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Adrenal mass in pregnancy: Diagnostic approach and dilemmas
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 5 9 e1 6 1
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/apme
Case Report
Adrenal mass in pregnancy: Diagnostic approach and dilemmas K. Swaminathan a,*, A. SureshKumar b, K. UshaRani c, R. Hemaleka d a
Consultant Endocrinologist, Department of Endocrinology, Apollo Speciality Hospital, Madurai 625 020, India Consultant Laparoscopic Surgeon, Department of Laparoscopic Surgery, Apollo Speciality Hospital, Madurai, India c Consultant Pathologist, Department of Pathology, Apollo Speciality Hospital, Madurai, India d Consultant Obstetrician & Gynaecologist, Department of Obstetrics & Gynaecology, Apollo Speciality Hospital, Madurai, India b
article info
abstract
Article history:
Adrenal incidentalomas refer to incidentally discovered adrenal masses during radiological
Received 13 April 2013
examination for other reasons. Such findings have only been rarely reported in pregnancy
Accepted 15 May 2013
due to predominant use of ultrasound rather than Computed Tomography (CT) in a pregnancy setting. The main concerns of such incidentally discovered adrenal masses in
Keywords:
pregnancy are whether they are functioning or malignant. Evaluation of functionality
Adrenal incidentalomas
presents its own set of challenges due to physiological changes that occur during preg-
Pregnancy
nancy. Any adrenal mass greater than 4 cm raises the suspicion of malignancy as well. We
Ganglioneuromas
report a rare case of a 7 cm left adrenal incidentaloma in pregnancy and the associated dilemmas in management of such a presentation. Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
1.
Introduction
An adrenal incidentaloma is a mass lesion greater than 1 cm in diameter, incidentally found during radiologic examination for other reasons.1 Such “adrenal incidentalomas” are increasingly recognised in clinical practice.2 This is attributed to routine use of sophisticated and sensitive imaging techniques, with a reported prevalence of 4.4%.3 Incidental findings of such masses pose dilemmas in evaluation and management, as current recommendations based on expert opinion4 are open to debate in terms of cost and clinical benefits. The uncertainties in management multiply with such adrenal incidentalomas in the context of pregnancy. We report a rare case of a large adrenal incidentaloma complicating second trimester of pregnancy. This case
outlines the huge decisional dilemmas, both for the patient and healthcare provider.
2.
Case report
A 26-year-old lady presented to us with an incidental finding of a 7 cm left adrenal mass during a routine ultrasound examination for pregnancy. She was 20 weeks gestation in her first pregnancy, with no significant past medical or surgical history. She had long standing multiple neurofibromas, consistent with Type 1 neurofibromatosis. There were no clinical symptoms or signs suggestive of a phaeochromocytoma or Cushing’s syndrome. Blood pressure showed normal recordings (110e120 mm Hg systolic and 70e80 mm Hg
* Corresponding author. Tel.: þ91 (0) 8526421150; fax: þ91 (0) 452 2580199. E-mail address: [email protected] (K. Swaminathan). 0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved. http://dx.doi.org/10.1016/j.apme.2013.05.012
160
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 5 9 e1 6 1
diastolic) on multiple occasions. Electrocardiogram and Echocardiography showed normal left ventricular function with no evidence of left ventricular hypertrophy. Fundi showed no evidence of hypertensive retinopathy. Electrolytes, especially potassium was within normal limits. Multiple urinary 24 h urinary fractionated metanephrines showed levels to be within normal limits. MRI (Magnetic Resonance Imaging) of the abdomen showed a 7 cm heterogeneous mass in the left adrenal gland with calcifications. In view of the size of the tumour, lack of a tissue diagnosis, the concern about malignancy and the possibility of a functional tumour with the background of Type 1 neurofibromatosis, a detailed discussion was done with the patient, her family and the obstetrician. Both the patient and the multidisciplinary team, after much deliberations, were keen for the tumour to be removed during the second trimester, accepting the pros and cons of surgery during this stage of pregnancy. The tumour was dissected through a laparoscopic approach under general anaesthesia at 22 weeks gestation. Macroscopic appearances showed a large encapsulated whitish grey mass (Fig. 1). Microscopic examination showed spindle shaped cells with mature ganglion cells consistent with a diagnosis of ganglioneuroma (Fig. 2). Post-operative recovery was uncomplicated and the patient delivered a healthy male baby at 38 weeks gestation.
