Case Study Asian Cardiovascular & Thoracic Annals 21(4) 464–466 ß The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492312456979 aan.sagepub.com
Tetralogy of Fallot with pheochromocytoma: An unusual therapeutic challenge Gautam Balakrishnan1, Ratnagiri Ravikumar2, Suresh Rao3 and Komarakshi R Balakrishnan4
Abstract An adult with unoperated tetralogy of Fallot diagnosed simultaneously with pheochromocytoma is extremely rare. This poses obvious diagnostic and therapeutic challenges. A 29-year-old woman with these conditions was successfully operated on for both diseases in the same hospitalization. There is some interesting speculation regarding the association of pheochromocytoma with uncorrected cyanotic congenital heart disease.
Keywords Adrenal gland neoplasms, heart defects, congenital, pheochromocytoma, tetralogy of Fallot
Introduction An extremely rare case of an adult preenting simultaneously with uncorrected Tetralogy of fallot (TOF) and pheochromocytoma, posing several challenges in management, was successfully operated on for both conditions during the same hospital admission.
Case report A bedridden 29-year-old woman presented with breathlessness on minimal exertion and dizziness. Her hemoglobin was 16 gdL 1 with oxygen saturation of 68% and blood pressure of 140/90 mmHg. Echocardiographic and hemodynamic evaluations revealed TOF with severe infundibular, valvar and supravalvar stenosis, a narrow pulmonary annulus, and no major aortopulmonary collaterals needing intervention. The gradient across the right ventricular outflow tract was 90 mmHg. A computed tomography angiogram showed multiple thrombi in the right pulmonary artery (Figure 1). A surprise finding was a right adrenal mass measuring 4 5 3 cm, accidentally discovered during the computed tomography angiogram, and subsequently confirmed to be a pheochromocytoma by raised urine metanephrine levels of 3.3 mg in 24 h (normal < 1 mg) and histopathology (Figure 2). There was no evidence of metastatic disease.
Adrenalectomy was performed first after careful preoperative preparation for a week. The aim was to achieve adequate adrenergic receptor blockade and optimization of the intravascular volume which is shrunk in pheochromocytoma due to excessive catecholamine release. The chances of blood pressure fluctuations during adrenalectomy were thus minimized. Phenoxybenzamine 20 mg and metoprolol 25 mg daily in divided doses were used, closely monitoring the SPO2 because vasodilators can lower systemic vascular resistance, and consequently SPO2 in TOF. Hypertensive surges due to tumor manipulation during surgery were controlled with sodium nitroprusside. Fluid infusion and a phenylephrine bolus were used to treat postexcision hypotension. The critical aspect of anesthetic care was to maintain the physiology to which the patient had become accustomed, keeping the SPO2 at approximately 70%, and not make any attempt to 1
Department Department 3 Department 4 Department India 2
of of of of
Internal Medicine, Fortis Malar Hospital, Chennai, India Cardiology, Fortis Malar Hospital, Chennai, India Anesthesia, Fortis Malar Hospital, Chennai, India Cardiothoracic Surgery, Fortis Malar Hospital, Chennai,
Corresponding author: Komarakshi R Balakrishnan, MD, Fortis Malar Hospital, First Main Road, Gandhi Nagar Adyar, Chennai 600020, India. Email: [email protected]
Balakrishnan et al.
Figure 1. Thrombi in the lobar and segmental branches of the right pulmonary artery (RPA).
increase it. TOF was repaired after 5 days. An atrialpulmonary approach was used with limited muscle resection and right ventricular outflow tract reconstruction using a transannular pericardial patch, extending a few mm into the right ventricle. Post-repair right ventricular systolic pressure was 32 mmHg for a systemic pressure of 110 mmHg, so no attempt was made to tackle the thrombi in the right pulmonary artery. The patient made an uncomplicated recovery, and remained well 18 months later.
Discussion There are several points of interest here. Pheochromocytoma was diagnosed incidentally and not due to specific symptoms. These patients have predominant vasoconstriction. Adults with TOF are vasodilated due to numerous aortopulmonary collaterals. Thus features of pheochromocytoma-like flushing and episodic hypertension were probably masked by the intense cyanosis and vasodilatation of TOF. Competing peripheral vascular tone in this patient made the management particularly challenging. Her relative anemia was most probably due to repeated phlebotomies to maintain the hemoglobin at a predetermined level, although dietary factors also may be contributory. Iron deficiency is known to be associated with an increased risk of stroke in cyanotic adults, and perhaps may be relevant to the pulmonary artery thrombus in this patient.1 We debated the best way to manage this challenging situation. The option of doing both procedures in the same sitting was discarded because we felt it was dangerous to perform a laparotomy followed by full body
465
Figure 2. Polygonal cells arranged in distinctive cell balls (zellballen) separated by fibrovascular stroma, typical of pheochromocytoma. Hematoxylin and eosin stain, original magnification 100.
