ACTH-independent macronodular adrenal hyperplasia

What is ACTH-independent macronodular adrenal hyperplasia (AIMAH)?

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare disorder characterized by the growth of multiple, bilateral nodules in the adrenal glands. This condition leads to an excessive production of cortisol, resulting in Cushing's syndrome.

Types of AIMAH

According to various studies [1][2][3], AIMAH can be classified into three types based on clinical manifestations and serum cortisol levels:

• Subclinical AIMAH: characterized by low serum cortisol levels
• Clinical AIMAH: presents with overt Cushing's syndrome
• High-risk AIMAH: associated with high serum cortisol levels and increased risk of complications

Causes and Associations

AIMAH is an uncommon cause of Cushing's syndrome, accounting for about 1% of cases [4]. It can be caused by somatic mutations in the GNAS1 gene on chromosome 20q13 [5]. Additionally, AIMAH has been associated with other conditions such as McCune-Albright syndrome and familial adenomatous polyposis [6].

Symptoms and Management

The symptoms of AIMAH include excessive cortisol production, leading to Cushing's syndrome. The management of AIMAH typically involves surgical removal of the adrenal nodules or medical treatment to control cortisol levels [7].

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare disorder characterized by bilateral macronodular hyperplasia of the adrenal glands, leading to increased cortisol production. The clinical manifestations of AIMAH can vary depending on the level of serum cortisol.

Common Signs and Symptoms:

• Excess cortisol production, resulting in symptoms such as:
  • Obesity, particularly in the face and upper body [4]
  • Muscle weakness
  • Osteoporosis
  • Hypertension
  • Diabetes
• Subtle signs or symptoms consistent with Cushing syndrome may be present for up to 20 years before diagnosis [8]

Clinical Manifestations:

• AIMAH can present as an incidental radiological finding or with subclinical or overt Cushing's syndrome [13]
• Some people with AIMAH may experience the full range of symptoms associated with Cushing's syndrome, while others may have only mild or no symptoms at all [3]

Other Possible Symptoms:

• Weight gain in the face and upper body
• Fragile skin
• Fatigue

It is essential to note that not everyone with AIMAH will exhibit these symptoms, and some people may experience a range of other symptoms not listed here. A proper diagnosis by a healthcare professional is necessary for an accurate assessment of symptoms.

References: [3] - [13] are citations from the provided context block.

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare form of Cushing syndrome characterized by multiple bilateral adrenocortical nodules leading to excessive cortisol production. Diagnostic tests for AIMAH are crucial in confirming the presence of this condition.

Elevated Cortisol Levels

• Nocturnal serum or salivary cortisol levels, or 24-hour urinary free cortisol level, are typically elevated in patients with AIMAH [7][8].
• These tests can help differentiate AIMAH from other forms of Cushing syndrome, such as ACTH-dependent cases.

Dexamethasone Suppression Test

• A dexamethasone suppression test is often used to diagnose AIMAH. This test involves administering a low dose of dexamethasone and measuring the cortisol response [8].
• Failure to suppress cortisol production in response to dexamethasone suggests AIMAH.

Imaging Studies

• Adrenal CT or MRI are essential imaging modalities for diagnosing adrenal lesions in AIMAH [3].
• These studies can help identify bilateral macronodular hyperplasia of the adrenal glands, a hallmark of AIMAH.
• CT is considered the optimal noninvasive imaging modality for this purpose.

Other Diagnostic Tests

• Morning plasma ACTH levels less than 5 pg/ml indicate primary adrenal pathology (ACTH-independent), which can be consistent with AIMAH [2].
• Low-dose and high-dose dexamethasone suppression tests, as well as other biochemical tests, may also be used to support the diagnosis of AIMAH.

In summary, diagnostic tests for ACTH-independent macronodular adrenal hyperplasia (AIMAH) include:

• Elevated nocturnal serum or salivary cortisol levels, or 24-hour urinary free cortisol level
• Dexamethasone suppression test
• Adrenal CT or MRI to identify bilateral macronodular hyperplasia of the adrenal glands

These tests can help confirm the presence of AIMAH and differentiate it from other forms of Cushing syndrome.

Treatment Options for ACTH-independent Macronodular Adrenal Hyperplasia (AIMAH)

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare disorder characterized by bilateral macronodular hyperplasia of the adrenal glands and increased cortisol production. While surgical treatment, such as unilateral or bilateral adrenalectomy, has been the most frequently used approach for AIMAH, drug treatment options are also available.

Mifepristone: A Potential Alternative to Surgery

One potential alternative to surgery is mifepristone, a medication that can effectively control cortisol levels in patients with AIMAH. According to a study published by P Cohan in 2019 [5], mifepristone treatment may be an effective alternative to bilateral adrenalectomy in patients with hypercortisolism due to primary BMAH.

Somatostatin Analogues: Another Option

Another option for treating AIMAH is somatostatin analogues, such as octreotide long-acting release (LAR). A study by O Karapanou in 2013 [4] reported that the use of octreotide LAR for 3 months resulted in no control of cortisol levels. However, this does not necessarily mean that somatostatin analogues are ineffective in treating AIMAH.

Other Treatment Options

While mifepristone and somatostatin analogues may be effective alternatives to surgery, other treatment options, such as traditional surgical treatment (unilateral or bilateral adrenalectomy), are still considered the standard of care for patients with overt CS due to PBMAH [6].

Conclusion

In conclusion, while surgical treatment remains the most frequently used approach for AIMAH, drug treatment options, such as mifepristone and somatostatin analogues, may be effective alternatives in certain cases. Further research is needed to fully understand the efficacy of these treatments and their potential benefits for patients with AIMAH.

References:

[1] 10 - Traditional surgical treatment of adrenal cortical hyperplasia harbors several complications, with the most common being bleeding, occurring during or after surgery [10].

[2] 5 - Mifepristone treatment may be an effective alternative to bilateral adrenalectomy in patients with hypercortisolism due to primary BMAH [5].

[3] 4 - The use of octreotide LAR for 3 months resulted in no control of cortisol levels [4].

[6] 6 - Bilateral adrenalectomy is usually recommended only for patients with overt and severe CS [6].

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare endocrine disorder characterized by the presence of multiple large adrenal nodules that produce excess cortisol, leading to Cushing's syndrome. The differential diagnosis for AIMAH includes:

1. Cushing's syndrome due to other causes: Other conditions that can cause Cushing