You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
in the pediatric population , the reported incidence of pheochromocytoma ( pheo ) is as high 
 as 0.3 per million per year ( 1 ) .
, 56% of patients with sporadic 
 pheo who are less than 18 yr of age have germline dna mutations ( 1 ) . genes thought to be associated with pheos include the 
 ret proto - oncogene , vhl ( von hippel - lindau ) , 
 nf1 ( neurofibromin 1 ) , sdhb ( succinate dehydrogenase 
 complex subunit b ) , sdhd ( succinate dehydrogenase complex subunit d ) , 
 sdhaf2 ( succinate dehydrogenase complex assembly factor 2 ) , 
 tmem127 ( transmembrane protein 127 ) , max ( myc - associated 
 factor x ) , phd2 ( prolyl hydroxylase 2 ) , h - ras ( harvey rat 
 sarcoma viral oncogene ) , and hif2a ( hypoxia - inducible factor 2 ) ( 2 , 3 ) .
hypoxia may be a risk factor for pheo along with genetic abnormalities . because the protein 
 products of vhl and sdh mediate the cellular response to 
 hypoxia by activating the hypoxia - inducible factor ( hif ) signaling pathway
, a pseudohypoxic 
 mechanism may underlie pheo ( the pseudohypoxia hypothesis ) ( 2 , 4 ) .
the mapk ( mitogen - activated protein 
 kinase ) and mtor ( mammalian target of rapamycin ) signaling pathways have also been 
 implicated in the development of pheo ( 2 , 4 ) .
although the direct relationship between systemic hypoxia and pheo development is unclear , 
 several cases of pheo in patients with cyanotic congenital heart disease ( cchd ) have been 
 reported ( 5,6,7,8,9,10,11,12,13,14,15,16 ) . according to a recent estimate , patients with cchd have a greater risk of 
 developing pheo or paraganglioma ( odds ratio : 6.0 ) than do those with non - cyanotic 
 congenital heart disease ( odds ratio : 0.9 ) ( 17 ) . in 
 addition , an epidemiologic study reported a relatively high incidence of pheo in people 
 living at high altitudes ( 18 ) .
these findings link 
 cchd and hypoxia with pheo . here , we present a case of pheo and tricuspid atresia ( ta ) that 
 was treated by performing the fontan surgery and that supports a relationship between pheo 
 and systemic hypoxia .
cyanosis was noted 8 h after her birth , at 
 which point her percutaneous oxygen saturation ( spo2 ) level was 80% .
palliative surgery ( the hemi - fontan surgery and 
 pulmonary artery banding ) was performed at osaka university hospital when she was 9 mo of 
 age , but the spo2 level remained around 80% . functional repair ( a modified fontan 
 surgery )
was performed at 2 yr of age , and the spo2 level improved to 9094% . at 
 3 yr of age
thereafter , venovenous shunts gradually developed from the hepatic and innominate veins to 
 the pulmonary vein , and the spo2 level was 8090% at 10 yr and 7 mo of age .
coil 
 embolization of the venovenous shunts was performed twice , at 10 yr and 10 mo of age and 12 
 yr and 10 mo of age , and the spo2 level subsequently improved to 9094% . at 15 yr of age ,
paroxysmal sweating , dizziness , and transient hypertension ( systolic blood 
 pressure : 180 mmhg ) were noted .
examinations showed normal thyroid function , normal plasma 
 renin activity , a normal plasma aldosterone level , and a slightly elevated level of total 
 plasma catecholamines ( 2.1 ng / ml , normal range : 0.150.74 ng / ml ) .
the patient was admitted to osaka university hospital for further evaluation at the age of 
 15 yr and 11 mo . there was no family history of pheo . on examination ,
her height was 161 cm , 
 weight was 56 kg , blood pressure was 122/62 mmhg , pulse rate was 84 beats / min , and 
 spo2 level was 90% ( room air ) .
secondary polycythemia was not detected 
 ( hemoglobin level : 13.2 g / dl ) . during cardiac catheterization and contrast angiography ,
therefore , these procedures were 
 discontinued , and she received continuous infusion of the -blocker phentolamine mesylate 
 ( regitine ) .
laboratory tests performed after cardiac catheterization revealed 
 a highly elevated level of total plasma catecholamines ( 8.0 ng / ml ) .
seven days after cardiac 
 catheterization , the catecholamine levels were as follows : fasting total plasma 
 catecholamines , 2.6 ng / ml ( normal range : 0.150.74 ng / ml ) , noradrenaline ( na ) , 2.6 ng / ml 
 ( normal range : 0.150.74 ng / ml ) , urinary noradrenaline , 1092 g / day ( normal range : 29120 
 g / day ) , and urinary normetanephrine ( nm ) , 3.57 mg / day ( normal range : 0.070.26 mg / day ) . 

