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International Journal of Urology (2014) 21, 1187–1188
doi: 10.1111/iju.12537
Letter to the Editor Case of pheochromocytoma associated with neurofibromatosis type 1 developing postoperative hypertension Neurofibromatosis type 1 (NF-1), known as von Recklinghausen disease, is an autosomal dominant disorder characterized by manifestations of cutaneous café au lait spots and neurofibromas along peripheral nerves. Pheochromocytoma occurs in 0.1–5.7% of patients with NF-1, which can be up to 13.0% in autopsy series. In addition, it is higher when patients with NF-1 have hypertension (20–50%). Patients with NF-1 have an increased risk of cardiovascular diseases.1 This suggests that surgical resection of pheochromocytoma might not contribute to normalization of blood pressure in patients with both pheochromocytoma and NF-1. We present a case of a 26-year-old man with pheochromocytoma associated with NF-1 who developed postoperative hypertension. A 26-year-old man presented with paroxysmal palpitation for 3 months. He had undergone operations for a lung abscess when he was aged 9 months and right optic glioma at 2 years. Physical examination showed multiple café au lait spots and neurofibromas (Fig. 1a), and these manifestations, all of which were compatible with NF-1, also appeared in his brother. Laboratory tests showed high plasma catecholamine concentrations including an adrenaline level of 3.8 ng/mL and noradrenaline level of 9.5 ng/mL. The 24-h test of urine vanillyl mandelic acid corrected by the creatinine level showed 13.7 mg/gCr. Abdominal contrast-enhanced computed tomography showed a large, heterogenous well-defined tumor of the right adrenal gland (Fig. 1b). Iodine-131 metaiodobenzylguani-
Fig. 1 (a) On physical examination, the patient had multiple café au lait spots and neurofibromas over the whole body. (b) Abdominal contrast-enhanced computed tomography shows a large, heterogenous well-defined mass in the right adrenal gland (arrow). The tumor size was 44 × 40 × 28 mm. (c) Tumor cells are in an alveolar growth pattern, and partly composed of some atypical cells varying in size. There is no evidence of a ganglioneuroma component. There are very few mitoses and no necrosis (hematoxylin–eosin stain; magnification: ×400). (d) In immunohistochemistry, tumor cells are strongly positive for chromogranin A (magnification: ×400). © 2014 The Japanese Urological Association
dine scintigraphy showed positive uptake in the right adrenal gland. After doxazosin 2 mg per day and atenolol 25 mg per day were given for 2 months to normalize blood pressure, he underwent laparoscopic right adrenalectomy. Pheochromocytoma was diagnosed at pathological findings (Fig. 1c,d). Postoperative blood pressure was less than 140/90 mmHg without medication during the hospital stay. After absence from hospital visit for 9 months, the patient presented with paroxysmal palpitation. Although tumor recurrence was suspected on the basis of clinical findings, with high blood pressure of 230/110 mmHg and a high pulse rate of 120 b.p.m., there was no evidence of recurrence. The plasma catecholamines, renin activity and aldosterone were normal. Blood pressure was controlled by amlodipine 2.5 mg per day, atenolol 25 mg per day and doxazosin 2 mg per day. Among one-quarter of patients with pheochromocytoma, hypertension persists despite tumor removal.2 This is thought to be due to irreversible vascular endothelial damage resulting from extended exposure to high concentrations of catecholamines.3 Likewise, cardiovascular damage can progress in patients with NF-1.1 Because neurofibromin, which is inactivated in NF-1, is expressed in vascular endothelium, smooth muscle and cardiac muscle, patients with NF-1 are more likely to have left ventricular hypertrophy, carotid artery intima-media thickness and hypertension.4 The present study shows not only the natural course of pheochromocytoma, but
(a)
(b)
(c)
(d)
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LETTER TO THE EDITOR
also that of NF-1. Removal of excess catecholamine resulted in decreased blood pressure. However, indolent endothelial damage resulting from pheochromocytoma and NF-1 became apparent during the follow-up period by the consistent influence of NF-1. Thus, it is suggested that the possibility of development of hypertension should be considered even if postoperative blood pressure is normalized by removal of catecholamines from pheochromocytoma in patients with NF-1. Takanobu Yamamoto M.D., Kohei Hashimoto M.D., Ph.D. and Naoki Itoh M.D., Ph.D. Department of Urology, NTT-East Corporation Sapporo Medical Center, Sapporo, Japan [email protected]
1188
Conflict of interest None declared.
References 1 Zinnamosca L, Petramala L, Cotesta D et al. Neurofibromatosis type 1 (NF1) and pheochromocytoma: prevalence, clinical and cardiovascular aspects. Arch. Dermatol. Res. 2011; 303: 317–25. 2 Manger WM, Gifford RW. Pheochromocytoma. J. Clin. Hypertens. (Greenwich) 2002; 4: 62–72. 3 Stolk RF, Bakx C, Mulder J, Timmers HJ, Lenders JW. Is the excess cardiovascular morbidity in pheochromocytoma related to blood pressure or to catecholamines? J. Clin. Endocrinol. Metab. 2013; 98: 1100–6. 4 Norton KK, Xu J, Gutmann DH. Expression of the neurofibromatosis I gene product, neurofibromin, in blood vessel endothelial cells and smooth muscle. Neurobiol. Dis. 1995; 2: 13–21.
