T1 and T2 weighted images with chemical shift imaging (CSI) is desirable with MRI of adrenals [3]. CSI relies on differentiating lesions by their lipid content, as malignant lesions do not have lipid in them. Multi-planar MRI helps in precise anatomical localisation and separation of adrenal masses from the surrounding structures, particularly the liver on the right side, spleen, stomach, pancreas and kidneys. Normal adrenal glands have T1 and T2 signal intensity equal or slightly lower than that of the normal liver [5].

This involves imaging using isotopes based on physiological and pathological aspects of the adrenal gland. These investigations are particularly helpful when lesions are not adequately characterised by CT or MRI. At present ¹⁸F FDG PET seems an ideal method for characterising these tumours as benign or malignant [6]. Of those tumours that are malignant secondary tumours from a lung or gastro-intestinal primaries are more common than a primary adrenocortical tumour. Within the adrenal gland itself ¹⁸F FDG PET can be positive in both primary and secondary malignancy within the adrenal gland with the probable diagnosis depending on the pattern of activity and clinical history.

The most common functional benign adrenocortical tumour is the aldosterone producing Conn’s syndrome. This was traditionally imaged with ⁷⁵Se methionine but this has been withdrawn from use. An alternative is ¹³¹I-iodocholesterol, but this is both very expensive and is associated with a very high radiation burden [7]. More recently a few centres have looked at ¹¹C-metomidate PET-CT this allows rapid high quality imaging of Conn’s syndrome and can be used to find and characterise tumours as small as 4 mm [8].

Most pheochromocytomas express the noradrenaline transport system [9]. This transport system is responsible for the uptake of noradrenaline and adrenaline. The alkylguanidine meta-iodobenzylguanidine (MIBG), a noradrenaline analogue, is used in the diagnosis of pheochromocytoma as its cells take up MIBG. Imaging with ¹²³I- or ¹³¹I-MIBG has been useful for characterising a suspicious adrenal gland in a patient with clinical suspicion of a pheochromocytoma and in staging patients with malignant pheochromocytomas where the advent of SPECT-CT allows even small lesions to be identified [10] (Fig. 25.2).

There is also the possibility of treating patients with metastatic pheochromocytomas with high activity ¹³¹I-mIBG with good results obtained for both symptom relief and palliation of symptoms [11].

With the advent of sophisticated radiological and biochemical investigations, there is a decreasing need for invasive tests such as needle biopsy or fine needle aspiration. If required the procedure is done with the CT guidance. Adrenal biopsy is not recommended unless it is part of staging a known malignancy [12]. Before biopsy, pheochromocytoma should be excluded with biochemical tests [13]. Because of its close proximity with diaphragm and pleura, potential complications include pneumo/hemothorax. Bleeding and infection are other complications.

A major problem in adrenal disease is that the glands frequently become nodular with age, presumably as part of a degenerative process, followed by a regenerative cycle. This tendency to nodularity is seen commonly in other endocrine glands, classically the thyroid. One task is to separate such natural nodularity from the diseases that require treatment. Another difficulty in adrenal pathology is distinguishing benign from malignant adrenal tumours by histological analysis. This lack of histological certainty means that careful clinical follow-up is often required.

Prevalence of incidentalomas peaks between the ages of 50–60 years, with a slight female preponderance [17]. Incidentalomas are particularly common in patients with features of the metabolic syndrome (insulin resistance, dyslipidaemia, obesity and hypertension).

The differential diagnosis of adrenal incidentaloma is extensive but most of them are non-secreting cortical adenomas [12] (Table 25.1). Detection rates of incidentalomas on imaging and autopsy are shown in Table 25.2.

A thorough clinical assessment is needed in patients who are diagnosed with incidentalomas. There may be a history of weight gain in patients with Cushing’s syndrome or hypercortisolism. In addition, there would be history of centripetal obesity, easy bruising, hypertension, virilisation and fatigue. In patients with pheochromocytoma, there may be a history of headache, weight loss, anxiety attacks, sweating and cardiac arrhythmias. In aldosteronism the physician has to look for hypertension, fluid retention and history of hypokalaemia [19].

