A case report of primary bilateral macronodular adrenal hyperplasia caused by a novel ARMC5 gene variant

Introduction : Primary bilateral macronodular adrenal hyperplasia (PBMAH), also known as adrenocorticotropic hormone-independent macronodular adrenal hyperplasia, is a rare cause of endogenous Cushing’s syndrome (CS) in clinical practice. The pathogenesis of PBMAH is complex; however, ARMC5 variants have been increasingly recognized as important pathogenic genetic factors, as reflected by the growing number of related studies. Case presentation A 59-year-old man was admitted because of long-standing poor glycemic and blood pressure control. Endocrine evaluation showed suppressed plasma adrenocorticotropic hormone (ACTH) levels, loss of the circadian cortisol rhythm, and failure of cortisol suppression after the low-dose dexamethasone suppression test. Imaging revealed multiple bilateral adrenal nodules. Histopathological examination showed nodular lesions composed predominantly of clear, lipid-rich cells, with a small number of cells with eosinophilic cytoplasm at the periphery of the nodules. Genetic testing identified an ARMC5 c.2125C > T (p.Q709*) nonsense variant. Based on the clinical manifestations and laboratory findings, the patient was diagnosed with PBMAH. The patient underwent left unilateral adrenalectomy, and outpatient follow-up showed reductions in antidiabetic and antihypertensive medications, with effective improvements in glycemic and blood pressure control. Conclusion This case confirms PBMAH caused by a novel nonsense variant in ARMC5 , thereby expanding the variant spectrum of ARMC5 . In patients with long-standing poorly controlled blood glucose and blood pressure, hypokalemia, and recurrent infections, related subclinical endocrine abnormalities should be considered, even in the absence of overt Cushingoid features. A diagnosis can be established through integrated endocrine evaluation, imaging assessment, and genetic testing. This case highlights the importance of screening for secondary endocrine causes in patients with hypertension and diabetes, particularly when clinical or biochemical findings suggest cortisol excess, and may inform clinical management and familial genetic counseling.