Systematic review of phaeochromocytoma in pregnancy

Systematic review

Systematic review of phaeochromocytoma in pregnancy M. A. Biggar1,3 and T. W. J. Lennard1,2 1

Department of Endocrine Surgery, Royal Victoria Infirmary, and 2 Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK, and Department of Surgery, Middlemore Hospital, Counties Manukau District Health Board, Otahuhu, Auckland, New Zealand Correspondence to: Professor T. W. J. Lennard, 3rd Floor Leech Building, The Medical School, Newcastle University, Newcastle upon Tyne NE1 7RU, UK (e-mail: [email protected])

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Background: Phaeochromocytoma in pregnancy is a rare and potentially dangerous situation for mother and fetus. This review aimed to assess current mortality rates and how medical and surgical management affect these. Methods: Articles in English published between 2000 and 2011 were obtained from a MEDLINE search. Eligible publications presented women diagnosed with phaeochromocytoma in the antenatal or immediate postnatal period, and reported management and outcomes. Results: A total of 135 reports were identified. After applying inclusion criteria, 77 pregnancies involving 78 fetuses were analysed. Fetal and maternal mortality rates were 17 per cent (13 of 78) and 8 per cent (6 of 77) respectively. Better outcomes were achieved when the diagnosis of phaeochromocytoma was made in the antenatal period than when it was made during labour or immediately postpartum (survival of both mother and fetus(es) in 48 of 56 versus 12 of 21 respectively; P = 0·012). When the diagnosis was made before 23 weeks’ gestation, there was no difference in outcomes when phaeochromocytoma surgery was carried out in the second trimester, compared with when it was postponed to the third trimester or after delivery (fetal death 2 of 18 versus 2 of 8 respectively; P = 0·563). Conclusion: This review, although limited by the rarity of the condition and level of available evidence, demonstrated that survival rates are improved if the diagnosis of phaeochromocytoma can be established antenatally. With diagnosis before 23 weeks’ gestation, no definite advantage of proceeding with tumour removal during the second trimester could be demonstrated.

Paper accepted 14 September 2012 Published online in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.8976

Introduction

Phaeochromocytoma during pregnancy is rare, occurring in 0·007 per cent of pregnancies1 . Women with phaeochromocytoma in pregnancy may present with nonspecific symptoms and the diagnosis may be difficult to make before a crisis occurs or labour begins. Unfortunately, many presenting features can be attributed to other common disturbances in pregnancy such as hyperemesis, thyrotoxicosis, gestational diabetes, a threatened miscarriage or pre-eclampsia, making early diagnosis difficult. Failure to diagnose this condition or suboptimal management can be disastrous for mother and/or fetus, owing to the effects of raised catecholamine levels. Although the fetus is shielded from the direct effects of high circulating levels of catecholamines by enzymatic metabolism within the placenta2 , effective control of maternal hypertension  2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd

is important for fetal viability, as hypertension may lead to uteroplacental insufficiency or placental abruption and fetal demise3,4 . Medical management with alpha-blockers requires a balance of maintaining sufficient uterine perfusion yet treating hypertension5 , whereas surgery to excise the tumour risks precipitating spontaneous abortion or premature labour. Case reports and limited series with their inherent limitations are the only sources of information on which to base best practice. Up to the 1970s, maternal and fetal mortality rates were reported to be 12–18 and 40–50 per cent respectively6,7 , but increased to 48 and 54 per cent if the diagnosis of phaeochromocytoma was not made before delivery7 . Operative resection was recommended during pregnancy if the diagnosis of phaeochromocytoma could be made in the first or second trimester, but resulted in maternal mortality rates of 20 per cent and fetal loss in up to 67 per cent6 . British Journal of Surgery 2013; 100: 182–190

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Diagnosis in the third trimester dictated a combined procedure of delivery and tumour excision, or delayed tumour excision following delivery, resulting in no maternal deaths but fetal mortality rates of 15–17 per cent6 . Preoperative alpha-blockade was recommended, and demonstrated to decrease the fetal mortality rate to zero when instigated in women diagnosed in the third trimester and to 17 per cent in those diagnosed at an earlier stage6 . By the late 1990s, the overall maternal mortality rate had reduced to 4 per cent and the fetal loss rate to 11 per cent8 . Antenatal diagnosis was associated with a reduced maternal mortality rate of 0–2 per cent, but with rates of fetal loss remaining significant at 11–15 per cent8,9 . The primary aim of this review of women with phaeochromocytoma during pregnancy was to assess maternal and fetal mortality rates in the 21st century. Secondary aims were to evaluate how modes of presentation, medical and surgical management affect survival outcomes, particularly in light of the increasing experience with laparoscopic surgery in the modern era.

