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APPROACH TO THE PATIENT |
Section on Medical Neuroendocrinology, Reproductive and Adult Endocrinology Program, National Institute of Child Health and Human Development, National Institutes of Health, National Institutes of Health, Bethesda, Maryland 20892-1109
Address all correspondence and requests for reprints to: Karel Pacak, M.D., Ph.D., D.Sc., Professor of Medicine, Chief, Section on Medical Neuroendocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, CRC, Room 1E-3140, 10 Center Drive MSC-1109, Bethesda, Maryland 20892-1109. E-mail: karel{at}mail.nih.gov.
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Abstract |
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 Top Abstract A Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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A Patient’s Presentation |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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In the past, other symptoms and problems included episodes of sweating lasting 1–2 min, palpitations, and dizziness (all three usually occurring once every 1–2 wk for the past 6 months), and blurred vision for the last 2–3 months. Past medical history was also significant for labile and difficult-to-control hypertension [treated with amlodipine (Norvasc) 10 mg and metoprolol (Toprol XL) 50 mg once a day] for the past 5 yr. He also had a history of severe weight gain (over 110 pounds) during the last 2 yr, compounded by low energy level. A few months before hospitalization, the patient was put on a diet and a weight loss medication (phentermine, 30 mg once a day for 2 months) resulting in a 70-pound weight loss; however, he continued to be hypertensive. In addition, he was previously diagnosed to have uncomplicated umbilical hernia, benign prostate hypertrophy, and bilateral knee osteoarthritis.
At the emergency room, in view of the recurrent episodes of syncope and recent history of abdominal pain associated with nausea, a work-up for cardio- and cerebrovascular events and a possible small bowel obstruction was initiated. Computed tomography (CT) of the abdomen revealed a 6.4-cm left adrenal gland mass, in addition to a small umbilical hernia with partial small bowel obstruction. Magnetic resonance imaging confirmed the diagnosis of the left adrenal mass that appeared heterogeneous with a bright signal on T2-weighted images. It also showed moderately distended loops of the small bowel. Electrocardiogram (ECG) did not show any ischemia.
The patient was taken to the operating room for urgent umbilical hernia repair. Upon induction of anesthesia, the patient developed a hypertensive crisis with a blood pressure of 250/150 mm Hg and tachycardia with a heart rate of 95 bpm. Therefore, surgery was immediately aborted. The patient was subsequently transferred to the intensive care unit, and an endocrinology consult was requested for suspicion of a possible pheochromocytoma. Biochemical evaluation for pheochromocytoma revealed elevated urine norepinephrine (NE) of 738 µg/24 h (with an upper reference limit of 100 µg/24 h) and epinephrine (EPI) of 779 µg/24 h (upper reference limit, 24 µg/24 h). Two days later, the patient underwent hernia repair with blood pressure and heart rate controlled by iv 
- and ß-adrenoceptor blockade. The patient was discharged on phenoxybenzamine (Dibenzyline), metoprolol, and amlodipine.
Subsequently, the patient was referred to the National Institutes of Health (NIH) for further evaluation of his left adrenal pheochromocytoma. The diagnosis of pheochromocytoma was confirmed, and the patient was put on preoperative - and ß-adrenoceptor blockade. Three weeks before surgery, the patient was started on phenoxybenzamine 10 mg per day by mouth, which was gradually titrated up to 30 mg three times a day. He was also put on atenolol 25 mg/d by mouth, which was gradually titrated up to 50 mg twice a day and metyrosine (Demser) 250 mg three times a day. ECG revealed a first-degree AV block with QT interval of 464 msec. A transthoracic echocardiogram showed a mildly dilated left atrium and ventricle. Therefore, a cardiology consult was obtained; but no further recommendations were given. After the patient’s blood pressure normalized, a liberal salt diet was recommended.
