Adrenocortical carcinoma is a rare type of tumor that should be suspected when lesions are >6 cm in size and/or if the patient presents with virilizing symptoms. Patients with AI and possible ACC should be biochemically screened for hypersecretion. One study determined 66 % of ACC were hormone-secreting tumors [7, 8].

Lesions definitively characterized as adenomas by imaging do not require biopsy. Functioning adenomas should be surgically excised while nonfunctioning adenomas should be followed up with interval imaging. Other benign nonfunctioning adrenal lesions include myelolipomas and adrenal cysts which also do not require biopsy. Suspected pheochromocytomas should not be biopsied; a thorough and properly performed biochemical assessment of plasma metanephrines can confirm this diagnosis. An unnecessary biopsy of a pheochromocytoma may cause a sudden hypertensive crisis due to the release of excessive catecholamines into circulation. These lesions should be treated with surgical resection. Lesions that cannot be confidently characterized by standard radiologic or laboratory criteria and lesions that are larger than 4 cm and lesions with markedly heterogeneous appearance on imaging should be referred for adrenal biopsy [12]. However, masses which are highly suspicious for adrenocortical carcinoma such as those isolated adrenal mass >4 cm with irregular margins/central necrosis and no known primary malignancy should be considered for wide surgical excision rather than biopsy. AIs found in patients with a medical history of extra-adrenal malignancy may be considered for adrenal biopsy. Mazziglia et al. showed that 40–75 % of AIs in this population indicate metastatic disease [13]. By comparison other studies have demonstrated a 0 % rate of malignancy in 973 patients with no history of cancer who presented with adrenal incidentaloma [14, 15]. Historically, percutaneous adrenal biopsy has had relatively limited indications due to high non-diagnostic rate, risk of tumor seeding, and possible catecholamine surge if the lesion may be a pheochromocytoma. A retrospective study performed by Mazzaglia et al. determined that needle biopsy of AI is often inadequate for distinguishing benign lesions from malignant lesions due to histologic similarity and recommend that biopsy only be considered for making diagnosis of metastatic disease in patients with known or suspected extra-adrenal malignancy [13]. As such, these lesions usually present as large (>4 cm), heterogeneous lesions.

Routine coagulation parameters such as INR and platelet count must be checked before biopsy to mitigate risk of hemorrhage. Anticoagulants should be discontinued at least 2–5 days prior to the procedure depending on the specific medication used (Table 27.1). In patients at high risk for deep vein thrombosis, a bridging technique can be utilized before and after biopsy using low-molecular-weight heparin [16]. Some radiologists will forego these recommendations with patients who are healthy and have no history of abnormal bleeding or use of anticoagulants. Adrenal biopsy is usually well tolerated and can be administered under local anesthesia or with conscious sedation. Prophylactic antibiotics are normally not recommended.

The adrenal glands are located in the retroperitoneum directly superior to the kidneys and encased in Gerota’s fascia (Fig. 27.1). There are rare anatomic variations in adrenal gland location. In the cases of solitary kidney or pelvic kidney, adrenal glands will be found in the same location but appear differently on imaging.

In cases in which fine-needle aspirate is necessary, small-caliber needles (20–22 gauge) should be used. For histologic analysis, cutting needles are to be used to provide core biopsy samples. During adrenal biopsies, coaxial technique using 16–19 gauge guide needles is used to allow for the retrieval of fine-needle aspirates and core biopsies. Chiba needles with slightly curved tips are commonly used to enhance redirecting, while Hawkins needles with interchangeable tips can be utilized if saline injection is anticipated for paravertebral widening [17].

Patients are oriented in the decubitus position which decreases diaphragmatic movements, lessening the risk of lung transgression. Patients can also be placed prone in order to attempt a posterior approach to the adrenal glands. If neither approach works, an anterior approach can be used, though it is associated with higher rates of complications [18]. A caudal-to-cephalic approach may be utilized to minimize risk of pleural transgression in both the prone and decubitus positions. In cases where the paravertebral space is minimal, injection of saline can be administered to widen the space. The saline will displace the parietal pleura laterally, decreasing the risk of pleural transgression. Ultrasound guidance can be used for large adrenal masses and gives the advantage of real-time observation. Otherwise, CT guidance is the standard imaging modality used for adrenal biopsy.

Complication rates for adrenal biopsy range from 0 to 12 % [19–22]. The most common complications associated with adrenal gland biopsy are pneumothorax and hemorrhage. Needle track seeding, hypertensive crisis, and adrenal abscesses are other less common complications that have be noted in literature. Following biopsy, patients usually remain under care for another 3 h to monitor hemostasis [17]. When post-biopsy hemorrhage does occur, it usually occurs in the abdomen or thorax and normally resolves without intervention [17]. Literature has demonstrated an increase in morbidity and mortality when the transhepatic approach and the anterior approach to the left adrenal gland which traverses the pancreas have been utilized [18]. In cases in which the pleural space was transgressed, a chest x-ray (CXR) must be ordered as well as 3 h follow-up CXR after the procedure to evaluate for a progressive pneumothorax. Patients found to have pneumothorax should be treated with a small-bore chest tube. Another serious complication of adrenal gland biopsy that may occur during the procedure is hypertensive crisis propagated by the release of catecholamines from the gland. Approximately 2.4 % of pheochromocytomas present atypically on imaging and thus can lead to unsuspecting biopsy of a catecholamine-secreting tumor [23]. If an acute hypertensive crisis does occur during biopsy, it can be treated with 1 mg of phentolamine via IV followed by an IV phentolamine drip. Intravenous nitroprusside can also be utilized to control hypertension as well as beta-adrenergic blockers to treat cardiac arrhythmias or hypotension. For lesions in which pheochromocytoma has not been conclusively ruled out, administration of alpha-blockers prior to the procedure should be considered.

