Pheochromocytoma medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Pheochromocytoma}}
{{Pheochromocytoma}}
{{CMG}}; {{AE}} {{AAM}}
{{CMG}}; {{AE}} {{AAM}} {{MAD}}


==Overview==
==Overview==
Treatment with [[alpha blockers]] (example: [[phenoxybenzamine]]) followed by [[beta blockers]] (example: [[atenolol]]) is required before surgery. Adjunctive [[chemotherapy]] and [[radiation]] are used in metastatic disease.
Pharmacological medical therapies for [[pheochromocytoma]] incldue treatment with [[alpha blockers]] (for example, [[phenoxybenzamine]]) followed by [[beta blockers]] (for example, [[atenolol]]) before surgery. Other drugs can be used such as [[Calcium channel blocker|calcium channel blockers]] and [[metyrosine]]. Adjunctive [[chemotherapy]] and [[radiation]] are used in metastatic disease. [[Hypertensive crisis]] can be managed by using [[Sodium nitroprusside|sodium nitroprusside,]] [[phentolamine]] and [[nicardipine]].


==Medical Therapy==
==Medical Therapy==
'''Preoperative medical therapy:'''
Pharmacological medical therapy is recommended in all patients with pheochromocytoma undergoing surgery to control [[hypertension]] and reduce [[morbidity]].


All patients doing surgery need preoperative treatment to control hypertension during surgery and hypotension after it. There are three medical regimens for treatment; Combined alpha and beta-adrenergic blockade, calcium channel blockers, and metyrosine<ref name="pmid14766711">{{cite journal| author=Tauzin-Fin P, Sesay M, Gosse P, Ballanger P| title=Effects of perioperative alpha1 block on haemodynamic control during laparoscopic surgery for phaeochromocytoma. | journal=Br J Anaesth | year= 2004 | volume= 92 | issue= 4 | pages= 512-7 | pmid=14766711 | doi=10.1093/bja/aeh083 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14766711  }}</ref>:
=== Preoperative medical therapy ===
* All patients undergoing surgery need preoperative treatment to control [[hypertension]] during surgery and [[hypotension]] after it.  
* According to Endocrine Society’s 2014 Clinical Practice Guidelines, there are three medical regimens for preoperative management of pheochromocytoma:<ref name="pmid248931352">{{cite journal| author=Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH et al.| title=Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2014 | volume= 99 | issue= 6 | pages= 1915-42 | pmid=24893135 | doi=10.1210/jc.2014-1498 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24893135  }}</ref><ref name="pmid14766711">{{cite journal| author=Tauzin-Fin P, Sesay M, Gosse P, Ballanger P| title=Effects of perioperative alpha1 block on haemodynamic control during laparoscopic surgery for phaeochromocytoma. | journal=Br J Anaesth | year= 2004 | volume= 92 | issue= 4 | pages= 512-7 | pmid=14766711 | doi=10.1093/bja/aeh083 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14766711  }}</ref>
** Combined [[Alpha blocker|alpha]] followed by [[beta-adrenergic blockers]]
** [[Calcium channel blocker|Calcium channel blockers]]
** [[Metyrosine]]


<u>[[alpha blocker|Aalpha adrenoceptor blocker]] ([[phenoxybenzamine]])</u> are used to counteract [[hypertension]] and the beta-1 adrenoceptor antagonist [[atenolol]] to reduce [[cardiac output]]. They can block sudden release of adrenaline during surgery and prevent hypertensive crisis. Patient is ready for surgery in 10 to 14 days after initiation of alpha-adrenergic blockade. Patients should take high sodium diet to antagonize orthostatic hypotension of alpha blockers.After adequate alpha-adrenergic blockade has been achieved, beta-adrenergic blockade is initiated 3 days before surgery. '''Beta-adrenergic blocker should never be started first because unopposed alpha-adrenergic receptor stimulation can lead to brisky increase in blood pressure. It''' should be used with caution due to risk of heart failure, pulmonary edema and asthma.  
==== [[alpha blocker|'''Aalpha adrenoceptor blocker''']] ====
* It is used to counteract [[hypertension]] and the [[Beta blockers|beta-1 adrenoceptor antagonist]] [[atenolol]] to reduce [[cardiac output]]. They can block the sudden release of [[adrenaline]] during surgical stress and prevent [[hypertensive crisis]]. The patient is ready for surgery after 10 to 14 days of initiation of [[Alpha-adrenergic blocking agent|alpha-adrenergic blockade]]. Patients should take high [[sodium]] diet to prevent [[orthostatic hypotension]] due to [[Alpha blocker|alpha blockers]]. After adequate [[Alpha-adrenergic blocker|alpha-adrenergic blockade]] has been achieved, a [[beta-adrenergic blocker]] is initiated 3 days before surgery.
'''[[Beta blockers|Beta-adrenergic blocker]]'''
* It should never be started first because unopposed [[Alpha-adrenergic agonist|alpha-adrenergic]] receptor stimulation can lead to the brisk increase in [[blood pressure]]. It should be used with caution due to the risk of [[heart failure]], [[pulmonary edema]], and [[asthma]].