The day before the planned surgery, the patient was admitted to NIH Clinical Center. His average blood pressure and heart rate were 134/76 mm Hg and 65 bpm, respectively. At midnight, the patient was given an extra dose of 40 mg of phenoxybenzamine, 12.5 mg of atenolol, and 500 mg of metyrosine. Additionally, he received 1 liter of 5% dextrose with 0.45% normal saline. During the surgery the following morning, there was no significant change in blood pressure during tumor manipulation and removal. Postoperatively, the patient developed a few hours of lasting hypotension (average blood pressure of 83/49 mm Hg and heart rate of 87 bpm), which was treated with a dopamine drip. Histopathological examination confirmed the diagnosis of pheochromocytoma.
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Pheochromocytoma as Catecholamine Excess and Storm |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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Practically all pheochromocytomas produce catecholamines with considerable variation in their content, depending on expression of biosynthetic enzymes as depicted in Fig. 1
(3, 4, 5). Most extraadrenal pheochromocytomas produce predominantly NE. Many adrenal tumors produce either NE and EPI, or few rarely produce predominantly EPI (e.g. in patients with multiple endocrine neoplasia type 2 and neurofibromatosis type 1). The concentrations of catecholamines in pheochromocytoma tissues are enormous (6), potentially creating a volcano that can erupt at any time. Significant eruptions result in a catecholamine storm called "attacks." In addition, smaller and continuous eruptions usually result in various symptoms and signs that are characteristic of constant adrenoceptor overstimulation by catecholamines (Table 1). For example, in our series we found that in patients with sporadic NE-secreting pheochromocytomas, the average NE content was about 1,760,000 pg/g tissue with about 53% of its release each day. In sporadic EPI-secreting pheochromocytomas, the average EPI content was about 3,801,000 pg/g tissue, with about 5% of its release each day (Eisenhofer, G., unpublished observations). At such levels, any direct tumor stimulation may lead to abrupt and significant catecholamine release that exceeds normal plasma values 1000 times or more (7, 8). These differences in catecholamine content and release explain different clinical presentations and ultimately necessitate specific treatment for each patient.
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Catecholamines and Adrenoceptors |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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). Both EPI and NE have overlapping but different effects on - and ß-adrenoceptors on various organs and systems (Table 2). In particular, EPI has a more potent effect on ß2-adrenoceptors than NE, whereas NE is a more potent ß1-adrenoceptor agonist than EPI. EPI is also a more potent -adrenoceptor agonist than NE. However, the proximity of sites of NE and EPI release to adrenoceptors and the resulting concentrations at effector sites are also important determinants of adrenoceptor-mediated responses to these two catecholamines (13, 14).
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1-adrenoceptor-mediated vasoconstriction resulting in hypertension (14, 17). Both catecholamines, although NE to a higher degree, stimulate ß1-adrenoceptors resulting in an increased heart rate. Furthermore, EPI is important as a metabolic hormone (18). In particular, EPI stimulates lipolysis, ketogenesis, thermogenesis, and glycolysis, and raises plasma glucose levels by stimulating glycogenolysis and gluconeogenesis. EPI also has potent effects on pulmonary function, causing ß2-adrenoceptor-mediated dilation of airways. Thus, patients with EPI-secreting pheochromocytomas more frequently show episodic symptoms and signs with palpitations, light-headedness or syncope, anxiety, and hyperglycemia than patients with tumors that secrete mainly NE, who more often have continuous symptoms and signs including hypertension, sweating, and headache (3, 17, 19). These catecholamine-specific effects on adrenoceptors explain the wide range of clinical presentations of patients with pheochromocytomas and serve as the basis for appropriate preoperative adrenergic blockade. Although some patients need significant amounts of adrenoceptor blockers, some may not, despite high circulating catecholamine concentrations (often seen in patients with metastatic pheochromocytoma). This may be explained by so called "desensitization" that occurs by two mechanisms: internalization of receptors, reducing their number on the cell surface; or decreased binding affinity of the catecholamine to the receptor (20, 21). This mechanism prevents, at least partially, a patient from the harmful effects of catecholamines, which often favor the administration of lower doses of adrenoceptor blockers and catecholamine synthesis inhibitors to minimize drug-related side effects. |
Current Views on Preoperative Blockade |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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-adrenoceptor antagonists, calcium channel blockers, or angiotensin receptor blockers were all recommended. For tachyarrhythmias, ß-adrenoceptor or calcium channel blockers were recommended, but it was emphasized that if ß-adrenoceptor blockers are used, they should be used only after adequate pretreatment with -adrenoceptor antagonists to avoid hypertensive crisis from unopposed -adrenoceptor overstimulation (usually 2 d after -adrenoceptor blockers are given) (30). The mechanism for ß-adrenoceptor blocker-associated adverse events is generally ascribed to inhibition of ß2-adrenoceptor-mediated vasodilatation, leaving -adrenoceptor-mediated vasoconstrictor responses to catecholamines unopposed (31). The main goal of preoperative management of a pheochromocytoma patient is to normalize blood pressure, heart rate, and function of other organs; restore volume depletion; and prevent a patient from surgery-induced catecholamine storm and its consequences on the cardiovascular system. Therefore, when preoperative adrenergic blockade is started, drug doses are usually much higher, the combination of various drugs is often necessary, and targets for cardiovascular indices are much stricter than they would be if no operation was performed.