3.
Discussion
Adrenal disorders complicating pregnancy are relatively rare but a timely diagnosis and management plan is essential as many of these disorders can be associated with significant maternal and foetal morbidity. Any adrenal incidentalomas raises two important questions a) whether the mass is functioning b) whether the mass is malignant. This assumes great significance during pregnancy in terms of decision to operate as implications can be potentially devastating for the mother and the baby. Our main concern with this patient’s adrenal mass was the possibility of a phaeochromocytoma complicating pregnancy, especially in view of her Type 1 neurofibromatosis. Traditionally, the prevalence of this association was thought to be in the order of 1% but recent studies have shown that the prevalence of phaeochromocytoma in type 1 neurofibromatosis may be as high as 15%.5
Fig. 1 e Macroscopic specimen of the large adrenal mass.
Fig. 2 e Microscopic appearances showing spindle shaped cells with mature ganglion cells (black arrow).
Phaeochromocytoma complicating pregnancy is a potentially dangerous condition for both the mother and the foetus. In a systematic review of 77 pregnancies complicated by phaechromocytomas, foetal and maternal mortality rates were 17% and 8% respectively. Survival of both the mother and foetus were much better when the diagnosis was made in the ante-natal period than during labour of immediate postpartum.6 Extensive testing failed to reveal features consistent with a phaeochromocytoma in our patient. Screening for Cushing’s syndrome was not done due to cost implications, normal blood pressure and lack of clinical features. The other concern with our patient was the possibility of malignancy, considering the size of the mass. The two major predictors of malignancy in an adrenal incidentaloma are the size of the mass and imaging characteristics. In a large Italian study of 1004 patients with adrenal incidentaloma, a mass size of 4 cm had the highest sensitivity in differentiating benign from malignant tumours, although the specificity was low.7 In a Mayo series, all the adrenal carcinomas were between 4 and 6 cm in diameter. Therefore, an adrenal mass of 7 cm diameter in our patient raised the genuine possibility of malignancy. However, adrenal mass size alone should not be used as a predictor to make treatment decisions. Imaging characteristics have a strong predictive value to guide management options. A CT scan could not be carried out in our patient in view of her pregnancy. The well circumscribed nature of the mass along with calcifications did raise the possibility of a benign adrenal ganglioneuroma in our patient. However, imaging studies may be misleading as both the benign (ganglioneuromas) and the malignant (ganglioneuroblastomas) forms of the tumour are identical radiologically. Ganglioneuromas are large slow growing tumours that arise from primitive sympathetic ganglion cells. They tend to occur more commonly in females with common locations being in the adrenal glands and the retroperitoneum. There have been occasional case reports of pelvic and retroperitoneal ganglioneuromas complicating pregnancy with features of obstructed labour.8,9 Adrenal ganglioneuromas complicating pregnancy is extremely rare with a single case report in
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 5 9 e1 6 1
1989.10 The patient in this report had undergone a successful second trimester right adrenalectomy. To the best of our knowledge, our case report is the second case of adrenal ganglioneuroma complicating pregnancy in the literature. It is always a challenge to both the families and the healthcare professionals to decide on the timing of surgery in patients with such large adrenal masses. This largely depends on the gestational age at presentation, size and position of the tumour, functionality and the possibility of malignancy. The dilemmas in our case were multi-fold. The presence of Type 1 neurofibromatosis with a large adrenal mass strongly raised the suspicion of a phaeochromocytoma. It was imperative to exclude a phaeochromocytoma as the complications of a poorly prepared patient on the operating table can be devastating. The next dilemma was to decide whether to intervene with surgery during the second trimester or to continue with a conservative line of management till delivery. While the MRI features were suggestive of a benign ganglioneuroma, the size of the mass was concerning. As discussed before, radiology cannot differentiate a benign ganglioneuroma from a malignant ganglioneuroblastoma. In the absence of firm evidence, lack of tissue diagnosis and the possibility of malignancy, the patient and the multi-disciplinary team mutually agreed to go ahead with surgery with high-risk consent. We acknowledge that a decision for “watchful waiting” may have also been equally reasonable. To summarise, we report a rare case of a large adrenal ganglioneuroma complicating pregnancy, on a background of generalised neurofibromatosis. This case highlights the challenges of evaluating such patients and the decisional dilemmas in management.