<u>Second line of treatment is [[calcium channel blocker]]</u> which is used to control blood pressure preoperatively and intravenous injection intraoperatively.
==== [[Calcium channel blocker]] ====
* It is used to control [[blood pressure]] preoperatively and an [[intravenous injection]] is given intraoperatively.
* Its main use is controlling [[blood pressure]] in case of failed [[Alpha blocker|alpha]] and [[beta blockers]] regimen or unaccepted side effects in that regimen.<ref name="pmid15819762">{{cite journal| author=Lebuffe G, Dosseh ED, Tek G, Tytgat H, Moreno S, Tavernier B et al.| title=The effect of calcium channel blockers on outcome following the surgical treatment of phaeochromocytomas and paragangliomas. | journal=Anaesthesia | year= 2005 | volume= 60 | issue= 5 | pages= 439-44 | pmid=15819762 | doi=10.1111/j.1365-2044.2005.04156.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15819762  }}</ref>


Its main use is controlling blood pressure in case of failed alpha and beta blockers regimen or unaccepted side effects in the that regimen.
==== [[Metyrosine]] ====
* It is the last medical line of treatment. It inhibits [[catecholamine]] synthesis.
* It is used in case of failure of other medical lines of treatment or in patients who cannot tolerate them.
* Clinicians use combined treatment in difficult cases and if [[radiofrequency ablation]] for [[metastatic]] foci will be used. [[Metyrosine]] side effects include [[crystalluria|crystalluria,]] [[Extrapyramidal symptom|extrapyramidal]] manifestations, and high cost.<ref name="pmid9129550">{{cite journal| author=Steinsapir J, Carr AA, Prisant LM, Bransome ED| title=Metyrosine and pheochromocytoma. | journal=Arch Intern Med | year= 1997 | volume= 157 | issue= 8 | pages= 901-6 | pmid=9129550 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9129550  }}</ref>


<u>[[Metyrosine]] is the last medical line of treatment</u>. It  inhibits catecholamine synthesis. It is used in case of failure of other medical lines of treatment or in patients who cannot tolerate them. Additionally, clinicans use combined treatment in difficult cases and if radiofrequency ablation for metastatic foci will be used. Metyrosine side effects include: [[crystaluria]] , [[Extrapyramidal symptom|extrapyramidal]] manifestations and high cost.
==== Dosing[[Pheochromocytoma medical therapy#cite note-pmid248931352-2|[2]]] ====
The following dosage regimen may be used:
{| class="wikitable"
!align="center" style="background:#4479BA; color: #FFFFFF;" + |Drug
!align="center" style="background:#4479BA; color: #FFFFFF;" + |Initial dose
!align="center" style="background:#4479BA; color: #FFFFFF;" + |Final dose
|-
|[[Phenoxybenzamine]]  
|10 mg b.i.d.
|1 mg/kg/d
|-
|[[Propranolol]]
|1 20 mg t.i.d.
|40 mg TID
|-
|[[Nifedipine]]                    
|30 mg/d
|60 mg/d
|}


== Surgical therapy ==
== Management of hypertensive crisis ==
* Preferred regimen (1): IV [[Sodium nitroprusside]] 0.3 to 0.5 mcg/kg/minute; maximum dose of 10 mcg/kg/minute for 10 minutes. The rate of a prolonged infusion should be no more than 3 mcg/kg/minute to avoid [[cyanide]] toxicity.
* Preferred regimen (2): IV [[Phentolamine]] ([[Alpha blocker|non-selective alpha-adrenergic]] blocker) 1 to 5 mg bolus; maximum single dose: 15 mg. The response to [[phentolamine]] is maximal in two to three minutes after starting of the initial dose.
* Preferred regimen (3): IV [[Nicardipine]] ([[calcium channel blocker]]) <ref name="pmid12974970">{{cite journal| author=Varon J, Marik PE| title=Clinical review: the management of hypertensive crises. | journal=Crit Care | year= 2003 | volume= 7 | issue= 5 | pages= 374-84 | pmid=12974970 | doi=10.1186/cc2351 | pmc=270718 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12974970  }} </ref>
 
