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Adrenal: Pheochromocytoma: Difference between revisions

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**# '''Sympathetic chain'''
**# '''Sympathetic chain'''
**# '''Perivesical'''
**# '''Perivesical'''
* '''≈5% of incidental adrenal masses will have a pheochromocytoma'''
* '''<span style="color:#ff0000">≈5% of incidental adrenal masses will have a pheochromocytoma'''


* '''Currently, malignant pheochromocytoma can only be defined by the presence of clinical metastases'''.
* '''<span style="color:#ff0000">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.
** A number of pathologic criteria to differentiate benign from malignant disease have been proposed, but to date there is no criterion agreed on.


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|'''3%'''
|'''3%'''
|-
|-
|'''von Hippel-Lindau syndrome, type 2'''
|'''<span style="color:#ff0000">Von Hippel-Lindau (VHL), type 2</span>'''
|'''HIPPPEEL'''
|'''<span style="color:#0000ff">HIPPPEEL</span>'''
 
#'''<span style="color:#ff0000">CNS and/or retinal </span><span style="color:#0000ff">H</span><span style="color:#ff0000">emangioblastomas</span>'''
# '''CNS and/or retinal Hemangioblastomas'''
# '''<span style="color:#ff0000">ccRCC (</span><span style="color:#0000ff">I</span><span style="color:#ff0000">ncreased risk) and renal cysts</span>'''
# '''ccRCC (Increased risk) and renal cysts'''
#'''<span style="color:#0000ff">P</span><span style="color:#ff0000">heochromocytoma</span>'''
# '''Pheochromocytoma'''
#'''<span style="color:#0000ff">P</span><span style="color:#ff0000">araganglioma</span>'''
# '''Paraganglioma'''
#'''<span style="color:#0000ff">P</span><span style="color:#ff0000">ancreatic neuroendocrine tumours and cysts</span>'''
# '''Pancreatic neuroendocrine tumours and cysts'''
#'''<span style="color:#0000ff">E</span><span style="color:#ff0000">pididymal cystadenoma</span>'''
# '''Epididymal cystadenoma'''
#'''<span style="color:#ff0000">Ear </span><span style="color:#0000ff">E</span><span style="color:#ff0000">ndolymphatic sac tumour</span>'''
# '''Ear Endolymphatic sac tumour'''
#'''<span style="color:#ff0000">Broad </span><span style="color:#0000ff">L</span><span style="color:#ff0000">igament tumours</span>'''
# '''Broad Ligament tumours'''
|10-20%
|10-20%
|5%
|5%
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=== Labs ===
=== Labs ===


* '''Metanephrine Testing'''
* '''Metanephrine/catecholamine Testing'''
** '''The enzyme phenylethanolamine-N-methyltransferase (PNMT), catalyzes the conversion of norepinephrine to epinephrine, is relatively unique to the adrenal medulla (the brain and organ of Zuckerkandl also express this enzyme).'''
** '''The enzyme phenylethanolamine-N-methyltransferase (PNMT), catalyzes the conversion of norepinephrine to epinephrine, is relatively unique to the adrenal medulla (the brain and organ of Zuckerkandl also express this enzyme).'''
*** '''Localization of PNMT to the adrenal medulla explains why the gland is the primary source of systemic epinephrine, despite the presence of similar chromaffin cells elsewhere in the sympathetic nervous system'''
*** '''Localization of PNMT to the adrenal medulla explains why the gland is the primary source of systemic epinephrine, despite the presence of similar chromaffin cells elsewhere in the sympathetic nervous system'''
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** '''Gold standard imaging modality for definitive staging in patients with pheochromocytoma.'''
** '''Gold standard imaging modality for definitive staging in patients with pheochromocytoma.'''
** Superior test characteristics to CT, MRI, and metaiodobenzylguanidine (MIBG) scintigraphy.
** Superior test characteristics to CT, MRI, and metaiodobenzylguanidine (MIBG) scintigraphy.
** Better accuracy than 123I-MIBG in nearly all patients, especially for identification of metastatic disease.
** Better accuracy than 123I-MIBG in nearly all patients, especially for identification of metastatic disease.[[File:Pheochromocytoma Scan.jpg|alt=Pheochromocytoma MIBG|thumb|Pheochromocytoma (dark circular shadow near body center) localized by MIBG scintigraphy. See corresponding CT below. Source: [[commons:File:Pheochromocytoma_Scan.jpg|Wikipedia]]]]
* '''MIBG'''
* '''MIBG'''
** Utilizes a small-molecule analog of norepinephrine
** Utilizes a small-molecule analog of norepinephrine
** High specificity but low sensitivity for diagnostic disease identification.
** High specificity but low sensitivity for diagnostic disease identification.
** '''Useful modality when a suspected pheochromocytoma cannot be localized or when metastatic disease issuspected.'''
** '''Useful modality when a suspected pheochromocytoma cannot be localized or when metastatic disease is suspected.'''
*** '''In the most common and urologically most relevant clinical scenario, a solitary adrenal mass on cross sectional imaging in the setting of a biochemical evaluation indicative of pheochromocytoma, MIBG or 18F-FDG PET may be safely be omitted''' '''because these functional studies only serve to confirm what is already known and do not alter management.''' '''However, MIBG or 18F-FDG PET imaging for large (>5 cm) tumors is likely prudent to assess for metastatic disease before surgery and thereby counsel the patient appropriately'''
*** '''In the most common and urologically most relevant clinical scenario, a solitary adrenal mass on cross sectional imaging in the setting of a biochemical evaluation indicative of pheochromocytoma, MIBG or 18F-FDG PET may be safely be omitted''' '''because these functional studies only serve to confirm what is already known and do not alter management.''' '''However, MIBG or 18F-FDG PET imaging for large (>5 cm) tumors is likely prudent to assess for metastatic disease before surgery and thereby counsel the patient appropriately'''
Insert image
Pheochromocytoma (dark circular shadow near body center) localized by MIBG scintigraphy.
Front and back views also show radioiodine collection in thyroid (neck) and bladder (pelvis).
See corresponding CT below.
Source: Wikipedia