heparinization for the TOF repair. Repair of TOF first was not considered because surges of high blood pressure and catecholamine release due to adrenal manipulation may be poorly tolerated in the vulnerable postoperative period. We believe this is the first report of surgery for pheochromocytoma and TOF repair in the same hospitalization. Of the 2 other patients reported, one presented with pheochromocytoma 20 years after repair of TOF, and the other had only a palliative shunt as a child and the TOF was uncorrected at the time of adrenelectomy.2 Neural crest cells contribute to the formation of the outflow tracts of the heart and the adrenal medulla. It is speculated that the chronic hypoxia due to longstanding cyanotic congenital heart disease stimulates catecholamine release from the adrenal medulla and this endocrine hyperactivity leads to hyperplasia and the development of pheochromocytoma.3 Interestingly, the rat pheochromocytoma cell line, PC12, is also known as a representative ‘‘oxygen-sensing’’ cell that can adapt to hypoxia.4 Mutations in the neurofibromatosis type 1 gene may induce the formation of tumors of neural crest origin in humans and mice, especially pheochromocytoma.5 Homozygosity for the neurofibromatosis type 1 mutation can lead to cardiac malformation in mice. These results suggest the existence of some as yet unclear relationship between pheochromocytoma and TOF. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement None declared.
466 Acknowledgment We acknowledge the contributions of Drs S Mahadevan, N Kapadia, S Choudhry and Vijit Cherian, and Lister Metropolis.
References 1. Ammash N and Warnes CA. Cerebrovascular events in adult patients with cyanotic congenital heart disease. J Am Coll Cardiol 1996; 28: 768–772. 2. Kita T, Imamura T, Date H, Kitamura K, Moriguchi S, Sato Y, et al. Two cases of pheochromocytoma associated with tetralogy of Fallot. Hypertens Res 2003; 26: 433–437.
Asian Cardiovascular & Thoracic Annals 21(4) 3. de la Monte SM, Hutchins GM and Moore GW. Peripheral neuroblastic tumors and congenital heart disease: possible role of hypoxic states in tumor induction. Am J Pediatr Hematol Oncol 1985; 7: 109–116. 4. Seta KA, Spicer Z, Yuan Y, Lu G and Millhorn DE. Responding to hypoxia: lessons from a model cell line [Review]. Sci STKE 2002; 2002: RE11. 5. Jacks T, Shih TS, Schmitt EM, Bronson RT, Bernards A and Weinberg RA. Tumor predisposition in mice heterozygous for a targeted mutation in NF1. Nat Genet 1994; 7: 353–361.
Tetralogy of Fallot with pheochromocytoma: An unusual therapeutic challenge Gautam Balakrishnan1, Ratnagiri Ravikumar2, Suresh Rao3 and Komarakshi R Balakrishnan4
Abstract An adult with unoperated tetralogy of Fallot diagnosed simultaneously with pheochromocytoma is extremely rare. This poses obvious diagnostic and therapeutic challenges. A 29-year-old woman with these conditions was successfully operated on for both diseases in the same hospitalization. There is some interesting speculation regarding the association of pheochromocytoma with uncorrected cyanotic congenital heart disease.
Keywords Adrenal gland neoplasms, heart defects, congenital, pheochromocytoma, tetralogy of Fallot
Introduction An extremely rare case of an adult preenting simultaneously with uncorrected Tetralogy of fallot (TOF) and pheochromocytoma, posing several challenges in management, was successfully operated on for both conditions during the same hospital admission.
Case report A bedridden 29-year-old woman presented with breathlessness on minimal exertion and dizziness. Her hemoglobin was 16 gdL 1 with oxygen saturation of 68% and blood pressure of 140/90 mmHg. Echocardiographic and hemodynamic evaluations revealed TOF with severe infundibular, valvar and supravalvar stenosis, a narrow pulmonary annulus, and no major aortopulmonary collaterals needing intervention. The gradient across the right ventricular outflow tract was 90 mmHg. A computed tomography angiogram showed multiple thrombi in the right pulmonary artery (Figure 1). A surprise finding was a right adrenal mass measuring 4 5 3 cm, accidentally discovered during the computed tomography angiogram, and subsequently confirmed to be a pheochromocytoma by raised urine metanephrine levels of 3.3 mg in 24 h (normal < 1 mg) and histopathology (Figure 2). There was no evidence of metastatic disease.
