Pheochromocytoma In Children Research Articles

Bilateral pheochromocytoma in children

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Pheochromocytoma in children – case report and short literature review

Pheochromocytoma in children – case report and short literature review

Operative management and outcomes in children with pheochromocytoma

This study aimed to evaluate management and prognosis in children with pheochromocytoma who were treated at an Egyptian tertiary center. The authors conducted an 8-year retrospective analysis for 17 patients who were presented from January 2013 to January 2021. Clinical criteria, operative details, and follow-up data were assessed. Overall (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method. An event was assigned with the occurrence of recurrence or metachronous disease, or death. Median age at diagnosis was 14 years (range: 6-17.5 years). Ten patients (58.8%) were males and seven (41.2%) were females. Hypertension-related symptoms were the main presentations in 15 patients (88%). None of the included children underwent genetic testing. Sixteen patients (94%) had unilateral tumors (right side: 12), whereas only one was presented with bilateral masses. The median tumor size was 7cm (range: 4-9cm). Metastatic workup did not reveal any metastatic lesions. All patients underwent open adrenalectomy, and clinical manifestations were completely resolved after surgery. Adjuvant therapy was not administered to any patient. There were no deaths or relapses at a median follow-up time of 40 months, whilst two children had metachronous disease after primary resection. Both were managed by adrenal-sparing surgery, and they achieved a second complete remission thereafter. Five-year OS and EFS were 100% and 88%, respectively. Complete surgical resection achieves excellent clinical and survival outcomes for pheochromocytoma in children. Meticulous, long-term follow-up is imperative for early detection of metachronous disease to facilitate adrenal-sparing surgery. Genetic assessment for patients and their families is essential; however, it was not available at our institution.

Laparoscopic adrenal-sparing approach for children with bilateral pheochromocytoma in Von Hippel-Lindau disease

IntroductionVon Hippel-Lindau disease (VHL) is a rare cause of hereditary bilateral Pheochromocytomas (PHEO). Traditionally, treatment has been total adrenalectomy due to a lifetime risk of developing new tumors. Limited data exists on the surgical management of bilateral PHEO in children with VHL. We reviewed our experience with laparoscopic partial adrenalectomy for bilateral PHEO. MethodsA retrospective review was performed of patients undergoing adrenalectomy for PHEO in children with VHL from 2004 to 2019. ResultsEight children with VHL diagnosed with bilateral PHEO underwent 16 adrenalectomies (10 synchronous, 5 metachronous, 1 for recurrence). Median age at diagnosis was 13 [range 8–17] years with a median tumor size of 2.3 [range 0.5–7.7] cm. Of 16 adrenalectomies, all were performed laparoscopically, 14 were partial adrenalectomies; 2 patients required a contralateral total adrenalectomy due to size and diffuse multinodularity. There were no postoperative complications. No patients required corticosteroid replacement at the end of the study period. Two patients had new ipsilateral tumors identified after a median follow up of 5 [range 4–6] years with one undergoing repeat partial adrenalectomy. There were no mortalities in the study period. ConclusionPartial adrenalectomy for bilateral PHEO in patients with VHL is safe and does not compromise outcomes. When technically feasible, laparoscopic partial adrenalectomy should be considered as a primary surgical approach for children with VHL. Level of EvidenceLevel IV - Case series with no comparison group

Pediatric pheochromocytoma in association with Von Hippel–Lindau disease: Focus on screening strategies

