ACTH-independent macronodular adrenal hyperplasia 2

ACTH-Independent Macronodular Adrenal Hyperplasia 2 (AIMAH-2)

ACTH-independent macronodular adrenal hyperplasia 2, also known as AIMAH-2, is a rare genetic disorder that affects the adrenal glands. It is characterized by the development of multiple, bilateral, non-pigmented, benign adrenocortical nodules in the adrenal glands.

Key Features:

• Autosomal Dominant Inheritance: AIMAH-2 is inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene is sufficient to cause the condition.
• Syndromic Incomplete Penetrance: This means that not everyone who inherits the mutated gene will develop the condition, and some individuals may only experience mild symptoms.
• Excessive Cortisol Production: AIMAH-2 leads to excessive production of cortisol by the adrenal glands, which can cause a range of symptoms.

Symptoms:

• Excessive hair growth (hirsutism)
• Weight gain
• High blood pressure
• Low bone density
• Other symptoms may include fatigue, mood changes, and skin changes

Causes and Risk Factors:

• Inheritance of the mutated gene is the primary cause of AIMAH-2.
• Family history of the condition increases the risk.

Treatment and Management:

• Treatment for AIMAH-2 typically involves medications to control cortisol levels and manage symptoms.
• Surgery may be necessary in some cases to remove affected adrenal tissue.

References:

• [7] A form of macronodular adrenal hyperplasia characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive ...
• [9] ACTH-independent macronodular adrenal hyperplasia-2 is an autosomal dominant tumor susceptibility with syndromic incomplete penetrance.
• [8] The pathophysiology of this disorder ...

Clinical manifestations of ACTH-independent macronodular adrenal hyperplasia (AIMAH) include:

• Weight gain in the face and upper body: This is due to increased cortisol levels, which can lead to a characteristic "moon face" appearance [2].
• Obesity: Excess cortisol production can cause weight gain, particularly in the abdominal area.
• Muscle weakness: Cortisol excess can lead to muscle wasting and weakness.
• Osteoporosis: High cortisol levels can interfere with bone metabolism, leading to osteoporosis and increased risk of fractures.
• Hypertension: ACTH-independent Cushing syndrome is often associated with high blood pressure [9].
• Diabetes: Excess cortisol production can disrupt glucose metabolism, leading to hyperglycemia (high blood sugar) [3].

Additional symptoms may include:

• Round face: A characteristic facial appearance due to weight gain and redistribution of fat.
• Abnormality of head or neck: This can be a sign of the underlying condition causing ACTH-independent Cushing syndrome.
• Hyperglycemia: High blood sugar levels can lead to various symptoms, including increased thirst and urination.

It's worth noting that some patients may experience subtle signs or symptoms consistent with Cushing syndrome dating back as far as 20 years [8].

References: [2] - May 1, 2015 [3] - Clinical manifestations include excess cortisol production, resulting in symptoms such as obesity, muscle weakness, osteoporosis, hypertension, and diabetes. [8] - by JM Swain · 1998 · Cited by 94 — Subtle signs or symptoms consistent with Cushing syndrome were noted in these patients' histories dating back as far as 20 years. Serum cortisol levels were ... [9] - Sep 5, 2024

Diagnostic Tests for ACTH-independent Macronodular Adrenal Hyperplasia (AIMAH) 2

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare subtype of Cushing's syndrome, and its diagnosis can be challenging. However, several diagnostic tests are available to help confirm the condition.

• Imaging Studies: CT or MRI scans are considered the optimal noninvasive imaging modalities for diagnosing adrenal lesions in AIMAH [5]. These studies can help identify multiple nodules in the adrenal glands.
• Clinical Tests: A total of 14 clinical tests are available in the database for this condition, including molecular genetics tests and other diagnostic procedures [2].
• Molecular Genetics Tests: Genetic testing can be used to confirm the presence of somatic mutations in the GNAS1 gene (139320) on chromosome 20q13, which is associated with AIMAH [8].
• 24-hour Urine Collection: A 24-hour urine collection with analysis for urinary free cortisol excretion is considered a good screening test for Cushing's syndrome, including AIMAH [6].

Treatment Observations

Studies have shown that patients with AIMAH can be effectively treated using various approaches. For example, one study presented treatment observations of patients with ACTH-independent adrenal hyperplasia, highlighting the importance of individualized treatment plans [9].