Currently, there is no consensus for when adrenergic blockade should be started when preparing a patient for surgery. In most medical centers, adrenergic blockade usually starts 7–14 d preoperatively to have adequate time to normalize blood pressure and heart rate and to expand the contracted blood volume (27, 32, 33, 34, 35, 36). In some patients who have organ damage from long-standing catecholamine excess (e.g. catecholamine-induced cardiomyopathy, vasculitis, recent myocardial infarction, and bowel movement dysfunction), adrenergic blockade can be initiated much earlier before the planned surgery. At our institution, our goal is to achieve preoperative blood pressure of 130/80 mm Hg or less while sitting and about 100 mm Hg systolic while standing (not less than 80/45 mm Hg) and target heart rate of about 60–70 bpm while sitting and 70–80 bpm while standing. At other institutions, the target blood pressure is either lower (37) or higher (9), depending on institutional experience. Nevertheless, recommendations regarding blood pressure and heart rate are supported by observational nonsystematic studies and personal experience rather than properly conducted prospective clinical studies.
-Adrenoceptor antagonists
Phenoxybenzamine (Dibenzyline; irreversible, noncompetitive, -adrenoceptor blocker) is most commonly used for preoperative blockade (Table 3). Phenoxybenzamine has a long-lasting effect that diminishes only after de novo -adrenoceptor synthesis. The initial dose of phenoxybenzamine is usually 10 mg twice a day and is increased until the clinical manifestations are controlled or side effects appear. Generally, a total daily dose of 1 mg/kg is sufficient. Some patients, however, may require much larger doses that, at our institution, are usually increased in increments of 10 to 20 mg every 2 to 3 d. If the initial dosage is too high, the patient will have significant postural hypotension with reflex tachycardia, dizziness, syncope, nasal congestion, and other side effects, and dose titration is warranted. As the correct dose is approached, paroxysmal hypertensive episodes are brought under control, and when the right dose is achieved the patient becomes normotensive or mildly hypotensive. Additionally, the prolonged action of phenoxybenzamine can contribute to hypotension in the first 24 h after tumor removal (38). Another option is to administer phenoxybenzamine by infusion (0.5 mg/kg·d) for 5 h a day, 3 d before the operation (39, 40). This approach, however, requires that the patient be admitted to the hospital and closely monitored; this period is usually too short to start catecholamine synthesis inhibitors to achieve maximum effect as discussed below. Two studies reported no correlation between duration of treatment (less than 1 wk vs. a longer time period) with phenoxybenzamine and cardiovascular intraoperative stability (41, 42). Furthermore, it should be mentioned that compared with 1-adrenoceptor blockers, phenoxybenzamine is an expensive drug; therefore, it is mainly limited to patients with appropriate health insurance.