The sensitivity of adrenal biopsy for detecting malignancy ranges from 81 to 100 % [24–26]. Several studies have reported that adrenal biopsy in this setting is unreliable and variable [13, 27, 28]. However, one prospective study of 220 adrenal biopsy demonstrated a correct diagnosis 76.8 % of biopsies. The study included 39 malignant tumors and showed a sensitivity of 94.6 % and a specificity of 95.3 % when determining malignancy [29]. While these results are exceptional, they may not be reflective of common adrenal biopsy practice since the radiologic selection criteria were very strict enriching the study cohort for malignant lesions; in addition, ACC-specific immunohistochemistry stains were used on core samples improving the diagnostic results as well. As it stands though, adrenal biopsy should be indicated for AI lesions that remain indeterminate after appropriately performed imaging (CT/PET and/or MRI) and biochemical assays which both may discourage adrenal biopsy.

Adrenal gland lesions are extremely common and are often found incidentally on radiographic imaging studies performed for other reasons. The vast majority of lesions can be diagnosed accurately with radiographic criteria alone. Furthermore, the overwhelming prevalence of benign adenomas even in patients with a history of malignancy results in a limited role for adrenal biopsy. Most published data indicate that adrenal biopsies have an unacceptably high non-diagnostic rate and do not reliably differentiate between benign and malignant primary adrenal tumors. Additionally, a small but significant risk of a hypertensive crisis due to an unrecognized or atypical pheochromocytoma also limits the application of adrenal biopsy. Finally, the theoretical risk of tumor seeding and increasing complexity of subsequent surgery are additional concerns that limit widespread application of adrenal biopsy. Currently, the usage of core biopsy for the differentiation of benign tumors from malignant tumors in the adrenal gland is not part of standard diagnostic algorithms for adrenal masses.

Adrenal gland lesions are indicated for biopsy if the mass is indeterminate after imaging and the patient has a history of malignancy or if the mass is indeterminate and larger than 4 cm. All patients should undergo plasma screening for catecholamines prior to the biopsy to rule out pheochromocytoma. Adrenal biopsy is a generally well-tolerated procedure, and in experienced hands complication risks are low. In specific and well-characterized patient populations, biopsy can be useful for the diagnosis of adrenal incidentalomas.

Adrenal venous sampling is the current standard of care for identifying and lateralizing surgically curable cases of hyperaldosteronism caused by aldosterone-secreting adrenal tumors. Studies have reported sensitivity of 95 % and specificity of 100 % for adrenal venous sampling for lateralizing aldosterone hypersecretion [30–36]. This technique, though, remains underutilized. It is often described as a technically challenging procedure with problematical complications such as adrenal vein rupture and embolism [35, 37]. Adrenal venous sampling also lacks a universally accepted set of standards for performance and interpretation of results. The classic presentation of primary aldosteronism (PA) is hypertension with hypokalemia and metabolic alkalosis. Most times, though, patients do not present with all three symptoms. The Endocrine Society has established guidelines to screen select patient populations. Patients with hypertension and hypokalemia, refractory hypertension, hypertension with an adrenal incidentaloma, or hypertension with history of familial/early onset hypertension should be screened for primary aldosteronism [38]. Diagnostic workup for primary aldosteronism includes plasma renin assay (PRA) and plasma aldosterone concentration (PAC), both retrieved peripherally. Decreased plasma renin with an increased PAC/PRA ratio is indicative of primary aldosteronism. Normal PAC/PRA ratio is usually in the range of 4–10 while patients with PA will have a ratio of 30–50 [39, 40]. Recent studies have suggested that primary aldosteronism accounts for 5–13 % of all hypertensive patients and that up to 62.3 % of patients with primary hyperaldosteronism may be curable with surgical resection [40–42]. It is important to note that the two most common causes of primary hyperaldosteronism are bilateral idiopathic hyperplasia and unilateral aldosterone-producing adenoma (as well as a chance of bilateral functioning adenomas) [38, 43]. This distinction is critical because clinical management of patients depends on accurate diagnoses. Patients with bilateral hyperplasia must be managed medically due to the inability to treat surgically. These patients are best treated with long-term usage of spironolactone or other aldosterone antagonist [38]. Adrenal venous sampling can be used to accurately lateralize functioning adenomas for surgical resection. Recent studies have shown that localizing the source of aldosterone-producing adenomas and bilateral lesions using MRI and CT is difficult and often leads to equivocal findings [44]. One prospective study of 203 patients noted that up to 46.4 % of patients may have been incorrectly treated based on CT-imaging alone [36]. This includes patients that may have had an inappropriate adrenalectomy and patients that would have been excluded for adrenalectomy. Another large study showed 37.8 % of the 950 patient population had CT/MRI results in disagreement with adrenal venous sampling outcome [44]. Mounting evidence continues to demonstrate the need for AVS usage when CT imaging is equivocal and/or when lateralization of lesion(s) is required.