Primary Bilateral Macronodular Adrenal Hyperplasia: A Rare Cause of Cushing's Syndrome – A Review of the Literature
Primary Bilateral Macronodular Adrenal Hyperplasia: A Rare Cause of Cushing's Syndrome – A Review of the Literature
Mohammad Reza Ghanbari Boroujeni,1Elahe Meftah,2Fatemeh Zarimeidani,3Rahem Rahmari,4Fatemeh Esfahanian,5,*
1. Students Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran 2. Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran 3. Students Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran 4. Students Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran 5. Department of Endocrinology, Vali-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome (CS), accounting for <2% of CS cases. Diagnosing PBMAH can be difficult and challenging for clinicians.
Methods: We conducted a comprehensive review of recent case reports on PBMAH available on Google Scholar and PubMed databases.
Results: The clinical manifestations of PBMAH can progress gradually for years, resulting in a lack of comprehensive epidemiological data and underdiagnosed cases. Characteristically, nodules in PBMAH exceed 10mm. The underlying mechanisms include aberrant receptor expression, local ACTH production, and genetic mutations, notably in ARMC5. While cortisol levels in PBMAH are usually mildly elevated, many patients remain asymptomatic, although some may develop overt CS. Diagnosis poses challenges due to its rarity and the absence of specific symptoms, necessitating a combination of clinical criteria, imaging, and potentially genetic testing. Surgical intervention is the mainstay of treatment for those with overt CS, with unilateral adrenalectomy emerging as a favorable option due to lower associated morbidity compared to bilateral adrenlaectomy. However, the optimal treatment strategy continues to be the subject of ongoing debate
Conclusion: PBMAH should be considered in the approach to patients with CS manifestations. The diagnosis and treatment of this condition can be challenging, and further studies on the best possible treatment of PBMAH are recommended.