abdominal computed tomography revealed a tumor 3.8 cm in diameter in the right adrenal 
 gland ( fig .
( a ) abdominal ct : there is a tumor in the right adrenal gland 
 ( white arrow ) .
( b ) i - mibg scintigraphy : there is marked accumulation of 
 i - mibg in the right adrenal gland ( black arrow ) . ) . because scintigraphy showed marked accumulation of 
 i - metaiodobenzylguanidine in the mass ( fig . 
 1 )
, we diagnosed pheo . to reduce systemic vascular resistance and maintain an 
 appropriate circulating blood volume in preparation for surgery , we gradually terminated 
 -blocker therapy ( carvedilol ) and began -blocker ( doxazosin ) therapy .
total right 
 adrenalectomy was performed after -blocker pretreatment on the 56th d after admission .
her 
 pulse rate before surgery was 6065 beats / min . after resection of the tumor , her blood 
 pressure decreased to 60 mmhg , and the pulse rate increased transiently to 70 beats / min 
 before returning to 6364 beats / min .
after the surgery , catecholamine hypersecretion had ceased , and the blood 
 na and urinary nm levels were 0.13 ng / ml and 0.12 mg / day , respectively .
her pulse rate was 
 60 beats / min on the 80th d after admission , and she was discharged from the hospital on the 
 81st d ( fig .
after diagnosis of pheochromocytoma , -blocker ( carvedilol ) therpay was discontinued , 
 and an -blocker ( doxazosin ) therapy was initiated , with gradual increases in the dose 
 until surgery .
unm : urinary normetanephrine 
 ( mg / day ) , sna : serum noradrenaline ( ng / ml ) . ) . abdominal computed tomography ( ct ) and i- metaiodobenzylguanidine 
 ( mibg ) scintigraphy . ( a ) abdominal ct : there is a tumor in the right adrenal gland 
 ( white arrow ) .
( b ) i - mibg scintigraphy : there is marked accumulation of 
 i - mibg in the right adrenal gland ( black arrow ) .
after diagnosis of pheochromocytoma , -blocker ( carvedilol ) therpay was discontinued , 
 and an -blocker ( doxazosin ) therapy was initiated , with gradual increases in the dose 
 until surgery .
unm : urinary normetanephrine 
 ( mg / day ) , sna : serum noradrenaline ( ng / ml ) .
histological examination of the resected mass showed numerous clear white tumor cells with 
 alveolar structures and abundant blood vessels .
the pheochromocytoma of the adrenal gland 
 scaled score is used to distinguish benign versus malignant neoplasms , and the maximum score 
 is 20 ( appendix )
. the tumor may be benign if the score is below 4 ( 19 ) .
the score of our patient s tumor was 0 , suggesting that it was 
 benign ( fig . 3fig .
( a ) hematoxylin - eosin ( he ) staining ( low 
 power view ) .
( b ) he staining ( high power view ) : there are numerous clear white tumor 
 cells and alveolar structures with abundant blood vessels .
( c ) immunohistochemistry for chromogranin a : the 
 brown staining indicates expression of chromogranin a in the tumor cells . ) .
after informed consent was obtained , genetic testing was performed to detect 
 germline mutations in the ret , vhl , sdhb , 
 sdhd , tmem127 , and max genes via 
 polymerase chain reaction and direct sequencing .
unfortunately , we 
 did not examine mutations in the dna of the tumor cells .
( a ) hematoxylin - eosin ( he ) staining ( low 
 power view ) .
( b ) he staining ( high power view ) : there are numerous clear white tumor 
 cells and alveolar structures with abundant blood vessels .
