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Adrenal (Excluding Mineralocorticoids)

SAT-416 - Prolonged HPA Axis Suppression in PRKACA-Mutant Mild Autonomous Cortisol Secretion: A Case Report

Saturday, June 13, 2026
9:30 AM - 4:30 PM CT
Background
Cortisol-producing adenomas (CPAs) are clinically classified into overt Cushing syndrome (CS) and mild autonomous cortisol secretion (MACS), both managed by adrenalectomy. Postoperative glucocorticoid replacement is generally withdrawn earlier in MACS than in overt CS. Biologically, CPAs comprise PKA-activating and non-PKA subtypes; somatic PRKACA activating mutations drive 40–60% of overt CS adenomas but are rare in MACS, and evidence on PKA-mutant MACS (PKA-MACS) remains limited.
Case Presentation
A 52-year-old woman was incidentally found to have a 26-mm left adrenal tumor on CT, with lipid-rich MRI features consistent with adenoma. Morning ACTH was 7.4 pg/mL, cortisol 10.3 μg/dL, and post–1 mg dexamethasone suppression test cortisol 8.3 μg/dL. In the absence of Cushingoid features, she was diagnosed with MACS. Left adrenalectomy was performed; histopathology revealed an adrenocortical adenoma without malignant features (Weiss score 0) with positive CYP17A1 and CYP11B1 immunostaining and marked atrophy of the attached non-tumoral cortex. Targeted sequencing of tumor tissue identified a somatic PRKACA p.Leu206Arg (L206R) variant. On postoperative day 10, early morning cortisol was 2.2 μg/dL and peak cortisol on rapid ACTH stimulation 2.6 μg/dL, confirming adrenal insufficiency (AI); hydrocortisone 20 mg/day was initiated. At postoperative month 5, acute infectious gastroenteritis precipitated an adrenal crisis during tapering, requiring hospitalization. Replacement was discontinued 4 years and 3 months after surgery, with no recurrence of AI.
Discussion
Although clinically MACS, the tumor harbored a PRKACA activating variant with marked atrophy of the adjacent cortex. The reported median postoperative AI duration after MACS surgery is 3.9 months (EJE 2026), far exceeded in the present case (4 years and 3 months). Moreover, adrenal crisis during tapering triggered by a minor intercurrent infection suggests profound, prolonged HPA-axis suppression. The frequency of PRKACA mutations in MACS is rare in Western populations but tends to be higher in Asian than in Western cohorts, as also observed in the present case (Endocr J 2026).
Conclusion
In patients clinically diagnosed as MACS who harbor a PRKACA activating variant, HPA-axis recovery may require a prolonged period.

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