Evaluation of adrenal incidentaloma has to address two important questions.

Being highly vascular, adrenal glands are likely sites for blood-borne metastasis from other organs most notably breast, lung, gastrointestinal tract, kidney, melanoma and lymphoma. Metastatic disease must be suspected in any patient with a history of cancer; three-quarters of incidental adrenal masses prove to be metastatic in patients with such a history. In patients with no prior history of cancer, two thirds of incidentally found adrenal lesions are reported to be benign.

Computed tomography (CT) scanning is effective in separating benign adrenal disease from malignancy. The main indicator of malignancy is size. For example, adrenocortical carcinoma was detected in 2 % of masses <4 cm in diameter, 6 % of masses 4.1–6.0 cm and 25 % of masses >25 cm [20]. Assessment of CT radiographic absorption (CT attenuation coefficient expressed as Hounsfield units, HU) of adrenal masses suggests that a value of >10 HU is an indicator of malignant potential, with specificity of 96–100 % and sensitivity of 68–79 % [21, 22]. Other radiographic features such as heterogeneous appearance of the gland, irregular border of the mass and involvement of surrounding structures are sinister. For patients who are unable to undergo a contrast-enhanced CT because of renal insufficiency or allergy to iodinated contrast media, chemical shift MRI can be performed as CT and MRI demonstrate similar accuracy in the diagnosis of adrenal masses [13].

The finding of intracellular lipid in a solid adrenal lesion by magnetic resonance imaging (MRI) is suggestive of an adrenocortical adenoma. Pheochromocytomas are characterised by hypointensity on T1-weighted MRI and hyperintensity on T2-weighted MRI. The presence of fat in the lesion may suggest a myelolipoma, which are benign non-functioning neoplasms consisting of mature adipose cells and haemopoetic tissue.

The main concern is that an adrenal incidentaloma is secreting cortisol. In this case, adrenalectomy may be more hazardous. Firstly, the contralateral adrenal may be suppressed, and a hypoadrenal crisis and hypotension may occur when the adenoma is removed and the circulating cortisol falls to low levels. Secondly, complications of infection, poor wound healing and haemorrhage are more likely if the high pre-operative cortisol levels are not detected and treated prior to operation. An elevated serum cortisol level and suppressed serum adrenocorticotropin (ACTH) or dehydroepiandrostenedione sulphate (DHEAS) are very suggestive of autonomous adrenal cortisol production. However, patients with mild over-secretion may have serum cortisol levels within the normal range and a low dose dexamethasone suppression test is often useful.

Conn’s syndrome should be suspected in any patient with hypertension with or without hypokalaemia. As a screening measure, patients should have an assessment of their electrolytes including bicarbonate and measurement of plasma aldosterone concentration and plasma renin activity with assessment of the ratio.

Clinically silent pheochromocytomas account for 5–11 % of incidentalomas [4, 23, 24]. These frequently present with no specific symptoms and should be excluded in any patient with an incidentaloma. Twenty-four hour urinary free catecholamines provide a useful screening tool with 96 % sensitivity and are widely available [25]. Other tests include plasma or urinary metanephrines and fractionated catecholamines, with sensitivity and specificity of around 95 %. Serum DHEAS as levels may be increased in adrenocortical carcinoma. Serum 17-hydroxyprogesterone should be assessed in view of the possibility of congenital adrenal hyperplasia.

Adrenalectomy is recommended for masses greater than 6 cm in diameter. Homogeneous lesions less than 4 cm diameter are considered low risk and may be followed by scanning. Masses, which measure 4–6 cm, or with heterogeneity, may be followed up or excised, although if features of rapid growth or decreased lipid content are present, surgery would be advisable. Over a 10-year follow-up, less than 30 % increase in size and less than 20 % develop biochemical abnormalities [20].