New Clinical Decision Support Score Based on Steroid Hormone Profiling in the Diagnosis of MACS

Official title

New Clinical Decision Support Score Based on Steroid Hormone Profiling in the Diagnosis of Adrenal Adenomas With Moderate Autonomous Cortisol Secretion or MACS

Overview

The recent development of quantitative steroid metabolome profiling could be of interest for the positive diagnosis of mild autonomous cortisol-secreting adenoma (MACS). The aim of the study is to develop a predictive model of MACS status or non-secreting adenoma (NSA) based on a panel of 19 serum steroids and three clinico-biological parameters (body mass index or BMI, fasting glycaemia, blood pressure) and to estimate its performance for the diagnosis of MACS in a cohort of patients followed in the endocrinology department of Bordeaux University Hospital.

Detailed description

Steroid assays are a central element in the aetiological diagnosis of adrenal tumors, but they are still limited to single assays (e.g. cortisol in Cushing's syndrome, aldosterone in primary hyperaldosteronism, etc.) which only partially reflect the endocrine disturbances caused by adrenal pathologies. The recent development of quantitative profiling of the circulating steroidome could lead to a reconsideration of the role of these single steroid assays in endocrinology. This involves simultaneously measuring of multiple steroids from a single blood or urine sample using liquid chromatography-mass spectrometry (LC-MS/MS). The steroid fingerprint obtained enables adrenal masses to be better characterised. Using machine learning methods, a predictive model of MACS status or NSA based on a panel of 19 serum steroids measured by LC-MS/MS and three clinico-biological parameters (body mass index or BMI, fasting glycaemia, blood pressure) will be develop. The blood sample used for the steroid assay will be taken at inclusion during a blood test carried out as part of routine care. Clinical, biological and morphological data obtained during the 24 months of study follow-up and as part of routine care will be collected retrospectively. All assays will be carried out in the hormonology laboratory of Bordeaux University Hospital (BUH) by LC-MS/MS. The development of the MACS/ANS status prediction model will be carried out by the BUH Methodological Support Unit for Clinical and Epidemiological Research (USMR). The performance and prognostic value of this new tool will be estimated in a cohort of patients followed in the BUH endocrinology department.

Primary outcome measures

• Assessment of the prediction model's performance [Time frame: 18 months after inclusion]

Secondary outcome measures (5)

• Correlation between blood steroid levels and blood pressure [Time frame: 18 months after inclusion]
• Correlation between blood steroid levels and Body Mass Index [Time frame: 18 months after inclusion day]
• Correlation between blood steroid levels and carbohydrate tolerance [Time frame: 18 months after inclusoin day]
• Correlation between blood steroid levels and bone mineral density [Time frame: 18 months after inclusion day]
• Correlation between blood steroid levels and bone architecture [Time frame: 18 months after inclusion day]

Eligibility criteria

Inclusion criteria

MACS and ANS group:

• 18 years ≤ Age
• Patient with one or more unilateral or bilateral adrenal nodules with spontaneous density < 20 HU on CT and major axis ≥ 1 cm and without associated overt pathological hormonal secretion.
• Patient with one or more uni or bilateral adrenal nodules not meeting the above density criteria but without malignancy criteria and stable in size on imaging after at least 6 months of follow-up and without associated overt pathological hormone secretion.
• Written consent of the patient for his participation in the research (at the latest on the day of inclusion and before any examination required by the research).
• Subject affiliated to or benefiting from a social security scheme.

Diagnostic criteria (determined after blood sampling) for continuation of the study:

MACS group:

• At least two elevated DST1mg (Cortisol > 50 nmol/L or 1.8 µg/dL) AND
• a plasma ACTH level ≤ 20 pg/mL

ANS group:

\- Normal DST1mg (Cortisol ≤ 50 nmol/L or 1.8 µg/dL). The definition criteria for MACS and ANS were based on the latest recommandations of learned societies.

Controls group:

• patients followed in the endocrinology department, free of any known adrenal pathology and with a DST1mg test < 50nmol/L.
• matched for age and sex to patients in groups 1 and 2.

Non -inclusion criteria:

• Adrenal incidentaloma < 1 cm in size.
• Use of exogenous corticosteroids, whether systemic or local (inhaled, eye and ear drops, ophthalmic ointment, topical skin products, joint infiltration) in the 6 months prior to the trial, and drugs that interfere with the metabolism of dexamethasone.
• Pregnant women.
• Patients with any other life-threatening condition.
• Patients with an intercurrent pathology at the time of blood sampling (fever, COVID infection, influenza....).
• Urinary free cortisol (UFC) > at the limit of laboratory normality.
• Patients under court protection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 1 center

• Hôpital du Haut-Lévêque — Pessac

Identifiers

NCT: NCT07352527 · CHUBX 2024/28

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