( c ) immunohistochemistry for chromogranin a : the 
 brown staining indicates expression of chromogranin a in the tumor cells .
we presented a case of pheo and ta treated by performing the fontan surgery . in patients 
 who undergo this procedure ,
venovenous shunts develop in response to the elevated systemic 
 venous pressure and carry blood from the systemic veins to the pulmonary veins via remnant 
 fetal vessels .
the spo2 level is normally above 90% ( 20 ) , and the subnormal level in our patient indicated hypoxia due to cchd 
 and the presence of venovenous shunts .
systemic hypoxia has been linked to pheo by data 
 showing a higher frequency of pheo in patients living at high compared with low altitudes 
 ( 18 ) .
although our patient did not live in a 
 high - altitude area , she had experienced systemic hypoxia since birth owing to cchd .
we 
 searched for previous reports of patients with both cchd and pheo and identified 17 such 
 patients ( table 1table 1case reports of pheochromocytoma with cyanotic congenital heart disease ) ( 5,6,7,8,9,10,11,12,13,14,15,16 ) .
the mean age of these patients at the time of diagnosis of pheo was 24.1 yr , 
 which was younger than the mean age ( 40 yr ) of patients with pheo without other diseases 
 ( 21 ) .
this difference suggests that systemic 
 hypoxia promotes the development of pheo in younger patients .
although the relationship 
 between cchd and pheo remains controversial , our findings suggest a positive 
 association . various genes , including ret , vhl , nf1 , 
 sdhb , sdhd , tmem127 , 
 max and hif2a ,
are thought to be associated with pheo , 
 and most of these genes can be divided into two clusters .
the genes in cluster 1 
 ( vhl , sdhb , sdhd , and 
 hif2a ) encode proteins that mediate oxygen - independent stabilization of 
 hif , while the genes in cluster 2 ( ret , nf1 , 
 tmem127 , and max ) encode proteins associated with 
 receptor tyrosine kinase signaling ( 22 ) .
the hif 
 pathway is a downstream target of proteins encoded by genes in both clusters ( 22 ) , and the blood level of hif1 is high in patients 
 with cchd ( 23 ) .
although we did not measure hif1 
 levels in our patient , it is possible that hypoxia promoted the development of pheo via the 
 hif1 pathway .
diagnosing pheo was difficult 
 for two reasons : 1 ) pheo was not immediately considered when our patient developed 
 paroxysmal sweating and dizziness because she also had cchd , and 2 ) paroxysmal hypertension 
 occurs in only 7% of young patients with pheo , and thus , is uncommon ( 24 ) .
although pheo is rare in children , we need to carefully consider its 
 possible occurrence in patients with cchd .
when hypertension is observed in children with 
 cchd , catecholamine levels should be examined before cardiac catheterization .
pheochromocytoma of the adrenal gland scaled scores are based on 12 criteria as follows : 
 large nests or diffuse growth , 2 points ; central ( middle of the large nests ) or confluent 
 tumor necrosis , 2 points ; high cellularity , 2 points ; cellular monotony , 2 points ; tumor 
 cell spindling , 2 points ; > 3 mitotic figures/10 high power fields , 2 points ; atypical 
 mitotic figure(s ) , 2 points ; extension into adipose tissue , 2 points ; vascular invasion , 1 
 point ; capsular invasion , 1 point ; profound nuclear pleomorphism , 1 point ; and nuclear 
 hyperchromasia , 1 point .
abstract.coincidental cyanotic congenital heart disease and pheochromocytoma is uncommon , although 
 some cases have been reported . 
 we describe a girl aged 15 yr and 11 mo with 
 pheochromocytoma and tricuspid atresia treated by performing the fontan surgery . 
 the 
 patient did not have any specific symptoms of syndrome related to pheochromoytoma or a 
 family history of pheochromocytoma . during cardiac catheterization , 
 her blood pressure 
 increased markedly , and an -blocker was administered . 
 catecholamine hypersecretion was 
 observed in the blood and urine , and abdominal computed tomography revealed a tumor in the 
 right adrenal gland . 
 scintigraphy showed marked accumulation of 
 123i - metaiodobenzylguanidine in the tumor , which led to a diagnosis of 
 pheochromocytoma . 
 we did not detect any germline mutations in the ret , 
 vhl , sdhb , sdhd , 
 tmem127 , or max genes . 
 this patient had experienced 
 mild systemic hypoxia since birth , which may have contributed to the development of 
 pheochromocytoma .