== Management of pheochromocytoma during pregnancy ==
* [[Phenoxybenzamine]] use is safe but [[beta-adrenergic blockers]] use has been associated with [[intrauterine growth retardation]].<ref name="pmid2242456">{{cite journal| author=Butters L, Kennedy S, Rubin PC| title=Atenolol in essential hypertension during pregnancy. | journal=BMJ | year= 1990 | volume= 301 | issue= 6752 | pages= 587-9 | pmid=2242456 | doi= | pmc=1663720 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2242456  }}</ref>
* Resection of the [[tumor]] can often be performed safely during the [[second trimester]].<ref name="pmid18001193">{{cite journal| author=Junglee N, Harries SE, Davies N, Scott-Coombes D, Scanlon MF, Rees DA| title=Pheochromocytoma in Pregnancy: When is Operative Intervention Indicated? | journal=J Womens Health (Larchmt) | year= 2007 | volume= 16 | issue= 9 | pages= 1362-5 | pmid=18001193 | doi=10.1089/jwh.2007.0382 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18001193  }}</ref>
* [[Tumor]] resection can be combined with a cesarean section during [[delivery]].
* Careful monitoring is needed to mother and [[fetus]].
 
== Management of familial pheochromocytoma ==
* Preoperative evaluation should include testing for associated [[Tumor|tumors]].
 
=== [[Medullary thyroid cancer]]: ===
Serum [[calcium]] must be measured to exclude [[medullary thyroid cancer]]. It should be removed first if it is found. [[Thyroidectomy]] is the only way to treat [[Medullary thyroid cancer|medullary thyroid]] related to [[Multiple endocrine neoplasia|MEN]].<ref name="pmid25810047">{{cite journal| author=Wells SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF et al.| title=Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. | journal=Thyroid | year= 2015 | volume= 25 | issue= 6 | pages= 567-610 | pmid=25810047 | doi=10.1089/thy.2014.0335 | pmc=4490627 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25810047  }}</ref> Surgical treatment has low [[morbidity]], even in children. [[Thyroid hormone|Thyroid]] replacement is started directly after surgery.
 
=== '''[[Primary hyperparathyroidism]]:''' ===
* [[Primary hyperparathyroidism]] and pheochromocytoma are features of [[MEN2b|MEN2B]] syndrome.
 
* Asymptomatic patients who do not undergo surgery need follow up only.
 
* If patients are symptomatic, [[hyperparathyroidism]] surgery is the only definitive treatment.<ref name="pmid8957482">{{cite journal| author=Herfarth KK, Bartsch D, Doherty GM, Wells SA, Lairmore TC| title=Surgical management of hyperparathyroidism in patients with multiple endocrine neoplasia type 2A. | journal=Surgery | year= 1996 | volume= 120 | issue= 6 | pages= 966-73; discussion 973-4 | pmid=8957482 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8957482  }}</ref>
* Surgery for pheoochromocytoma should be done first if both pheochromocytoma and [[hyperparathyroidism]] are found together.


'''Adrenalictomy:''' Laparoscopic transabdominal and retroperitoneal approaches have been used successfully for non-metastatic abdominal pheochromocytmas. Complicationa are less in laparoscopic than open surgery. Catecholamine secretion falls to normal level within a week.
* Preoperative localization is preferred by [[CT scan]], [[ultrasound]], and [[sestamibi scan]] (resection of the enlarged glands only is the preferred procedure in this situation).
* Subtotal parathyroidectomy and total parathyroidectomy, carry the risk of [[hypoparathyroidism]].<ref name="pmid258100472">{{cite journal| author=Wells SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF et al.| title=Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. | journal=Thyroid | year= 2015 | volume= 25 | issue= 6 | pages= 567-610 | pmid=25810047 | doi=10.1089/thy.2014.0335 | pmc=4490627 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25810047  }}</ref>
* Complication and recurrence rate is low<ref name="pmid7913027">{{cite journal| author=Wells SA, Donis-Keller H| title=Current perspectives on the diagnosis and management of patients with multiple endocrine neoplasia type 2 syndromes. | journal=Endocrinol Metab Clin North Am | year= 1994 | volume= 23 | issue= 1 | pages= 215-28 | pmid=7913027 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7913027  }}</ref>
* Family members should undergo [[RET gene|RET]] [[mutation]] [[Screening (medicine)|screening]].