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postpartum, as it was evident that in such patients the management of the pregnancy and the phaeochromocytoma were unaffected by each other. Assessment of study quality or bias was not formally undertaken owing to the case-based nature of the included studies. Primary outcome measures – maternal and fetal mortality rates – were calculated. Secondary outcomes were mortality rates in the following subgroups: antenatal versus postnatal diagnosis of phaeochromocytoma; and, in the group of patients diagnosed before 23 weeks’ gestation, surgery of phaeochromocytoma during pregnancy in the second trimester versus non-operative management. Where possible, this article followed the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement guidelines10 .

Statistical analysis Survival statistics were compared by two-tailed Fisher’s exact test, generated using GraphPad QuickCalcs (GraphPad Software, La Jolla, California, USA). The significance level was set at P = 0·050.

Methods

A systematic review of English language articles identified using MEDLINE and the search terms ‘(phaeochromocytoma or pheochromocytoma) and (pregnancy or pregnant)’, which were published during the period 2000–2011, was undertaken in February 2012. Reference lists were checked for possible additional articles. Published data were extracted by one author using a pro forma of predefined data fields: maternal age, pregnancy trimester at time of presentation and diagnosis, investigations used to secure the diagnosis and locate the phaeochromocytoma(s), location of the lesion(s), methods of medical management, gestational age at time of delivery (or fetal demise), timing and method of tumour removal and delivery, fetal and maternal outcomes, and the reporting of maternal genetic abnormalities. Articles were included if they contained the description of pregnancy in association with phaeochromocytoma in the same woman. Studies without original patient data, such as reviews, letters and basic science articles, were excluded. Patients were excluded if the information provided was insufficiently detailed (defined as the inability to ascertain all of the following: method of delivery, timing of phaeochromocytoma surgery, fetal survival and maternal outcome) or unable to be accessed. Reports were screened for duplication and duplicated data were excluded. Following data extraction, the above protocol was amended also to exclude patients in whom the diagnosis or presentation of phaeochromocytoma occurred more than 1 month  2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd

Results

Of 135 available reports, 74 were excluded (Fig. 1) because of inability to access full text, no case was reported, insufficient case details, patient duplication or the presentation/diagnosis of phaeochromocytoma was more than 1 month postpartum. The remaining suitable reports contained 77 women with phaeochromocytoma during pregnancy, involving 78 fetuses. Data are summarized in Tables 1 and 2, and are available in full as an electronic supplementary file (Table S1, supporting information)5,11 – 70 .

Presentation and investigation The median maternal age at the time of presentation was 29 (range 18–40) years. Women most commonly presented with a combination of hypertension, palpitations, chest pain, sweating, abdominal pain and nausea. One woman presented with a spontaneous abortion63 . The majority of women experienced presenting symptoms during the second (25, 32 per cent) or third (32, 42 per cent) trimester of pregnancy. The diagnosis was made during pregnancy in most women, but in the immediate postpartum period in approximately onefifth – typically as a result of complications that manifested during labour or delivery. In a minority of women the diagnosis was made only after intrauterine fetal death (3) or death of the mother (3). www.bjs.co.uk

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Potentially relevant reports identified and screened for retrieval n = 135

Reports retrieved for more detailed evaluation n = 108

Potentially appropriate reports to be included in the analysis n = 78

Reports excluded n = 27 Basic science article only; no case(s) n = 17 Inability to access full text n = 10

Reports excluded n = 30 Review only; no case reported n = 22 Did not include phaeochromocytoma and pregnancy coinciding in the same patient n = 8

Reports excluded from analysis n = 10 Insufficient case detail n = 5 Patient duplication n = 5

Reports included in analysis n = 68

Reports with usable information, by outcome n = 61 Fig. 1

Reports withdrawn n = 7 Diagnosis or presentation of phaeochromocytoma > 1 month postpartum n = 7

