Adrenal incidentaloma

The term adrenal incidentaloma refers to an adrenal mass identified incidentally during imaging investigations performed for reasons unrelated to a suspected adrenal disorder. In clinical practice, adrenal incidentaloma is one of the most frequent endocrine conditions associated with the widespread use of computed tomography (CT) and magnetic resonance imaging (MRI) for abdominal, urological, vascular and oncological diseases. The operational definition typically includes lesions measuring at least one centimetre that are clinically inapparent at the time of detection. Management, however, cannot be based on size alone. The central issue is to establish with a high degree of reliability whether the lesion is benign and whether it secretes hormones autonomously, even in the absence of overt clinical manifestations.

In most cases, an adrenal incidentaloma is a nonfunctioning adrenocortical adenoma or an adenoma associated with subtle, chronic cortisol secretion, now classified as mild autonomous cortisol secretion, which is associated with hypertension, diabetes, visceral obesity and skeletal fragility. A clinically relevant minority includes pheochromocytoma, aldosterone-producing adenoma, metastasis, adrenocortical carcinoma, myelolipoma and cystic or haemorrhagic lesions. For this reason, an adrenal incidentaloma represents an endocrine and radiological triage problem. High-risk conditions must be recognised promptly, unnecessary investigations should be avoided in clearly benign lesions, and targeted follow-up should be arranged when residual uncertainty may result in clinical harm.

Adrenal incidentaloma is an increasingly common finding because the use of abdominal and thoracoabdominal imaging has risen substantially over recent decades. Its observed prevalence increases with age and reflects both the greater likelihood of imaging in older populations and the progressive accumulation of adrenal nodules over time. Clinically, adrenal incidentalomas are particularly common in patients investigated for abdominal pain, urinary calculi, hepatobiliary disease, vascular disorders and oncological follow-up, settings in which the adrenal glands are visualised even though they are not the primary target of the examination.

The actual epidemiology depends on reporting thresholds and the technical characteristics of the examination. Multidetector CT more readily identifies small lesions, while MRI sensitivity to certain tissue components may increase the likelihood of describing lipid-containing or haemorrhagic masses. This technology-driven epidemiology makes contextual interpretation essential. A nodule measuring only a few millimetres and mentioned in a report does not necessarily have the same significance as a mass measuring several centimetres in a patient with a history of cancer.

The risk factors that increase the clinical importance of an adrenal incidentaloma are not limited to those that increase the likelihood of detection. They also include factors that increase the probability of autonomous hormone secretion or malignancy. Advanced age, hypertension, type 2 diabetes, visceral obesity and dyslipidaemia are common among patients with adrenal incidentalomas and may represent independent comorbidities. In a clinically relevant proportion of cases, however, they may also serve as indicators of unrecognised chronic cortisol secretion. The relationship is not deterministic, but the coexistence of cardiometabolic comorbidities increases the probability that the incidentaloma is not simply an innocuous finding.

An oncological setting radically changes the pre-test probability. Although adrenal masses detected during the staging or follow-up of extra-adrenal malignancies do not fall within the strictest definition of an incidentaloma, they are very common in clinical practice and pose the same decision-making problem: rapidly distinguishing benign lesions from metastases or aggressive primary tumours. In these patients, the oncological history, type of primary tumour and biological behaviour of the disease guide radiological assessment and determine the need for further investigations.

A further epidemiological aspect concerns the distribution of underlying causes. Adrenocortical adenomas account for the largest proportion, but a clinically important component consists of lesions associated with mild autonomous cortisol secretion. Recognition of this condition has increased following standardisation of the dexamethasone suppression test. At the same time, awareness that pheochromocytoma may cause few or no symptoms has led to more systematic biochemical testing in lesions that are not clearly benign on imaging, reducing the risk of missed diagnoses with potentially serious consequences during invasive procedures or surgical stress.

Finally, the clinical burden of an adrenal incidentaloma depends on the patient’s vulnerability. Cardiovascular comorbidities, frailty, osteoporosis and reduced functional reserve amplify the effects of even modest hormone secretion and influence the appropriateness of surgical treatment. The clinical epidemiology of adrenal incidentaloma therefore overlaps with internal medicine in adults and older people. The same radiological finding may require different strategies in a young, otherwise healthy individual and in a patient with cardiovascular disease, diabetes and difficult-to-control hypertension.

