Update on primary micronodular bilateral adrenocortical diseases.

Area of Science:

• Endocrinology
• Genetics
• Rare Diseases

Background:

• Primary micronodular bilateral adrenocortical hyperplasias (MiBAH) are rare endocrine disorders.
• Significant advancements in understanding MiBAH pathophysiology and genetics have occurred over the past two decades.
• This review focuses on primary pigmented nodular adrenocortical disease (PPNAD), a key subtype of MiBAH.

Purpose of the Study:

• To summarize recent progress in the pathophysiology and genetics of MiBAH.
• To review current investigation and therapeutic strategies for MiBAH, with a focus on PPNAD.
• To highlight the clinical and genetic complexities of PPNAD and Carney complex (CNC).

Main Methods:

• Review of recent large patient cohorts of PPNAD.
• Analysis of retrospective studies on PPNAD complications.
• Examination of genetic studies identifying new variants in the PRKAR1A gene.
• Evaluation of therapeutic outcomes, including unilateral adrenalectomy.

Main Results:

• PPNAD presents with variable Cushing's syndrome phenotypes and an earlier age of onset compared to other ACTH-independent causes.
• Increased risk of osteoporotic fractures observed in PPNAD patients.
• The 6-day oral dexamethasone test shows a paradoxical increase in urinary-free cortisol in PPNAD (mean 48%).
• New genetic variants in PRKAR1A associated with PPNAD and Carney complex (CNC) have been identified.
• Unilateral adrenalectomy has led to Cushing's syndrome remission in some PPNAD patients.

Conclusions:

• MiBAH, PPNAD, and CNC are rare but challenging conditions.
• Integrated clinical and genetic approaches are crucial for comprehensive management.
• Effective investigation and prevention strategies can be offered to patients and families affected by these disorders.