Adrenal Incidentaloma

An adrenal incidentaloma is an adrenal mass discovered incidentally on cross-sectional imaging performed for an unrelated indication. It is an increasingly common clinical scenario given the widespread and increasing use of computed tomography and magnetic resonance imaging.

Epidemiology and classification

Adrenal incidentalomas are identified in a meaningful proportion of abdominal imaging studies performed for unrelated indications, with prevalence increasing with age.

The great majority prove to be benign, non functioning adrenal adenomas. They require no specific intervention beyond confirmation of this benign, non functional status.

Functional lesions include cortisol producing adenomas (causing overt or, more commonly, mild autonomous cortisol secretion), aldosterone producing adenomas (Conn syndrome), and phaeochromocytoma.

Non functioning lesions include the common benign adenoma, together with less common entities.

• Myelolipoma: a benign, fat containing lesion with a characteristic imaging appearance.
• Adrenal cyst.
• Metastatic disease, importantly, particularly relevant in a patient with a known primary malignancy.
• Primary adrenocortical carcinoma, rarely.

• The great majority of adrenal incidentalomas are entirely asymptomatic, identified purely as an incidental imaging finding. The patient has no relevant symptoms directly attributable to the adrenal mass at the time of discovery.
• Where a functional lesion is present, relevant symptoms may become apparent only on careful, targeted questioning rather than being volunteered spontaneously.
• Mild autonomous cortisol secretion gives subtle features of mild cortisol excess: weight gain, hypertension, glucose intolerance, reduced bone density.
• Phaeochromocytoma gives paroxysmal symptoms (headache, palpitations, sweating).
• An aldosterone producing lesion gives hypertension with hypokalaemia.
• Features raising specific concern for malignancy include a large lesion size (with risk of malignancy increasing significantly above approximately 4 cm), irregular margins, heterogeneous internal characteristics, and rapid growth on serial imaging.
• In a patient with a known primary malignancy elsewhere, consider the likelihood of adrenal metastasis based on the primary tumour type and overall disease context.
• Specifically establish a history of a known primary malignancy elsewhere. It is directly relevant to the differential diagnosis, and a possible adrenal metastasis warrants a substantially different approach from an incidentally identified lesion in a patient without any malignancy history.

• Unenhanced computed tomography attenuation value (measured in Hounsfield units) is the key initial imaging characteristic. A value of 10 Hounsfield units or below strongly supports a benign, lipid rich adenoma, given the characteristic high intracellular lipid content of these lesions.
• A higher attenuation value is less specific and may warrant further characterisation. This includes assessment of contrast washout characteristics, or dedicated magnetic resonance imaging with chemical shift sequences, to refine the assessment of benign versus malignant likelihood.
• Hormonal evaluation is essential for every newly identified adrenal incidentaloma regardless of imaging characteristics. It comprises three components, listed next.
• An overnight 1 mg dexamethasone suppression test screens for autonomous cortisol secretion. Failure of adequate cortisol suppression supports this diagnosis.
• Plasma free metanephrines or 24 hour urinary fractionated metanephrines screen for phaeochromocytoma. This is essential given the potential for catastrophic perioperative complications if an unrecognised phaeochromocytoma is biopsied or resected without appropriate alpha blockade preparation.
• In any patient with hypertension or hypokalaemia, assess the plasma aldosterone to renin ratio (screening for primary aldosteronism).
• Where imaging characteristics or the clinical context (known extra-adrenal malignancy, atypical appearance) raise specific concern for malignancy, further evaluation including positron emission tomography imaging may be pursued.
• In carefully selected cases where biopsy would directly influence management, image guided biopsy may be pursued. Perform it only after phaeochromocytoma has been biochemically excluded, given the risk of precipitating a hypertensive crisis if an unrecognised phaeochromocytoma is biopsied.
• Evaluation is generally guided by specialist endocrinology and, where relevant, oncology input.
• Repeat imaging at an appropriate interval (typically six to twelve months) is recommended for lesions with indeterminate initial characteristics, to assess for interval growth.
• Interval growth would raise concern for malignancy and warrant further, more intensive evaluation or surgical consideration.

• Non functioning adenomas with clearly benign imaging characteristics (low attenuation on unenhanced computed tomography, stable size on any repeat imaging performed) require no specific treatment or ongoing hormonal surveillance beyond the initial evaluation. Their risk of subsequent malignant transformation or development of clinically significant hormonal function is essentially negligible.
• Mild autonomous cortisol secretion (formerly often termed subclinical Cushing syndrome) is identified through failure of adequate suppression on the dexamethasone suppression test in the absence of overt clinical Cushing syndrome features.
• It warrants individualised management, given evidence of an associated increased risk of hypertension, diabetes, and reduced bone density even in the absence of overt clinical hypercortisolism.
• Consider surgical adrenalectomy in patients with relevant, potentially hormone related comorbidity (poorly controlled hypertension, diabetes, or significant osteoporosis).
• Patients without such comorbidity may be managed with surveillance and targeted management of any incident hormone related complications as they arise.
• Confirmed phaeochromocytoma, aldosterone producing adenoma, or overt cortisol producing adenoma with clinical Cushing syndrome are managed according to the standard principles for the underlying condition. Surgical adrenalectomy is generally the definitive treatment, following preoperative medical preparation specific to the functional diagnosis.
• Alpha blockade for phaeochromocytoma is of particular critical importance, given the risk of perioperative hypertensive crisis without this preparation.
• Surgical resection is generally recommended for lesions with imaging characteristics or growth pattern raising significant concern for malignancy, regardless of hormonal function status. Histological confirmation is important and, where malignancy is confirmed, appropriate oncological staging and treatment follow.
• Suspected or confirmed adrenal metastasis in a patient with a known primary malignancy is managed within the broader oncological treatment plan for that underlying malignancy. Consider biopsy where confirmation would directly influence overall management.
• Consider surgical resection in carefully selected patients with isolated, resectable adrenal metastatic disease, as part of a broader oligometastatic disease management strategy.
• Regular endocrinology follow up underpins structured, longitudinal management of this now common and increasingly frequently encountered clinical scenario. Surveillance approach and interval are individualised according to the initial lesion characteristics, hormonal evaluation results, and any relevant interval findings.