Conflicts of interest All authors have none to declare.
161
Acknowledgements We would like to acknowledge Dr. Ramesh Babu and Dr. Abdul Khader for their help with this patient’s management.
references
1. Young Jr WF. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. 2007;356(6):601. 2. Aron DC. The adrenal incidentaloma: disease of modern technology and public health problem. Rev Endocr Metab Disord. 2001 Aug;2(3):335e342. 3. Bovio S, Cataldi A, Reimondo G, et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest. 2006 Apr;29(4):298e302. 4. NIH state-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”). NIH Consens State Sci Statements. 2002 Feb 4e6;19(2):1e25. 5. Zinnamosca L, Petramala L, Cotesta D, et al. Neurofibromatosis type 1 (NF1) and pheochromocytoma: prevalence, clinical and cardiovascular aspects. Arch Dermatol Res. 2011 Jul;303(5):317e325. 6. Biggar MA, Lennard TW. Systematic review of phaeochromocytoma in pregnancy. Br J Surg. 2013 Jan;100(2):182e190. 7. Mantero F, Terzolo M, Arnaldi G, et al. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab. 2000;85(2):637. 8. Kamin G, Theissig F, Lo¨ffler F, Lu¨ckert G. Retroperitoneal ganglioneuroma as a cause of obstructed labor. Zentralbl Gynakol. 1986;108(16):1003e1005. 9. Kurzel RB, Durso N. Pelvic ganglioneuroma during pregnancy. A case report. 10. Marks F, Young BK, Raghavendra BN, et al. Diagnosis of adrenal ganglioneuroma in pregnancy with magnetic resonance imaging and ultrasonography. A case report. J Reprod Med. 1989 Jan;34(1):59e61.
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/apme
Case Report
Adrenal mass in pregnancy: Diagnostic approach and dilemmas K. Swaminathan a,*, A. SureshKumar b, K. UshaRani c, R. Hemaleka d a
Consultant Endocrinologist, Department of Endocrinology, Apollo Speciality Hospital, Madurai 625 020, India Consultant Laparoscopic Surgeon, Department of Laparoscopic Surgery, Apollo Speciality Hospital, Madurai, India c Consultant Pathologist, Department of Pathology, Apollo Speciality Hospital, Madurai, India d Consultant Obstetrician & Gynaecologist, Department of Obstetrics & Gynaecology, Apollo Speciality Hospital, Madurai, India b
article info
abstract
Article history:
Adrenal incidentalomas refer to incidentally discovered adrenal masses during radiological
Received 13 April 2013
examination for other reasons. Such findings have only been rarely reported in pregnancy
Accepted 15 May 2013
due to predominant use of ultrasound rather than Computed Tomography (CT) in a pregnancy setting. The main concerns of such incidentally discovered adrenal masses in
Keywords:
pregnancy are whether they are functioning or malignant. Evaluation of functionality
Adrenal incidentalomas
presents its own set of challenges due to physiological changes that occur during preg-
Pregnancy
nancy. Any adrenal mass greater than 4 cm raises the suspicion of malignancy as well. We
Ganglioneuromas
report a rare case of a 7 cm left adrenal incidentaloma in pregnancy and the associated dilemmas in management of such a presentation. Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
1.
Introduction
An adrenal incidentaloma is a mass lesion greater than 1 cm in diameter, incidentally found during radiologic examination for other reasons.1 Such “adrenal incidentalomas” are increasingly recognised in clinical practice.2 This is attributed to routine use of sophisticated and sensitive imaging techniques, with a reported prevalence of 4.4%.3 Incidental findings of such masses pose dilemmas in evaluation and management, as current recommendations based on expert opinion4 are open to debate in terms of cost and clinical benefits. The uncertainties in management multiply with such adrenal incidentalomas in the context of pregnancy. We report a rare case of a large adrenal incidentaloma complicating second trimester of pregnancy. This case
outlines the huge decisional dilemmas, both for the patient and healthcare provider.
