http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2014; 27(18): 1930–1934 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.880883
CASE SERIES
Diagnosis and treatment of pheochromocytoma during pregnancy
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 12/29/14 For personal use only.
Dexin Dong and Hanzhong Li Department of Urology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
Abstract
Keywords
Objective: To investigate the diagnosis and treatment of pheochromocytoma during pregnancy. Materials and methods: The data of four cases of pheochromocytoma was analyzed retrospectively. Their ages were 41, 28, 32 and 30 years old, and the four patients were at 32nd week, 12th week, 14th week and 13th week of gestation. All patients had hypertension during pregnancy, accompanied with headache, dizziness, palpitation and sweating. The 24-h urinary catecholamines (24 h UCA) increased significantly. Ultrasound and MRI confirmed the diagnosis of pheochromocytoma. Results: One case had Cesarean section at 32 weeks of gestation, and a healthy baby girl was delivered smoothly. Laparoscopic resection of the right adrenal pheochromocytoma was performed at the same time, and an adrenal tumor of 7.0 cm was resected successfully. Two cases chose abortion and laparoscopic resection of pheochromocytoma was performed. One case chose abortion and refused further treatment. Histopathology confirmed the diagnosis of pheochromocytoma. Conclusions: For hypertension in pregnant women during pregnancy, typical paroxysmal hypertension accompanied by triad of headache, palpitation and sweating, pheochromocytoma should be considered. Early diagnosis can reduce the maternal and fetal mortality significantly. Second trimester of pregnancy is the ideal time for surgical treatment. Laparoscopic resection of pheochromocytoma during pregnancy is safe and effective.
Gestation, laparoscopy, pheochromocytoma, pregnancy
Introduction Pheochromocytoma is a rare disease with an incidence of 0.5 0.8% and pheochromocytoma during pregnancy is extremely rare [1]. Fewer than 200 cases of pheochromocytoma during pregnancy have been published in the literature. High fetal mortality and high maternal mortality have been reported in association with unrecognized pheochromocytoma [2].
Materials and methods There are four patients in this case series. Their age ranged from 28 to 41, average in 32.75 years old. The four patients were at the gestation of 32 week, 12 week, 14 week and 13 week. All patients had hypertension during pregnancy, accompanied with headache, dizziness, palpitation and sweating. Ultrasound and MRI confirmed the diagnosis of pheochromocytoma. The tumors located in the right adrenal gland in two cases, left adrenal in one case and bilateral adrenal in l case. The tumor diameter ranged from 4.4 to 9.1 cm, with an average of 6.03 cm (Table 1).
Address for correspondence: Hanzhong Li, Department of Urology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China. E-mail: [email protected]
History Received 10 December 2013 Accepted 5 January 2014 Published online 29 January 2014
All patients had routine admissive laboratory tests and adrenal-related endocrinological exams including serum cortisol, ACTH, 24 h UFC, 24 h UCA, rennin, angiotensin and aldosterone in supine and orthostatic position. The patients had ultrasonography and MRI examination. The 24 h UCA increased significantly in four patients.
Results Case 1 had phenoxybenzamine to control blood pressure for 1 month. At 32 weeks of gestation, the fetus had intrauterine hypoxia. Cesarean section was performed under general anesthesia immediately, and a healthy baby girl was delivered smoothly. At the same time, laparoscopic right adrenalectomy was performed successfully and a right adrenal tumor of 7.0 cm was removed completely. Operation time was 90 min, and bleeding was about 200 ml. The blood pressure came to normal, and dizziness, palpitation and sweating disappeared. The patient discharged in 5 days after operation. The pathological result was adrenal pheochromocytoma (Figure 1). Case 2 had phenoxybenzamine and urapidil to control blood pressure. At 13 weeks of gestation, the pregnancy was terminated under intravenous anesthesia. Sodium nitroprusside and urapidil were used to control blood pressure during operation. After adequate drug preparations for 4 weeks,
Pheochromocytoma during pregnancy
14 82 62 Follow up (month)
Operation Intraoperative complication Post-operative complication Pathological result
Termination of pregnancy and induced abortion. Laparoscopic resection of adrenal tumor. No No Adrenal combined pheochromocytoma (pheochromocytoma and ganglioneuroma). 60 Cesarean section, and a healthy baby was delivered. Laparoscopic resection of adrenal tumor. No No Adrenal pheochromocytoma
Termination of pregnancy and induced abortion. Laparoscopic resection of adrenal tumor. No No Adrenal pheochromocytoma.