Adrenal incidentaloma is not an aetiological diagnosis but an umbrella term that encompasses lesions of cortical and medullary origin, benign and malignant tumours, and non-neoplastic conditions. Understanding its pathophysiology begins with the organisation of the adrenal gland. The cortex, divided into the zona glomerulosa, zona fasciculata and zona reticularis, produces mineralocorticoids, glucocorticoids and androgens, while the medulla produces catecholamines. This arrangement explains why two masses of the same size may have completely different clinical implications. A cortical adenoma may be hormonally silent or secrete hormones, whereas a chromaffin tumour may cause hypertensive crises even when symptoms are intermittent or masked.

From an aetiological perspective, the most common cause is an adrenocortical adenoma, which is often nonfunctioning. A substantial proportion consists of adenomas with persistent but not overt cortisol secretion, now described as mild autonomous cortisol secretion, a condition lying on a continuum between physiological cortisol regulation and overt Cushing syndrome. Less commonly, an incidentaloma may represent a pheochromocytoma, an aldosterone-producing adenoma, metastasis, adrenocortical carcinoma, myelolipoma, cyst or pseudocyst, organised adrenal haemorrhage, or an infectious or infiltrative lesion in specific clinical settings.

The pathogenesis of cortical adenomas involves clonal growth mechanisms and, in some subtypes, alterations in intracellular pathways regulating steroidogenesis and proliferation. Conceptually, autonomous cortisol secretion is often associated with impaired physiological adrenocorticotropic hormone (ACTH)-dependent control, with cortisol production becoming relatively detached from circadian rhythms and stress-related modulation. Secretion may be quantitatively modest but chronic. Chronic exposure is the main determinant of biological harm because it generates a continuous glucocorticoid signal that modifies metabolism, blood pressure, bone tissue and inflammatory responses.

The pathophysiology of mild autonomous cortisol secretion involves systemic effects even in the absence of a typical Cushingoid phenotype. At the cardiovascular level, cortisol increases vascular responsiveness to catecholamines and angiotensin II, promotes endothelial dysfunction and may contribute to hypertension and cardiac remodelling. Metabolically, it promotes insulin resistance, increases gluconeogenesis and redistributes adipose tissue towards the visceral compartment. In bone, it increases resorption and reduces formation, predisposing to osteopenia and fragility fractures. In skeletal muscle, it promotes protein catabolism and reduced proximal strength, contributing to frailty and an increased risk of falls.

Pheochromocytomas and paragangliomas, although not always discovered as incidentalomas in the strict sense, share a characteristic pathophysiology. Episodic or continuous catecholamine secretion affects blood pressure, heart rate and glucose metabolism. The central clinical point is that presentation may be intermittent and is not always dominated by the classical triad. The absence of overt crises does not exclude the disease. Biochemical assessment is therefore critical in lesions that are not clearly benign on imaging, because an unrecognised pheochromocytoma may become dangerous during biopsy, surgery or systemic stress.

In aldosterone-producing lesions, the pathophysiology commonly manifests as hypertension, which is often resistant, and possible hypokalaemia, although hypokalaemia may be absent. Aldosterone exerts profibrotic and proinflammatory effects on the cardiovascular and renal systems. Identification of mineralocorticoid excess therefore has prognostic as well as therapeutic value. In a patient with an adrenal incidentaloma and hypertension or unexplained hypokalaemia, assessment of the renin-aldosterone axis is not an optional investigation but a step that may substantially alter management.

Finally, the pathophysiology of adrenal malignancy includes adrenocortical carcinoma and metastases. Adrenocortical carcinoma is rare but aggressive and may be functioning or nonfunctioning. Its importance in the incidentaloma setting derives from the need to recognise radiological and clinical risk features early, because timely intervention in experienced centres influences outcome. Adrenal metastases reflect the biology of the primary tumour and its tendency to disseminate. Their probability increases in the presence of an oncological history and radiological patterns that are not compatible with a lipid-rich adenoma.