Selection of articles for review

Biochemical investigations used to secure the diagnosis of phaeochromocytoma involved measurement of urinary or plasma catecholamines and/or their metabolites. Imaging modalities employed during pregnancy included magnetic resonance imaging (MRI), ultrasound scan or both. Computed tomography (CT) was used only occasionally during pregnancy. CT and/or metaiodobenzylguanidine (MIBG) functional imaging studies were added postpartum in seven women. Of the case reports that employed imaging solely postpartum (or following intrauterine fetal demise) (16 patients), CT and/or MIBG imaging were used in ten women in addition to ultrasound examination and/or MRI. Phaeochromocytoma occurred predominantly in the adrenal (47 women), with adjacent neurofibroma in one patient41 , and was bilateral in 11 patients. Extra-adrenal lesions occurred in 14 women and one had multiple extraadrenal lesions. The overall rate of multiple tumours was 18 per cent (13 of 72).

Management Alpha-adrenergic blocking agents were commonly used following diagnosis (phenoxybenzamine 40, prazosin 8, doxazocin 7). Beta-blockers were added in some patients (atenolol 10, labetalol 10, propranolol 8, metoprolol 5). The use of other agents during surgery – such as magnesium sulphate or sodium nitroprusside – was noted  2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd

in some reports; however, reporting was too inconsistent to ascertain the prevalence of their use. Of the 56 women in whom a diagnosis of phaeochromocytoma was made antenatally (while the pregnancy was still viable and had not progressed to labour), surgery to remove the phaeochromocytoma was undertaken during pregnancy in 18, concurrently with subsequent delivery in 17 and in the postpartum period in 18. The group of 18 women who underwent resectional surgery during pregnancy represented a majority of the 27 women presenting with a viable pregnancy who had not yet reached 23 weeks’ gestation. All 18 underwent surgery during the second trimester (range 13–23 weeks) by various approaches, which were described in 14 patients – laparoscopic (6), open (6), retroperitoneal endoscopic (1) and laparoscopic–robotic (1). In the remaining 21 women, the diagnosis of phaeochromocytoma was made in the immediate postnatal period or after fetal demise. In this group, in surviving mothers, the lesion was removed after an interval of 2–8 weeks following delivery (or fetal demise). The preferred method of delivery in the presence of a known phaeochromocytoma was by caesarean section – in all but three women.

Outcomes Overall 64 (83 per cent) of the 77 pregnancies resulted in the successful birth and survival of all offspring. When www.bjs.co.uk

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Summary of reported data on phaeochromocytoma in pregnancy

Table 1

n Reports identified Patients/pregnancies Fetuses Features at presentation (n = 72) Hypertension Hypertensive crisis Timing of phaeochromocytoma diagnosis (n = 77) Antenatal Postnatal Postmortem or after fetal demise Biochemical investigations (n = 68) Urinary Plasma Both Imaging modalities used during pregnancy (n = 47) MRI Ultrasonography Both MRI and ultrasonography Computed tomography + one of the above Location of lesion (n = 72) Right adrenal Left adrenal Bilateral adrenal Extra-adrenal Medical management (n = 63) Alpha-blocker(s) Beta-blocker(s) Method of delivery (n = 68)* Caesarean section Vaginal delivery Surgical management of catecholamine-producing lesion(s) with antenatal diagnosis (n = 56) Excision during pregnancy Excision concurrently with delivery Excision after delivery Excision after fetal death Excision after elective termination Lesion not resectable Genetic susceptibility identification (n = 29) MEN2A MEN2B VHL SDHB

61 77 78 49 (68) 11 (15) 56 (73) 15 (19) 6 (8) 39 (57) 2 (3) 21 (31) 17 (36) 12 (26) 14 (30) 4 (9) 29 (40) 18 (25) 11 (15) 14 (19) 57 (90) 33 (52) 52 (76) 16 (24)

18 (32) 17 (30) 18 (32) 1 (2) 1 (2) 1 (2) 9 (31) 1 (3) 8 (28) 5 (17)