NE 4696 E 231 DA 1831 Ne 2543 E 145 DA 1409
Tumor location Tumor size (cm)
Endocrine examination Ne [(169 ± 71) nmo1/l], E [(22 ± 13) nmo1/l], DA [(1474 ± 685) nmo1/l] Fetus
Termination of pregnancy and induced abortion. Refuse operation.
NE 251 E 553 DA 1099
Bilateral adrenal Right:4.4 4.1, 5.2 4.3 Left: 9.1 6.0 NE 5475 E 853 DA 711
30 13 + 4 Hypertension during pregnancy, accompanied with headache, dizziness and sweating. Left Adrenal 5.2 4.5 4.2 32 14 + 3 Hypertension during pregnancy and sweating.
28 12 + 4 Hypertension during pregnancy, accompanied with headache, dizziness, palpitation, sweating, nausea and vomiting. Right adrenal 4.8 3.4 3.2 41 32 + 1 Hypertension during pregnancy, accompanied with headache, dizziness, palpitation and sweating. Right adrenal 7.5 5.9 6.1 Patient age (year) Gestation (week + day) Clinical manifestation
Index
Table 1. Clinical data of the four patients.
Case 1
Case 2
Case 3
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 12/29/14 For personal use only.
Case 4
DOI: 10.3109/14767058.2014.880883
1931
laparoscopic right adrenalectomy was performed, and a right adrenal tumor of 4.5 cm was removed completely. Operation time was about 50 min, and the amount of bleeding was about 100 ml. Pathological result was combined pheochromocytoma (pheochromocytoma and ganglioneuroma). Postoperative blood pressure returned to normal, and the patient was discharged in 4 days after operation. Case 3 terminated pregnancy at 15 weeks of gestation under intravenous anesthesia. Intraoperative sodium nitroprusside and urapidil were used to control blood pressure. Octreotide scan confirmed the diagnosis of bilateral adrenal pheochromocytoma. And phenoxybenzamine was taken orally to treat bilateral pheochromocytoma. The patient refused for further treatment and was discharged. Case 4 had phenoxybenzamine to control blood pressure for 4 weeks. At 13 weeks of gestation, the pregnancy was terminated under intravenous anesthesia. Sodium nitroprusside and urapidil were used to control blood pressure during operation. After adequate drug preparations for 4 weeks, laparoscopic left adrenalectomy was performed, and a left adrenal tumor of 5.2 cm was removed completely. Operation time was about 60 min, and the amount of bleeding was about 80 ml. Pathological result was renal pheochromocytoma. Post-operative blood pressure returned to normal, and the patient was discharged in 4 days after operation. Followed up for 14 to 82 months with an average of 54.5 months, the three patients after laparoscopic surgery had normal blood pressure without tumor recurrence. The baby girl delivered by the first patient is healthy. The third patient who refused operation had phenoxybenzamine 5 mg twice a day to keep blood pressure in normal range.
Discussion Pheochromocytoma during pregnancy is clinically rare, with the approximate incidence of 0.007% [3]. Catecholamine secreted by pheochromocytoma can cause severe hypertension or hypertensive crisis, and general antihypertensive drug is difficult to control blood pressure. Drugs can cause great harm to fetus and pregnant women during pregnancy. Antihypertensive drug can cause placental ischemia, placental abruption, intrauterine growth retardation, fetal hypoxia and even fetal death. And uncontrolled hypertension can cause hypertensive crisis, cardiac failure, pulmonary edema, and cerebral and vascular accident [4]. The case 1 had high blood pressure and related symptoms in early stage of pregnancy. Although the diagnosis of pheochromocytoma was made in late pregnancy, fetal hypoxia still occurs. Before 1970, only 25% of pheochromocytoma during pregnancy was diagnosed before birth, and the mortality rates of fetus and maternal women were about 50%. After 1970, the diagnosis rate was 83%, and the mortality rates of fetus and maternal women dropped to 10 and 2%, respectively [5]. According to the published literature, Wolf et al. estimated that the mortality rate of maternal women was 17 to 24%, and the mortality rate of fetus was 50 to 62%. In the cases with timely diagnosis and treatment, the mortality rate of pregnant women dropped to 1 to 5%, and the mortality rate of fetus dropped to 14 to 15%. However, the high maternal
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 12/29/14 For personal use only.
