All patients with skull base paragangliomas should have biochemical testing for catecholamine hypersecretion (Fig. 7.1) [5, 13]. Preoperative screening is indicated because up to 8% of skull base paragangliomas are functional [4], which poses a risk for anesthetic and surgical induction of a hypertensive crisis [13, 15, 16]. The index of suspicion for a catecholamine hypersecretion from a skull base paraganglioma should be high in the following scenarios: resistant hypertension, spells with associated pallor, a family history of paraganglioma, a genetic syndrome that predisposes to paraganglioma (e.g., germline succinate dehydrogenase [SDHx] mutation), and a past history of resected pheochromocytoma or paraganglioma [17, 18].

The metabolism of catecholamines is primarily intratumoral, with formation of metanephrine from epinephrine and normetanephrine from norepinephrine [19]. Most reference laboratories now measure fractionated catecholamines (dopamine, norepinephrine, and epinephrine) and fractionated metanephrines (metanephrine and normetanephrine) by tandem mass spectrometry or high-performance liquid chromatography with electrochemical detection [20–22]. These techniques have overcome the problems with fluorometric analysis, which included false-positive results caused by α-methyldopa, labetalol, sotalol, and imaging contrast agents.

The most reliable case-detection strategy for catecholamine hypersecretion is the measurement of fractionated metanephrines and catecholamines in a 24-h urine collection (sensitivity, 98%; specificity, 98%) [15, 23]. Measurement of urinary or plasma dopamine (as part of fractionated catecholamines) or plasma methoxytyramine (the primary dopamine metabolite) can be very useful in detecting the rare skull base paraganglioma with selective dopamine hypersecretion [23, 24]. It is important to recognize that plasma metanephrine fractions are not direct metabolites of dopamine and may be normal in the setting of a dopamine-secreting tumor [7, 23, 25]. In addition, in some patients with dopamine-secreting paragangliomas , the 24-h urinary dopamine concentration may not be increased due to the sulfation of dopamine in the kidney. Thus, in addition to measurement of fractionated metanephrines in the blood or urine, a case can be made for measurement of fractionated plasma catecholamines or plasma methoxytyramine (Fig. 7.1).

Although it is preferred that patients not receive any medication during biochemical testing, treatment with most medications may be continued. Tricyclic antidepressants are the drugs that interfere most frequently with the interpretation of catecholamines and metanephrines. To effectively screen for catecholamine-secreting tumors, treatment with tricyclic antidepressants and other psychoactive agents listed in Table 7.2 should be tapered and discontinued at least 2 weeks before any hormonal assessments.

Imaging of the chest, abdomen, or pelvis is not needed in most patients with skull base paragangliomas. However, imaging outside of the neck is indicated in two clinical settings: apparent catecholamine-secreting skull base paraganglioma (because the catecholamine hypersecretion may actually be from a synchronous paraganglioma not located in the skull base) and known disease-causing germline mutation (e.g., SDHx) because these patients are at high risk of multiple paragangliomas and pheochromocytoma (Fig. 7.1). In those clinical settings, computed tomography (CT) or magnetic resonance imaging of the abdomen and pelvis should be obtained (sensitivity, >95%; specificity, >65%) [13, 26]. The most common locations of catecholamine-secreting paragangliomas include superior abdominal para-aortic region, 46%; inferior abdominal para-aortic region, 29%; urinary bladder, 10%; mediastinum, 10%; head and neck, 3%; and pelvis, 2% [4].

In addition to the computed abdominal and pelvic imaging, functional total body imaging should be considered in patients with apparent catecholamine-secreting skull base paragangliomas. One option for functional total body imaging is ¹²³I-labeled metaiodobenzylguanidine (MIBG) . This radiopharmaceutical agent accumulates preferentially in catecholamine-producing tumors; however, this imaging study is not as sensitive as was initially hoped (sensitivity, 80%; specificity, 99%) [27, 28]. It is important for the clinician to recognize the medications that may interfere with ¹²³I-MIBG uptake (e.g., tricyclic antidepressants, labetalol, calcium channel blockers) and have the patient discontinue them before imaging is performed [29]. In addition, somatostatin-based gallium 68 (68-Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE) for positron emission tomography (PET) CT is a very sensitive imaging agent to detect paragangliomas [30–32]. Where available, 68-Ga DOTATATE PET-CT is replacing ¹²³I-MIBG as a functional total body imaging option to screen for additional paragangliomas or metastatic disease. Finally, due to activation of aerobic glycolysis in patients with pheochromocytoma or paraganglioma associated with SDHx mutations, PET scanning with 18F-fluorodeoxyglucose (FDG) is the ideal imaging technique for localization of primary and metastatic tumors in patients with SDHx mutations [33, 34].

Patients with nonfunctioning skull base paragangliomas do not need preoperative adrenergic blockade. However, some form of preoperative pharmacologic preparation is indicated for all patients with catecholamine-secreting paragangliomas, including those who are asymptomatic and normotensive [13, 35–37]. Combined α- and β-adrenergic blockade is one approach to control blood pressure and prevent intraoperative hypertensive crises [6]. α-Adrenergic blockade should be started 7–10 days preoperatively to normalize blood pressure and expand the contracted blood volume. A longer duration of preoperative α-adrenergic blockade is indicated for patients with recent myocardial infarction, catecholamine cardiomyopathy, or catecholamine-induced vasculitis. Blood pressure should be monitored with the patient in the seated and standing positions twice daily. Target blood pressure is low-normal blood pressure for age (e.g., <120/80 mm Hg in the seated position), with systolic blood pressure greater than 90 mm Hg (standing); both targets should be modified on the basis of the patient’s age and comorbid disease. Orthostasis is not a goal of treatment, but rather a side effect. Therefore, on the second or third day of α-adrenergic blockade, patients are encouraged to start a diet high in sodium content (≥5000 mg/day) because of the catecholamine-induced volume contraction and the orthostasis associated with α-adrenergic blockade. This degree of volume expansion may be contraindicated in patients with congestive heart failure or renal insufficiency. After adequate α- adrenergic blockade has been achieved, β-adrenergic blockade is initiated, typically 2–3 days preoperatively.