2.
Case report
A 26-year-old lady presented to us with an incidental finding of a 7 cm left adrenal mass during a routine ultrasound examination for pregnancy. She was 20 weeks gestation in her first pregnancy, with no significant past medical or surgical history. She had long standing multiple neurofibromas, consistent with Type 1 neurofibromatosis. There were no clinical symptoms or signs suggestive of a phaeochromocytoma or Cushing’s syndrome. Blood pressure showed normal recordings (110e120 mm Hg systolic and 70e80 mm Hg
* Corresponding author. Tel.: þ91 (0) 8526421150; fax: þ91 (0) 452 2580199. E-mail address: [email protected] (K. Swaminathan). 0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved. http://dx.doi.org/10.1016/j.apme.2013.05.012
160
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 5 9 e1 6 1
diastolic) on multiple occasions. Electrocardiogram and Echocardiography showed normal left ventricular function with no evidence of left ventricular hypertrophy. Fundi showed no evidence of hypertensive retinopathy. Electrolytes, especially potassium was within normal limits. Multiple urinary 24 h urinary fractionated metanephrines showed levels to be within normal limits. MRI (Magnetic Resonance Imaging) of the abdomen showed a 7 cm heterogeneous mass in the left adrenal gland with calcifications. In view of the size of the tumour, lack of a tissue diagnosis, the concern about malignancy and the possibility of a functional tumour with the background of Type 1 neurofibromatosis, a detailed discussion was done with the patient, her family and the obstetrician. Both the patient and the multidisciplinary team, after much deliberations, were keen for the tumour to be removed during the second trimester, accepting the pros and cons of surgery during this stage of pregnancy. The tumour was dissected through a laparoscopic approach under general anaesthesia at 22 weeks gestation. Macroscopic appearances showed a large encapsulated whitish grey mass (Fig. 1). Microscopic examination showed spindle shaped cells with mature ganglion cells consistent with a diagnosis of ganglioneuroma (Fig. 2). Post-operative recovery was uncomplicated and the patient delivered a healthy male baby at 38 weeks gestation.
3.
Discussion
Adrenal disorders complicating pregnancy are relatively rare but a timely diagnosis and management plan is essential as many of these disorders can be associated with significant maternal and foetal morbidity. Any adrenal incidentalomas raises two important questions a) whether the mass is functioning b) whether the mass is malignant. This assumes great significance during pregnancy in terms of decision to operate as implications can be potentially devastating for the mother and the baby. Our main concern with this patient’s adrenal mass was the possibility of a phaeochromocytoma complicating pregnancy, especially in view of her Type 1 neurofibromatosis. Traditionally, the prevalence of this association was thought to be in the order of 1% but recent studies have shown that the prevalence of phaeochromocytoma in type 1 neurofibromatosis may be as high as 15%.5
Fig. 1 e Macroscopic specimen of the large adrenal mass.
Fig. 2 e Microscopic appearances showing spindle shaped cells with mature ganglion cells (black arrow).
