Pheochromocytoma medical therapy
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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]
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.
Medical Therapy
Preoperative medical therapy:
All patients going to 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[1]:
- Aalpha adrenoceptor blocker (phenoxybenzamine) 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.
- Second line of treatment is calcium channel blocker which is used to control blood pressure preoperatively and intravenous injection intraoperatively.
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 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. Additionally, clinicans use combined treatment in difficult cases and if radiofrequency ablation for metastatic foci will be used. Metyrosine side effects include: crystaluria , extrapyramidal manifestations and high cost.
Management of hypertensive crisis
- 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.
- 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.
Management of familiar pheochromocytoma
- Preoperative evaluation should include testing for associated tumors.
- Medullary thyroid tumor :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.[2]
- Primary hyperparathyroidism is part of MEN2A only:
- Asymptomatic patients who do not undergo surgery and need follow up only.
- If patients are symptomatic, hyperparathyroidism surgery is the only defenetive treatment.[3]
- If both pheochromocytoma and hperparathyroidism are found together, pheochromocytoma surgery should be done first.
- Preoperative localization is preferred by CT, US and sistamibi scan so resection of the enlarged glands only is the preferred procedure in this situation.
- Subtotal parathyroidectomy and total parathyroidectomy,carryrisk of hypoparathyroidism.[4]
- Complication and recurrence rate are low[5]
- family members should undergo RET mutation screening.
Management of malignant pheochromocyotma
- Asymptomatic patients, follow up is better than intervention due to high risk of complications in surgeries.
- Symptomatic patients Open procedures are recommended [34] [35] due to large tumor size and high vascularity. Primary and metastatic lesions should be resected if possible.[30]
Local therapy
- Some authors suggest administration of 131-iodine-labeled meta-iodobenzylguanidine (131I-MIBG) after resection [36]. [4,18].
- There are many types of local therapy: external beam radiation therapy (EBRT), radio frequency ablation, , cryoablation, or ethanol injection.
- External beam radiation therapy (EBRT) can relieve symptoms and decrease pain in non resectable cases. It can induce massive catecholamine secretion and a hypertensive crisis [39]. All of them need preoperative medical management to decrease chances of hypertensive crisis .
- Other ablation procedure (RFA, cryoablation, or ethanol injection) was based upon the lesion target location; head, neck ,thorax or retroperitoneal.
- Liver tumors were treated with either RFA or ethanol injection or transarterial chemoembolization for liver For patients with multiple liver metastases is available option for patients not fit for surgeries.
- Percutaneous tumor ablation is limited to patients with one or a few small tumors. 47-51
Systemic therapy
Chemotherapy
- Metastatic pheochromocytoma is treated with Averbuc protocol which is a combination of cyclophosphamide, vincristine, dacarbazine.[6] and doxorubicin.
- For patients with rapidly progressive tumors or bone-predominant extensive disease, chemotherapy is a preferred option even if 123I-MIBG scintigraphy is positive [4].
- Chemotherapy should be considered for patients with unresectable and rapidly growing pheochromocytoma and large number of metastases.
- [9,86-88].
- The median duration of response was 20 months with median survival 3.3 years [87].
- Most common side effects are GIT upset, peripheral neuropathy and BM supression.[89].
- Molecularly therapy: sunitinib and pazopanib are tyrosine kinase receptors inhibitor, vascular endothelial growth factor receptors (VEGFRs)
Radiation
- 131I-MIBG radiation therapy has been used for the treatment of MIBG-avid metastases;[6] patients with good uptake of 123I-MIBG Unresectable progressive pheochromocytoma and low number of metastases. Therapy can be repeated for recuurent cases. [36]. [63].
- High doses show serious side effects include: leukopenia, thrombocytopenia due to bone marrow depression and hypothyroidism.[60,66,67] and acute leukemia [65,67].
- Pheochromocytomas express somatostatin receptors patients with metastatic or recurrent pheochromocytoma may benefit from
- radiolabeled somatostatin analogs.68-71] Long-term potential side effects of therapy with radiolabeled somatostatin analogs may include loss of renal function, pancytopenia, and myelodysplastic syndrome [66].
Contraindicated medications
Pheochromocytoma is considered an absolute contraindication to the use of the following medications:
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 6.0 6.1 National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq#link/_179_toc