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-adrenoceptor blocking agents of use are prazosin (Minipress), terazosin (Hytrin), and doxazosin (Cardura) (Table 3) (43, 44). All three are specific, competitive, and therefore short-acting 1-adrenergic antagonists. Prazosin is administered in doses of 2 to 5 mg two or three times a day, terazosin is given in doses of 2 to 5 mg per day, and doxazosin in doses of 2 to 8 mg per day. However, all three have the potential for severe postural hypotension immediately after the first dose; thus, they should be given just as the patient is ready to go to bed. Thereafter, the dosage can be increased as needed; titration can be achieved more quickly with much less side effects (no reflex tachycardia, less postoperative hypotension) compared with phenoxybenzamine. In patients with EPI-secreting tumors, the absence of reflex tachycardia (due to no effect on presynaptic 2-adrenoceptors, which if inhibited increase NE release) can be advantageous in patients who also have coronary artery disease. In volume-depleted patients, 1-adrenergic antagonists must be used cautiously because hypotensive effects may be more significant. Although some studies suggest that these drugs can control blood pressure pre-, intra-, and postoperatively as effectively as phenoxybenzamine, other studies do not support such conclusions (25, 45, 46). Because of a short half-life of 1-adrenergic antagonists, these drugs should also be given in the morning before surgery. In some institutions, phenoxybenzamine is used first and then replaced by 1-adrenergic antagonists before surgery to reduce postoperative hypotension (37).
In summary, -adrenoceptor blockade has a significant impact on surgical outcome as demonstrated in the study of Goldstein et al. (47) where 69% of patients without -adrenoceptor blockade experienced perioperative complications compared with only 3% with blockade. Experience at our and other institutions along with current pheochromocytoma expert views confirm these conclusions and results (2, 48, 49, 50), whereas previously published data suggested that preoperative -adrenoceptor blockade may not be necessary (51). Thus, currently it depends on institutional preference whether to use - or specific 1-adrenergic antagonists because they both are well accepted in the preoperative management of a pheochromocytoma patient. Regardless of which -adrenoceptor antagonist and its dose are used, no complete -adrenoceptor can be achieved as presented by a number of patients with intraoperative hypertension and tachyarrhythmia (38, 41, 52).
ß-Adrenoceptor antagonists
ß-Adrenoceptor blocking agents are needed when catecholamine- or -blocker-induced tachyarrhythmia occurs (Table 3). A ß-adrenoceptor blocker should never be used in the absence of an -adrenoceptor blocker because the former will exacerbate EPI-induced vasoconstriction by blocking its vasodilator component. This will make hypertensive episodes worse in subjects who are on a ß-adrenoceptor blocker alone. Currently, cardioselective ß1-adrenoceptor blockers are preferable (Table 3). Atenolol (Tenormin) is administered in doses of 12.5 to 25 mg two or three times a day, and metoprolol (Lopressor) in doses 25–50 mg three to four times a day (Toprol XL in doses 25–200 mg once a day). Propranol (Inderal) as a nonselective ß-adrenoceptor blocker is also used and is given in doses of 20 to 80 mg one to three times a day.
Combined - and ß-adrenoceptor antagonists
Although labetalol (Normodyne or Trandate), a drug with both - and ß-antagonistic activity, has been used for preoperative adrenoceptor blockade, it should not be used as the primary choice for blockade (53, 54, 55). With labetalol, one is forced to use a fixed ratio of - to ß-antagonistic activity that is about 1:7 (if given orally) (56), which may result in paradoxical episodes of hypertension or even hypertensive crisis (57). Note that the - to ß-antagonistic activity should be at least 4:1 to achieve adequate antihypertensive effect (58). Carvedilol (Coreg) is another new antihypertensive drug with similar effects as labetalol. Thus, these drugs are not recommended for preoperative adrenoceptor blockade, except in the situation when a patient is on - and ß-adrenoceptor blockers that need to be replaced (e.g. due to side effects). Moreover, labetalol significantly reduces the uptake of 131I-metaiodobenzylguanidine (MIBG) and needs to be stopped about 2 wk before 131I-MIBG scintigraphy (59).