Major intraoperative complications include: intraoperative tumor capsule rupture, hypertensive crisis, myocardial infarctions, or cerebrovascular haemorrhages.
== Management of malignant pheochromocytoma ==
* For [[asymptomatic]] patients, follow up is better than intervention due to high risk of complications in surgeries.


Hyperdynamic instability after tumor resection is poosible. Hypoglycemia can occur after tumour resection due to unopposed insulin effect after decline of catecholamines levels.  
* For [[symptomatic]] patients, open procedures are recommended due to large [[tumor]] size and high [[vascularity]]. Primary and [[metastatic]] lesions should be resected if possible.  


'''''Prognosis'''''
=== '''Local therapy''' ===
* Some authors suggest administration of 131-iodine-labeled meta-iodo-benzylguanidine (131I-MIBG) after resection. <ref name="pmid20664475">{{cite journal| author=Chen H, Sippel RS, O'Dorisio MS, Vinik AI, Lloyd RV, Pacak K et al.| title=The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. | journal=Pancreas | year= 2010 | volume= 39 | issue= 6 | pages= 775-83 | pmid=20664475 | doi=10.1097/MPA.0b013e3181ebb4f0 | pmc=3419007 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20664475  }}</ref>
* There are many types of local therapy:
** [[External beam radiotherapy|External beam radiation therapy]] ([[External beam radiation therapy|EBRT]])
** [[Radiofrequency ablation|Radio frequency ablation]]
** [[Cryoablation]]
** [[Ethanol]] injection


Good prognosis pateints include: small tumor size, short duration of surgery, systolic blood pressure less than 160 mmhg, and low levels of urinary catecholamines.Postoperative hypotension can be avoided by adequate fluid replacement. Recurrence is more in patients with familial pheochromocytoma and extraadrenal tumors.
* <u>[[External beam radiotherapy|External beam radiation therapy]] (EBRT</u>)  can relieve symptoms and decrease pain in non-resectable cases. It may induce massive [[catecholamine]] secretion and a [[hypertensive crisis]]. All of them need preoperative medical management to decrease chances of [[hypertensive crisis]].
* Other ablation procedures ([[radiofrequency ablation]], [[cryoablation]], or [[ethanol]] injection) are based on the lesion target location; [[head]], [[neck]], [[thorax]] or [[retroperitoneal]].
* [[Liver]] [[Tumor|tumors]] are treated with either [[Radiofrequency ablation|radioferequency ablation]], [[ethanol]] injection or [[Chemoembolization|transarterial chemoembolization]]. These procedures may be used in patients with multiple [[liver]] [[metastases]].
* [[Percutaneous]] [[tumor]] [[ablation]] is limited to patients with one or a few small tumors.<ref name="pmid16543673">{{cite journal| author=Watanabe D, Tanabe A, Naruse M, Tsuiki M, Torii N, Noshiro T et al.| title=Transcatheter arterial embolization for the treatment of liver metastases in a patient with malignant pheochromocytoma. | journal=Endocr J | year= 2006 | volume= 53 | issue= 1 | pages= 59-66 | pmid=16543673 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16543673  }}</ref>


Familial pheochromocytoma  have a high incidence of bilateral disease. partial adrenalectomy is recommended for these patients with bilateral pheochromocytomas to prevent permanent glucocorticoid deficiency. Complete bilateral adrenalectomy is recommended for MEN2 patients. There is highrt rate of reccurence than in sporadic cases. Follow up for long duration after surgery is needed. Most patients should have annual biochemical screening.
=== '''Systemic therapy''' ===


