Pediatrics International (2015) 57, 875–879

doi: 10.1111/ped.12664

Original Article

Pediatric patients with pheochromocytoma: Experience of a tertiary health center Erdal Eren,1 Halil Saglam,1 Yusuf Caliskan,2 Irfan Kiristioglu2 and Omer Tarim1 Departments of 1Pediatric Endocrinology and 2Pediatric Surgery, Uludag University, Faculty of Medicine, Bursa, Turkey Abstract

Background: The aim of this retrospective study was to investigate pheochromocytoma (pheo), which is a rare endocrine tumor in the pediatric population. Methods: The medical records of five children with pheo were studied. The age, gender, clinical presentation, family history, physical findings, coexisting pathology, laboratory evaluation, surgical treatment, and postoperative course were investigated. Results: The patients were four girls and one boy with a mean age of 13.2 years (range, 9.57–15.95 years). None of the patients had paroxysmal hypertension and one had normal blood pressure. No malign pheo was identified. Mean height and weight standard deviation scores (SDS), body mass index (BMI), and BMI SDS were 0.24, 0.04, 20.9 kg/m2, and 0.20 at the time of diagnosis, and 0.03, 0.43, 23.8 kg/m2 and 0.49 1 year after operation, respectively. BMI increased significantly after operation. Three patients had normal epinephrine and metanephrine, but elevated norepinephrine and normetanephrine on 24 h urine. Vanillylmandelic acid on 24 h urine sample was elevated in all patients. Ultrasonography failed to visualize tumors in two patients with bilateral pheo. One patient had postoperative severe hypotension. Insulin resistance associated with severe acanthosis nigricans observed in one patient regressed postoperatively. Conclusions: Pheo in children may present with different symptoms and findings. Decreased catecholamine in the postoperative period may lead to weight gain.

Key words catecholamine, child, height, pheochromocytoma, weight. Pheochromocytoma (pheo) is a neoplasm that originates from the adrenal medulla. Its incidence is reported to be 1/100 000 and children comprise 10% of the patients.1 Despite its low incidence, it is the most frequent endocrine tumor in childhood.2,3 The clinical findings are the result of excessive secretion of catecholamines. Although the diagnosis and treatment of pheo is well defined in adults, experience in pediatrics is still low. The typical symptomatological triad of the disease consists of episodic headache, sweating, and palpitation, but the clinical presentation in children may be different. For instance, hypertension may be continuous rather than paroxysmal. A recent study has shown that excessive catecholamine secretion may cause, in vitro, abnormalities in the endocrine function of the fat tissue.4 Theoretically, postoperative decrease in catecholamines may lead to accumulation of fat and weight gain. Here, we report the clinical and laboratory findings, as well as the changes in bodyweight, in patients with pheo, before and after operation.

Correspondence: Erdal Eren, MD, Department of Pediatric Endocrinology, Uludag University, Faculty of Medicine, Gorukle Yerleskesi, Bursa, Turkey. Email: [email protected] Received 19 December 2013; revised 7 January 2015; accepted 26 March 2015.

© 2015 Japan Pediatric Society

Methods The medical records of five children with pheo who were treated and followed at Uludag University Hospital, Turkey, between 2003 and 2010 were retrospectively studied. Age, gender, clinical presentation, family history, physical findings, coexisting pathology, laboratory evaluation, surgical treatment, and postoperative course were investigated. Height, weight, body mass index (BMI), and their standard deviation score (SDS) were determined at the time of diagnosis and 1 year after operation.5 BMI was calculated as weight (kg)/height (m)2. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated as glucose (mg/dL) × insulin (mIU/mL)/405. The concentration of vanillylmandelic acid (VMA), metanephrine, normetanephrine, epinephrine, and norepinephrine in 24 h urine sample was measured on high-performance liquid chromatography. Ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI) were appropriately utilized. The diagnosis was confirmed on histopathology of the surgical specimens, and which included tumor dimensions, presence or absence of necrosis, and histochemical staining. Statistical analysis

Statistical analysis was performed using SPSS for Windows version 16.0 (SPSS Inc, Chicago, USA). The difference between

876 E Eren et al. dependent groups was evaluated using Wilcoxon analysis. The level of significance was defined as α = 0.05 (P < 0.05). Results are given as arithmetic mean and range (minimum–maximum).