1932
D. Dong & H. Li
J Matern Fetal Neonatal Med, 2014; 27(18): 1930–1934
Figure 1. MRI of the first patient with right adrenal pheochromocytoma in mid-pregnangcy (Arrows show the tumor and the fetus).
catecholamine hyperlipidemia did not have great harm on the fetus [6]. The clinical manifestations of pheochromocytoma during pregnancy had no difference with general pheochromocytoma. The symptoms included paroxysmal or persistent high blood pressure, probably with triad of headaches, palpitations and sweating, even with dizziness, nausea, fatigue, anxiety and other symptoms [7]. These symptoms might be misdiagnosed as gestational hypertension or preeclampsia, and stationary pheochromocytoma without fluctuation of blood pressure is even more difficult for correct diagnosis. The differential diagnosis of pheochromocytoma during pregnancy and pre-eclampsia should be noted: First, the former can occur at any time in pregnancy and before pregnancy. Careful history collection is helpful for diagnosis. The latter occurs after 20 weeks of pregnancy.
Second, the former can be manifested asparoxysmal or persistent hypertension associated with triad of headaches, palpitations and sweating, while the latter is persistent hypertension. Third, the former rarely has proteinuria, while the latter is more likely associated with proteinuria. Fourth, the former hypertension persists after childbirth, while the latter returns to normal blood pressure after childbirth. Therefore, for those who has high blood pressure difficult to control in early pregnancy, and for those who has typical symptoms of paroxysmal headaches, palpitations and sweating, and for those whose symptoms do not disappear after childbirth, pheochromocytoma during pregnancy should be considered. The diagnosis of pheochromocytoma during pregnancy includes qualitative diagnosis and localization diagnosis. The qualitative diagnosis includes the measurement of blood and urine catecholamine and their metabolites.
Pheochromocytoma during pregnancy
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 12/29/14 For personal use only.
DOI: 10.3109/14767058.2014.880883
Under normal circumstances, pregnancy and pre-eclampsia do not affect the concentrations of catecholamine [11]. Twenty-four hour urinary catecholamine was used widely due to the higher sensitivity and specificity. 24-h urinary vanillyl mandelic acid has been replaced by catecholamines because of high false negative rate. The sensitivity of blood norepinephrine is more than 98% [8]. The localization diagnosis includes B-ultrasound, MR and CT. Ultrasound is convenient with no harm to fetus, and is often the first method to discover pheochromocytoma during pregnancy. The disadvantage is poor sensitivity, especially for small adrenal pheochromocytoma and extra-adrenal paraganglioma. CT examination is an important means for diagnosis of pheochromocytoma with high sensitivity. However, the application of CT is limited due to fetal exposure to radiation in pregnancy. MRI examination can avoid possible radiation on fetus, and have high sensitivity and specificity, and it is the best diagnostic method for pheochromocytoma during pregnancy [9]. Nuclear examination such as 131I iodo benzyl guanidine (MIBG) scintigraphy and octreotid are specific and sensitive diagnosis method, but only for those after termination of pregnancy and for those after childbirth. Surgery is the preferred treatment of choice for pheochromocytoma during pregnancy, and adequate preoperative medication is needed. a-receptor blocker is used to control blood pressure and for expansion of blood volume, and phenoxybenzamine, prazosin and similar drugs are safe for pregnant women. b-receptor blocker is used to control fast heart rate, but should be used after oral medication of a-receptor blocker to prevent induced hypertension [9]. The operation time and operation approach for treatment of pheochromocytoma during pregnancy remains controversial. Mid-pregnancy is considered to be an ideal time for surgery, because of the relatively stable period of pregnancy with low incidence of spontaneous abortion. In this period, the fetal organ development has been basically completed, and the uterine size has less impact on surgery [10]. According to