Calcium channel blockers
Perhaps less effective than -adrenoceptor blockers, calcium channel blockers provide another option for preparing the patient preoperatively (22, 26, 60, 61). These drugs block NE-mediated calcium influx into vascular smooth muscle, thereby controlling hypertension and tachyarrhythmias. It is the view of the author and others that currently, there are three main roles of these drugs in pheochromocytoma patients (9, 37): 1) to supplement adrenoceptor blockers in patients with inadequate blood pressure control, obviating the need to increase the dosage of -adrenoceptor blockers; 2) to replace adrenoceptor blockers in patients with severe side effects; and 3) to prevent adrenoceptor blocker-induced sustained hypotension in patients with only intermittent hypertension. Calcium channel blockers do not cause hypotension or orthostatic hypotension during normotensive period (62). These agents may also prevent catecholamine-associated coronary spasm; therefore, they may be useful when pheochromocytoma is associated with catecholamine-induced coronary vasospasm. In some medical institutions, calcium channel blockers are the primary preoperative treatment of choice in normotensive patients with pheochromocytoma (51). Amlodipine (Norvasc) is given in a dose from 10–20 mg, and nicardipine (Cardene) in a dose from 60–90 mg per day. Nifedipine (Adalat) is given in a dose from 30–90 mg and verapamil (Covera-HS, Calan-SR) in a dose from 180–540 mg per day. Both nifedipine and verapamil have extended-release action.
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Catecholamine Synthesis Inhibition |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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-Methyl-L-tyrosine or metyrosine (Demser) is an analog of tyrosine that competitively inhibits tyrosine hydroxylase, the rate-limiting step in catecholamine biosynthesis (63). It significantly but not completely depletes catecholamine stores with maximum effect after about 3 d of treatment (Fig. 1) (64). The drug is usually used to control high blood pressure in patients with pheochromocytoma, particularly those with extensive metastatic disease or preoperatively in patients with biochemically active tumors (65, 66, 67, 68). It is preferably used together with other adrenergic blockers due to incomplete depletion of catecholamine stores regardless of the dose used (27, 37, 67, 69). Despite the well-documented effect of metyrosine on catecholamine synthesis, this treatment has been adopted by only a few institutions (37, 66, 69). This is partially due to the limited availability of this drug and its side effects evident at high doses.
Metyrosine facilitates blood pressure control both before and during surgery, especially during the induction of anesthesia and surgical manipulation of the tumor when extensive sympathetic activation or catecholamine release occurs (66, 67). At our institution, treatment is started in all surgical candidates at a dose of 250 mg orally every 8 to 12 h and, thereafter, the dose is increased by 250 to 500 mg every 2 to 3 d or as necessary up to a total dose of 1.5 to 2.0 g per day. We treat for 1–3 wk before surgery depending on blood pressure and heart rate normalization. The drug, a substituted amino acid, called -methyl-L-tyrosine, readily crosses the blood–brain barrier. Thus, it inhibits catecholamine synthesis in the brain as well as in the periphery, frequently causing sedation (often sleepiness), depression, anxiety, and galactorrhea, and rarely causes extrapyramidal signs (e.g. parkinsonism in elderly patients) (27, 37). If these side effects do not resolve quickly when the dosage is lowered, the drug should be discontinued. Metyrosine also causes diarrhea and crystalluria, especially when doses are higher than 4 g per day, although such a dose is rarely used. Metyrosine and -adrenoceptor blockers when used together result in less labile blood pressure during anesthesia and surgery (but elevated blood pressure still occurs in up to 30–80% of patients), reduced intraoperative blood loss, and reduced volume replacement during surgery compared with the use of -adrenoceptor blockers alone (66, 67 and 70 ; and author’s personal observations).
In summary, although large randomized, prospective, and controlled studies are lacking, data from retrospective studies suggest that -adrenoceptor blockade is currently the preferred choice in preoperative management of hypertensive pheochromocytoma patients to improve surgical outcome (Fig. 2) (28, 37, 47, 71). Calcium channel blockers and ß-adrenoceptor blockers (72) are most often used as co-drugs when blood pressure cannot be well controlled while on -adrenoceptor blockade or if tachyarrhythmia occurs. At some medical institutions metyrosine is given to all patients, and at others only to those patients who have highly active tumors associated with difficult-to-treat symptoms and signs of catecholamine excess.