IntroductionVon Hippel–Lindau disease (VHL) is a syndrome of familial predisposition to the development of malignant and benign tumours, due to mutations in the VHL tumour suppressor gene. Pheochromocytoma is a tumour that develops in the adrenal gland, rare in pediatric age, and may be associated with genetic abnormalities including mutations in the VHL gene. Systematic screening of pheochromocytoma in children carrying a VHL mutation has been proposed. However, some VHL patients who have been screened may develop symptoms associated with pheochromocytoma despite screening. Here, we report on such a case. Clinical caseA 13-year-old boy, known to be a carrier of a mutation of the VHL gene, undergoing annual screening, was admitted to our hospital for clinical symptoms related to a right adrenal pheochromocytoma discovered on abdominal imaging. After hemodynamic stabilisation, the pheochromocytoma was surgically resected. Histology confirmed the diagnosis of pheochromocytoma. The postoperative care was simple. The event-free period is currently 2 years. DiscussionThe present case has led us to reflect on the French and international screening strategies for pheochromocytoma in children carrying a mutation of the VHL gene. Between 2013 and 2018, six different recommendations were proposed for pheochromocytoma screening in secondary prevention for children with a VHL mutation, with variability regarding the age of onset and complementary examinations to be carried out. Despite the existence of these recommendations, our case demonstrates that a pheochromocytoma can develop by escaping well-performed screening. The role of early abdominal imaging should be redefined to improve the efficiency of screening. ConclusionThe discovery of a pheochromocytoma in a child must be systematically investigated for an underlying genetic cause. In the particular case of children carrying a mutation of the VHL gene, annual abdominal imaging should be included in the pheochromocytoma screening protocol from the age of 5 years.

Pheochromocytoma in Children and Adolescents With Multiple Endocrine Neoplasia Type 2B.

Multiple endocrine neoplasia type 2B (MEN2B) is characterized by early-onset medullary thyroid cancer in virtually all cases and a 50% lifetime risk of pheochromocytoma (PHEO) development. The literature on PHEO in patients with MEN2B is limited with most data being reported from adult studies that primarily address MEN2A. The aim of the current study is to describe PHEO development in a cohort of pediatric patients with MEN2B. Retrospective chart review of patients with MEN2B evaluated at the National Institutes of Health in the period between July 2007 and February 2018. A total of 38 patients were identified (21 males and 17 females). Mean age at MEN2B diagnosis was 10.6 ± 3.9 years. Eight patients (21%) developed PHEO in the course of follow-up to date, all of whom were sporadic cases with the classic M918T RET mutation. PHEO was diagnosed based on biochemical and/or imaging screening studies in five patients, whereas three patients presented with symptoms of excess catecholamines. PHEO was diagnosed at a mean age 15.2 ± 4.6 (range, 10 to 25) years and 4.0 ± 3.3 years after MEN2B diagnosis. Only one patient was diagnosed with PHEO as the initial manifestation of MEN2B after she presented with hypertension and secondary amenorrhea. Undiagnosed PHEO can be associated with substantial morbidity. Current American Thyroid Association guidelines recommend PHEO screening starting at age 11 for the high-/highest risk group. The youngest patient diagnosed with PHEO in our cohort was an asymptomatic 10-year-old, suggesting that PHEO development may begin before the screening-recommended age of 11, though remains clinically undetectable and thus the current screening guidelines seem appropriate.

Pheochromocytoma in children and adolescents

Eleven subjects aged <20 yr with histologically proven pheochromocytoma between 1987 and 2006 were analyzed. Family history was present in 18%. In 2 patients, pheochromocytoma was part of VHL and in one it was associated with MEN 2. Twenty four hour urine VMA level was elevated in 100% and metanephrine level in 73%. CT/ MRI were showing the tumor in all. Prazosin extended release tablets (maximum 30 mg/day) were used in 73% and doxazosin (maximum 12 mg/ day) in 27%. Intraoperative BP fluctuations were seen in 27%. All were biochemically cured after surgery. Preoperative á blockade with extended release prazosin and doxazosin were effective in controlling perioperative BP fluctuations. Hence these drugs can be used in children and adolescents without fear of postoperative hypotension.

Update on pediatric pheochromocytoma

Pheochromocytomas are rare tumors in children arising from chromaffin cells of adrenal medullary or extra-adrenal paraganglionic tissue. The tumors are characterized by synthesis, metabolism, and secretion of catecholamines. The formerly used guidelines for pheochromocytoma have been changed by recent discoveries, implementation of new approaches, and understanding of biochemistry, genetics, imaging, pathophysiology, and nomenclature of these tumors. In children, pheochromocytomas are more frequently familial, extra-adrenal, bilateral, and multifocal than in adults. Because of a highly variable clinical presentation, pheochromocytoma is often referred to as the great mimic. Measurements of plasma or urinary fractionated metanephrines are recommended as first-line biochemical tests for diagnosis, with optimum diagnostic sensitivity to be preferred over specificity. In general, localization studies must be used secondary to clinical and biochemical evidence. Adequate preoperative treatment with alpha-blockade is mandatory, including for pheochromocytomas that do not secrete but only synthesize catecholamines. Because approximately 40% of pheochromocytomas in children have a hereditary basis, proper genetic testing should be performed, with appropriate implications for future follow-up and treatment options. The risk for development of malignant disease depends highly on the underlying mutation, which may also impact recommendations concerning screening and surgical or systemic treatment. This article reviews recent advances in biochemistry, genetics, and imaging and outlines recommendations for improved evaluation and treatment of children with benign or malignant pheochromocytomas.