literature and our experience, the treatment of pheochromocytoma during pregnancy should be based on different physiological characteristics and functional status of pheochromocytoma. For patients in early pregnancy, a receptor blocker can be used to control blood pressure, and surgery is recommended in mid-pregnancy. For those patients who choose abortion, surgery can be performed after adequate medical preparation. For patients in mid-pregnancy, surgery is recommended after adequate medical preparation. For patients in late pregnancy, oral medication such as a receptor blocker is recommended to control blood pressure. Surgery is recommended after full-term pregnancy, and surgical resection of pheochromocytoma can be performed with childbirth at the same time. Cesarean section is recommended, and it can make the maternal and child mortality rate decrease from 33 to 19% compared with vaginal delivery [10,11]. Laparoscopic surgery during pregnancy is safe and effective. But there are little experience with pheochromocytoma during pregnancy, and there are many concerns. First, pneumoperitoneum might affect the blood supply of uterus. Second, increased abdominal pressure might induce premature. Third, increased abdominal pressure might induce
1933
hypertension. Fourth, hypercapnia might cause fetal acidosis. Fifth, pneumoperitoneum cause fetal hypoxia by decreased cardiac output [12]. Laparoscopic surgery for pheochromocytoma during pregnancy is safe and effective. Laparoscopic surgery for pheochromocytoma during pregnancy was reported in literature [10,13,14]. The first case in our series was performed by laparoscopic resection of pheochromocytoma after childbirth. Laparoscopic surgery for pheochromocytoma during pregnancy has many advantages. Laparoscopic surgery can reduce surgical trauma, blood loss and post-operative analgesic consumption. Laparoscopic surgery can avoid excessive compression of tumors and reduce intraoperative hemodynamic fluctuations. Retroperitoneal laparoscopic surgery can avoid the intraperitoneal interference of the uterus. For skilled laparoscopic surgeons, laparoscopic resection of pheochromocytoma is safe and effective for pregnancy after adequate preparation.
Conclusions For those who has high blood pressure difficult to control in early pregnancy, and for those who has typical symptoms of paroxysmal headaches, palpitations and sweating, and for those whose symptoms do not disappear after childbirth, pheochromocytoma during pregnancy should be considered. Early diagnosis can greatly reduce the maternal and fetal mortality rate. Treatment should be based on the period of pregnancy and functional status of pheochromocytoma. Mid-pregnancy is an ideal time for surgical treatment, and laparoscopic surgery after adequate medical preparation is safe and effective.
Declaration of interest The authors have no conflict of interest to declare.
References 1. Pace DE, Chiasson PM, Schlachta CM, et al. Minimally invasive adrenalectomy for pheochromocytoma during pregnancy. Surg Laparosc Endosc Percutan Tech 2002;12:122–5. 2. Schenker JG, Granat M. Pheochromocytoma and pregnancy: an updated appraisal. Aust N Z J Obstet Gynecol 1982;22:1–10. 3. Mannelli M, Bemporad D. Diagnosis and management of pheochromocytoma during pregnancy. J Endocrinol Invest 2002; 25:567–71. 4. Phupong V, Witoonpanich P, Snabboon T, et al. Bilateral pheochromocytoma during pregnancy. Arch Gynecol Obstet 2005;271:276–9. 5. Ahlawat SK, Jain S, Kumari S, et al. Pheochromocytoma associated with pregnancy: case report and review of the literature. Obstet Gynecol Surv 1999;54:728–37. 6. Moretti A, Minuto M, Berti P, et al. Unusual association of adrenal pheochromocytoma and para-aortic neurofibroma in pregnancy. J Endocrinol Invest 2006;29:738–41. 7. Phoon JW, Kanalingam D, Chua HL. Adrenal tumours in pregnancy: diagnostic challenge and management dilemma. Singapore Med J 2013;54:141–5. 8. Lenders JW, Pacak K, Walther MM, et al. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA 2002;287:1427–34. 9. Grodski S, Jung C, Kertes P, et al. Phaeochromocytoma in pregnancy. Intern Med J 2006;36:604–6. 10. Kim PT, Kreisman SH, Vaughn R, Panton ON. Laparoscopic adrenalectomy for pheochromocytoma in pregnancy. Can J Surg 2006;49:62–3.