Values in parentheses are percentages. *Not applicable in nine patients owing to termination or fetal death. MRI, magnetic resonance imaging; MEN, multiple endocrine neoplasia; VHL, von Hippel–Lindau syndrome; SDHB, succinate dehydrogenase subunit B mutation. Table 2

considering the 78 fetuses involved in these 77 pregnancies, the fetal mortality rate was 17 per cent (13 of 78). One fetal loss resulted from an early elective termination of a pregnancy in the first trimester (maternal choice), after a diagnosis of phaeochromocytoma had been made as part of screening investigations in a family with a genetic mutation58 . Other reasons for pregnancies not resulting in healthy babies were: death in utero (8), death in the immediate postpartum period (2) and death with the mother (2). The overall maternal mortality rate was 8 per cent (6 of 77). In two women an emergency caesarean section was able to save the baby, before the death of the mother50,70 ; in a third the mother died 2 days after vaginal delivery of a viable pregnancy25 . In two other women, maternal and fetal death occurred simultaneously following presentation in crisis, before any attempt at delivery could be undertaken15,53 . In the remaining woman, both mother and fetus died 3 days after caesarean section39 . There was a difference in fetal and maternal outcomes depending on whether the diagnosis of phaeochromocytoma was established antenatally. More successful outcomes (both mothers and fetus(es) surviving) occurred in the antenatal diagnosis group, compared with the delayed diagnosis group (48 of 56 versus 12 of 21 respectively; P = 0·012). Considering maternal mortality alone, all mothers survived when the diagnosis was made antenatally (56 patients), compared with a substantial maternal mortality rate (6 of 21) when it was not (P < 0·001). In the group of women presenting with hypertensive crisis, the maternal death rate was especially high (6 of 11 women) and accounted for all the maternal deaths in this series. These were accompanied by a lesser, but noteworthy, fetal mortality rate (3 of 11). Comparing women presenting with hypertensive crisis versus no hypertensive crisis, differences in maternal death rates reached statistical significance (6 of 11 versus 0 of 66; P < 0·001) whereas fetal death rates did not (3 of 11 versus 11 of 67; P = 0·405). There was no change in the significance level of comparative statistics when outcomes were recalculated after exclusion of the women with elective termination of a pregnancy in the first trimester (data not shown).

Fetal and maternal outcomes

Fetal death Maternal death Successful outcome of pregnancy (mother and fetus(es) survived)

Overall

When antenatal diagnosis made

When antenatal diagnosis not possible

P*

13 of 78 (17) 6 of 77 (8) 61 of 77 (79)

7 of 57 (12) 0 of 56 (0) 48 of 56 (86)

6 of 21 (29) 6 of 21 (29) 12 of 21 (57)

0·100 < 0·001 0·012

Values in parentheses are percentages. *Antenatal versus postnatal diagnosis (two-tailed Fisher’s exact test).

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In the group of 27 women in whom the diagnosis was made antenatally and before 23 weeks’ gestation, 22 pregnancies reached a successful outcome. Eighteen of the 27 women underwent surgical excision of the phaeochromocytoma during pregnancy, two of whom subsequently suffered fetal death in utero. Two of the 18 women had an unrecognized additional phaeochromocytoma: one woman underwent bilateral adrenalectomy for bilateral phaeochromocytoma in the 23rd week of pregnancy, experienced intrauterine death of a singleton fetus 3 days after surgery and subsequently a third intrathoracic phaeochromocytoma was found59 ; another woman underwent right adrenalectomy during pregnancy but an additional left phaeochromocytoma was discovered postpartum on CT16 . One woman underwent an elective termination in the first trimester58 . Of the remaining eight women, two experienced intrauterine death of the fetus54,60 . More successful pregnancy outcomes were observed when resection was undertaken during pregnancy than when a medical management approach was adopted with delayed surgery (2 of 18 versus 2 of 8); however, numbers were small and of no statistical significance (P = 0·563).

Genetics and tumour biology Twenty-three (30 per cent) of the 77 mothers were reported to have a genetic mutation. Six case reports stated specifically that genetic testing was undertaken and was negative. Of the remainder, genetic testing was either not carried out (2), or no information was provided with regard to the issue of genetic predisposition (46). Only one woman had a malignant phaeochromocytoma; she died from metastatic disease 1 year postpartum33,34 . Discussion

