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Single determination of plasma ACTH using an immunoradiometric assay with high detectability differentiates between
M Klose1, A Kofoed-Enevoldsen, L Ostergaard Kristensen
1Department of Internal Medicine and Endocrinology, Herlev University Hospital, Denmark.
Insights
A single adrenocorticotropic hormone (ACTH) measurement effectively distinguishes ACTH-dependent from ACTH-independent Cushing's syndrome. This simple test aids in diagnosing the specific cause of Cushing's syndrome.
Area of Science:
- Endocrinology
- Clinical Diagnostics
- Hormone Assays
Background:
- Cushing's syndrome results from prolonged exposure to excess cortisol.
- Differentiating between ACTH-dependent and ACTH-independent causes is crucial for appropriate treatment.
- Accurate diagnostic tools are essential for patient management.
Purpose of the Study:
- To evaluate the diagnostic utility of a highly sensitive ACTH assay.
- To determine if a single ACTH measurement can differentiate ACTH-dependent from ACTH-independent Cushing's syndrome.
- To compare the effectiveness of ACTH measurements with corticotropin-releasing hormone (CRH) tests.
Main Methods:
- Retrospective analysis of 56 Cushing's syndrome patient records.
- Measurement of basal morning plasma 1-39 ACTH using an immunoradiometric assay (IRMA).
- Performance of peripheral corticotropin-releasing hormone (CRH) tests in a subset of patients.
Main Results:
- A single ACTH measurement with a cut-off of 2.4 pmol/L completely separated the two groups.
- Mean ACTH levels were significantly higher in ACTH-dependent (14.4 pmol/L) versus ACTH-independent (0.6 pmol/L) Cushing's syndrome.
- Repeated ACTH measurements or CRH stimulation further increased separation but were not superior to single measurements in most cases.
Conclusions:
- A single basal morning ACTH determination is generally sufficient to differentiate ACTH-dependent and ACTH-independent Cushing's syndrome.
- Repeated ACTH measurements may be necessary for borderline cases (ACTH 2-3 pmol/L).
- The peripheral CRH test did not offer advantages over repeated ACTH measurements for diagnosis.
Abstract:
The purpose of this retrospective study was to elucidate the value of an ACTH assay with high detectability to differentiate between ACTH-dependent and -independent Cushing's syndrome. The study was based on the case records of 56 patients with Cushing's syndrome comprising 34 patients with ACTH-dependent Cushing's syndrome and 22 patients with ACTH-independent Cushing's syndrome. Basal morning plasma 1-39 ACTH was measured using an immunoradiometric assay (IRMA) with a normal range of 1.8-11 pmol/L. Peripheral corticotrophin-releasing hormone (CRH) tests were performed in 24 and 17 patients with ACTH-dependent and -independent Cushing's syndrome, respectively. Using a single ACTH measurement, a complete separation was observed between the two defined groups, with a cut-off value of 2.4 pmol/L. Mean ACTH concentration was 14.4 pmol L (range 2.5-47.7 pmol/L) in ACTH-dependent Cushing's syndrome and 0.6 pmol/L (range 0.2-2.2 pmol/L) in ACTH-independent Cushing's syndrome. The range of separation between the two groups was further increased by using two ACTH measurements in each patient or peripheral stimulation with CRH. It is concluded that in the majority of patients with Cushing's syndrome a single basal morning ACTH determination is sufficient to discriminate between ACTH-dependent and ACTH-independent Cushing's syndrome. In borderline cases with ACTH in the range 2-3 pmol/L, repeated measurements might be necessary. The peripheral CRH test was not superior to repeated ACTH measurements.
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