By definition, an adrenal incidentaloma is identified without an initial endocrine suspicion, but this does not mean that it is always clinically silent. Clinical presentation depends primarily on possible hormone secretion and on the patient’s overall context. In many cases, the medical history reveals common comorbidities such as hypertension and diabetes, which may be independent conditions but, when associated with specific clinical features, may suggest subtle and chronic hormone excess.

During history taking, features of catecholamine excess may include episodes of headache, palpitations, sweating, tremor, pallor, somatic anxiety and sudden loss of energy, sometimes misinterpreted as panic attacks. Hypertension may be paroxysmal or sustained and may be associated with hyperglycaemia or worsening glycaemic control. The absence of typical crises, however, does not exclude pheochromocytoma, because some forms show less episodic secretion or have symptoms attenuated by antihypertensive therapy.

When mineralocorticoid excess is suspected, the clinical history may reveal resistant hypertension, a need for several antihypertensive agents, early-onset hypertension or a family history of premature cardiovascular events. If present, hypokalaemia may cause fatigue, cramps, muscle weakness or arrhythmias, but it is often absent or intermittent. The key clinical feature is hypertension that appears disproportionate to the patient’s overall profile, particularly when accompanied by target-organ damage at a relatively young age.

Mild autonomous cortisol secretion tends to produce a less obvious phenotype than overt Cushing syndrome. The patient may report predominantly abdominal weight gain or may instead have a normal body weight but difficult-to-control diabetes and hypertension. Proximal muscle weakness, reduced functional capacity, easy bruising or increased skin fragility may be present, although these findings are often nonspecific. Women may develop menstrual irregularities or worsening osteopenia, while in older adults the clinical expression may be dominated by functional decline and an increased fracture risk.

During the physical examination, the approach should be systematic and directed towards signs of hormone excess. Accurate blood pressure measurement, assessment for tachycardia and arrhythmias, and observation for fine tremor, sweating and autonomic manifestations may suggest catecholamine excess. Assessment of muscle bulk, proximal strength and balance may identify muscle frailty compatible with chronic glucocorticoid exposure. Classical Cushingoid features should be sought, but their absence does not exclude mild autonomous cortisol secretion.

In some cases, an adrenal incidentaloma is associated with compressive symptoms or pain, although this is less typical and should raise consideration of a large lesion, haemorrhage, necrosis or aggressive components. The sudden onset of abdominal or lumbar pain in a patient with an adrenal mass may suggest adrenal haemorrhage, particularly in the setting of anticoagulant therapy or severe physiological stress, or necrosis within a lesion. In the presence of fever, rapid weight loss and systemic symptoms, the clinical context becomes decisive in distinguishing neoplastic or infectious causes, while remembering that many adrenal malignancies do not cause fever or pain until advanced stages.

Overall, the clinical manifestations of adrenal incidentaloma require integrated interpretation. The mass is often a silent radiological finding, but the patient’s history may contain several endocrine clues. Clinical value lies in recognising patterns compatible with hormone hypersecretion and translating these findings into targeted investigations, while avoiding both underestimation of clinically important conditions and overdiagnosis through unnecessary repeated testing.

Clinical assessment of an adrenal incidentaloma begins with a radiological finding, but the central diagnostic uncertainty concerns two questions: whether the lesion is benign or potentially malignant, and whether it is functioning or nonfunctioning. Suspicion of malignancy should increase when imaging features are not compatible with a lipid-rich adenoma, when the lesion is heterogeneous, has irregular margins or contains areas of necrosis or haemorrhage, or when it shows significant growth over time. The patient’s background also influences risk. A history of extra-adrenal malignancy, particularly one with a tendency to metastasise, increases the probability that an adrenal mass is secondary.

Pheochromocytoma should be suspected in the presence of paroxysmal or labile hypertension, episodes of headache, palpitations and sweating, but also when hypertension appears disproportionate or is associated with unexplained hyperglycaemia. In practice, many catecholamine crises are interpreted as anxiety disorders, and discovery of an adrenal incidentaloma may provide an opportunity to reassess previous suggestive episodes. Certain medications, obstructive sleep apnoea and stress-related conditions may modify the clinical presentation and create diagnostic confusion, making appropriate biochemical assessment necessary when imaging is not clearly reassuring.