The overall fetal and maternal mortality rates in this review of phaeochromocytoma in pregnancy were 17 and 8 per cent respectively. Mortality rates – which had been declining towards the end of the 20th century owing to improved diagnosis and awareness – have now plateaued or even increased slightly. This trend parallels antenatal diagnosis rates, which peaked between 1969 and 1997 at 83 per cent, but over the past two decades decreased to levels of 66–70 per cent8,71 ; the rate was 73 per cent in the present review. Consistent with historical data, best outcomes in this review were associated with antenatal diagnosis, such that the maternal mortality rate was zero. A high index of suspicion for phaeochromocytoma is required when encountering hypertension in the first trimester that is labile or paroxysmal, associated with  2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd

M. A. Biggar and T. W. J. Lennard

other symptoms, or resistant to conventional antihypertensive treatment. Hypertension accompanied by proteinuria, liver enzyme derangement or low platelet counts is more likely to represent pre-eclampsia than phaeochromocytoma. A less common presentation is an acute hypertensive crisis associated with cardiorespiratory failure, which occurs in 7–11 per cent of the general population72,73 , but notably occurred with greater frequency (15 per cent) in this review of pregnant patients. An asymptomatic phaeochromocytoma may become symptomatic in pregnancy owing to increases in intra-abdominal pressure, mechanical effects of a gravid uterus, uterine contractions, haemorrhage into the tumour, the stresses associated with labour or even vigorous fetal movements24,54 . In pregnancy, women presenting in crisis rarely attain sufficient stability to gain a prenatal diagnosis, and the mortality risk to mother and fetus is greatest. The diagnosis is made when a single or multiple mass(es) producing excess catecholamines is demonstrated. Raised levels of catecholamines and their metabolites are found in the blood or urine. In normal pregnancy, or classical pregnancy-induced hypertension, plasma catecholamine levels do not increase74 ; however, rare exceptions have been reported in pre-eclampsia3,75 . CT and MIBG scintigraphy are the most sensitive and specific modalities for identifying the underlying lesion(s), but are contraindicated in pregnancy. Ultrasonography has good sensitivity in the first trimester, but is often unreliable in later pregnancy when fundal height interferes with visibility71 . MRI is considered safe in pregnancy and is an effective means of imaging the adrenal glands, but is less reliable for imaging extra-adrenal tumours. The rate of extra-adrenal and bilateral tumours in this review is higher than in the general population76,77 , but might be expected with the higher prevalence of genetic predisposition syndromes in this young patient group. Optimal localization methods used for identifying extraadrenal lesions (MIBG scintigraphy and CT) should be used postpartum to ensure that all tumours are identified. The most accepted medical management is alphablockade, phenoxybenzamine being the most frequently used agent, to control hypertension. Although this drug has been shown to cross the placenta28,78 , it has been used successfully in pregnancy. The safety of beta-blockers in pregnancy is more controversial, as a causative link with intrauterine growth retardation has been suggested79 . However, short-term use is accepted to control tachycardia after alpha-blockade has been established. The issue of whether these pharmacological agents can be used safely for a prolonged period, spanning all three trimesters, is contentious. Prolonged medical treatment www.bjs.co.uk

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when phaeochromocytoma is diagnosed before 23 weeks’ gestation is not well supported by experiences published in the medical literature. Three of the eight patients in whom this ‘waiting’ strategy was applied in the present series had adverse outcomes: two women experienced intrauterine death of the fetus during the ‘waiting’ period54,59 , and a third woman developed metastatic disease33,34 . Although the development of metastatic disease may not have been prevented had the phaeochromocytoma been excised sooner, certainly caution is warranted. The complications that can accompany prolonged medical treatment may be more a consequence of the natural history of phaeochromocytoma rather than the effects of the blocking agents on the fetus per se. It must also be noted that the reported numbers are few and significant publication or selection bias may be present, in so far as patients considered high risk might have been managed medically, with the explicit aim of avoiding surgery. Of the 13 women diagnosed in the latter part of the second trimester (between 23 and 27 weeks) and managed medically, only two experienced adverse outcomes (intrauterine death of one twin5 and one infant death at 3 days postpartum64 ). Currently, there is a widespread recommendation that, when phaeochromocytoma is diagnosed before 23 weeks’ gestation, excision should generally be undertaken during pregnancy, particularly in the laparoscopic era when this can be performed with lower morbidity than with conventional open surgery. Catecholamine release and haemodynamic stability during surgery for phaeochromocytoma has been demonstrated to be more favourable with a laparoscopic rather than an open approach80 and would therefore be expected to be safer for the fetus. Although surgery during pregnancy can have an adverse impact on the fetus, experience from other laparoscopic procedures during pregnancy, such as cholecystectomy or appendicectomy, demonstrates that the second trimester is the safest time, with rates of fetal demise or subsequent labour in the order of 5 per cent in the elective setting. Reports from this review indicate favourable outcomes: of 18 excisions performed during pregnancy, 16 resulted in a healthy mother and baby. Beyond 23 weeks, the uterine fundal size is likely to restrict access and therefore preclude surgery, particularly with the laparoscopic technique81 . The approach in this setting is to treat the patient medically and await fetal maturity, with an aim of delivering the baby in the final trimester followed by phaeochromocytoma excision. Ultimately, the well-being of the fetus and the success of medical management of the mother’s blood pressure are deciding factors in determining the timing of delivery. Intrauterine growth