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J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 12/29/14 For personal use only.
11. Plu I, Sec I, Barre`s D, Lecomte D. Pregnancy, cesarean, and pheochromocytoma: a case report and literature review. J Forensic Sci 2013;58:1075–9. 12. Haddad S, Al-Raiy B, Madkhali A, et al. Cardiorespiratory crisis at the end of pregnancy: a case of pheochromocytoma. Middle East J Anesthesiol 2013;22:195–202.
J Matern Fetal Neonatal Med, 2014; 27(18): 1930–1934
13. Biggar MA, Lennard TW. Systematic review of pheochromocytoma in pregnancy. Br J Surg 2013;100:182–90. 14. Frayssinet C, Vezzosi D, Huyghe E, et al. Retroperitoneal laparoscopic adrenalectomy in a pregnant woman presenting MEN2a with apheochromocytoma: case report and review of the literature. Ann Endocrinol 2008;69:53–7.
CASE SERIES
Diagnosis and treatment of pheochromocytoma during pregnancy
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 12/29/14 For personal use only.
Dexin Dong and Hanzhong Li Department of Urology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
Abstract
Keywords
Objective: To investigate the diagnosis and treatment of pheochromocytoma during pregnancy. Materials and methods: The data of four cases of pheochromocytoma was analyzed retrospectively. Their ages were 41, 28, 32 and 30 years old, and the four patients were at 32nd week, 12th week, 14th week and 13th week of gestation. All patients had hypertension during pregnancy, accompanied with headache, dizziness, palpitation and sweating. The 24-h urinary catecholamines (24 h UCA) increased significantly. Ultrasound and MRI confirmed the diagnosis of pheochromocytoma. Results: One case had Cesarean section at 32 weeks of gestation, and a healthy baby girl was delivered smoothly. Laparoscopic resection of the right adrenal pheochromocytoma was performed at the same time, and an adrenal tumor of 7.0 cm was resected successfully. Two cases chose abortion and laparoscopic resection of pheochromocytoma was performed. One case chose abortion and refused further treatment. Histopathology confirmed the diagnosis of pheochromocytoma. Conclusions: For hypertension in pregnant women during pregnancy, typical paroxysmal hypertension accompanied by triad of headache, palpitation and sweating, pheochromocytoma should be considered. Early diagnosis can reduce the maternal and fetal mortality significantly. Second trimester of pregnancy is the ideal time for surgical treatment. Laparoscopic resection of pheochromocytoma during pregnancy is safe and effective.
Gestation, laparoscopy, pheochromocytoma, pregnancy
Introduction Pheochromocytoma is a rare disease with an incidence of 0.5 0.8% and pheochromocytoma during pregnancy is extremely rare [1]. Fewer than 200 cases of pheochromocytoma during pregnancy have been published in the literature. High fetal mortality and high maternal mortality have been reported in association with unrecognized pheochromocytoma [2].
Materials and methods There are four patients in this case series. Their age ranged from 28 to 41, average in 32.75 years old. The four patients were at the gestation of 32 week, 12 week, 14 week and 13 week. All patients had hypertension during pregnancy, accompanied with headache, dizziness, palpitation and sweating. Ultrasound and MRI confirmed the diagnosis of pheochromocytoma. The tumors located in the right adrenal gland in two cases, left adrenal in one case and bilateral adrenal in l case. The tumor diameter ranged from 4.4 to 9.1 cm, with an average of 6.03 cm (Table 1).
Address for correspondence: Hanzhong Li, Department of Urology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China. E-mail: [email protected]
History Received 10 December 2013 Accepted 5 January 2014 Published online 29 January 2014
All patients had routine admissive laboratory tests and adrenal-related endocrinological exams including serum cortisol, ACTH, 24 h UFC, 24 h UCA, rennin, angiotensin and aldosterone in supine and orthostatic position. The patients had ultrasonography and MRI examination. The 24 h UCA increased significantly in four patients.
