Editing Adrenal: Pheochromocytoma (section)

== Management ==

* '''<span style="color:#ff0000">Pheochromocytoma is a surgical disease. Complete resection of the tumor is advised whenever possible'''
** There is no level 1 evidence exists regarding optimal preoperative or perioperative management

=== General principles (4): ===
# '''<span style="color:#ff0000">Pre-operative cardiology or anesthesia consultation because of risk for cardiomyopathy'''
#* '''Preoperative cardiac workup, including electrocardiography and echocardiography, and assessment of hypertension-induced end-organ dysfunction are indicated.'''
# '''<span style="color:#ff0000">Restoration intravascular volume'''
#'''<span style="color:#ff0000">Pre-operative medications (α-Blockade followed by β-blockade)'''
# '''<span style="color:#ff0000">Monitored bed post-operatively'''

==== Restoration intravascular volume ====
* '''<span style="color:#ff0000">Most important component of preoperative management'''
* Most centers '''admit patients the day before surgery and initiate aggressive IV fluid resuscitation'''

==== Pre-operative medications ====
* '''Indications'''
**'''<span style="color:#ff0000">All patients with pheochromocytoma and an abnormal metabolic evaluation undergo preoperative catecholamine blockade, including patients who do not exhibit evidence of blood pressure elevation and lack classic symptomatology.'''
*** '''Catecholamine release during intraoperative tumor manipulation can result in hazardous blood pressure elevation and cardiac arrhythmias.'''
*** Recent data suggest that preoperative α-blockade may not be necessary in normotensive asymptomatic patients
* '''<span style="color:#ff0000">α-Blockade'''
** '''Helps in both hemodynamic and glucose control'''
** '''<span style="color:#ff0000">Phenoxybenzamine'''
*** '''Most common α- blocker used for preoperative catecholamine blockade of pheochromocytoma.'''
*** '''MOA: irreversible, non-selective α receptor blocker'''
**** Intraoperative catecholamine surges typically do not override its actions, because reversal of the blockade is possible only through synthesis of new receptor molecules.
**** Non-selective nature '''may lead to tachycardia and β-adrenergic blockade may be necessary'''
**** '''Prolonged hypotension in the immediate postoperative period and central nervous system effects such as somnolence may be expected'''
**** '''Newer selective and competitive α1-adrenergic blockers such as doxazosin, prazosin, and terazosin obviate the drug-induced need for β-blockade.'''
*** '''<span style="color:#ff0000">Started 7-14 days before surgery.'''
**** Can be started at 10 mg twice daily with a stepwise increase of 10 to 20 mg every 2 to 3 days until a final dose of 1 mg/kg if tolerated.
***** During this time blood pressure checks should be conducted at least 3 times a day.
***** The last dose of phenoxybenzamine is usually given on the night before surgery, and the next morning’s dose is withheld to minimize potentially prolonged hypotension after tumor resection.
*** '''If phenoxybenzamine not effective for blockade, start metyrosine'''
**** MOA of metyrosine: blocks the biosynthesis of catecholamines by inhibiting the conversion of tyrosine to L-dopa
**** Generally added for extensive disease with large increases in catecholamines.
*** Acute hypertensive attacks can also be treated with a short-acting alpha blocker such as phentolamine.
* '''<span style="color:#ff0000">β-blockade'''
** '''Must be given with caution in patients with myocardial depression'''
** '''<span style="color:#ff0000">Should never be started before appropriate α-blockade'''
*** '''In the absence of α-blockade, β antagonists cause a potentiation of the action of epinephrine on the α1 receptors, resulting in hypertension''', owing to blockade of the arteriolar dilation at the β2 receptor. For this reason, '''selective β1 adrenoreceptor blockers, such as atenolol and metoprolol, are usually preferred.'''
** '''<span style="color:#ff0000">May be added when (2)'''
**# '''<span style="color:#ff0000">Systolic blood pressure is <100 mmHg'''
**# '''<span style="color:#ff0000">Tachycardia or reflex tachycardia develops.'''
* Calcium channel blockers
** Some studies report that sole use of calcium channel blockers is sufficient for safe pheochromocytomas resection. This approach avoids the reflex tachycardia and postoperative hypotension that are seen with use of phenoxybenzamine. This strategy be reserved for patients who are normotensive with paroxysmal hypertension and a normal baseline blood pressure.
** Usually, preoperative calcium channel blockade for 2 weeks is sufficient.

==== Monitored bed post-operatively ====
* '''In the immediate postoperative period, consider overnight ICU admission for active monitoring'''
** '''If phenoxybenzamine was used for preoperative α-blockade, hypotension is common''', given the lasting effects of the agent. Moreover, in a high catecholamine state, α2-adrenoreceptor stimulation inhibits insulin release. The withdrawal of this adrenergic stimulus after tumor resection may result in '''rebound hyperinsulinemia and subsequent hypoglycemia'''

=== Post-operative follow-up ===
* '''<span style="color:#ff0000">Repeat metabolic testing should be performed ≈2 weeks after adrenalectomy to document normalization of catecholamine levels'''
* Postoperative cross-sectional imaging is reasonable to document tumor resection and appropriate healing of the resection bed.
** Subsequent imaging should be guided by results of biochemical testing
* '''<span style="color:#ff0000">Annual biochemical follow-up is mandatory for all patients with resected pheochromocytoma.'''
* '''<span style="color:#ff0000">Lifelong screening for recurrence is recommended'''
** 10-year recurrence rates are as high as 16%.
** No consensus on follow-up protocols exists.
* In a patient with persistent hypertension 2-3 months after adrenalectomy, residual tumor somewhere else in the body must be considered. The patient should initially have plasma free metanephrine levels measured. If this is abnormal, MIBG scan may be helpful in identifying the location of this lesion.

=== Special Scenarios ===

==== Treatment of Hereditary Pheochromocytoma ====
* Given that for patients with MEN-2 and VHL, the risk of malignancy is low whereas the risk of bilateral disease is significant, '''partial cortical-sparing adrenalectomy''' has been advocated. This strategy is used to avoid lifelong hormonal replacement, with its associated morbidity

==== Treatment of Malignant Pheochromocytoma ====
* '''Currently, malignant pheochromocytoma can only be defined by the presence of clinical metastases'''.
** A number of pathologic criteria to differentiate benign from malignant disease have been proposed, but to date there is no criterion agreed on.
*Currently therapy for metastatic pheochromocytoma is largely '''palliative'''.
* '''Surgical metastasectomy of resectable disease is the standard of care'''
** Little evidence exists to demonstrate that it prolongs patient survival or is more effective for symptomatic relief than medical treatment with α/β-blockade and α-methyl-p-tyrosine
* Chemotherapy is primarily used in patients in whom MIBG therapy has failed or in those whose tumors do not demonstrate MIBG uptake on initial MIBG imaging studies.

==== Treatment of Pheochromocytoma in Pregnancy ====
* In a late term pregnancy, the patient should be treated with alpha-adrenergic blockade with phenoxybenzamine until the fetus has reached maturity to manage the hypertension. At this point, she should undergo caesarean section and tumor resection in one operation. The patient should not undergo the stress of vaginal delivery.