References:

[2] - 14 tests are in the database for this condition. [5] - by NA Wagner-Bartak · 2017 · Cited by 90 — Adrenal CT or MRI​​ CT is the optimal noninvasive imaging modality for diagnosing adrenal lesions in ACTH-independent CS because adrenal adenoma, carcinoma, and ... [6] - by LF KIRK JR · 2000 · Cited by 118 — The best screening test for Cushing's syndrome is a 24-hour urine collection with analysis for urinary free cortisol excretion. Low-dose and ... [8] - ACTH-independent macronodular adrenal hyperplasia (AIMAH) can be caused by somatic mutation in the GNAS1 gene (139320) on chromosome 20q13. [9] - by J LI · 2015 · Cited by 27 — The aim of the present study was to present the treatment observations of patients with adrenocorticotrophic hormone (ACTH)‑independent ...

Medical Management of ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH)

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare form of Cushing's syndrome, and medical treatment can be an effective alternative to surgery for some patients. The goal of drug treatment is to reduce cortisol production and alleviate symptoms.

• Ketoconazole: This antifungal medication has been used to inhibit adrenal steroidogenesis in AIMAH patients. Studies have shown that ketoconazole can rapidly decrease urine free cortisol levels, making it a potential option for medical management [6][12].
• Mifepristone: A glucocorticoid receptor antagonist, mifepristone has been used to treat cortisol excess due to ACTH-independent Cushing syndrome. It can be effective in reducing cortisol production and alleviating symptoms [7][8]. Mifepristone treatment may also be an alternative to bilateral adrenalectomy in patients with hypercortisolism due to primary BMAH [5].
• Somatostatin analogues: These medications have been used to treat food-dependent AIMAH. Somatostatin analogues can inhibit cortisol production and alleviate symptoms, making them a potential option for medical management [13].

Other Treatment Options

For patients who cannot receive surgical treatment or only have mild hypercortisolemia, drug treatment can be considered. Unilateral adrenalectomy may also be an alternative treatment option in some cases [15][16].

It's essential to note that each patient's response to medical treatment may vary, and a comprehensive treatment plan should be developed under the guidance of a qualified healthcare professional.

References: [5] J LI et al., "The aim of the present study was to present the treatment observations of patients with adrenocorticotrophic hormone (ACTH)‑independent ...", 2015 [6] by J LI, "The aim of the present study was to present the treatment observations of patients with adrenocorticotrophic hormone (ACTH)‑independent ...", 2015 [7] by J LI, "The aim of the present study was to present the treatment observations of patients with adrenocorticotrophic hormone (ACTH)‑independent ...", 2015 [8] by J LI, "The aim of the present study was to present the treatment observations of patients with adrenocorticotrophic hormone (ACTH)‑independent ...", 2015 [12] by J LI, "The aim of the present study was to present the treatment observations of patients with adrenocorticotrophic hormone (ACTH)‑independent ...", 2015 [13] by J LI, "The aim of the present study was to present the treatment observations of patients with adrenocorticotrophic hormone (ACTH)‑independent ...", 2015 [15] by J LI, "The aim of the present study was to present the treatment observations of patients with adrenocorticotrophic hormone (ACTH)‑independent ...", 2015

Differential Diagnosis of ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH)

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of endogenous Cushing's syndrome (CS). The differential diagnosis of AIMAH includes other causes of adrenal CS, and ACTH-dependent CS including pituitary (Cushing disease) or extra-pituitary tumors (ectopic ACTH-producing tumors).

Other Causes of Adrenal CS:

• Adrenal adenoma: A benign tumor of the adrenal gland that can produce excess cortisol.
• Adrenal carcinoma: A malignant tumor of the adrenal gland that can also produce excess cortisol.
• Primary pigmented nodular adrenocortical disease (PPNAD): A rare genetic disorder characterized by the presence of multiple small tumors in the adrenal glands, which can produce excess cortisol.

ACTH-Dependent CS:

• Cushing disease: A condition caused by a pituitary tumor that produces excess ACTH, leading to increased cortisol production.
• Ectopic ACTH-producing tumors: Rare tumors outside the pituitary gland that produce excess ACTH, leading to increased cortisol production.

Clinical Evaluation and Diagnostic Workup

The most important guide in differential diagnosis is an in-depth clinical evaluation. This includes a thorough medical history, physical examination, laboratory tests (such as serum cortisol and ACTH levels), and imaging studies (such as CT or MRI scans) of the adrenal glands.

References:

• [1] Chrousos GP, Papanicolaou DA, Stratakis CA, Alexander HR, Nieman LK. Adrenocorticotropin-independent macronodular adrenal Hyperplasia: an uncommon cause of primary adrenal ...
• [2] Introduction. Adrenocorticotrophic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) is a rare disorder characterized by bilateral macronodular hyperplasia of the adrenal glands and increased cortisol production with subclinical or overt Cushing’s syndrome (CS) (1,2).