Primary Bilateral Macronodular Adrenal Hyperplasia: A Case Series from a Tertiary Hospital

Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare etiology of Cushing’s syndrome characterized by the presence of multiple adrenal macronodules and variable levels of cortisol excess. Its pathogenesis is complex, involving mechanisms such as aberrant hormone receptors, adrenal paracrine ACTH production, and genetic germline pathogenic variants. However, management is not well established. Methods: This was a retrospective, observational study. We evaluated patients with PBMAH at our tertiary center. We aimed to describe the clinical, hormonal, and radiological characteristics; treatment approaches; and outcomes. Results: Twenty patients were included in this study. Patients had a mean age at diagnosis of PBMAH of 56.1 ± 11.1 years, and 10 patients (50.0%) were females. Most cases were initially investigated for adrenal incidentalomas. Median 8:00 a.m. serum cortisol after 1 mg dexamethasone overnight suppression test was 223.5 (73.1–698.6) nmol/L (8.11 [2.65–25.3] µg/dL), late-night salivary cortisol was 1.48 (0.765–3.21) times the upper limit of normal (ULN), and 24 h-UFC was 1.61 (0.42–3.64) times the ULN. One patient presented with the co-secretion of cortisol and aldosterone. Mean total adrenal size was 98.5 ± 25.6 mm, and the largest nodule size was 32.1 ± 9.09 mm. In six (31.6%) patients, the largest nodule had an attenuation higher than 10 HU. Germline pathogenic variants in ARMC5 were found in four (50.0%) of the eight tested patients who underwent genetic testing. Treatment strategies varied, with unilateral adrenalectomy often successfully controlling hypercortisolism in five (83.3%) of 6 patients with modest excess cortisol secretion. For mild autonomous cortisol secretion, active surveillance of comorbidities and appropriate treatment were not associated with progression of cortisol secretion after a median follow-up of 34.0 (10.5–83.0) months. Conclusion: This study underscores the need for personalized management strategies and identifies areas for future research to optimize the care of patients with PBMAH.