© 2014 The Japanese Urological Association
Copyright of International Journal of Urology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
International Journal of Urology (2014) 21, 1187–1188
doi: 10.1111/iju.12537
Letter to the Editor Case of pheochromocytoma associated with neurofibromatosis type 1 developing postoperative hypertension Neurofibromatosis type 1 (NF-1), known as von Recklinghausen disease, is an autosomal dominant disorder characterized by manifestations of cutaneous café au lait spots and neurofibromas along peripheral nerves. Pheochromocytoma occurs in 0.1–5.7% of patients with NF-1, which can be up to 13.0% in autopsy series. In addition, it is higher when patients with NF-1 have hypertension (20–50%). Patients with NF-1 have an increased risk of cardiovascular diseases.1 This suggests that surgical resection of pheochromocytoma might not contribute to normalization of blood pressure in patients with both pheochromocytoma and NF-1. We present a case of a 26-year-old man with pheochromocytoma associated with NF-1 who developed postoperative hypertension. A 26-year-old man presented with paroxysmal palpitation for 3 months. He had undergone operations for a lung abscess when he was aged 9 months and right optic glioma at 2 years. Physical examination showed multiple café au lait spots and neurofibromas (Fig. 1a), and these manifestations, all of which were compatible with NF-1, also appeared in his brother. Laboratory tests showed high plasma catecholamine concentrations including an adrenaline level of 3.8 ng/mL and noradrenaline level of 9.5 ng/mL. The 24-h test of urine vanillyl mandelic acid corrected by the creatinine level showed 13.7 mg/gCr. Abdominal contrast-enhanced computed tomography showed a large, heterogenous well-defined tumor of the right adrenal gland (Fig. 1b). Iodine-131 metaiodobenzylguani-
Fig. 1 (a) On physical examination, the patient had multiple café au lait spots and neurofibromas over the whole body. (b) Abdominal contrast-enhanced computed tomography shows a large, heterogenous well-defined mass in the right adrenal gland (arrow). The tumor size was 44 × 40 × 28 mm. (c) Tumor cells are in an alveolar growth pattern, and partly composed of some atypical cells varying in size. There is no evidence of a ganglioneuroma component. There are very few mitoses and no necrosis (hematoxylin–eosin stain; magnification: ×400). (d) In immunohistochemistry, tumor cells are strongly positive for chromogranin A (magnification: ×400). © 2014 The Japanese Urological Association
dine scintigraphy showed positive uptake in the right adrenal gland. After doxazosin 2 mg per day and atenolol 25 mg per day were given for 2 months to normalize blood pressure, he underwent laparoscopic right adrenalectomy. Pheochromocytoma was diagnosed at pathological findings (Fig. 1c,d). Postoperative blood pressure was less than 140/90 mmHg without medication during the hospital stay. After absence from hospital visit for 9 months, the patient presented with paroxysmal palpitation. Although tumor recurrence was suspected on the basis of clinical findings, with high blood pressure of 230/110 mmHg and a high pulse rate of 120 b.p.m., there was no evidence of recurrence. The plasma catecholamines, renin activity and aldosterone were normal. Blood pressure was controlled by amlodipine 2.5 mg per day, atenolol 25 mg per day and doxazosin 2 mg per day. Among one-quarter of patients with pheochromocytoma, hypertension persists despite tumor removal.2 This is thought to be due to irreversible vascular endothelial damage resulting from extended exposure to high concentrations of catecholamines.3 Likewise, cardiovascular damage can progress in patients with NF-1.1 Because neurofibromin, which is inactivated in NF-1, is expressed in vascular endothelium, smooth muscle and cardiac muscle, patients with NF-1 are more likely to have left ventricular hypertrophy, carotid artery intima-media thickness and hypertension.4 The present study shows not only the natural course of pheochromocytoma, but
(a)
(b)
(c)
(d)
1187
LETTER TO THE EDITOR
also that of NF-1. Removal of excess catecholamine resulted in decreased blood pressure. However, indolent endothelial damage resulting from pheochromocytoma and NF-1 became apparent during the follow-up period by the consistent influence of NF-1. Thus, it is suggested that the possibility of development of hypertension should be considered even if postoperative blood pressure is normalized by removal of catecholamines from pheochromocytoma in patients with NF-1. Takanobu Yamamoto M.D., Kohei Hashimoto M.D., Ph.D. and Naoki Itoh M.D., Ph.D. Department of Urology, NTT-East Corporation Sapporo Medical Center, Sapporo, Japan [email protected]
1188
Conflict of interest None declared.
References 1 Zinnamosca L, Petramala L, Cotesta D et al. Neurofibromatosis type 1 (NF1) and pheochromocytoma: prevalence, clinical and cardiovascular aspects. Arch. Dermatol. Res. 2011; 303: 317–25. 2 Manger WM, Gifford RW. Pheochromocytoma. J. Clin. Hypertens. (Greenwich) 2002; 4: 62–72. 3 Stolk RF, Bakx C, Mulder J, Timmers HJ, Lenders JW. Is the excess cardiovascular morbidity in pheochromocytoma related to blood pressure or to catecholamines? J. Clin. Endocrinol. Metab. 2013; 98: 1100–6. 4 Norton KK, Xu J, Gutmann DH. Expression of the neurofibromatosis I gene product, neurofibromin, in blood vessel endothelial cells and smooth muscle. Neurobiol. Dis. 1995; 2: 13–21.
© 2014 The Japanese Urological Association
Copyright of International Journal of Urology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
