What does bilateral adrenal hyperplasia indicate?

From the Guidelines

Bilateral adrenal hyperplasia indicates a condition where both adrenal glands are abnormally enlarged, often due to excessive stimulation of the adrenal cortex, and is typically managed with medical treatment, such as mineralocorticoid receptor antagonists (MRAs), rather than surgery. This condition is commonly associated with primary aldosteronism, a disorder of hormone regulation that can lead to hypertension and hypokalemia 1. The diagnosis of bilateral adrenal hyperplasia typically involves adrenal vein sampling or functional imaging with radiolabelled tracers to distinguish it from unilateral primary aldosteronism 1.

Key Points

• Bilateral adrenal hyperplasia is a condition characterized by the abnormal enlargement of both adrenal glands
• It is often associated with primary aldosteronism, a disorder of hormone regulation
• Medical treatment with MRAs, such as spironolactone or eplerenone, is the preferred management approach for bilateral adrenal hyperplasia 1
• Surgery is not typically an option for bilateral adrenal hyperplasia, whereas it may be considered for unilateral primary aldosteronism 1

Treatment Approach

The treatment of bilateral adrenal hyperplasia focuses on managing the symptoms of hormone excess, particularly hypertension and hypokalemia. The use of MRAs, such as spironolactone or eplerenone, is recommended to control blood pressure and electrolyte imbalances 1. The effective dose of spironolactone can be titrated up to 300-400 mg once daily, if necessary, while eplerenone may be used as an alternative, despite requiring twice-daily administration 1. Newer agents, such as finerenone and exarenone, and the aldosterone synthase inhibitor baxdrostat, are also being tested for treating primary aldosteronism 1.

Diagnosis and Evaluation

The diagnosis of bilateral adrenal hyperplasia typically involves a combination of blood hormone testing, imaging studies, and sometimes genetic testing 1. Adrenal vein sampling is considered the standard for distinguishing bilateral adrenal hyperplasia from unilateral primary aldosteronism 1. Functional imaging with radiolabelled tracers may also be used to evaluate adrenal function and morphology 1. A thorough endocrinological evaluation is necessary to determine the underlying cause of bilateral adrenal hyperplasia and to guide treatment decisions.

From the FDA Drug Label

Long-term maintenance therapy for patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism). Bilateral adrenal hyperplasia indicates a condition known as idiopathic hyperaldosteronism, which is a type of primary hyperaldosteronism.

• This condition is characterized by the overproduction of aldosterone.
• It is associated with bilateral micro or macronodular adrenal hyperplasia. 2

From the Research

Bilateral Adrenal Hyperplasia Indications

Bilateral adrenal hyperplasia can indicate several conditions, including:

• Cushing's syndrome (CS) due to aberrant G-protein-coupled receptors (GPCRs) expression and their ligands 3, 4, 5
• Primary bilateral macronodular adrenal hyperplasia (PBMAH), a highly heterogeneous entity with variable clinical expression 5
• Adrenocortical hyperplasia, a non-malignant enlargement of the adrenal glands, which can be incidental or related to indolent disease process 6
• Micronodular adrenal hyperplasia, including primary pigmented micronodular adrenal dysplasia (PPNAD) and isolated micronodular adrenal hyperplasia (iMAD) 7

Associated Conditions

Bilateral adrenal hyperplasia can be associated with:

• Autonomous cortisol secretion, which can be evaluated using the 1 mg overnight dexamethasone suppression test 5
• Primary aldosteronism and pheochromocytoma, which should be tested for in incidentally detected cases 5
• Carney complex, a condition that can be diagnosed after systematic screening in patients presenting with PPNAD 7

Diagnostic Approaches

The diagnostic approach for bilateral adrenal hyperplasia includes:

• Imaging characterization, which should be done separately for each lesion 5
• Hormonal characterization, including testing for primary aldosteronism, pheochromocytoma, and evaluation for autonomous cortisol secretion 5
• CT and MRI as primary modalities of choice for adult adrenal imaging, while ultrasound and MRI are most commonly used in pediatric cases 6