Experience with the Mixed Meal Test in Diagnosing GIP-Dependent Cortisol Hypersecretion at a Tertiary Center

Abstract

Objectives

Aberrant expression of glucose-dependent insulinotropic peptide receptors (GIPR) might regulate increased steroidogenesis in patients with ACTH-independent cortisol hypersecretion. This study investigated the presence of aberrant GIPR expression in patients with ACTH-independent cortisol hypersecretion and bilateral adrenal adenomas.

Methods

Patients with bilateral adrenal adenomas, ACTH-independent CS and aberrant GIPR screened via mixed meal test were included. Patients’ demographic features and laboratory and imaging findings were obtained retrospectively.

Results

Twenty-one patients were included. Overt CS findings were present in 14.3% of the patients. One patient (4.7%) had a complete positive response (537% increase) and one patient (4.7%) had a partial response (41% increase) to the mixed meal test. In the remaining 19 patients, a mean change of -10.1% (range: −56.5% to+24.7%) in cortisol levels was observed at 120 min compared to baseline. The patient with a complete positive response was confirmed using 100 µg of IV octreotide. The patient underwent unilateral adrenalectomy after an inadequate long-term response to octreotide LAR therapy. The histopathology revealed bilateral macronodular adrenal cortical disease. We identified a germline heterozygous frameshift variant in the KDM1A gene in the patient’s blood sample and a recurrent deletion of the p arm of chromosome 1 harboring the KDM1A locus in the adrenal sample.

Conclusion

These results may provide useful insights into the screening of aberrant GIPR expression in patients with ACTH-independent hypercortisolism. It is essential to further investigate which patients require screening. Moreover, a significant cortisol peak observed during the mixed meal test in the presence of these receptors has drawn attention.

Keywords

adrenal adenoma - autonomous cortisol secretion - Cushing’s syndrome - KDM1A - primary bilateral macronodular adrenal hyperplasia - GIP-dependent cortisol secretion

Publikationsverlauf

Eingereicht: 27. Februar 2025

Angenommen nach Revision: 29. Juli 2025

Artikel online veröffentlicht:
08. September 2025

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