* '''MRI'''
* '''MRI'''
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*** '''If the lesion is not an adenoma, an adrenal mass protocol CT with IV contrast allows for evaluation of tumor washout.'''
*** '''If the lesion is not an adenoma, an adrenal mass protocol CT with IV contrast allows for evaluation of tumor washout.'''
**** '''Benign adrenal lesions wash out >50% on delayed imaging while pheochromocytoma, adrenocortical carcinoma and metastatic tumors do not.'''
**** '''Benign adrenal lesions wash out >50% on delayed imaging while pheochromocytoma, adrenocortical carcinoma and metastatic tumors do not.'''
*** '''Pheochromocytomas usually measure greater than 10 HU on unenhanced CT and >100 HU on contrast imaging,''' and are often well circumscribed in appearance with or without necrotic or cystic elements. Nevertheless, any evaluation of an adenoma should still include testing for plasma free metanephrines to rule out pheochromocytoma.
*** [[File:Phaeochromozytoma CT coronal.jpg|thumb|CT scan with enhancement demonstrating suspicous left adrenal mass. See corresponding MIBG scan above. Source: [[commons:File:Phaeochromozytoma_CT.jpg|Wikipedia]]]]'''Pheochromocytomas usually measure greater than 10 HU on unenhanced CT and >100 HU on contrast imaging,''' and are often well circumscribed in appearance with or without necrotic or cystic elements. Nevertheless, any evaluation of an adenoma should still include testing for plasma free metanephrines to rule out pheochromocytoma.
 
Insert image


* CT scan with enhancement demonstrating suspicous left adrenal mass.  See corresponding MIBG scan above.  Source: Wikipedia
* CT scan with enhancement demonstrating suspicious left adrenal mass.  See corresponding MIBG scan above.  Source: Wikipedia


=== Other ===
=== Other ===
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** There is no level 1 evidence exists regarding optimal preoperative or perioperative management
** There is no level 1 evidence exists regarding optimal preoperative or perioperative management


=== '''General principles (4):''' ===
=== General principles (4): ===
# '''<span style="color:#ff0000">Pre-operative cardiology or anesthesia consultation because of risk for cardiomyopathy'''
# '''<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.'''
#* '''Preoperative cardiac workup, including electrocardiography and echocardiography, and assessment of hypertension-induced end-organ dysfunction are indicated.'''
# '''<span style="color:#ff0000">Pre-operative medications (α-Blockade followed by β-blockade)'''
# '''<span style="color:#ff0000">Restoration intravascular volume'''
# '''<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'''
# '''<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 ====
==== Pre-operative medications ====
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* '''<span style="color:#ff0000">β-blockade'''
* '''<span style="color:#ff0000">β-blockade'''
** '''Must be given with caution in patients with myocardial depression'''
** '''Must be given with caution in patients with myocardial depression'''
** '''Should never be started before appropriate α-blockade'''
** '''<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.'''
*** '''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">May be added when (2)'''
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** 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.
** 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.
** Usually, preoperative calcium channel blockade for 2 weeks is sufficient.
==== Restoration intravascular volume ====
* '''Most important component of preoperative management'''
* Most centers '''admit patients the day before surgery and initiate aggressive IV fluid resuscitation'''


==== Monitored bed post-operatively ====
==== Monitored bed post-operatively ====
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** '''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'''
** '''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''' ===
=== Post-operative follow-up ===
* '''Repeat metabolic testing should be performed ≈2 weeks after adrenalectomy to document normalization of catecholamine levels'''
* '''<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.
* 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
** Subsequent imaging should be guided by results of biochemical testing
* '''Annual biochemical follow-up is mandatory for all patients with resected pheochromocytoma.'''
* '''<span style="color:#ff0000">Annual biochemical follow-up is mandatory for all patients with resected pheochromocytoma.'''
* '''Lifelong screening for recurrence is recommended'''
* '''<span style="color:#ff0000">Lifelong screening for recurrence is recommended'''
** 10-year recurrence rates are as high as 16%.
** 10-year recurrence rates are as high as 16%.
** No consensus on follow-up protocols exists.
** No consensus on follow-up protocols exists.
* In a patient with pesistent 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.
* 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 Hereditary Pheochromocytoma'''
==== Treatment of Pheochromocytoma in Pregnancy ====
** 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
* 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.
* '''Treatment of Malignant Pheochromocytoma'''
** 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.


== Questions ==
== Questions ==
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