neck paragangliomas may be in the carotid sheath or in the carotid body and thus require proximal and distal vascular control for resection. Preoperative embolization may simplify carotid body tumor resection and reduce blood loss [24]. Most chest paragangliomas require a median sternotomy and may involve the heart and great vessels with cardiac bypass, although videoscopic removal may be possible in some cases [25].
==== [[Chemotherapy]] ====
* [[Metastasis|Metastatic]] pheochromocytoma is treated with Averbuc protocol, which is a combination of [[cyclophosphamide]], [[vincristine]], [[dacarbazine]] and [[doxorubicin]].<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq#link/_179_toc</ref>
* For patients with rapidly progressive [[tumors]] or [[bone]]-predominant extensive disease, [[chemotherapy]] is a preferred option even if 123I-[[Scintigraphy|MIBG scintigraphy]] is positive.
* [[Chemotherapy]] should be considered for patients with unresectable and rapidly growing pheochromocytoma and a large number of [[metastases]].
* The median duration of response is 20 months with median survival of 3.3 years.<ref name="pmid18780317">{{cite journal| author=Huang H, Abraham J, Hung E, Averbuch S, Merino M, Steinberg SM et al.| title=Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients. | journal=Cancer | year= 2008 | volume= 113 | issue= 8 | pages= 2020-8 | pmid=18780317 | doi=10.1002/cncr.23812 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18780317  }}</ref>
* Most common side effects are [[gastrointestinal]] upset, [[peripheral neuropathy]] and [[bone marrow suppression]].<ref name="pmid3395037">{{cite journal| author=Averbuch SD, Steakley CS, Young RC, Gelmann EP, Goldstein DS, Stull R et al.| title=Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. | journal=Ann Intern Med | year= 1988 | volume= 109 | issue= 4 | pages= 267-73 | pmid=3395037 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3395037  }}</ref>


== Management of hypertensive crisis ==
==== '''[[Molecule|Molecular Therapy]]''' ====
* Sodium nitroprusside is the first line of treatment  because of its rapid onset of action and short duration of effect. The rate of a prolonged infusion should be no more than 3 mcg/kg per minute to avoid cyanide toxicity.
* [[Sunitinib]] is a [[tyrosine kinase]] receptor inhibitor and [[VEGF receptors|vascular endothelial growth factor receptors inhibitor]].
* Phentolamine is nonselective alpha-adrenergic blocker. The response to phentolamine is maximal in two to three minutes after starting of initial dose.
* Nicardipine is calcium channel blocker and the last line of treatment after failure of previous two lines.


===Chemotherapy===
* [[Pazopanib]] is [[Tyrosine kinase inhibitors|tyrosine kinase receptors inhibitor]].
Metastatic pheochromocytoma is treated with Averbuc protocol which is a combination of [[cyclophosphamide]], [[vincristine]], and [[dacarbazine]].<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq#link/_179_toc</ref>


===Radiation===
==== [[Radiation therapy]] ====
<sup>131</sup>I-MIBG radiation therapy has been used for the treatment of MIBG-avid metastases.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq#link/_179_toc</ref>
* <sup>131</sup>I-MIBG [[radiation therapy]] may be used for the treatment of MIBG-avid [[metastases]].<ref name="cancergov" />
* Patients with a good uptake of <sup>131</sup>I-MIBG in cases of unresectable progressive pheochromocytoma lead to a lower number of [[metastases]]. Therapy can be repeated for recurrent cases.<ref name="pmid11453952">{{cite journal| author=Mukherjee JJ, Kaltsas GA, Islam N, Plowman PN, Foley R, Hikmat J et al.| title=Treatment of metastatic carcinoid tumours, phaeochromocytoma, paraganglioma and medullary carcinoma of the thyroid with (131)I-meta-iodobenzylguanidine [(131)I-mIBG]. | journal=Clin Endocrinol (Oxf) | year= 2001 | volume= 55 | issue= 1 | pages= 47-60 | pmid=11453952 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11453952  }}</ref>
* High doses show serious side effects including, [[leukopenia]], [[thrombocytopenia]] due to [[Bone marrow suppression|bone marrow depression]], [[hypothyroidism]] and [[acute leukemia]].<ref name="pmid23860527">{{cite journal| author=Sze WC, Grossman AB, Goddard I, Amendra D, Shieh SC, Plowman PN et al.| title=Sequelae and survivorship in patients treated with (131)I-MIBG therapy. | journal=Br J Cancer | year= 2013 | volume= 109 | issue= 3 | pages= 565-72 | pmid=23860527 | doi=10.1038/bjc.2013.365 | pmc=3738119 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23860527  }}</ref><ref name="pmid22221516">{{cite journal| author=Gulenchyn KY, Yao X, Asa SL, Singh S, Law C| title=Radionuclide therapy in neuroendocrine tumours: a systematic review. | journal=Clin Oncol (R Coll Radiol) | year= 2012 | volume= 24 | issue= 4 | pages= 294-308 | pmid=22221516 | doi=10.1016/j.clon.2011.12.003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22221516  }}</ref>
* Pheochromocytomas express [[somatostatin receptors]]. Patients with [[metastatic]] or recurrent pheochromocytoma may benefit from [[Radiolabel|radiolabeled]] [[somatostatin]] analogs.<ref name="pmid19140390">{{cite journal| author=Hubalewska-Dydejczyk A, Trofimiuk M, Sowa-Staszczak A, Gilis-Januszewska A, Wierzchowski W, Pach D et al.| title=[Somatostatin receptors expression (SSTR1-SSTR5) in pheochromocytomas]. | journal=Przegl Lek | year= 2008 | volume= 65 | issue= 9 | pages= 405-7 | pmid=19140390 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19140390  }}</ref>Long-term potential side effects of therapy with [[Radiolabel|radiolabeled]] [[somatostatin]] analogs may include loss of [[renal]] function, [[pancytopenia]], and [[myelodysplastic syndrome]].<ref name="pmid22221516" />