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-adrenoceptor or calcium channel blockers preoperatively. Exceptions where treatment may not be required for blood pressure and heart rate control include patients with parasympathetic-derived head and neck paragangliomas that do not produce catecholamines or patients with very rare tumors producing only dopamine (5, 36). |
Drugs with Interfering Effects on Catecholamine Turnover |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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and Table 3) (76). NE and EPI release can be provoked by glucagon, steroids, histamine, angiotensin II, and vasopressin. Displacement of catecholamines from storage vesicles by sympathomimetic amines (e.g. tyramine in cheese, bananas, wine, soy sauce, avocados, and any fermented, smoked, or aged meat and fish), followed by their release into circulation provides another example of how pheochromocytomas may be pharmacologically provoked (77). Of the drugs used for obesity management, phentermine (Adipex, Fastin, and Zantryl), phendimetrazine (Bontril, Adipost, and Plegine), methamphetamine (Desoxyn), and phenylethylamine (Fenphedra) are sympathomimetic amines with a direct action on adrenoceptors. Over-the-counter use of nasal decongestants, such as formulations containing ephedrine, pseudoephedrine, or phenylpropanolamine, and currently some weight loss medications provide the most common source of drug interference. Drugs that decrease NE reuptake [e.g. tricyclic and other antidepressants: amitriptyline (Elavil, Endep), nortriptyline (Aventyl, Pamelor), edronax (Reboxitine), duloxetine (Cymbalta), venlafaxine (Effexor); cocaine; weight loss medication sibutramine (Meredia); and those that influence NE metabolism, e.g. monoamine oxidase inhibitors: deprenyl (Selegiline)] contribute significantly to high circulating NE levels (mainly derived from sympathetic nerve terminals). NE reuptake inhibitors can interfere with the biochemical and imaging studies by two mechanisms: 1) blocking tumor cell uptake of 123I- and 131I-MIBG and other imaging agents (18F-fluorodopamine) that use the NE transporter; and 2) blocking reuptake of NE by neuronal cell membrane NE transporter, thereby leading to false-positive elevations of plasma NE and downstream metabolites (metanephrines) (78). Regardless of tumor presence, they may increase catecholamine levels and increase the propensity for a hypertensive crisis. NE metabolism modulators such as monoamine oxidase inhibitors block the conversion of metanephrines to methoxyhydroxyphenylglycol, leading to false-positive elevations in plasma and urinary metanephrines (13). Furthermore, these inhibitors allow tyramine from the diet to escape into the systemic circulation where it promotes NE release from sympathetic nerves (cheese effect) in normal people and catecholamine release by tumors in patients with pheochromocytoma. Linezolid (Zyvox), a novel oxazolidinone antibiotic, has monoamine oxidase inhibitory properties; thus, caution is warranted in pheochromocytoma patients. Dopamine receptor antagonists, such as metoclopramide (Reglan), chlorpromazine (Thorazine), and prochlorperazine (Compazine), used as antipsychotic and antiemetic drugs, can also provoke catecholamine release from pheochromocytoma. |
Cardiovascular Evaluation, Blood Volume Restoration, and Other Recommendations |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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Normalization of blood volume minimizes the possibility of protracted hypotension or shock resulting from sudden diffuse vasodilation at the time of tumor removal. If the blood pressure is controlled and the patient is given a normal or high-salt diet (usually 3 d after -adrenoceptor blocker is given), the patient’s diminished blood volume is typically restored to normal, and the degree of postural hypotension decreases. However, the treatment with -adrenoceptor blockers alone will result in blood volume restoration in only about 60% of patients (81). If catecholamine-induced hyperglycemia is found preoperatively, close monitoring should be initiated, and occasionally treatment may be necessary if hyperglycemia is severe.
In patients with a large left adrenal pheochromocytoma, splenectomy is likely; therefore, vaccination against pneumococcus, Haemophilus influenzae, and meningococcus should be given preoperatively.
Strenuous physical activity should be limited, and smoking and alcohol consumption should be avoided because they all significantly increase catecholamine release from a tumor.