Aldosterone excess should be suspected particularly in patients with both hypertension and an adrenal incidentaloma, especially when hypertension is resistant, spontaneous or diuretic-induced hypokalaemia is present, early target-organ damage has developed or the family history suggests premature cardiovascular events. The rationale is that aldosterone may directly promote cardiovascular and renal remodelling and that specific correction of the excess may improve prognosis and blood pressure control.

Mild autonomous cortisol secretion should be considered when an adrenal incidentaloma is associated with hypertension, diabetes, visceral obesity, dyslipidaemia, osteoporosis or fragility fractures, particularly when these conditions are difficult to control or worsen without an alternative explanation. Classical Cushingoid features are not required. Suspicion must nevertheless remain selective and contextual because cardiometabolic comorbidities are common even without hormone hypersecretion. The relevant factors are the combination of comorbidities, their severity, their resistance to treatment and the overall clinical coherence of the presentation.

Finally, adrenal incidentaloma should also be regarded as a management problem. An apparently benign lesion that has been incompletely assessed may create future risks, for example if biopsy or surgery is performed without excluding pheochromocytoma or without appropriate radiological stratification. Clinical suspicion is therefore not only diagnostic but also organisational. The pathway should be timely, ordered and consistent with guideline recommendations so that an incidental finding is converted into a safe clinical decision.

Diagnosis of an adrenal incidentaloma requires a structured pathway integrating dedicated imaging and endocrine assessment, with the aim of reliably defining the nature of the lesion and identifying possible hormone secretion. The first principle is that every adrenal mass requires accurate radiological characterisation because the distinction between a benign adenoma and an indeterminate or suspicious lesion determines both the need for further investigations and the follow-up strategy. Hormone excess must be assessed in parallel because it may be clinically subtle yet prognostically relevant.

According to the European Society of Endocrinology guidelines for the management of adrenal incidentalomas, initial assessment should include a clinical evaluation for signs of hormone hypersecretion and an essential set of biochemical tests primarily directed towards cortisol, catecholamines and, in selected settings, aldosterone. Test selection and interpretation also depend on the pre-test probability and imaging characteristics. A lesion with typical features of a lipid-rich adenoma has a very low risk of malignancy and, in the absence of clinical suspicion, may warrant a more conservative strategy.

Diagnostic assessment of adrenal incidentaloma

• Definition of oncological risk: dedicated imaging to establish whether the lesion is compatible with a benign adenoma or has indeterminate or suspicious features.
• Assessment of cortisol excess: a 1 mg dexamethasone suppression test, interpreted in the context of clinical factors and associated comorbidities.
• Exclusion of pheochromocytoma when indicated: measurement of plasma free metanephrines or fractionated urinary metanephrines in lesions that are not typical of a benign adenoma or when suggested by the clinical context.
• Assessment of the renin-aldosterone axis in selected patients: aldosterone-renin ratio in the presence of hypertension, particularly when associated with unexplained hypokalaemia.

Radiological assessment is central. Unenhanced CT allows measurement of attenuation in Hounsfield units, a useful parameter for identifying lipid-rich adenomas, which typically show low attenuation and a homogeneous appearance. When the lesion is not clearly lipid-rich, dedicated contrast-enhanced CT protocols with washout assessment or chemical-shift MRI may be used to demonstrate signal loss in lipid-containing lesions. Morphology, homogeneity, margins and the presence of necrosis or haemorrhage contribute to risk stratification, as does lesion size. Size alone is not an absolute criterion but forms part of the overall assessment.

From an endocrine perspective, the dexamethasone suppression test is the principal investigation for detecting autonomous cortisol secretion. Interpretation should not be mechanical. Medication use, adherence, variations in corticosteroid-binding globulin and physiological stress may affect the results, which should therefore be interpreted together with the clinical presentation and associated comorbidities. When mild autonomous cortisol secretion is suspected, assessment should be completed by evaluating its clinical effect, particularly on blood pressure, glucose metabolism and bone health, because treatment decisions depend more on the clinical burden of secretion than on a single laboratory value.

When indicated, assessment for pheochromocytoma requires appropriate biochemical testing and careful consideration of confounding factors. Medications, stress, sleep apnoea and renal impairment may influence metanephrine concentrations. The key clinical principle is to avoid invasive procedures or surgery without excluding clinically significant catecholamine secretion, because periprocedural risk may be substantial. When tests are positive or strongly suggestive, further diagnostic and therapeutic management follows dedicated specialist pathways.