Phéochromocytome révélé par un accident vasculaire cérébral chez un enfant

Pheochromocytoma is uncommon in children. We report herein a case in a 6-year-old boy whose pheochromocytoma was revealed by cerebral ischemia as a consequence of acute-cardiac failure. Twenty-four-hour urinary catecholamines were markedly increased. Abdominal ultrasonography and computed tomography located the tumor on the left adrenal gland. After surgical excision, hypertension disappeared. Diagnosis and treatment of pheochromocytoma in children are discussed.

Laparoscopic Adrenalectomy for Pheocromocytoma in Children: Is It Safe?

PURPOSE Laparoscopic adrenalectomy (LA) is a safe and effective procedure for removal of adrenal masses in adults, but few reports describe this technique in children. Reports of LA for treatment of pheochromocytoma in children are even rarer. We present our experience with LA in the treatment of pheochromocytoma in three pediatric patients. MATERIAL AND METHODS LA was performed in fifteen children between 2001 and 2006. In three cases, aged 8, 9 and 14 years, the clinical diagnosis was pheochromocytoma. Two patients were male (one with a family history) and one female, and all presented with unilateral tumors. All underwent clinical evaluation and preoperative adrenergic blockade. The transperitoneal laparoscopic approach, under general anesthesia and titrated nitroprusside administration, was employed in all cases. We analyse the operative and anesthetic data, pathology and postoperative outcome of these patients. RESULTS Operative times were 162, 120 and 130 minutes. The tumor was completely ressected in all cases, and there were no conversions or perioperative or anesthetic complications, except moderate hypertensive peaks that required a surgical pause and nitroprusside administration. No patient required a blood transfusion. The postoperative hospital stays were 7, 2 and 8 days, respectively. Resolution of clinical and biochemical parameters was accomplished in all patients. No patient had tumor with microscopic malignant features, and there was no recurrence nor metastatic spread with a follow-up of 24, 36 and 15 months. CONCLUSIONS This series suggests that LA in cases of pheocromocitoma in pediatric patients is feasible and safe.

Pheochromocytoma in children and adolescents: a clinical spectrum

Purpose The purpose of the study was to identify the spectrum of disease characteristics of pheochromocytoma in children. Methods Records of 21 consecutive children diagnosed with pheochromocytoma were reviewed. Patients' age, sex, presentation, associated conditions, diagnostic and imaging modalities used, preoperative preparation, operative details, outcome, and follow-up were recorded. Results The study included 21 children. Patients were diagnosed clinically and confirmed by biochemical tests. Tumors were localized by imaging studies and all were confirmed pathologically. Patients included 17 with adrenal and 4 with extra-adrenal tumors including 1 in the urinary bladder. Seventeen had sporadic and 4 had familial pheochromocytoma. Associated manifestations were the predominant features in 1 of the 4 patients with familial pheochromocytoma. The patient with bladder pheochromocytoma presented with gross hematuria. Hypertension and visual disturbances were prominent findings in the other patients with sporadic form. Two patients (1 sporadic and 1 familial) had malignant pheochromocytoma. One patient with benign pheochromocytoma had multiple recurrences in chromaffin-containing sites. All patients were treated surgically. Seventeen patients were treated preoperatively with alpha-adrenergic blockade. Two patients continued to have significant visual disturbances. One patient with malignant pheochromocytoma died of the disease, and 1 with recurrent pheochromocytoma had neurologic consequences. Conclusions Pheochromocytoma in children has unique characteristics. To our knowledge, this series is one of the largest reports of adrenal pheochromocytoma in children. It also reflects the spectrum of pheochromocytoma in this age group.

