORCID https://orcid.org/0000-0002-0438-1491
Filomena BottiglieriEndocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.
Maria Grazia TarsitanoDepartment of Medical and Surgical Science, University Magna Grecia, Catanzaro, Italy.
Andrea M IsidoriDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.ORCID https://orcid.org/0000-0002-9037-5417
Annamaria ColaoEndocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.ORCID https://orcid.org/0000-0003-4049-2559
Antongiulio FaggianoEndocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy.ORCID https://orcid.org/0000-0002-9324-3946
Elisa GiannettaDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy.ORCID https://orcid.org/0000-0003-3614-6151
NIKE group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: 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. Methods: 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. Results: 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). Conclusions: 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. Significance statement: 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.

Indexed as

CalcitoninCalcium GluconateCarcinoma, NeuroendocrineThyroid NeoplasmsFemaleHumansMaleSensitivity and SpecificitySex FactorsThyroidectomyCalcitoninCalcium Gluconatecalcitonincalcium stimulation testmedullary thyroid cancermeta-analysissex difference

Identifiers

PMID40334050
PMCPMC12125618

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.