For the renin-aldosterone axis, screening with the aldosterone-renin ratio is indicated in patients with hypertension or hypokalaemia, with careful consideration of ongoing medications that may interfere with renin and aldosterone concentrations. The purpose is to identify potentially correctable aldosterone excess. If screening is positive, the pathway includes confirmation and, when appropriate, assessment of lateralisation because the presence of an adrenal nodule on imaging does not automatically establish unilateral hormone production.

Adrenal biopsy is not a first-line investigation and has selected indications, particularly when metastasis is suspected in a patient with a known malignancy and radiological characterisation remains inconclusive. A fundamental safety principle is that biopsy must not be performed without excluding pheochromocytoma because it may precipitate a severe hypertensive crisis. In addition, biopsy does not reliably distinguish a benign adenoma from adrenocortical carcinoma and is therefore not useful for providing reassurance when carcinoma is suspected.

In summary, diagnosis of an adrenal incidentaloma is a progressive process. Dedicated imaging defines oncological risk, while essential hormonal tests identify clinically relevant secretion. The aim is to conclude the diagnostic phase with an operational classification that guides management, minimises radiation exposure, anxiety and unnecessary follow-up in benign nonfunctioning lesions, and accelerates assessment in suspicious or endocrinologically active cases.

Classification of adrenal incidentaloma has practical value because it translates a radiological finding into a clinical management plan. The first classification axis concerns the radiological nature of the lesion: masses with typical features of a benign adenoma, indeterminate lesions and radiologically suspicious lesions. This distinction determines the need for further investigations, the timing of follow-up and, in selected cases, the indication for surgery. Interpretation must be integrated with the clinical context because the same imaging pattern may have a different significance in a patient with or without a history of cancer.

A second axis concerns endocrine function. Lesions are divided into nonfunctioning masses and lesions associated with hormone hypersecretion. Among functioning lesions, the most frequent category in the incidentaloma setting is mild autonomous cortisol secretion, which is not equivalent to overt Cushing syndrome but may be associated with increased cardiometabolic risk. Other forms include pheochromocytoma and aldosterone-producing adenoma. More rarely, androgen-secreting or oestrogen-secreting tumours may be present. These forms tend to raise concern for more aggressive disease and require detailed specialist assessment.

Severity does not correspond directly to lesion size. A small lesion may be clinically important if it secretes catecholamines or aldosterone, whereas a larger lesion may be benign and nonfunctioning but still require assessment of oncological risk. Clinical severity should be understood as the combination of immediate and cumulative risk. Immediate risk is relevant in an unrecognised pheochromocytoma or a lesion suspicious for carcinoma, while cumulative risk is associated with mild autonomous cortisol secretion acting over time on blood pressure, glycaemic control and bone health.

A useful functional classification also considers the burden of comorbidities. A patient with mild autonomous cortisol secretion and well-controlled hypertension and diabetes may be managed conservatively, whereas a patient with the same biochemical profile but resistant hypertension, rapidly worsening diabetes and osteoporosis with fractures may be considered for a more active strategy. This approach prevents a laboratory value from becoming an automatic treatment indication and recognises that the objective of care is to reduce clinical events rather than merely normalise numerical values.

A further clinical category consists of bilateral adrenal incidentalomas. Bilaterality broadens the differential diagnosis and may include hyperplasia, metastases, haemorrhage, infiltrative disorders or multiple adenomas. In these cases, endocrine and radiological assessment must be particularly rigorous because management may differ substantially from that of unilateral lesions and assessment for possible adrenal insufficiency may be required in specific settings.

Finally, classification should produce an operational outcome: a reassuring benign nonfunctioning lesion, a benign lesion with mild autonomous cortisol secretion managed according to clinical risk, a specific functioning lesion requiring a dedicated pathway, an indeterminate lesion requiring reassessment, or a lesion suspicious for malignancy requiring referral to a multidisciplinary team and, when appropriate, a specialist centre. Translation of diagnostic findings into action is the true purpose of classification and represents the endpoint of the initial assessment.

