From the Guidelines
ACTH-independent macronodular adrenal hyperplasia type 2 (AIMAH2) is a rare genetic disorder characterized by the enlargement of both adrenal glands with multiple nodules that produce excess cortisol independently of adrenocorticotropic hormone (ACTH) control. This condition is caused by mutations in the ARMC5 gene, which functions as a tumor suppressor, as supported by recent studies 1. Patients with AIMAH2 typically develop Cushing's syndrome symptoms including:
- Central obesity
- Muscle weakness
- High blood pressure
- Diabetes
- Thin skin with easy bruising The condition usually manifests in adulthood, often between 40-60 years of age.
Treatment Options
Treatment primarily involves surgical removal of the affected adrenal glands (bilateral adrenalectomy), after which patients require lifelong glucocorticoid and mineralocorticoid replacement therapy, as recommended by recent guidelines 1. In some cases with milder disease, medical therapy with steroidogenesis inhibitors like ketoconazole or metyrapone may be used to control cortisol excess.
Importance of Early Diagnosis
Early diagnosis is important as prolonged exposure to excess cortisol can lead to serious complications including:
- Cardiovascular disease
- Osteoporosis
- Increased susceptibility to infections AIMAH2 has an autosomal dominant inheritance pattern, so family screening is recommended when a case is identified, highlighting the need for genetic counseling and testing in affected families 1.
From the Research
Definition and Characteristics
- Adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia type 2 is not explicitly defined in the provided studies, but based on the information available, ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome, characterized by bilateral adrenal gland enlargement and ACTH-independent hypercortisolism 2, 3, 4.
- The condition is typically marked by the presence of multiple nodules in the adrenal cortex, leading to an overproduction of cortisol 4.
- AIMAH can present with overt Cushing's syndrome or subclinical hypercortisolism, and the diagnosis is often suspected through imaging studies and confirmed by histological examination of the adrenal tissue 3.
Pathophysiology and Etiology
- The pathophysiology of AIMAH has been linked to the presence of aberrant membrane-bound receptors in the adrenal gland, which can respond to various ligands and stimulate cortisol production 3.
- These aberrant receptors can be identified through screening protocols and may offer opportunities for novel pharmacological therapies 3.
- The exact etiology of AIMAH is not fully understood, but it is thought to involve a complex interplay of genetic and environmental factors 3.
Treatment Options
- Bilateral adrenalectomy has traditionally been considered the treatment of choice for AIMAH, but it requires lifelong steroid replacement therapy and carries a risk of adrenal insufficiency crisis 2, 5.
- Unilateral adrenalectomy has been proposed as a potential alternative treatment, particularly in cases where the disease is asymmetric or in patients with poor glycemic control 2, 5.
- Pharmacological therapies targeting the aberrant receptors or their ligands may also be a viable treatment option for some patients with AIMAH 3, 6.