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Hospital Admission |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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). Occasionally, sodium nitroprusside (Nipride) and labetalol or phentolamine (Regitine) infusion can be used preoperatively in patients with drug-resistant hypertension or hypertensive crisis, respectively (37). Sodium nitroprusside and phentolamine have a rapid onset of action but also end of effect. All these drugs are given to patients upon admission to the intensive care unit. |
Special Considerations |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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For pediatric patients, there are no other special considerations except when metyrosine is administered. Parents must be given clear instructions to report to a physician immediately if their child develops symptoms of depression and anxiety after taking metyrosine (84).
In pregnant patients, none of the - and ß-adrenoceptor blockers have been associated with any problem except propranolol, which, anecdotally, was reported to be associated with intrauterine growth retardation, fetal bradycardia, and hypoglycemia as well as premature labor (85). Timing of surgery and delivery should be decided through a close discussion and work among obstetricians, endocrinologists, anesthesiologists, and surgeons (36).
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Back to the Patient |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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-Adrenergic blockers should be used for preoperative preparation of a patient. ß-Adrenergic blockers should be used if tachyarrhythmia is present and only after -adrenergic blockers have been administered. Calcium channel blockers seem to be a useful alternative in low-risk patients. Furthermore, to ensure ideal preoperative preparation of patients with pheochromocytoma, very close communication between the endocrine, surgical, medical, cardiology, pediatric, oncology, radiology, and anesthesia teams is essential. Such teamwork should be directed to meet the three most essential goals: treat hypertension and tachyarrhythmias, restore the vascular volume, and treat any tumor or catecholamine excess-associated medical problems. With all these current recommendations in place, the Hippocrates phrase "To do good or to do no harm" reflects a physician’s best effort toward a pheochromocytoma patient before surgery.
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Acknowledgments |
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Footnotes |
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The author has nothing to disclose.
Abbreviations: CT, Computed tomography; ECG, electrocardiogram; EPI, epinephrine; MIBG, metaiodobenzylguanidine; NE, norepinephrine.
Received August 1, 2007.
Accepted September 18, 2007.
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References |
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TopAbstractA Patient's PresentationPheochromocytoma as...Catecholamines and AdrenoceptorsCurrent Views on Preoperative...Catecholamine Synthesis...Drugs with Interfering Effects...Cardiovascular Evaluation, Blood...Hospital AdmissionSpecial ConsiderationsBack to the PatientReferences |
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1- and 2-adrenergic receptor-mediated vasopressor responses in rat harboring pheochromocytoma. Circ Res 61:86–98 Blockade in preoperative preparation of patients with pheochromocytomas. Int Surg 87:191–194[Medline]- and ß-blocking agents. Int J Clin Pharmacol Ther Toxicol 23:617–628[Medline]-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. Lancet 2:1092–1094[Medline]-Methyl-p-tyrosine: a review of its pharmacology and clinical use. Drugs 21:81–89[Medline] methyl tyrosine for resistant hypertension. J Pediatr 91:143–147[CrossRef][Medline]-receptor blockade for blood volume and hemodynamics in pheochromocytoma. Anaesthesist 39:313–318[Medline]This article has been cited by other articles:
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  H. K Ghayee, B. Havekes, E. P M Corssmit, G. Eisenhofer, S. R Hammes, Z. Ahmad, A. Tessnow, I. Lazurova, K. T Adams, A. T Fojo, et al. Mediastinal paragangliomas: association with mutations in the succinate dehydrogenase genes and aggressive behavior Endocr. Relat. Cancer, March 1, 2009; 16(1): 291 - 299. [Abstract] [Full Text] [PDF]
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 M. L. Brown, G. E. Zayas, M. D. Abel, W. F. Young Jr, and H. V. Schaff Mediastinal Paragangliomas: The Mayo Clinic Experience Ann. Thorac. Surg., September 1, 2008; 86(3): 946 - 951. [Abstract] [Full Text] [PDF]
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 J. T. Adler, G. Y. Meyer-Rochow, H. Chen, D. E. Benn, B. G. Robinson, R. S. Sippel, and S. B. Sidhu Pheochromocytoma: Current Approaches and Future Directions Oncologist, July 1, 2008; 13(7): 779 - 793. [Abstract] [Full Text] [PDF]
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