Adrenalectomy was performed first after careful preoperative preparation for a week. The aim was to achieve adequate adrenergic receptor blockade and optimization of the intravascular volume which is shrunk in pheochromocytoma due to excessive catecholamine release. The chances of blood pressure fluctuations during adrenalectomy were thus minimized. Phenoxybenzamine 20 mg and metoprolol 25 mg daily in divided doses were used, closely monitoring the SPO2 because vasodilators can lower systemic vascular resistance, and consequently SPO2 in TOF. Hypertensive surges due to tumor manipulation during surgery were controlled with sodium nitroprusside. Fluid infusion and a phenylephrine bolus were used to treat postexcision hypotension. The critical aspect of anesthetic care was to maintain the physiology to which the patient had become accustomed, keeping the SPO2 at approximately 70%, and not make any attempt to 1
Department Department 3 Department 4 Department India 2
of of of of
Internal Medicine, Fortis Malar Hospital, Chennai, India Cardiology, Fortis Malar Hospital, Chennai, India Anesthesia, Fortis Malar Hospital, Chennai, India Cardiothoracic Surgery, Fortis Malar Hospital, Chennai,
Corresponding author: Komarakshi R Balakrishnan, MD, Fortis Malar Hospital, First Main Road, Gandhi Nagar Adyar, Chennai 600020, India. Email: [email protected]
Balakrishnan et al.
Figure 1. Thrombi in the lobar and segmental branches of the right pulmonary artery (RPA).
increase it. TOF was repaired after 5 days. An atrialpulmonary approach was used with limited muscle resection and right ventricular outflow tract reconstruction using a transannular pericardial patch, extending a few mm into the right ventricle. Post-repair right ventricular systolic pressure was 32 mmHg for a systemic pressure of 110 mmHg, so no attempt was made to tackle the thrombi in the right pulmonary artery. The patient made an uncomplicated recovery, and remained well 18 months later.
Discussion There are several points of interest here. Pheochromocytoma was diagnosed incidentally and not due to specific symptoms. These patients have predominant vasoconstriction. Adults with TOF are vasodilated due to numerous aortopulmonary collaterals. Thus features of pheochromocytoma-like flushing and episodic hypertension were probably masked by the intense cyanosis and vasodilatation of TOF. Competing peripheral vascular tone in this patient made the management particularly challenging. Her relative anemia was most probably due to repeated phlebotomies to maintain the hemoglobin at a predetermined level, although dietary factors also may be contributory. Iron deficiency is known to be associated with an increased risk of stroke in cyanotic adults, and perhaps may be relevant to the pulmonary artery thrombus in this patient.1 We debated the best way to manage this challenging situation. The option of doing both procedures in the same sitting was discarded because we felt it was dangerous to perform a laparotomy followed by full body
465
Figure 2. Polygonal cells arranged in distinctive cell balls (zellballen) separated by fibrovascular stroma, typical of pheochromocytoma. Hematoxylin and eosin stain, original magnification 100.
heparinization for the TOF repair. Repair of TOF first was not considered because surges of high blood pressure and catecholamine release due to adrenal manipulation may be poorly tolerated in the vulnerable postoperative period. We believe this is the first report of surgery for pheochromocytoma and TOF repair in the same hospitalization. Of the 2 other patients reported, one presented with pheochromocytoma 20 years after repair of TOF, and the other had only a palliative shunt as a child and the TOF was uncorrected at the time of adrenelectomy.2 Neural crest cells contribute to the formation of the outflow tracts of the heart and the adrenal medulla. It is speculated that the chronic hypoxia due to longstanding cyanotic congenital heart disease stimulates catecholamine release from the adrenal medulla and this endocrine hyperactivity leads to hyperplasia and the development of pheochromocytoma.3 Interestingly, the rat pheochromocytoma cell line, PC12, is also known as a representative ‘‘oxygen-sensing’’ cell that can adapt to hypoxia.4 Mutations in the neurofibromatosis type 1 gene may induce the formation of tumors of neural crest origin in humans and mice, especially pheochromocytoma.5 Homozygosity for the neurofibromatosis type 1 mutation can lead to cardiac malformation in mice. These results suggest the existence of some as yet unclear relationship between pheochromocytoma and TOF. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement None declared.
466 Acknowledgment We acknowledge the contributions of Drs S Mahadevan, N Kapadia, S Choudhry and Vijit Cherian, and Lister Metropolis.
References 1. Ammash N and Warnes CA. Cerebrovascular events in adult patients with cyanotic congenital heart disease. J Am Coll Cardiol 1996; 28: 768–772. 2. Kita T, Imamura T, Date H, Kitamura K, Moriguchi S, Sato Y, et al. Two cases of pheochromocytoma associated with tetralogy of Fallot. Hypertens Res 2003; 26: 433–437.
Asian Cardiovascular & Thoracic Annals 21(4) 3. de la Monte SM, Hutchins GM and Moore GW. Peripheral neuroblastic tumors and congenital heart disease: possible role of hypoxic states in tumor induction. Am J Pediatr Hematol Oncol 1985; 7: 109–116. 4. Seta KA, Spicer Z, Yuan Y, Lu G and Millhorn DE. Responding to hypoxia: lessons from a model cell line [Review]. Sci STKE 2002; 2002: RE11. 5. Jacks T, Shih TS, Schmitt EM, Bronson RT, Bernards A and Weinberg RA. Tumor predisposition in mice heterozygous for a targeted mutation in NF1. Nat Genet 1994; 7: 353–361.