Results Case 1 had phenoxybenzamine to control blood pressure for 1 month. At 32 weeks of gestation, the fetus had intrauterine hypoxia. Cesarean section was performed under general anesthesia immediately, and a healthy baby girl was delivered smoothly. At the same time, laparoscopic right adrenalectomy was performed successfully and a right adrenal tumor of 7.0 cm was removed completely. Operation time was 90 min, and bleeding was about 200 ml. The blood pressure came to normal, and dizziness, palpitation and sweating disappeared. The patient discharged in 5 days after operation. The pathological result was adrenal pheochromocytoma (Figure 1). Case 2 had phenoxybenzamine and urapidil to control blood pressure. At 13 weeks of gestation, the pregnancy was terminated under intravenous anesthesia. Sodium nitroprusside and urapidil were used to control blood pressure during operation. After adequate drug preparations for 4 weeks,
Pheochromocytoma during pregnancy
14 82 62 Follow up (month)
Operation Intraoperative complication Post-operative complication Pathological result
Termination of pregnancy and induced abortion. Laparoscopic resection of adrenal tumor. No No Adrenal combined pheochromocytoma (pheochromocytoma and ganglioneuroma). 60 Cesarean section, and a healthy baby was delivered. Laparoscopic resection of adrenal tumor. No No Adrenal pheochromocytoma
Termination of pregnancy and induced abortion. Laparoscopic resection of adrenal tumor. No No Adrenal pheochromocytoma.
NE 4696 E 231 DA 1831 Ne 2543 E 145 DA 1409
Tumor location Tumor size (cm)
Endocrine examination Ne [(169 ± 71) nmo1/l], E [(22 ± 13) nmo1/l], DA [(1474 ± 685) nmo1/l] Fetus
Termination of pregnancy and induced abortion. Refuse operation.
NE 251 E 553 DA 1099
Bilateral adrenal Right:4.4 4.1, 5.2 4.3 Left: 9.1 6.0 NE 5475 E 853 DA 711
30 13 + 4 Hypertension during pregnancy, accompanied with headache, dizziness and sweating. Left Adrenal 5.2 4.5 4.2 32 14 + 3 Hypertension during pregnancy and sweating.
28 12 + 4 Hypertension during pregnancy, accompanied with headache, dizziness, palpitation, sweating, nausea and vomiting. Right adrenal 4.8 3.4 3.2 41 32 + 1 Hypertension during pregnancy, accompanied with headache, dizziness, palpitation and sweating. Right adrenal 7.5 5.9 6.1 Patient age (year) Gestation (week + day) Clinical manifestation
Index
Table 1. Clinical data of the four patients.
Case 1
Case 2
Case 3
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 12/29/14 For personal use only.
Case 4
DOI: 10.3109/14767058.2014.880883
1931
laparoscopic right adrenalectomy was performed, and a right adrenal tumor of 4.5 cm was removed completely. Operation time was about 50 min, and the amount of bleeding was about 100 ml. Pathological result was combined pheochromocytoma (pheochromocytoma and ganglioneuroma). Postoperative blood pressure returned to normal, and the patient was discharged in 4 days after operation. Case 3 terminated pregnancy at 15 weeks of gestation under intravenous anesthesia. Intraoperative sodium nitroprusside and urapidil were used to control blood pressure. Octreotide scan confirmed the diagnosis of bilateral adrenal pheochromocytoma. And phenoxybenzamine was taken orally to treat bilateral pheochromocytoma. The patient refused for further treatment and was discharged. Case 4 had phenoxybenzamine to control blood pressure for 4 weeks. At 13 weeks of gestation, the pregnancy was terminated under intravenous anesthesia. Sodium nitroprusside and urapidil were used to control blood pressure during operation. After adequate drug preparations for 4 weeks, laparoscopic left adrenalectomy was performed, and a left adrenal tumor of 5.2 cm was removed completely. Operation time was about 60 min, and the amount of bleeding was about 80 ml. Pathological result was renal pheochromocytoma. Post-operative blood pressure returned to normal, and the patient was discharged in 4 days after operation. Followed up for 14 to 82 months with an average of 54.5 months, the three patients after laparoscopic surgery had normal blood pressure without tumor recurrence. The baby girl delivered by the first patient is healthy. The third patient who refused operation had phenoxybenzamine 5 mg twice a day to keep blood pressure in normal range.