Treatment of an adrenal incidentaloma depends on the combination of oncological risk and endocrine function. Most lesions are benign and nonfunctioning and primarily require reassurance and a surveillance strategy proportionate to the residual risk. Suspicious or functioning lesions require active management, often through a multidisciplinary team involving endocrinology, radiology, surgery and, in oncological cases, medical oncology.

When imaging identifies a mass with typical features of a benign adenoma and endocrine assessment excludes clinically relevant hypersecretion, the principal therapeutic intervention is to avoid excessive follow-up. The aim is to reduce radiation exposure, costs and patient anxiety while maintaining an appropriate margin of safety based on robust radiological and clinical criteria. Management also includes optimisation of comorbidities because hypertension and diabetes, even when not caused by the incidentaloma, influence the patient’s overall risk.

Mild autonomous cortisol secretion requires personalised management. Surgery may be considered in selected patients with a unilateral lesion and comorbidities potentially related to cortisol excess, particularly when those conditions remain difficult to control despite optimal treatment. The decision must balance expected benefits against operative risks and should take age and frailty into account. In many patients, particularly those with well-controlled comorbidities or high surgical risk, conservative management with intensive control of cardiometabolic risk factors may be appropriate.

In pheochromocytoma, treatment is generally surgical, but the preoperative phase is decisive for safety. Adequate adrenergic blockade and careful haemodynamic preparation are required to prevent intraoperative crises and postoperative complications. Perioperative management should be provided by an experienced team because tumour manipulation may cause major catecholamine fluctuations. In suspected or confirmed pheochromocytoma, surgery is not always an immediate emergency, but establishing a safe and dedicated pathway is a priority.

For aldosterone-producing forms, the strategy depends on lateralisation and on the patient’s clinical profile. When unilateral production is confirmed, adrenalectomy may provide substantial benefit in blood pressure control and overall risk reduction. In bilateral disease or when surgery is not appropriate, treatment with mineralocorticoid receptor antagonists is a central therapeutic measure. Treatment is not merely symptomatic. Reducing aldosterone excess means reducing a direct driver of cardiovascular and renal damage.

When a lesion is radiologically suspicious for adrenocortical carcinoma or has features that make conservative management inappropriate, surgery should be considered in a high-volume centre with specific expertise. Completeness of resection and the appropriateness of the surgical approach substantially influence outcomes. When metastasis is suspected, the strategy depends on the primary tumour, disease stage, resectability and the diagnostic or therapeutic value of adrenal intervention. In some cases, the diagnosis may be established through advanced imaging and follow-up, whereas others require a more interventional approach.

In all categories, treatment includes clear communication with the patient. An adrenal incidentaloma often causes anxiety because the concept of a mass is readily associated with cancer. An explanation based on actual risk, the rationale for investigations and a clearly defined monitoring plan reduces inappropriate behaviour, including requests for unnecessary repeated imaging or unsupervised discontinuation of treatment. In benign lesions, the most effective treatment is often a structured pathway that limits medicalisation and protects the patient from unnecessary procedures.

Follow-up of an adrenal incidentaloma should be proportionate to risk and guided by a clear clinical objective: identifying meaningful changes promptly without imposing repeated investigations on patients with clearly benign lesions. The first component of monitoring is accurate initial radiological characterisation because a robust baseline assessment markedly reduces the need for subsequent imaging. When a lesion is homogeneous and compatible with a benign adenoma, the probability of malignant transformation is very low and prolonged follow-up may offer no meaningful benefit.

In indeterminate lesions, radiological monitoring may be appropriate to assess dimensional and morphological stability. The aim is not to pursue minimal variations but to identify changes compatible with different biological behaviour, such as significant growth or the development of heterogeneity, necrosis or irregular margins. The timing of follow-up examinations should be selected according to the degree of uncertainty and the patient’s risk profile, avoiding both excessively frequent imaging and intervals that are too long when residual risk is clinically relevant.

Endocrine follow-up depends on the initial functional assessment and the risk of clinical evolution. In patients with mild autonomous cortisol secretion, monitoring focuses more on the course of associated comorbidities than on routine repetition of hormonal tests in the absence of clinical change. Worsening hypertension, diabetes or skeletal fragility may indicate a greater clinical effect of cortisol secretion and may reopen discussion of a more active strategy, including surgery in selected cases.

