Related Experiment Video
Updated: Apr 19, 2026
A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
Genetic basis of bilateral macronodular hyperplasia
Insights
Bilateral macronodular hyperplasia (BMAH) is often genetic, not ACTH-independent. Mutations in the ARMC5 gene are linked to this condition, which can cause Cushing syndrome.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- Bilateral macronodular hyperplasia (BMAH), previously termed ACTH-independent macronodular hyperplasia (AIMH), is a condition characterized by adrenal hyperplasia.
- It can lead to Cushing syndrome or subclinical hypercortisolism.
Observation:
- Recent studies indicate that hyperplastic adrenal tissue in BMAH can ectopically produce ACTH, challenging the 'ACTH-independent' classification.
- While historically considered sporadic, a significant genetic component is now recognized in most BMAH cases.
Findings:
- Mutations in the ARMC5 gene, a potential tumor suppressor, are frequently identified in familial BMAH cases and are implicated as the primary cause.
- The inefficient cortisol production by these hyperplastic nodules necessitates the development of large nodules to manifest clinically.
- Clinical symptoms typically emerge later in life, often in the fifth to sixth decades.
Implications:
- BMAH is an underdiagnosed genetic disorder with implications for endocrine health.
- Screening for BMAH and its genetic underpinnings is recommended for affected individuals and their at-risk family members.
Objective:
To review the genetic basis of bilateral macronodular hyperplasia (BMAH).
Methods:
Case presentation, review of literature, table, and bullet point conclusions.
Results:
BMAH, also known as adrenocorticotropic hormone (ACTH)-independent macronodular hyperplasia (AIMH), can cause Cushing syndrome or mild hypercortisolism. Recent studies have demonstrated that hyperplastic tissue reproduces ectopic ACTH, implying that BMAH is the more proper term, as the syndrome is not ACTH-independent. BMAH was thought to be sporadic, but recent data have shown that there is likely a genetic component in the majority of cases. Mutations in ARMC5, a putative suppressor gene, have been found in many familial cases of BMAH and are thought to be responsible for the disorder. As these nodules inefficiently produce cortisol, large nodules are required to produce a clinical syndrome. ARMC5 likely requires a second somatic mutation to become clinically apparent. Clinical manifestations are not generally noted until the fifth to sixth decades of life.
Conclusion:
BMAH is an underrecognized genetic condition that can lead to Cushing syndrome and should be screened for in patients and susceptible family members.
Related Concept Videos
01:27Adrenal Gland Disorders
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
01:19Cushing Syndrome II: Pathophysiology
01:21Smooth Endoplasmic Reticulum
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
01:26Cushing Syndrome I: Introduction
01:17Anatomy of the Adrenal Glands
These glands possess a distinctive yellow tinge due to the stored cholesterol and fatty acids required for hormone synthesis. They are encased in a fibrous capsule and cushioned by fat.
The adrenal gland comprises two distinct...
01:31Hormones of the Adrenal Glands
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...