Recent advances in the diagnosis and treatment of pheochromocytoma in children

Background The purpose of this study was to analyze the effects of changes in the diagnosis and treatment of pheochromocytoma in a pediatric population. Methods We reviewed the medical records of all children who had resection of pheochromocytoma or paraganglioma at a major children’s hospital since 1968. Results Fifteen children underwent surgery at 11.9 ± 4.2 years of age. Presenting symptoms included headache, hypertension, and sweating. Three children had a mutation of the succinate dehydrogenase enzyme, and 1 child had nonsyndromic, familial pheochromocytoma. The most sensitive diagnostic modalities included 24-hour urinary and plasma norepinephrine and 24-hour urinary total metanephrines, magnetic resonance imaging, and 123I–meta-iodobenzylguanidine scintigraphy. Laparoscopic cortical-sparing adrenalectomy was performed in 3 patients with von Hippel-Lindau disease. Compared with those with open procedures (n = 7), patients who had laparoscopic resection (n = 5) had a statistically shorter hospital length of stay, and time to eating ambulation. Conclusions The addition of 123I–meta-iodobenzylguanidine scanning, genetic testing, and laparoscopic surgery has changed the diagnosis and treatment of pheochromocytoma in children. Laparoscopic cortical-sparing adrenalectomy can be accomplished safely and is the preferred treatment for children at risk for multifocal disease.

Pheochromocytoma complicated with severe ventricular tachycardia: report of one case.

Pheochromocytoma in children shows much worse complications than that in the adult patients. An 11-year-old girl was transferred to our emergency room after suffering from headache, dizziness, cold sweating and palpitation for 3 days. Severe hypertension, remarkable blood pressure fluctuation between 260/160 and 65/50 mmHg, decrease of cardiac contractility, as well as abnormal electrocardiogram findings including ST-T segment elevation and QT interval prolongation were noted soon after admission. Later, a 4x4.5x2.5 cm tumor in the right adrenal gland area was found by computed axial tomogram study. Assessment of the urine catecholamine metabolites showed high levels of vanillylmandelic acid, normetanephrine and norepinephrine indicating an active adrenal pheochromocytoma produced mainly norepinephrine. Although several antihypertensive drugs were used, ventricular tachycardia and Torsade de pointe still occurred on her for 3 times, each was preceded by a period of blood pressure fluctuation and burst out concomitantly at the peak of a hypertension crisis. From this case, we found that when the specific alpha-blocker like phenoxybenzamine or phentolamine was not available to us, labetalol by continuous intravenous infusion was the only effective drug to protect the patient from attacks of hypertensive crisis and ventricular tachycardia. Her right adrenal gland was resected smoothly when BP was well under control. Histological examination showed the adrenal medulla was full of pheochromocytoma cells.

MP-16.05: Characteristics of pheochromocytoma in children

Pheochromocytoma is rare in children. Pheochromocytoma may be sporadic or a part of familial syndrome. Manifestations of pheochromocytoma vary in children from those in adults. In this study, we try to identify disease characteristics of pheochromocytoma in children.

Pheochromocytoma in children

The results of an examination, treatment, and postoperative follow-up of 520 patients with pheochromocytomas who were operated on at the Endocrinology Research Center, Russian Academy of Medical Sciences, in 1957 to 2002 have been analyzed. The patients’ mean age was 39.3±9.2 years; 50 (9.6%) patients aged less than 16 years. There were 213 (41.0%) males in the total group and 32 (62.0%) in the pediatric group. Bilateral adrenal lesion was detected in 68 (13.1%), including 16 (32%) of the 50 children aged less than 16 years. Extraadrenal tumors were ascertained in 36 (6.9%). The concomitance of pheochromocytoma with hereditary syndromes was observed in 36 (6.9%) cases. Two hundred and sixty patients were followed up for 4 to 25 years (mean 8.4+1.9). Recurrence ofpheochromocytoma was revealed in 49 (18.8%) patients; the genuine recurrence (a tumor at the site of primary surgery or metastasis) was found in 16 (6.15%) patients. The genuine recurrence of pheochromocytoma was seen in 6 (12.0%) of the 50 children; its main cause was organ-preserving surgery for multicenter adrenal lesion.