Results The patients were four girls and one boy with a mean age of 13.2 years (range, 9.57–15.95) years. Two patients presented with hypertension, one patient with weight loss, vomiting, and flushing, and one patient with diminished vision. One patient was diagnosed during investigation for urinary infection. One patient was being followed for a diagnosis of von Hippel–Lindau (VHL) syndrome, and had retinal capillary hemangiomas, cysts in the ovary, pancreas, and kidney, and a history of renal carcinoma in her father and uncle. One patient had neurofibromatosis type 1 (NF1) with normal blood pressure at presentation. Mean height and weight SDS, and BMI were 0.24, 0.04, and 20.9 kg/m2 at the time of diagnosis, and 0.03, 0.43, and 23.8 kg/m2 1 year after operation, respectively. The difference was statistically significant (P < 0.05) for all parameters. BMI SDS increased in all the patients except for patient number 4. Two patients had severe (grade 3 and 4) retinopathy while three patients had normal fundoscopy. Three patients had normal epinephrine and metanephrine, but elevated norepinephrine and normetanephrine in 24 h urine sample. VMA in 24 h urine sample was elevated in all patients. The clinical and laboratory findings are given in Table 1. Other hormonal parameters (such as thyroid function test, parathormone, and cortisol) were studied in all patients to exclude multiple endocrine neoplasia type 2 (MEN2) and adrenal tumor. All were normal. Mean tumor size was 53.4 × 48.2 × 33.6 mm. Fibrous capsule was determined in all pathological samples and necrosis was identified in three patients. Lymphatic invasion and necrosis were marked in a patient with pheo diagnosed with VHL type 1. The specimen of the patient with NF1 showed capsular invasion, but not necrosis or lymphatic invasion. Immunohistochemistry was positive for synaptophysin and chromogranin A in all patients (Table 1). The pathology specimen of patient 5 is shown in Figure 1. USG failed to show the tumors in two patients with bilateral pheo. In contrast, MRI was successful as a diagnostic test in four patients (Fig. 2). One patient’s tumor was visualized on CT. The patients were treated with alpha-blocker (prazosin) and beta-blocker (propranolol) for 2 weeks before operation. Adrenalectomy was performed for the right adrenal in two, for the left in one, and bilaterally in two patients. Intraoperative hypertension due to manipulation of the tumor or anesthetic medication was treated with sodium nitroprusside (Nipruss; Adeka, İstanbul, Turkey) infusion at a rate of 0.5–10 μg/kg/min. No surgical complication was observed. One patient had postoperative severe hypotension. Insulin resistance associated with severe acanthosis nigricans observed in one patient regressed postoperatively. Fasting glucose, insulin, and HOMA-IR were 114 mg/dL, 41.6 mIU/mL, and 11.5 before surgery, and 76 mg/dL, 12.1 mIU/mL, and 2.27 after surgery.

Discussion Pheochromocytoma originates from adrenal chromaffin cells and secretes epinephrine, norepinephrine, or dopamine. Approximately © 2015 Japan Pediatric Society

98% of patients have abdominal or pelvic tumors, and 2% have thoracic tumors. Among 21 cases reported by Bissada et al., 17 (81%) had adrenal and four (19%) had extra-adrenal tumor.6 Pheo was familial in four cases (19%). The largest cohort reported to date in the pediatric age group consisted of 58 patients with extraadrenal tumor in 22% and familial disease in 39%.7 Genetic predisposition in adults with pheo was reported to be 10–20%.8 Ganesh et al. reported familial pheo in 18% of 11 pediatric patients.9 Two of the present patients had a family history of renal carcinoma, but it was not clear whether those family members who had died had pheo as well. The hereditary forms of pheo include MEN2, VHL syndrome, von Recklinghausen NF1, and familial paraganglioma. One of the present patients had NF1 and one had VHL. Patients with MEN2 and VHL present at a younger age with moderate hypertension and mild symptoms.10 Pheo develops in 10–20% of the patients with VHL and in

Pediatric patients with pheochromocytoma: Experience of a tertiary health center.

The aim of this retrospective study was to investigate pheochromocytoma (pheo), which is a rare endocrine tumor in the pediatric population...
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