What is the clinical significance of an adrenal adenoma in adults, particularly those with a history of hypertension, Cushing's syndrome, or other endocrine disorders?

Clinical Significance of Adrenal Adenomas

All patients with adrenal adenomas require comprehensive hormonal evaluation regardless of symptoms, as up to 30-50% have autonomous cortisol secretion that increases cardiovascular morbidity and mortality, and specific hormone-secreting tumors demand targeted treatment to prevent life-threatening complications. 1, 2

Mandatory Hormonal Screening

Every patient with an adrenal adenoma must undergo systematic hormonal evaluation to identify potentially life-threatening conditions:

• Screen all patients for autonomous cortisol secretion using a 1 mg dexamethasone suppression test (cortisol >50 nmol/L or 1.8 µg/dL is abnormal), as this is present in 30-50% of incidentalomas and causes increased cardiovascular disease, hypertension, diabetes, obesity, dyslipidemia, and osteoporosis even without overt Cushing's syndrome 1, 3, 2, 4

• Screen for pheochromocytoma with fractionated plasma-free metanephrines before any biopsy or surgery, as missing this diagnosis can result in fatal hypertensive crisis during procedures 1, 5

• Screen for primary aldosteronism with plasma aldosterone and renin activity in all patients, particularly those with hypertension or hypokalemia, as this causes treatment-resistant hypertension and cardiovascular damage 1, 5

Size-Based Malignancy Risk Stratification

Tumor size directly correlates with malignancy risk and determines management:

• Adenomas <4 cm with benign imaging features (unenhanced CT <10 HU, homogeneous, lipid-rich on chemical shift MRI) can be observed with repeat imaging at 6-12 months, then discontinued if stable 1

• Adenomas 4-6 cm require closer surveillance with repeat imaging at 3-6 months, and adrenalectomy if enlarging >1 cm per year 1

• Adenomas >6 cm have significant malignancy risk and require adrenalectomy for suspected carcinoma, with staging imaging of chest, abdomen, and pelvis 1, 2

Critical Imaging Limitations

Clinicians must understand that imaging alone cannot reliably exclude malignancy or pheochromocytoma:

• Approximately one-third of pheochromocytomas washout in the characteristic range of benign adenomas on contrast-enhanced CT, creating false reassurance 1

• Approximately one-third of benign adenomas do not washout in the adenoma range, and malignant masses can also washout like adenomas, potentially causing adrenal cortical carcinoma or hypervascular metastases to be mistaken for benign lesions 1

• Chemical shift MRI showing heterogeneous signal intensity drop is controversial, as microscopic fat has been identified in pheochromocytoma, adrenal cortical carcinoma, and some metastases 1

Hormone-Specific Clinical Presentations

Recognizing specific hormone excess patterns is essential for preventing morbidity:

Autonomous Cortisol Secretion

• Presents with hypertension, hyperglycemia, hypokalemia (often treatment-resistant), muscle atrophy, weakness, osteoporosis, central obesity, easy bruising, and psychiatric symptoms including depression and sleep disturbances 5, 6

• Even "subclinical" autonomous cortisol secretion causes significant metabolic complications including arterial hypertension (87% of patients), obesity (50%), and diabetes (25%) that improve after adrenalectomy 6

Primary Aldosteronism

• Characteristically causes hypertension, hypokalemia, metabolic alkalosis, muscle cramping and weakness, and headaches that may be resistant to standard antihypertensive therapy 1, 5

Pheochromocytoma

• Presents with episodic or sustained severe hypertension, paroxysmal headaches, palpitations, anxiety attacks, excessive sweating, and pallor 1, 5

• Family history of von Hippel-Lindau disease, multiple endocrine neoplasia type 2, familial paraganglioma syndrome, or neurofibromatosis type 1 increases suspicion 1

Surgical Indications

Surgery is indicated for specific high-risk scenarios:

• Adrenalectomy is recommended for autonomous cortisol secretion with progressive metabolic comorbidities (hypertension, diabetes, obesity, osteoporosis) attributable to cortisol excess, particularly in younger patients, as surgery improves hypertension, achieves weight loss, and improves diabetes control 3, 4, 6

• All pheochromocytomas require surgical removal due to risk of hypertensive crisis and cardiovascular complications 1, 5

• Unilateral aldosterone-producing adenomas require adrenalectomy (laparoscopic preferred), while bilateral disease requires medical management with spironolactone or eplerenone 1

• Tumors with aggressive imaging features (irregular/inhomogeneous morphology, lipid-poor, no washout, >3 cm, or secretion of multiple hormones) require adrenalectomy for suspected malignancy 1

Critical Post-Adrenalectomy Risk

Temporary or permanent adrenal insufficiency is a major risk after removing hormone-secreting adenomas:

• Four of seven patients with autonomous cortisol secretion developed temporary adrenal insufficiency after unilateral adrenalectomy, requiring glucocorticoid replacement 6

• Hydrocortisone 100 mg must be administered during anesthesia and surgery to prevent adrenal crisis, with continuation for at least 5 days postoperatively and gradual weaning as the contralateral adrenal recovers 7

Special Populations

Patients with extra-adrenal malignancy require different evaluation:

• Rule out pheochromocytoma before performing image-guided needle biopsy in patients with history of malignancy and suspected adrenal metastasis 1

• Never biopsy suspected adrenal cortical carcinoma due to risk of tumor seeding the needle tract 1