An Overview of Magnetic Resonance Imaging Relating to Diagnosis, Extraction and Follow-up of a Pheochromocytoma

This essay defnes what constitutes a pheochromocytoma and its detection specifcally by MRI. It includes examples of protocols and types of sequences used by MRI to demonstrate this adrenal tumour. MR has a high sensitivity for detection of adrenal pheochromocytomas of 93-100%, but its sensitivity decreases when used for detection of extra-adrenal, metastatic or recurrent lesions (90%). The specifcity of MRI in excluding pheochromocytomas has been shown to be limited, often even as low as 50%. Despite this, MRI has the potential to be the sole imaging modality needed to diagnosis, monitor treatment and even aid in the removal of a pheochromocytoma from the body. MRI is especially useful as the initial imaging procedure for imaging pheochromocytomas in children, during pregnancy, or in patients with a known allergic reaction to contrast agents. This article also gives a detailed description of how a pheochromocytoma is extracted by way of a laparoscopic procedure.

Utility of plasma free metanephrines for detecting childhood pheochromocytoma.

Measurements of plasma free metanephrines, normetanephrine (NMN) and metanephrine (MN), provide a sensitive test for diagnosis of pheochromocytoma in adults but have not been evaluated in children. We therefore established reference ranges for plasma and urinary metanephrines and the catecholamines, norepinephrine (NE) and epinephrine (E), in 86 healthy children (age 5-17). A group of 158 healthy adults (age 18-72) served as a comparison group. Pediatric reference ranges were applied to examine the diagnostic utility of the various tests in 45 children evaluated for pheochromocytoma (age 8-17; 38 with von Hippel-Lindau syndrome), with tumors found on 12 occasions. Upper reference limits for E and MN were higher and those for NE and NMN lower in children than in adults. Boys had higher plasma levels of E and MN and higher urinary excretion of all four amines than girls. Plasma free metanephrines provided a diagnostic test with values for sensitivity (100%) and specificity (94%) that were equal to or higher than those of other tests. In two children screened for pheochromocytoma on multiple occasions, use of pediatric reference ranges for plasma free metanephrines indicated the tumor a year earlier than indicated using adult reference ranges. The findings indicate that plasma free metanephrines provide a sensitive tool for detection of pheochromocytoma in children. Age appropriate reference ranges should be used and gender differences should be considered.

Pheochromocytoma in children

Background/Purpose: Etiopathogenesis, management, and outcome of pediatric pheochromocytoma (PHEO) still is obscure because of limited number of cases. Therefore, a retrospective clinical study was performed to present an updated picture of the entire spectrum of pediatric PHEO based on the authors' 30 years' experience consisting of one of the largest noncollected series treated in a single medical center. Methods: Records of patients treated for PHEO in the authors' unit from 1970 to 1999, inclusive, were reviewed retrospectively. Information recorded for each patient included age, sex, past medical and family history, clinical characteristics, diagnostic methods, treatment, pathologic findings, and outcome. Results: Sixteen children with a mean age of 10.7 ± 2.9 years consisting of 12 boys and 4 girls were treated for PHEO. Most of the tumors were right sided (n = 6) and bilateral (n = 6). Sporadic cases of PHEO accounted for 14 patients (88%), whereas 2 children had von Hippel-Lindau (VHL) disease and multiple endocrine neoplasia type 2b (MEN2b). Hypertension was the most common symptom followed by headache and sweating. The diagnosis of PHEO was made by laboratory and radiologic studies. Preoperative medical therapy was done in all patients. Laparotomy confirmed that 11 patients had localized, 4 patients had regional, and 1 patient had metastatic disease. The localized tumors were excised totally by bilateral (n = 4) and unilateral (n = 6) adrenalectomy. Surgical procedures performed for regional disease were total excision (n = 2), incisional biopsy (n = 1) and partial excision (n = 1). Incisional biopsy could be taken only from a patient with metastatic disease at presentation. Two patients with localized disease and 2 patients with regional disease had benign recurrences in right (n = 2) and left (n = 2) adrenal glands within 3 to 7 years after operation. Total excision of the recurrent tumors was done in all patients. Pathologic examination found apparently malignant features in 3 patients who presented with regional (n = 2) or metastatic (n = 1) disease and underwent incisional biopsy (n = 2) or partial excision (n = 1). Pathologic features suggestive of malignancy were noted in 4 patients presenting with regional (n = 2) and localized disease (n = 2). Apparently benign pathologic features were noted in the remaining 9 patients. There was not any operative mortality in our series. Adjuvant chemotherapy was commenced postoperatively in all patients with malignant and suggestive of malignant pathologic features. During the long-term follow-up for 16 years, 3 patients died (19%). One patient with VHL disease died of astrositoma 5 years after her recurrent PHEO was excised. Of the 3 patients with malignant disease, 2 patients in whom only incisional biopsies were done had distant metastases and died of disease within 2 years. Another patient with malignancy who had MEN2b was lost to follow-up. Conclusions: Early diagnosis and total excision are the most important aspects of accurate treatment for childhood PHEO. Pre- intra- and postoperative medical management is as important as the surgical procedure. Our surgical treatment policy is mainly minimizing the risk of recurrence while preserving adequately functioning adrenal medullar tissue. Incomplete excision and advanced-stage disease are the major determinants of poor outcome. None of the clinical, laboratory, or pathologic features are reliable predictors for recurrence and discrimination of malignancy. Because of the steadily increasing incidence of precancerous genetic syndromes related to adrenal glands and poor prognosis of advanced-stage PHEO, childhood cases of hypertensive disorders should receive a detailed and vigorous diagnostic evaluation and appropriate treatment as given to adults. J Pediatr Surg 36:447-452. Copyright © 2001 by W.B. Saunders Company.

