Adrenal Adenoma: Symptoms, Types, Causes and Treatment

Adrenal adenomas are among the most common tumors discovered in the adrenal glands. While usually benign, they can sometimes cause significant health issues depending on their hormonal activity. Understanding the symptoms, types, causes, and treatment options for adrenal adenomas is crucial for both patients and healthcare professionals. This in-depth article will guide you through each aspect, synthesizing the latest clinical and scientific findings.

Symptoms of Adrenal Adenoma

Adrenal adenomas can be silent or cause a range of symptoms depending on whether they produce hormones. Because the adrenal glands regulate crucial hormones like cortisol, aldosterone, and androgens, the presentation can be diverse—ranging from subtle metabolic changes to severe systemic effects. Recognizing these symptoms early is essential for appropriate diagnosis and management.

Symptom	Description	Hormonal Activity	Source(s)
Hypertension	High blood pressure, often resistant to control	Aldosterone excess	2 5
Weight gain	Especially in the face, trunk, and abdomen	Cortisol excess	1 2
Osteoporosis	Weakened bones, fractures	Cortisol excess	2 3
Muscle weakness	Particularly proximal muscles	Cortisol excess	1 2
Easy bruising	Fragile skin, slow wound healing	Cortisol excess	2
Depression/Mood	Affective changes, irritability	Cortisol excess	2
Hypokalemia	Low potassium, muscle cramps	Aldosterone excess	5 9
Incidental finding	No symptoms, found on imaging	Non-functional	5 14

Table 1: Key Symptoms

Symptom Presentation in Adrenal Adenoma

The symptoms of adrenal adenoma are largely determined by whether the tumor is functional (producing hormones) or non-functional.

Functional Adenomas: The Hormone Effect

• Aldosterone-producing adenomas (Conn's syndrome) often present with:

  • High blood pressure that is hard to control with regular medication
  • Low potassium levels, which may cause muscle weakness, fatigue, or cramps
  • Sometimes, headaches or increased thirst and urination 5 9

• Cortisol-producing adenomas (Cushing's syndrome) can cause:

  • Rapid, central weight gain (face, trunk, abdomen)
  • Weakness in the upper legs and arms
  • Easy bruising, thin skin, and slow-healing wounds
  • Mood changes like depression or irritability
  • Osteoporosis, leading to fractures even with minimal trauma 1 2 3

• Non-functional adenomas are often discovered incidentally during imaging for unrelated reasons and may have no symptoms at all 5 14.

Non-Specific and Overlapping Symptoms

Because many symptoms (like hypertension or mood changes) are common in the general population, adrenal adenomas can go unnoticed for years. Some patients present with surprising symptoms—such as sudden fractures due to osteoporosis—before the tumor is detected 2 3.

Incidentalomas: When Symptoms Are Absent

A significant portion of adrenal adenomas are discovered incidentally on scans performed for other reasons. These "incidentalomas" may never cause symptoms but must be evaluated to rule out hormonal activity or malignancy 5 14.

Types of Adrenal Adenoma

Not all adrenal adenomas are the same. They are classified based on which hormone, if any, they secrete. Understanding the subtypes is critical for diagnosis, management, and predicting the clinical course.

Type	Hormone Secreted	Prevalence Among Adenomas	Source(s)
Non-functional	None	~50% of cases	5 14
Cortisol-producing	Cortisol	10.5% (including subclinical)	5 1 4
Aldosterone-producing	Aldosterone	5.1%	5 9 10
Rare/Other types	Androgens/catechol.	Uncommon	14 8

Table 2: Adrenal Adenoma Types

Main Subtypes of Adrenal Adenoma

Non-Functional Adenomas

• Definition: Do not secrete excess hormones.
• Frequency: The most common adrenal incidentaloma; about half of all detected adrenal adenomas 5.
• Clinical Course: Usually asymptomatic and require monitoring rather than immediate intervention.

Functional Adenomas

1. Cortisol-producing Adenomas

   • Cause Cushing's syndrome if cortisol excess is overt.
   • Some may cause "subclinical Cushing's syndrome," with mild or no obvious symptoms but measurable hormonal disturbances 1 5 4 14.
   • Black/brown and yellow adenomas are histological subtypes identified by their appearance and cell composition 4.

2. Aldosterone-producing Adenomas

   • Cause primary aldosteronism (Conn's syndrome), leading to high blood pressure and low potassium.
   • Most prevalent in patients with treatment-resistant hypertension 5 9 10.

3. Androgen- or Estrogen-producing Adenomas

   • Rare; may cause symptoms related to excess androgens (e.g., hirsutism, virilization) or estrogens 14.

4. Pheochromocytoma-like Presentation

   • While true pheochromocytoma arises from the adrenal medulla, some cortical adenomas may mimic these symptoms, though this is rare 2 8.

Bilateral vs. Unilateral Adenomas

• Unilateral adenomas: Most common; typically single and located in one adrenal gland.
• Bilateral adenomas: Less common but can occur, especially in genetic syndromes or in "subclinical" cases 2 3 7.

Causes of Adrenal Adenoma

What triggers the formation of an adrenal adenoma? Research has shown both genetic and environmental factors play a role. In recent years, advances in genetics have shed light on the molecular underpinnings of these tumors.

