Overview
Definition:
An adrenal incidentaloma is an adrenal mass discovered incidentally during imaging performed for reasons unrelated to suspected adrenal pathology
In adolescents, it is crucial to differentiate between benign adenomas and potentially malignant or hormonally active tumors, requiring a targeted hormonal workup.
Epidemiology:
Adrenal incidentalomas are less common in children and adolescents compared to adults, with prevalence estimates varying
Malignant tumors and functioning adenomas are relatively more common in younger populations
Incidence increases with age.
Clinical Significance:
Untreated hormonally active adrenal incidentalomas can lead to significant morbidity and mortality, including hypertension, hypokalemia, diabetes mellitus, growth disturbances, and even adrenal crisis
Differentiating benign from malignant lesions is critical for appropriate management and prognosis in adolescents.
Clinical Presentation
Symptoms:
Often asymptomatic
However, symptoms may arise from hormonal overproduction: Hypertension, hypokalemia, muscle weakness, fatigue, unexplained weight gain or loss, abdominal striae, hirsutism, virilization, menstrual irregularities, emotional lability, polyuria, polydipsia.
Signs:
Hypertension, hypokalemia (serum K+ < 3.5 mmol/L), Cushingoid features (moon facies, central obesity, thin skin, striae), signs of virilization (clitoromegaly, hirsutism), goiter
In rare cases, palpable abdominal mass.
Diagnostic Criteria:
Diagnosis is based on incidental finding of an adrenal mass on imaging
The subsequent hormonal workup aims to detect autonomous hormone production or malignancy.
Diagnostic Approach
History Taking:
Detailed family history of endocrine tumors or hypertension
History of rapid weight gain/loss, fatigue, increased thirst/urination, menstrual irregularities, signs of precocious puberty, palpitations, headaches, sweating
Medications, especially steroids.
Physical Examination:
Thorough assessment of blood pressure, BMI, and presence of Cushingoid features, virilization, or other endocrine stigmata
Palpation for abdominal masses
Careful examination of skin for striae and pigmentation.
Investigations:
Initial screening tests include: 1
Overnight low-dose dexamethasone suppression test (LDDST) for Cushing's syndrome (plasma cortisol > 1.8 mcg/dL or 50 nmol/L after 1 mg dexamethasone at midnight is suspicious)
2
24-hour urinary fractionated metanephrines and normetanephrines for pheochromocytoma (elevated levels indicate suspicion)
3
Plasma renin activity and plasma aldosterone concentration with the aldosterone-to-renin ratio (ARR) for primary hyperaldosteronism (a ratio > 20-30 with suppressed plasma renin activity is suggestive, but further confirmation is needed)
4
Serum potassium levels (hypokalemia may suggest hyperaldosteronism or pheochromocytoma)
Imaging (CT/MRI) provides morphological information but hormonal workup is key for functional assessment
Size > 4 cm, irregular borders, heterogeneity, and rapid growth on repeat imaging suggest malignancy but do not replace hormonal evaluation.
Differential Diagnosis:
Benign adrenal adenoma (non-functioning), adrenal carcinoma, pheochromocytoma, Cushing's syndrome (adenoma, hyperplasia, or ectopic ACTH), primary hyperaldosteronism, congenital adrenal hyperplasia variants, adrenal metastasis, adrenal cyst, adrenal hemorrhage.
Management
Initial Management:
The primary goal is to rule out clinically significant hormone hypersecretion and malignancy
Initial management focuses on targeted hormonal screening based on clinical suspicion and imaging characteristics
Size thresholds for further investigation are debated but generally >2 cm or growing lesions warrant more thorough assessment.
Medical Management:
If a specific hormone excess is confirmed: Cushing's syndrome: Medical therapy with ketoconazole, metyrapone, or osilodrostat
Pheochromocytoma: Alpha-adrenergic blockade (e.g., prazosin, terazosin) followed by beta-adrenergic blockade (e.g., propranolol) if tachyarrhythmias are present
Primary hyperaldosteronism: Aldosterone antagonists like spironolactone or eplerenone.
Surgical Management:
Surgical excision (adrenalectomy) is indicated for: 1
Confirmed significant hormone hypersecretion (Cushing's syndrome, pheochromocytoma, primary hyperaldosteronism resistant to medical therapy or causing severe complications)
2
Suspected or confirmed adrenal malignancy (based on imaging or biopsy)
3
Lesions > 4-6 cm, irrespective of hormonal activity, due to higher risk of malignancy
Laparoscopic adrenalectomy is the preferred approach for benign lesions.
Supportive Care:
Monitoring of blood pressure, electrolytes, and glucose levels
Nutritional support tailored to hormonal status
Psychosocial support for adolescents and families dealing with diagnosis and treatment.
Complications
Early Complications:
Perioperative complications of adrenalectomy: bleeding, infection, adrenal crisis (especially if bilateral adrenalectomy or significant hypothalamic-pituitary axis suppression)
Hypertensive crisis during pheochromocytoma manipulation
Electrolyte imbalances.
Late Complications:
Recurrence of hormone hypersecretion if resection is incomplete or if multifocal disease
Development of contralateral adrenal adenoma
Growth impairment or metabolic sequelae from prolonged hormone excess
Metastasis in cases of adrenal carcinoma.
Prevention Strategies:
Adequate pre-operative blockade for pheochromocytoma
Careful intraoperative technique to minimize bleeding and damage
Appropriate post-operative hormonal replacement if needed
Thorough follow-up to detect recurrence or new lesions.
Prognosis
Factors Affecting Prognosis:
Tumor type (benign vs
malignant), degree of hormone hypersecretion, presence of metastasis, promptness and efficacy of treatment, and patient's overall health status
For benign adenomas with appropriate management, prognosis is generally excellent.
Outcomes:
Successful treatment of hormone-secreting tumors leads to normalization of biochemical parameters and improvement in clinical symptoms
Complete resection of adrenal carcinoma offers the best chance of cure but is often challenging
Surveillance is crucial for all patients.
Follow Up:
Regular clinical evaluations, blood pressure monitoring, and biochemical tests (hormonal assays) are essential
Imaging surveillance (CT/MRI) may be required depending on the initial diagnosis, especially for larger or suspicious lesions, and for adrenal carcinoma to monitor for recurrence or metastasis.
Key Points
Exam Focus:
Distinguish between functioning and non-functioning incidentalomas
Remember screening tests for Cushing's, pheochromocytoma, and hyperaldosteronism
Understand indications for surgery vs
medical management
Adrenal crisis prevention post-adrenalectomy.
Clinical Pearls:
Always consider the possibility of a functioning tumor even in asymptomatic adolescents with incidentalomas
Aggressively investigate masses >4 cm or those with suspicious imaging features
For suspected pheochromocytoma, alpha-blockade MUST precede beta-blockade.
Common Mistakes:
Failing to perform adequate hormonal workup for incidentalomas
Initiating beta-blockers before alpha-blockers in suspected pheochromocytoma
Inadequate follow-up leading to missed recurrence or complications
Assuming all incidentalomas are benign adenomas.