Pheochromocytoma medical therapy: Difference between revisions

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__NOTOC__
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{{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]]


Any surgical option requires prior treatment with both the non-selective [[alpha blocker|alpha adrenoceptor blocker]] ([[phenoxybenzamine]]) to counteract [[hypertension]] and the beta-1 adrenoceptor antagonist [[atenolol]] to reduce [[cardiac output]]. Given before surgery, these can also block the effect of a sudden release of adrenaline during tumour resection, which would otherwise endanger the anaesthetised patient.
==== [[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]].


Medical preparation for surgery — No universally accepted method of preparation for surgery in children with pheochromocytomas has been established. In our practice we generally use alpha-adrenergic blockade with phenoxybenzamine(Dibenzyline)  [10]. some clinicians may choose to a selective alpha-1 antagonist (eg, doxazosin, terazosin, prazosin).
==== [[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>


On the second or third day of alpha-adrenergic blockade, patients are encouraged to start a diet high in sodium content because of the catecholamine-induced volume contraction and the orthostasis associated with alpha-adrenergic blockade.
==== [[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>


After adequate alpha-adrenergic blockade has been achieved, beta-adrenergic blockade is initiated, which typically occurs two to three days preoperatively. The beta-adrenergic blocker should never be started first, because blockade of vasodilatory peripheral beta-adrenergic receptors with unopposed alpha-adrenergic receptor stimulation can lead to a further elevation in blood pressure. The clinician should exercise caution if the patient is asthmatic or has heart failure. Chronic catecholamine excess can produce a cardiomyopathy that may become evident with the initiation of beta-adrenergic blockade, resulting in acute pulmonary edema. Therefore, when the beta-adrenergic blocker is administered, it should be used cautiously and at a low dose. The dose is then increased as necessary to control the tachycardia. the patient is ready for surgery in 10 to 14 days after starting the alpha-adrenergic blockade.
==== 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
|}


administration of a calcium channel blocker for blood pressure control 64,65
== 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>


most clinicians reserve metyrosine primarily for patients who cannot be treated with the combined alpha and beta-adrenergic blockade protocol because of intolerance or cardiopulmonary concerns.  The use of metyrosine has also become more problematic because of increases in cost.
== 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]].


===Chemotherapy===
== Management of familial pheochromocytoma ==
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>
* Preoperative evaluation should include testing for associated [[Tumor|tumors]].  


===Radiation===
=== [[Medullary thyroid cancer]]: ===
<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>
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.
 
* 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]].
 
== Management of malignant pheochromocytoma ==
* For [[asymptomatic]] patients, follow up is better than intervention due to high risk of complications in surgeries.
 
* For [[symptomatic]] patients, open procedures are recommended due to large [[tumor]] size and high [[vascularity]]. Primary and [[metastatic]] lesions should be resected if possible.
 
=== '''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
 
* <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>
 
=== '''Systemic therapy''' ===
 
==== [[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>
 
==== '''[[Molecule|Molecular Therapy]]''' ====
* [[Sunitinib]] is a [[tyrosine kinase]] receptor inhibitor and [[VEGF receptors|vascular endothelial growth factor receptors inhibitor]].
 
* [[Pazopanib]] is [[Tyrosine kinase inhibitors|tyrosine kinase receptors inhibitor]].
 
==== [[Radiation therapy]] ====
* <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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