Discussion Pheochromocytoma during pregnancy is clinically rare, with the approximate incidence of 0.007% [3]. Catecholamine secreted by pheochromocytoma can cause severe hypertension or hypertensive crisis, and general antihypertensive drug is difficult to control blood pressure. Drugs can cause great harm to fetus and pregnant women during pregnancy. Antihypertensive drug can cause placental ischemia, placental abruption, intrauterine growth retardation, fetal hypoxia and even fetal death. And uncontrolled hypertension can cause hypertensive crisis, cardiac failure, pulmonary edema, and cerebral and vascular accident [4]. The case 1 had high blood pressure and related symptoms in early stage of pregnancy. Although the diagnosis of pheochromocytoma was made in late pregnancy, fetal hypoxia still occurs. Before 1970, only 25% of pheochromocytoma during pregnancy was diagnosed before birth, and the mortality rates of fetus and maternal women were about 50%. After 1970, the diagnosis rate was 83%, and the mortality rates of fetus and maternal women dropped to 10 and 2%, respectively [5]. According to the published literature, Wolf et al. estimated that the mortality rate of maternal women was 17 to 24%, and the mortality rate of fetus was 50 to 62%. In the cases with timely diagnosis and treatment, the mortality rate of pregnant women dropped to 1 to 5%, and the mortality rate of fetus dropped to 14 to 15%. However, the high maternal
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 12/29/14 For personal use only.
1932
D. Dong & H. Li
J Matern Fetal Neonatal Med, 2014; 27(18): 1930–1934
Figure 1. MRI of the first patient with right adrenal pheochromocytoma in mid-pregnangcy (Arrows show the tumor and the fetus).
catecholamine hyperlipidemia did not have great harm on the fetus [6]. The clinical manifestations of pheochromocytoma during pregnancy had no difference with general pheochromocytoma. The symptoms included paroxysmal or persistent high blood pressure, probably with triad of headaches, palpitations and sweating, even with dizziness, nausea, fatigue, anxiety and other symptoms [7]. These symptoms might be misdiagnosed as gestational hypertension or preeclampsia, and stationary pheochromocytoma without fluctuation of blood pressure is even more difficult for correct diagnosis. The differential diagnosis of pheochromocytoma during pregnancy and pre-eclampsia should be noted: First, the former can occur at any time in pregnancy and before pregnancy. Careful history collection is helpful for diagnosis. The latter occurs after 20 weeks of pregnancy.
Second, the former can be manifested asparoxysmal or persistent hypertension associated with triad of headaches, palpitations and sweating, while the latter is persistent hypertension. Third, the former rarely has proteinuria, while the latter is more likely associated with proteinuria. Fourth, the former hypertension persists after childbirth, while the latter returns to normal blood pressure after childbirth. Therefore, for those who has high blood pressure difficult to control in early pregnancy, and for those who has typical symptoms of paroxysmal headaches, palpitations and sweating, and for those whose symptoms do not disappear after childbirth, pheochromocytoma during pregnancy should be considered. The diagnosis of pheochromocytoma during pregnancy includes qualitative diagnosis and localization diagnosis. The qualitative diagnosis includes the measurement of blood and urine catecholamine and their metabolites.
Pheochromocytoma during pregnancy
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Florida International University on 12/29/14 For personal use only.
