Original Title: Dosages sanguins du cortisol et de la dexaméthasone par chromatographie liquide couplée à la spectrométrie de masse en tandem (LC-MS/MS) lors d’un test de suppression à la dexaméthasone

Authors' objectives: A request to introduce a new test to the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter the Répertoire) was submitted to the Ministère de la Santé et des Services sociaux (MSSS) by the Grappe Montréal-CHUM (hereinafter referred to as the requesting laboratory). The MSSS mandated the Institut national d’excellence en santé et en services sociaux (INESSS) to evaluate the relevance of introducing to the Répertoire the measurement of the dexamethasone level in a blood sample following a dexamethasone suppression test. Since concerns were raised during this assessment regarding cortisol level measurement, the report was titled “Blood cortisol and dexamethasone measurements using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in the context of a dexamethasone suppression test”.

Authors' results and conclusions: RESULTS (#1 POPULATIONAL DIMENSION): Hypercortisolism is characterized by excessive cortisol secretion in the body and is associated with an increased mortality rate. The challenge resides in identifying mild cases of hypercortisolism, since their clinical manifestations overlap with those of more common conditions, such as obesity, hypertension and diabetes, which complicates this diagnosis. The DST is recommended as a first-line test in non-overt cases of hypercortisolism, because salivary and urinary cortisol measurements may be normal in patients with moderate autonomous cortisol secretion. A post-DST cortisol level <50 nmol/l is generally considered a normal response and suggests that the patient does not have hypercortisolism. A dexamethasone measurement would be performed in patients suspected of endogenous hypercortisolism whose post-DST cortisol level is elevated. In clinical practice in Quebec, the care trajectory of patients suspected of having hypercortisolism varies from case to case according to the level of clinical suspicion and the treating physician. In fact, clinicians from different specialties can prescribe a DST and interpret its results. (#2 CLINICAL DIMENSION ): According to the literature and clinicians, a post-DST cortisol level ≥ 50 nmol/l suggests hypercortisolism. Even though there is no consensus in the literature regarding the minimum dexamethasone level necessary for cortisol secretion inhibition, clinicians consider the value proposed by the requesting laboratory, ≥ 4.5 nmol/l, appropriate. According to the literature, post-DST dexamethasone measurement increases the specificity in the diagnosis of hypercortisolism by approximately 2% but does not decrease its sensitivity. In the selected studies, between 11% and 31% of the patients with an elevated post-DST cortisol level had not achieved a sufficient dexamethasone concentration to inhibit cortisol secretion. Measuring the dexamethasone level could therefore have an impact on these patients’ care trajectory. In unequivocal cases of hypercortisolism, the etiology of hypercortisolism is promptly investigated. A dexamethasone measurement would therefore have no impact on their care trajectory. (#3 ORGANIZATIONAL DIMENSION ): The result turnaround time for a post-DST cortisol test by immunoassay is currently less than 24 hours. Since the turnaround times for cortisol and dexamethasone measurements by LC-MS/MS are estimated at two weeks, it would not be appropriate, according to clinicians, to replace a locally available cortisol test by immunoassay with a LC-MS/MS-based test for all DSTs. It is therefore proposed that dexamethasone and cortisol levels be measured by LC-MS/MS only when the post-DST cortisol level by immunoassay is ≥ 50 nmol/l (or according to a locally established threshold). If the post-DST cortisol level is elevated, the sample would be sent automatically to a designated laboratory for dexamethasone and cortisol measurements by LC-MS/MS. An interpretive guide should be provided with the results of the dexamethasone measurements. (#4 SOCIOCULTURAL DIMENSION): Several organizations of interest and expert consensus, mostly in endocrinology, indicate that a dexamethasone measurement evaluates whether its concentration was sufficient to inhibit cortisol secretion following a DST, thereby preventing false-positive results. The availability of this test is, however, described as being limited, and no consensus threshold has been set. (#5 ECONOMIC DIMENSION - COST-EFFECTIVENES): No study evaluating the cost-effectiveness of the analysis to measure dexamethasone was found in the scientific literature. Its cost-effectiveness cannot be properly determined in the Quebec context, given that its costs and clinical benefits are not known. (#5.1 ECONOMIC DIMENSION - BUDGET IMPACT ANALYSIS): A budget impact analysis considering the costs associated with introducing to the Répertoire the test for simultaneous measurements of cortisol and dexamethasone by LC-MS/MS was performed. The weighted value of this analysis is 10.52. It is estimated that 7328 dexamethasone measurements would be performed over a 3-year time frame if the test is added to the Répertoire, which could lead to additional expenses over 3 years of approximately $101,600. It should be noted that a decrease in certain costs compared to the current situation cannot be entirely ruled out. However, the extent of this reduction is unknown because of the uncertainty regarding the practice changes resulting from the introduction of this analysis to the Répertoire and because of the variability in the care trajectory of patients with suspected hypercortisolism.

Authors' recommendations: Considering the findings for the five value dimensions, INESSS recommends the introduction to the Répertoire of the blood cortisol and dexamethasone measurements by LC-MS/MS following a DST. INESSS recommends putting the following measures in place to effectively guide the use of this test: • Blood cortisol and dexamethasone measurements by LC-MS/MS following a DST should be performed as a reflex test if the post-DST cortisol level, as determined by an immunoassay, is ≥ 50 nmol/l. A threshold cortisol level indicative of overt hypercortisolism and for which a dexamethasone measurement would not be done should also be established by the designated laboratory jointly with the user clinicians; • The addition of this test should be accompanied by the creation of two codes in the Répertoire, namely, for: 1) DST with blood cortisol immunoassay (test currently performed); 2) DST with blood cortisol and dexamethasone measurements by LC-MS/MS (reflex test to the first code when the post-DST cortisol level, as determined by an immunoassay, is ≥ 50 nmol/l [or according to a locally established threshold]); • Interpretive guide should be provided with the results of the dexamethasone measurement; • The designated laboratory or laboratories must meet the requirements set out in ISO standard 15189.

Authors' methods: The assessment process included a review of the scientific literature, a search of the grey literature, and consultations with clinicians and other stakeholders. The methodology was based on the five dimensions outlined in the statement of principles of INESSS framework for the appraisal of the value of interventions in health and social services: populational, clinical, organizational, sociocultural and economic. All the scientific, contextual and experiential data were interpreted and synthesized to guide the deliberative process of the Comité scientifique permanent (CDP) – Approches Diagnostiques et dépistage for the development of recommendations.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/dosages-sanguins-du-cortisol-et-de-la-dexamethasone-par-chromatographie-liquide-couplee-a-la-spectrometrie-de-masse-en-tandem-lc-ms-ms-lors-dun-test-de-suppression-a-la-dexamethasone.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/dosages-sanguins-du-cortisol-et-de-la-dexamethasone-par-chromatographie-liquide-couplee-a-la-spectrometrie-de-masse-en-tandem-lc-ms-ms-lors-dun-test-de-suppression-a-la-dexamethasone.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)