Phaeochromocytoma complicating pregnancy is a potentially dangerous condition for both the mother and the foetus. In a systematic review of 77 pregnancies complicated by phaechromocytomas, foetal and maternal mortality rates were 17% and 8% respectively. Survival of both the mother and foetus were much better when the diagnosis was made in the ante-natal period than during labour of immediate postpartum.6 Extensive testing failed to reveal features consistent with a phaeochromocytoma in our patient. Screening for Cushing’s syndrome was not done due to cost implications, normal blood pressure and lack of clinical features. The other concern with our patient was the possibility of malignancy, considering the size of the mass. The two major predictors of malignancy in an adrenal incidentaloma are the size of the mass and imaging characteristics. In a large Italian study of 1004 patients with adrenal incidentaloma, a mass size of 4 cm had the highest sensitivity in differentiating benign from malignant tumours, although the specificity was low.7 In a Mayo series, all the adrenal carcinomas were between 4 and 6 cm in diameter. Therefore, an adrenal mass of 7 cm diameter in our patient raised the genuine possibility of malignancy. However, adrenal mass size alone should not be used as a predictor to make treatment decisions. Imaging characteristics have a strong predictive value to guide management options. A CT scan could not be carried out in our patient in view of her pregnancy. The well circumscribed nature of the mass along with calcifications did raise the possibility of a benign adrenal ganglioneuroma in our patient. However, imaging studies may be misleading as both the benign (ganglioneuromas) and the malignant (ganglioneuroblastomas) forms of the tumour are identical radiologically. Ganglioneuromas are large slow growing tumours that arise from primitive sympathetic ganglion cells. They tend to occur more commonly in females with common locations being in the adrenal glands and the retroperitoneum. There have been occasional case reports of pelvic and retroperitoneal ganglioneuromas complicating pregnancy with features of obstructed labour.8,9 Adrenal ganglioneuromas complicating pregnancy is extremely rare with a single case report in
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 5 9 e1 6 1
1989.10 The patient in this report had undergone a successful second trimester right adrenalectomy. To the best of our knowledge, our case report is the second case of adrenal ganglioneuroma complicating pregnancy in the literature. It is always a challenge to both the families and the healthcare professionals to decide on the timing of surgery in patients with such large adrenal masses. This largely depends on the gestational age at presentation, size and position of the tumour, functionality and the possibility of malignancy. The dilemmas in our case were multi-fold. The presence of Type 1 neurofibromatosis with a large adrenal mass strongly raised the suspicion of a phaeochromocytoma. It was imperative to exclude a phaeochromocytoma as the complications of a poorly prepared patient on the operating table can be devastating. The next dilemma was to decide whether to intervene with surgery during the second trimester or to continue with a conservative line of management till delivery. While the MRI features were suggestive of a benign ganglioneuroma, the size of the mass was concerning. As discussed before, radiology cannot differentiate a benign ganglioneuroma from a malignant ganglioneuroblastoma. In the absence of firm evidence, lack of tissue diagnosis and the possibility of malignancy, the patient and the multi-disciplinary team mutually agreed to go ahead with surgery with high-risk consent. We acknowledge that a decision for “watchful waiting” may have also been equally reasonable. To summarise, we report a rare case of a large adrenal ganglioneuroma complicating pregnancy, on a background of generalised neurofibromatosis. This case highlights the challenges of evaluating such patients and the decisional dilemmas in management.
Conflicts of interest All authors have none to declare.
161
Acknowledgements We would like to acknowledge Dr. Ramesh Babu and Dr. Abdul Khader for their help with this patient’s management.
references
1. Young Jr WF. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. 2007;356(6):601. 2. Aron DC. The adrenal incidentaloma: disease of modern technology and public health problem. Rev Endocr Metab Disord. 2001 Aug;2(3):335e342. 3. Bovio S, Cataldi A, Reimondo G, et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest. 2006 Apr;29(4):298e302. 4. NIH state-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”). NIH Consens State Sci Statements. 2002 Feb 4e6;19(2):1e25. 5. Zinnamosca L, Petramala L, Cotesta D, et al. Neurofibromatosis type 1 (NF1) and pheochromocytoma: prevalence, clinical and cardiovascular aspects. Arch Dermatol Res. 2011 Jul;303(5):317e325. 6. Biggar MA, Lennard TW. Systematic review of phaeochromocytoma in pregnancy. Br J Surg. 2013 Jan;100(2):182e190. 7. Mantero F, Terzolo M, Arnaldi G, et al. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab. 2000;85(2):637. 8. Kamin G, Theissig F, Lo¨ffler F, Lu¨ckert G. Retroperitoneal ganglioneuroma as a cause of obstructed labor. Zentralbl Gynakol. 1986;108(16):1003e1005. 9. Kurzel RB, Durso N. Pelvic ganglioneuroma during pregnancy. A case report. 10. Marks F, Young BK, Raghavendra BN, et al. Diagnosis of adrenal ganglioneuroma in pregnancy with magnetic resonance imaging and ultrasonography. A case report. J Reprod Med. 1989 Jan;34(1):59e61.