Twenty-Five-Year Surgical Experience with Pheochromocytoma in Children

Our objective was to analyze the presentation, diagnostic localization, operative management, histology, and long-term outcome of a single center's experience with pheochromocytomas in children. A chart review was done to identify all operatively managed pheochromocytomas in patients age 18 years or younger. Open and laparoscopic cases were included. We reviewed the presentation, diagnostic imaging, localization, operative management, pathology, and postoperative outcome of these patients. Clinic visits, contact with the tumor registry, and telephone interviews were used for follow-up. From 1973 through 1999, there were 11 children (four males and seven females) with 14 pheochromocytomas. Two (18.2%) patients had bilateral adrenal lesions and one patient had both adrenal and extra-adrenal tumors. Six (54.5%) patients had extra-adrenal lesions. The average age at operation was 14.7 years (range 9-18 years). Nine (82%) patients had significant hypertension at presentation. CT was used to localize the tumor in eight patients and urine catecholamine levels were used to confirm the diagnosis. Two of the cases were associated with inherited syndromes (multiple endocrine neoplasia 2A and von Hippel-Lindau). Ten patients underwent an open operation and one patient had a laparoscopic resection. The average patient follow-up was 9.2 years (range 9 months to 25 years). There were no operative complications and all patients were alive and well at the time of last follow-up. Three patients (27.2%) had tumors with microscopic malignant features. No tumors recurred or had evidence for metastatic spread. We conclude that peak incidence of pheochromocytomas in children is in early adolescence. Resection can be carried out safely with minimal morbidity and mortality. Current best management of this entity includes establishment of a biochemical diagnosis, adequate preoperative blockade, appropriate imaging, and an individualized operative approach based on tumor location and size.

PHEOCHROMOCYTOMA: Special Considerations in Children

Pheochromocytoma is a rare but important tumor in children. Appropriate evaluation and management are essential for a favorable outcome. Pheochromocytomas are more often multifocal and extra-adrenal in children when compared with adults. This pattern makes the diagnosis, localization, and surgical management more challenging. Nonetheless, the standard biochemical evaluation is usually diagnostic, and MR imaging is currently the best tool for tumor localization. The possibility of a familial syndrome must always be considered and should always be thoroughly evaluated when children present with a pheochromocytoma. Conversely, children with a familial syndrome should undergo annual screening for pheochromocytoma from a young age. Given the greater likelihood of a metachronous recurrence in children, consideration should be given to adrenal-sparing surgery in selected patients. When managed appropriately, the outlook for pheochromocytoma in children is excellent. Unfortunately, the uncommon malignant tumors are still difficult to treat. Perhaps the unique genetic characteristics of pheochromocytoma will ultimately be exploited in the management of the aggressive forms of this disease.