DOI: 10.3109/14767058.2014.880883
Under normal circumstances, pregnancy and pre-eclampsia do not affect the concentrations of catecholamine [11]. Twenty-four hour urinary catecholamine was used widely due to the higher sensitivity and specificity. 24-h urinary vanillyl mandelic acid has been replaced by catecholamines because of high false negative rate. The sensitivity of blood norepinephrine is more than 98% [8]. The localization diagnosis includes B-ultrasound, MR and CT. Ultrasound is convenient with no harm to fetus, and is often the first method to discover pheochromocytoma during pregnancy. The disadvantage is poor sensitivity, especially for small adrenal pheochromocytoma and extra-adrenal paraganglioma. CT examination is an important means for diagnosis of pheochromocytoma with high sensitivity. However, the application of CT is limited due to fetal exposure to radiation in pregnancy. MRI examination can avoid possible radiation on fetus, and have high sensitivity and specificity, and it is the best diagnostic method for pheochromocytoma during pregnancy [9]. Nuclear examination such as 131I iodo benzyl guanidine (MIBG) scintigraphy and octreotid are specific and sensitive diagnosis method, but only for those after termination of pregnancy and for those after childbirth. Surgery is the preferred treatment of choice for pheochromocytoma during pregnancy, and adequate preoperative medication is needed. a-receptor blocker is used to control blood pressure and for expansion of blood volume, and phenoxybenzamine, prazosin and similar drugs are safe for pregnant women. b-receptor blocker is used to control fast heart rate, but should be used after oral medication of a-receptor blocker to prevent induced hypertension [9]. The operation time and operation approach for treatment of pheochromocytoma during pregnancy remains controversial. Mid-pregnancy is considered to be an ideal time for surgery, because of the relatively stable period of pregnancy with low incidence of spontaneous abortion. In this period, the fetal organ development has been basically completed, and the uterine size has less impact on surgery [10]. According to literature and our experience, the treatment of pheochromocytoma during pregnancy should be based on different physiological characteristics and functional status of pheochromocytoma. For patients in early pregnancy, a receptor blocker can be used to control blood pressure, and surgery is recommended in mid-pregnancy. For those patients who choose abortion, surgery can be performed after adequate medical preparation. For patients in mid-pregnancy, surgery is recommended after adequate medical preparation. For patients in late pregnancy, oral medication such as a receptor blocker is recommended to control blood pressure. Surgery is recommended after full-term pregnancy, and surgical resection of pheochromocytoma can be performed with childbirth at the same time. Cesarean section is recommended, and it can make the maternal and child mortality rate decrease from 33 to 19% compared with vaginal delivery [10,11]. Laparoscopic surgery during pregnancy is safe and effective. But there are little experience with pheochromocytoma during pregnancy, and there are many concerns. First, pneumoperitoneum might affect the blood supply of uterus. Second, increased abdominal pressure might induce premature. Third, increased abdominal pressure might induce
1933
hypertension. Fourth, hypercapnia might cause fetal acidosis. Fifth, pneumoperitoneum cause fetal hypoxia by decreased cardiac output [12]. Laparoscopic surgery for pheochromocytoma during pregnancy is safe and effective. Laparoscopic surgery for pheochromocytoma during pregnancy was reported in literature [10,13,14]. The first case in our series was performed by laparoscopic resection of pheochromocytoma after childbirth. Laparoscopic surgery for pheochromocytoma during pregnancy has many advantages. Laparoscopic surgery can reduce surgical trauma, blood loss and post-operative analgesic consumption. Laparoscopic surgery can avoid excessive compression of tumors and reduce intraoperative hemodynamic fluctuations. Retroperitoneal laparoscopic surgery can avoid the intraperitoneal interference of the uterus. For skilled laparoscopic surgeons, laparoscopic resection of pheochromocytoma is safe and effective for pregnancy after adequate preparation.
Conclusions For those who has high blood pressure difficult to control in early pregnancy, and for those who has typical symptoms of paroxysmal headaches, palpitations and sweating, and for those whose symptoms do not disappear after childbirth, pheochromocytoma during pregnancy should be considered. Early diagnosis can greatly reduce the maternal and fetal mortality rate. Treatment should be based on the period of pregnancy and functional status of pheochromocytoma. Mid-pregnancy is an ideal time for surgical treatment, and laparoscopic surgery after adequate medical preparation is safe and effective.
Declaration of interest The authors have no conflict of interest to declare.
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