===Contraindicated medications===
===Contraindicated medications===

Latest revision as of 00:29, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2] Mohammed Abdelwahed M.D[3]

Overview

Pharmacological medical therapies for pheochromocytoma incldue treatment with alpha blockers (for example, phenoxybenzamine) followed by beta blockers (for example, atenolol) before surgery. Other drugs can be used such as calcium channel blockers and metyrosine. Adjunctive chemotherapy and radiation are used in metastatic disease. Hypertensive crisis can be managed by using sodium nitroprusside, phentolamine and nicardipine.

Medical Therapy

Pharmacological medical therapy is recommended in all patients with pheochromocytoma undergoing surgery to control hypertension and reduce morbidity.

Preoperative medical therapy

Aalpha adrenoceptor blocker

Beta-adrenergic blocker

Calcium channel blocker

Metyrosine

Dosing[2]

The following dosage regimen may be used:

Drug Initial dose Final dose
Phenoxybenzamine 10 mg b.i.d. 1 mg/kg/d
Propranolol 1 20 mg t.i.d. 40 mg TID
Nifedipine 30 mg/d 60 mg/d

Management of hypertensive crisis

Management of pheochromocytoma during pregnancy

Management of familial pheochromocytoma

  • Preoperative evaluation should include testing for associated tumors.

Medullary thyroid cancer:

Serum calcium must be measured to exclude medullary thyroid cancer. It should be removed first if it is found. Thyroidectomy is the only way to treat medullary thyroid related to MEN.[8] Surgical treatment has low morbidity, even in children. Thyroid replacement is started directly after surgery.

Primary hyperparathyroidism:

  • Asymptomatic patients who do not undergo surgery need follow up only.
  • If patients are symptomatic, hyperparathyroidism surgery is the only definitive treatment.[9]
  • Surgery for pheoochromocytoma should be done first if both pheochromocytoma and hyperparathyroidism are found together.

Management of malignant pheochromocytoma

  • For asymptomatic patients, follow up is better than intervention due to high risk of complications in surgeries.

Local therapy

Systemic therapy

Chemotherapy

Molecular Therapy

Radiation therapy

Contraindicated medications

Pheochromocytoma is considered an absolute contraindication to the use of the following medications:

References

  1. ↑ Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH; et al. (2014). "Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline". J Clin Endocrinol Metab. 99 (6): 1915–42. doi:10.1210/jc.2014-1498. PMID 24893135.
  2. ↑ Tauzin-Fin P, Sesay M, Gosse P, Ballanger P (2004). "Effects of perioperative alpha1 block on haemodynamic control during laparoscopic surgery for phaeochromocytoma". Br J Anaesth. 92 (4): 512–7. doi:10.1093/bja/aeh083. PMID 14766711.
  3. ↑ Lebuffe G, Dosseh ED, Tek G, Tytgat H, Moreno S, Tavernier B; et al. (2005). "The effect of calcium channel blockers on outcome following the surgical treatment of phaeochromocytomas and paragangliomas". Anaesthesia. 60 (5): 439–44. doi:10.1111/j.1365-2044.2005.04156.x. PMID 15819762.
  4. ↑ Steinsapir J, Carr AA, Prisant LM, Bransome ED (1997). "Metyrosine and pheochromocytoma". Arch Intern Med. 157 (8): 901–6. PMID 9129550.
  5. ↑ Varon J, Marik PE (2003). "Clinical review: the management of hypertensive crises". Crit Care. 7 (5): 374–84. doi:10.1186/cc2351. PMC 270718. PMID 12974970.
  6. ↑ Butters L, Kennedy S, Rubin PC (1990). "Atenolol in essential hypertension during pregnancy". BMJ. 301 (6752): 587–9. PMC 1663720. PMID 2242456.
  7. ↑ Junglee N, Harries SE, Davies N, Scott-Coombes D, Scanlon MF, Rees DA (2007). "Pheochromocytoma in Pregnancy: When is Operative Intervention Indicated?". J Womens Health (Larchmt). 16 (9): 1362–5. doi:10.1089/jwh.2007.0382. PMID 18001193.
  8. ↑ Wells SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF; et al. (2015). "Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma". Thyroid. 25 (6): 567–610. doi:10.1089/thy.2014.0335. PMC 4490627. PMID 25810047.
  9. ↑ Herfarth KK, Bartsch D, Doherty GM, Wells SA, Lairmore TC (1996). "Surgical management of hyperparathyroidism in patients with multiple endocrine neoplasia type 2A". Surgery. 120 (6): 966–73, discussion 973-4. PMID 8957482.
  10. ↑ Wells SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF; et al. (2015). "Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma". Thyroid. 25 (6): 567–610. doi:10.1089/thy.2014.0335. PMC 4490627. PMID 25810047.
  11. ↑ Wells SA, Donis-Keller H (1994). "Current perspectives on the diagnosis and management of patients with multiple endocrine neoplasia type 2 syndromes". Endocrinol Metab Clin North Am. 23 (1): 215–28. PMID 7913027.
  12. ↑ Chen H, Sippel RS, O'Dorisio MS, Vinik AI, Lloyd RV, Pacak K; et al. (2010). "The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer". Pancreas. 39 (6): 775–83. doi:10.1097/MPA.0b013e3181ebb4f0. PMC 3419007. PMID 20664475.
  13. ↑ Watanabe D, Tanabe A, Naruse M, Tsuiki M, Torii N, Noshiro T; et al. (2006). "Transcatheter arterial embolization for the treatment of liver metastases in a patient with malignant pheochromocytoma". Endocr J. 53 (1): 59–66. PMID 16543673.
  14. ↑ 14.0 14.1 National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq#link/_179_toc
  15. ↑ Huang H, Abraham J, Hung E, Averbuch S, Merino M, Steinberg SM; et al. (2008). "Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients". Cancer. 113 (8): 2020–8. doi:10.1002/cncr.23812. PMID 18780317.
  16. ↑ Averbuch SD, Steakley CS, Young RC, Gelmann EP, Goldstein DS, Stull R; et al. (1988). "Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine". Ann Intern Med. 109 (4): 267–73. PMID 3395037.
  17. ↑ Mukherjee JJ, Kaltsas GA, Islam N, Plowman PN, Foley R, Hikmat J; et al. (2001). "Treatment of metastatic carcinoid tumours, phaeochromocytoma, paraganglioma and medullary carcinoma of the thyroid with (131)I-meta-iodobenzylguanidine [(131)I-mIBG]". Clin Endocrinol (Oxf). 55 (1): 47–60. PMID 11453952.
  18. ↑ Sze WC, Grossman AB, Goddard I, Amendra D, Shieh SC, Plowman PN; et al. (2013). "Sequelae and survivorship in patients treated with (131)I-MIBG therapy". Br J Cancer. 109 (3): 565–72. doi:10.1038/bjc.2013.365. PMC 3738119. PMID 23860527.
  19. ↑ 19.0 19.1 Gulenchyn KY, Yao X, Asa SL, Singh S, Law C (2012). "Radionuclide therapy in neuroendocrine tumours: a systematic review". Clin Oncol (R Coll Radiol). 24 (4): 294–308. doi:10.1016/j.clon.2011.12.003. PMID 22221516.
  20. ↑ Hubalewska-Dydejczyk A, Trofimiuk M, Sowa-Staszczak A, Gilis-Januszewska A, Wierzchowski W, Pach D; et al. (2008). "[Somatostatin receptors expression (SSTR1-SSTR5) in pheochromocytomas]". Przegl Lek. 65 (9): 405–7. PMID 19140390.

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