retardation, decreased fetal movements, decelerations on fetal cardiac monitoring, persistent labile hypertension in the mother or the strong suspicion of malignant phaeochromocytoma are indications for early delivery. Surgery for the phaeochromocytoma if blockade is completed may be either concurrent with the caesarean section or delayed by 2–6 weeks. The advantages of the delayed strategy are that a MIBG scan can be performed postpartum to confirm localization and rule out a second lesion, haemodynamic changes of pregnancy can resolve and blockade can be completed if time since diagnosis has been short. The traditional dictum that vaginal delivery is a contraindication in the presence of phaeochromocytoma is based largely on high mortality outcomes resulting from labour in the setting of a previously undiagnosed phaeochromocytoma. However, effective alpha-blockade has been shown to allow a safe vaginal delivery in some women, particularly the multiparous woman, who is likely to have a quick and uncomplicated labour42,71 . However, most authors agree that a caesarean section is a more controlled process for delivery and is therefore advocated71 . Particular care must be taken to consider the possibility of multiple lesions in this young patient group and therefore to confirm physiological catecholamine secretion after excision of the tumour(s). Failure to perform this may risk a further lesion coming to light subsequently, as occurred in two patients in the present review16,59 . Genetic predisposition testing is also imperative in this young patient population with offspring. Up to 24 per cent of patients with phaeochromocytoma carry a germline mutation77 . In the present review, 30 per cent of women had an identified genetic susceptibility to phaeochromocytoma; however, it is likely that the true figure is higher than this, as many reports did not specifically mention whether genetic testing was undertaken. The higher than expected incidence of extraadrenal tumours in the present review supports this77 . This review is based on retrospective data from case reports, with a risk of both publication and reporting bias (not all studies reported all results). However, because of the rarity of this condition, it is unlikely that randomized conditions would ever be possible and power calculations to test a null hypothesis are unlikely to be practicable. Therefore, a systematic accumulation of experience is likely to remain the only guide for clinicians making decisions when phaeochromocytoma and pregnancy coincide. The corollary of this is that reporting of individual patients should continue, so that at least publication bias can be minimized in future analyses. Phaeochromocytoma in pregnancy is a potentially dangerous clinical scenario for mother and fetus. When the

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diagnosis can be made antenatally and before the development of advanced cardiorespiratory compromise and before labour, maternal outcomes are uniformly good and risks to the fetus can be minimized. The diagnosis may be delayed or missed when presenting features such as hypertension occur, owing to other more common differentials in pregnancy. Pregnancy limits the ability to perform complete imaging, leading to the possibility that small extra-adrenal or multiple tumours may be missed. This is of importance in this young patient population, which may harbour a higher rate of genetic susceptibility mutations, with a resulting tendency for increased rates of bilateral and extra-adrenal tumours. Current experience suggests that removal of the phaeochromocytoma in a timely fashion following diagnosis leads to best outcomes. In the era of laparoscopic surgery, this can generally be achieved safely even during pregnancy if the diagnosis and necessary preparations can be made before 23 weeks’ gestation. If the diagnosis is made after 23 weeks, medical management as a bridge to surgery should continue until the later stages of pregnancy when fetal maturity is reached and the delivery can be undertaken in a controlled and planned fashion with subsequent removal of the phaeochromocytoma.

Disclosure

The authors declare no conflict of interest.

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Supporting information

Additional supporting information may be found in the online version of this article: Table S1 Summary of case reports of phaeochromocytoma in pregnancy (Word document)

 2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd

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British Journal of Surgery 2013; 100: 182–190