Cause/Factor	Mechanism/Effect	Related Type(s)	Source(s)
Genetic mutations	Altered cell growth/hormone production	Functional adenomas	7 9 10 11 13
Age	Higher incidence with age	All types	5
Gender	Slight female predominance	Cushing’s/aldosteronism	1 5
Syndromic associations	Carney complex, McCune-Albright, etc.	Bilateral/functional	7
Environmental/unknown	Not well defined	Non-functional	5 14

Table 3: Causes and Risk Factors

Genetic and Molecular Drivers

Cortisol-Producing Adenomas

• PKA Pathway Mutations: Mutations in the PRKACA gene (which codes for a subunit of protein kinase A) are found in a significant proportion of cortisol-producing adenomas, leading to unregulated cortisol synthesis 7 11.
• Other Genes: Mutations in GNAS, PRKAR1A, PDE11A, and PDE8B have also been linked to cortisol-producing tumors 7.

Aldosterone-Producing Adenomas

• Ion Channel Mutations: The most common are KCNJ5 potassium channel mutations, which result in increased sodium influx, cell depolarization, and overproduction of aldosterone 9 13.
• Calcium Channel Mutations: CACNA1D mutations are also implicated, leading to excessive calcium signaling and aldosterone production 10.
• Other Genes: Mutations in ATPases (ATP1A1, ATP2B3), CLCN2, CACNA1H, and others have been identified 7 13.

WNT/β-catenin Pathway

• Both adenomas and carcinomas can harbor CTNNB1 mutations, leading to abnormal β-catenin accumulation and promoting tumor development 12.

Syndromic and Familial Forms

• Carney Complex & McCune-Albright Syndrome: These rare genetic syndromes are associated with adrenal tumors, typically due to mutations affecting the PKA pathway 7.
• Familial Hyperaldosteronism: Inherited mutations in KCNJ5 can lead to bilateral adrenal hyperplasia and severe hypertension 9.

Non-Genetic and Environmental Factors

• Age: Incidence of adrenal adenomas rises with age, often seen in older adults undergoing abdominal imaging 5.
• Gender: Slight female predominance is observed, especially in hormone-secreting adenomas 1 5.
• Environmental: No definitive environmental risk factors have been confirmed, though most non-functional adenomas are thought to arise sporadically 5 14.

Treatment of Adrenal Adenoma

The management of adrenal adenoma depends on its type, size, hormonal function, and risk of malignancy. Advances in surgical and non-surgical therapies have greatly improved outcomes for most patients.

Treatment Modality	Indication/Use	Key Benefits	Source(s)
Surgical removal (adrenalectomy)	Functional, large, or suspicious lesions	Curative for functional	1 5 15 16
Laparoscopic/Adrenal-sparing	Small, accessible tumors	Preserves adrenal tissue	16
Thermal ablation	Aldosterone-producing, non-surgical	Less invasive	17 18
Medication (e.g., steroids)	Post-op replacement, symptom control	Manages deficiency	1 2
Observation/Monitoring	Non-functional, small, benign-appearing	Avoids overtreatment	5 14

Table 4: Treatment Approaches

Surgical Approaches

Adrenalectomy

• Indication: Gold standard for functional adenomas (producing excess hormones), large tumors, or those with suspicious imaging features.
• Outcomes: Surgery is typically curative for hormone-producing adenomas, especially when confined to one side 1 5 15.
• Approach: Laparoscopic adrenalectomy is minimally invasive and associated with faster recovery and fewer complications 16.
• Adrenal-sparing Surgery: In select cases (e.g., small aldosterone-producing adenomas), surgeons may remove only the tumor, preserving healthy adrenal tissue 16.

Postoperative Management

• Steroid Replacement: Patients who undergo adrenalectomy for cortisol-producing adenomas may need temporary or, rarely, lifelong steroid replacement until the other adrenal gland recovers 1 2.

Non-Surgical Options

Thermal/Catheter-based Ablation

• Indication: For patients with aldosterone-producing adenoma who are not surgical candidates or prefer less invasive therapy.
• Method: Uses heat or catheter-based techniques to destroy the tumor without removing the entire gland 17 18.
• Effectiveness: Shown to lower blood pressure and normalize hormone levels in many cases, though adrenalectomy remains more effective for complete biochemical remission 17 18.

Observation/Monitoring

• Indication: Small, non-functional adenomas with benign imaging characteristics.
• Approach: Regular imaging and hormonal evaluation to watch for changes in size or function, minimizing unnecessary interventions 5 14.

Medical Therapy

• For Non-surgical Patients: Medications may control hormone excess or manage symptoms in patients unable to undergo surgery.
• Steroid Replacement: Essential in some postoperative cases, especially after removal of cortisol-producing tumors 1 2.

Special Considerations

• Adrenal Incidentalomas: Careful evaluation is needed to exclude hormone excess or malignancy. Most non-functional, small incidentalomas can be safely monitored 5 14.
• Malignancy Risk: Larger tumors (>4 cm), rapid growth, or suspicious imaging features may prompt surgical removal to exclude adrenocortical carcinoma 5 14 15.

Conclusion

Adrenal adenomas are common benign tumors with diverse presentations and clinical significance. Understanding their symptoms, types, causes, and treatment options is key to optimal patient care.

Key Points:

• Adrenal adenomas may be functional (hormone-secreting) or non-functional; symptoms depend on hormone excess or tumor size.
• Types include non-functional, cortisol-producing (Cushing's), and aldosterone-producing (Conn's) adenomas—each with distinct clinical profiles.
• Genetic mutations, especially in PKA and ion channel genes, are major drivers of functional adenomas.
• Treatment is tailored to tumor type, size, and patient factors—ranging from observation to surgery or ablation.
• Surgical removal is curative for most functional adenomas; non-functional, small tumors may only need monitoring.

With advances in imaging, genetics, and minimally invasive therapies, most patients with adrenal adenoma can expect excellent outcomes when managed appropriately.