In patients with initially nonfunctioning lesions, the need for periodic repetition of hormonal screening should be assessed cautiously and selectively. A clinically useful approach is to define thresholds for repeating tests, such as the development of suggestive signs or symptoms, resistant hypertension or hypokalaemia, unexpected worsening of glycaemic control, fragility fractures or radiological changes. This reduces the risk of indefinite surveillance without measurable clinical benefit.

After surgery, follow-up depends on the final diagnosis and residual adrenal function. In patients operated on for mild autonomous cortisol secretion or other cortisol-secreting lesions, monitoring of the hypothalamic-pituitary-adrenal axis and possible transient or persistent adrenal insufficiency is essential because chronic ACTH suppression may result in slow recovery. Clinical and laboratory monitoring should be accompanied by patient education regarding symptoms of adrenal insufficiency and management during physical stress.

Finally, follow-up should be integrated within a continuity-of-care pathway. Adrenal incidentalomas are often detected in non-endocrine departments and may otherwise remain without clearly assigned clinical responsibility. A shared pathway between radiology, internal medicine and endocrinology, supported by reports containing the elements required for risk stratification and clear recommendations regarding subsequent actions, reduces clinical variability and improves quality of care. It also prevents both underestimation of clinically relevant lesions and excessive monitoring of benign lesions without meaningful clinical consequences.

The prognosis of adrenal incidentaloma is favourable in most cases because the largest proportion consists of benign, nonfunctioning lesions. Prognostic impact, however, depends not only on oncological risk but also on the presence of subtle hormone secretion, particularly cortisol secretion, which may increase long-term cardiovascular events and frailty. The true prognostic value of assessment therefore lies in the ability to classify the lesion correctly and reduce exposure to avoidable clinical risks.

The most concerning complications are associated with malignant or potentially aggressive forms, including adrenocortical carcinoma and metastases. In these cases, the complication is not limited to local or metastatic progression but also includes delayed diagnosis caused by an excessively reassuring interpretation of an indeterminate mass. Prognosis improves when radiological stratification is accurate and suspicious cases are referred promptly to experienced multidisciplinary teams.

From an endocrine perspective, the most relevant complications are cardiometabolic and skeletal. Mild autonomous cortisol secretion is associated with a higher prevalence of hypertension, diabetes and dyslipidaemia and may contribute to an increased risk of cardiovascular events and mortality in specific populations. The most tangible clinical complication is often the progressive loss of control of associated comorbidities, resulting in greater exposure to myocardial infarction, stroke, heart failure and functional decline, particularly in older adults and patients with pre-existing cardiovascular disease.

Bone is an important target organ. Chronic glucocorticoid exposure, even when mild but persistent, may reduce bone quality and increase the risk of fragility fractures. The clinical consequence is not limited to the fracture itself but includes a subsequent cascade of loss of independence, chronic pain and increased hospitalisation risk. Glucocorticoid-related myopathy also contributes to falls and frailty, creating a cycle between loss of muscle strength and fracture risk.

In unrecognised pheochromocytoma, the most serious potential complication is a catecholamine crisis precipitated by invasive procedures, anaesthesia or physiological stress. Diagnostic appropriateness is therefore a direct component of complication prevention. Even in diagnosed cases, perioperative management is critical because major blood pressure fluctuations and arrhythmias may occur before, during and after surgery, requiring specialist expertise and close monitoring.

Treatment-related complications depend on the selected intervention. Surgery carries general and specific risks, including postoperative adrenal insufficiency in patients with cortisol secretion, and requires appropriate follow-up. Medical treatment of aldosterone-producing forms requires monitoring of potassium and renal function and careful dose titration. Within a well-structured clinical pathway, these complications are preventable and manageable and should not preclude appropriate treatment when the expected clinical benefit is substantial.

Overall, adrenal incidentaloma is a condition with a generally favourable prognosis but with a clinically important tail of risk confined to specific subgroups. Reduction of complications depends on rigorous initial assessment, operational classification and selective follow-up, with the aim of avoiding both missed diagnoses of important disease and excessive medicalisation of benign lesions without meaningful clinical consequences.