ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare etiology of endogenous Cushing’s syndrome and is frequently associated with germline variants in the ARMC5 gene. Craniopharyngiomas are uncommon epithelial tumors of the sellar–suprasellar region that may lead to panhypopituitarism. The coexistence of AIMAH and craniopharyngioma is extremely uncommon. This report presents a case of genetically confirmed ARMC5-related AIMAH concurrently identified with papillary craniopharyngioma–induced panhypopituitarism in an adult patient, emphasizing the diagnostic considerations raised by this unusual combination.

A 64-year-old male with diabetes, hypertension, and dyslipidemia underwent abdominal imaging after elevated CA19-9 was detected during routine health screening. Endocrine evaluation for the adrenal lesions included a 1-mg overnight dexamethasone suppression test, basal ACTH measurement, and 24-hour urine free cortisol assessment. Genetic testing for ARMC5 variants was performed. Because of abnormal pituitary findings on MRI, comprehensive basal pituitary hormone measurements and combined stimulation tests were conducted. Surgical resection and histopathologic review were performed for the sellar mass.

Abdominal CT revealed bilateral macronodular adrenal enlargement. Cortisol remained unsuppressed (>10 µg/dL) after dexamethasone, with suppressed ACTH (<5 pg/mL), confirming ACTH-independent cortisol secretion. A pathogenic ARMC5 mutation consistent with AIMAH was identified. Pituitary MRI showed a 2.5-cm sellar/suprasellar mass, and hormonal testing confirmed panhypopituitarism. The patient underwent endoscopic transsphenoidal resection, and pathology was consistent with papillary craniopharyngioma. Despite biochemical evidence of AIMAH, the 24-hour urine free cortisol was only modestly elevated (34.3 µg), and the patient exhibited no overt cushingoid features. Clinical surveillance and biochemical monitoring were planned, including family screening for ARMC5 variants.

This case highlights the uncommon coexistence of papillary craniopharyngioma–induced panhypopituitarism and ARMC5-related ACTH-independent macronodular adrenal hyperplasia, underscoring the clinical importance of thorough evaluation when multiple endocrine abnormalities are present.