MASH1 induces neuron transdifferentiation of adrenal medulla chromaffin cells / 中南大学学报(医学版)

OBJECTIVES@#Nerve growth factor (NGF) induces neuron transdifferentiation of adrenal medulla chromaffin cells (AMCCs) and consequently downregulates the secretion of epinephrine (EPI), which may be involved in the pathogenesis of bronchial asthma. Mammalian achaete scute-homologous 1 (MASH1), a key regulator of neurogenesis in the nervous system, has been proved to be elevated in AMCCs with neuron transdifferentiation in vivo. This study aims to explore the role of MASH1 in the process of neuron transdifferentiation of AMCCs and the mechanisms.@*METHODS@#Rat AMCCs were isolated and cultured. AMCCs were transfected with siMASH1 or MASH1 overexpression plasmid, then were stimulated with NGF and/or dexamethasone, PD98059 (a MAPK kinase-1 inhibitor) for 48 hours. Morphological changes were observed using light and electron microscope. Phenylethanolamine-N-methyltransferase (PNMT, the key enzyme for epinephrine synthesis) and tyrosine hydroxylase were detected by immunofluorescence. Western blotting was used to test the protein levels of PNMT, MASH1, peripherin (neuronal markers), extracellular regulated protein kinases (ERK), phosphorylated extracellular regulated protein kinases (pERK), and JMJD3. Real-time RT-PCR was applied to analyze the mRNA levels of MASH1 and JMJD3. EPI levels in the cellular supernatant were measured using ELISA.@*RESULTS@#Cells with both tyrosine hydroxylase and PNMT positive by immunofluorescence were proved to be AMCCs. Exposure to NGF, AMCCs exhibited neurite-like processes concomitant with increases in pERK/ERK, peripherin, and MASH1 levels (all P<0.05). Additionally, impairment of endocrine phenotype was proved by a signifcant decrease in the PNMT level and the secretion of EPI from AMCCs (all P<0.01). MASH1 interference reversed the effect of NGF, causing increases in the levels of PNMT and EPI, conversely reduced the peripherin level and cell processes (all P<0.01). MASH1 overexpression significantly increased the number of cell processes and peripherin level, while decreased the levels of PNMT and EPI (all P<0.01). Compared with the NGF group, the levels of MASH1, JMJD3 protein and mRNA in AMCCs in the NGF+PD98059 group were decreased (all P<0.05). After treatment with PD98059 and dexamethasone, the effect of NGF on promoting the transdifferentiation of AMCCs was inhibited, and the number of cell processes and EPI levels were decreased (both P<0.05). In addition, the activity of the pERK/MASH1 pathway activated by NGF was also inhibited.@*CONCLUSIONS@#MASH1 is the key factor in neuron transdifferentiation of AMCCs. NGF-induced neuron transdifferentiation is probably mediated via pERK/MASH1 signaling.

Feocromocitoma y Paraganglioma: un reto más allá de la clínica / Pheochromocytoma and Paraganglioma: a Challenge beyond the Clinic

Resumen Los feocromocitomas y paragangliomas son tumores raros que se originan en las células cromafines. Tienen un amplio espectro clínico que va desde el hallazgo incidental hasta manifestaciones por la producción exagerada de catecolaminas. El diagnóstico bioquímico se realiza mediante medición de metanefrinas libres en plasma. El tratamiento ideal es la escisión quirúrgica completa previo bloqueo de receptores a y 6 adrenérgicos. En caso de enfermedad metastásica, las opciones de tratamiento sistêmico actuales son limitadas y con escasa tasa de respuesta. Está en investigación el uso de antiangiogénicos.

Abstract Pheochromocytomas and Paragangliomas are rare tumors, originated from the chromaffin cells. They have a broad clinical spectrum from incidental finding to full clinical manifestations explain to overproduction of catecholamines. The biochemistry diagnosis is made by the measurement of free Metanephrines in plasma. Complete surgical removal is the optimal treatment, previously having a y 6 adrenergic receptors blockage. In case of metastasic disease, treatment options are palliative, limited and with a low rate response; the use of antiangiogenic treatments is under investigation.

Epidemiology and Prognosis of Pheochromocytoma/Paraganglioma in Korea: A Nationwide Study Based on the National Health Insurance Service

BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors originating from chromaffin cells. PPGLs are associated with a high mortality rate and several complications. To date, no epidemiological studies have been conducted on PPGLs in Asia. This study aimed to investigate the epidemiology and prognosis of PPGLs in Korea using nationwide data.METHODS: Using the National Health Insurance Service Database, subjects with a principal diagnosis of PPGLs on two or more occasions between 2003 and 2014 who satisfied the operational definition of PPGLs were included. Incidence, prevalence, complications, metastasis, and mortality were investigated.RESULTS: In total, 1048 subjects with a mean age of 47.6±16.1 years were included. There was no sex preponderance. The overall prevalence of PPGLs was 2.13 per 100,000 persons, and the overall age-standardized incidence rate was 0.18 per 100,000 person-years. Malignant PPGLs accounted for 17.7% (185 of 1,048) of cases, and 94 subjects exhibited metastasis at the time of diagnosis. Among initially non-metastatic PPGLs, 9.5% (nine of 954) eventually metastasized after a mean duration of 78.1±41.4 months. The 5-year survival rates for non-metastatic and metastatic PPGLs at diagnosis were 97% and 84%, respectively. Multivariable Cox regression models adjusted for covariates showed that metastatic PPGLs were associated with a 2.40-fold higher risk of mortality than non-metastatic PPGLs (95% confidence interval, 1.38 to 4.17; P=0.002).CONCLUSION: PPGLs are rare in Korea, and the prognosis of these endocrine tumors varies depending on whether they are benign or malignant. This epidemiological study paves the way for further research on PPGLs.

Melatonin inhibits nicotinic acetylcholine receptor functions in bovine chromaffin cells

Melatonin is a neurotransmitter that modulates various physiological phenomena including regulation and maintenance of the circadian rhythm. Nicotinic acetylcholine receptors (nAChRs) play an important role in oral functions including orofacial muscle contraction, salivary secretion, and tooth development. However, knowledge regarding physiological crosstalk between melatonin and nAChRs is limited. In the present study, the melatonin-mediated modulation of nAChR functions using bovine adrenal chromaffin cells, a representative model for the study of nAChRs, was investigated. Melatonin inhibited the nicotinic agonist dimethylphenylpiperazinium (DMPP) iodide-induced cytosolic free Ca²⁺ concentration ([Ca²⁺](i)) increase and norepinephrine secretion in a concentration-dependent manner. The inhibitory effect of melatonin on the DMPP-induced [Ca²⁺](i) increase was observed when the melatonin treatment was performed simultaneously with DMPP. The results indicate that melatonin inhibits nAChR functions in both peripheral and central nervous systems.

Acute Aortic Dissection in a Patient with Pheochromocytoma / 대한내과학회지

Pheochromocytomas are neoplasms of the adrenal gland that are derived from chromaffin cells. One of the most important features of this tumor is that it can synthesize and release catecholamines such as norepinephrine and epinephrine. Due to this, arterial hypertension is one of the most common manifestations of the tumor. Although arterial hypertension is a substantial risk factor for aortic dissection, aortic dissection is actually a rare manifestation of pheochromocytoma. Here, we report a patient with pheochromocytoma who presented with acute type B aortic dissection.

A Case of Pheochromocytoma Initially Manifesting as Acute Myocardial Infarction

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors arising from chromaffin cells in the adrenal medulla. Typical classic triad are consisted of headaches, palpitations, and profuse diaphoresis. But some patients with pheochromocytomas have other cardiovascular manifestations such as left ventricular hypertrophy, congestive heart failure, and cardiac arrhythmia. Rarely, pheochromocytomas manifest as acute myocardial infarction leading to delayed diagnosis and treatment. We experienced one case of pheochromocytoma initially manifesting as acute myocardial infarction which showed normal coronary artery on coronary angiography. Pheochromocytoma should be suspected and evaluated in patients with acute myocardial infarction whose coronary angiography shows normal coronary without definite thrombosis.

A Case Report of Recurrent Malignant Paraganglioma with Lung and Spine Metastasis that Occurred Sixteen Years after Primary Tumor Excision / 대한내과학회지

Paragangliomas are rare tumors that arise from the extra-adrenal chromaffin cells, and malignancy is defined by the presence of metastases to sites that normally lack chromaffin tissue. The main therapeutic targets are tumor reduction and control of excessive catecholamine secretion. Currently, the adjuvant therapy to surgery is radiotherapy treatment using high-dose MIBG; chemotherapy is currently evolving. We report herein a case of malignant paraganglioma with lung and spine metastasis that occurred 16 years after primary tumor excision and was treated with high dose MIBG radiotherapy and chemotherapy.

Inhibitory Effects of Ginsenoside-Rb2 on Nicotinic Stimulation-Evoked Catecholamine Secretion

The aim of the present study was to investigate whether ginsenoside-Rb2 (Rb2) can affect the secretion of catecholamines (CA) in the perfused model of the rat adrenal medulla. Rb2 (3~30 microM), perfused into an adrenal vein for 90 min, inhibited ACh (5.32 mM)-evoked CA secretory response in a dose- and time-dependent fashion. Rb2 (10 microM) also time-dependently inhibited the CA secretion evoked by DMPP (100 microM, a selective neuronal nicotinic receptor agonist) and high K+ (56 mM, a direct membrane depolarizer). Rb2 itself did not affect basal CA secretion (data not shown). Also, in the presence of Rb2 (50 microg/mL), the secretory responses of CA evoked by veratridine (a selective Na+ channel activator (50 microM), Bay-K-8644 (an L-type dihydropyridine Ca2+ channel activator, 10 microM), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 microM) were significantly reduced, respectively. Interestingly, in the simultaneous presence of Rb2 (10 microM) and L-NAME (an inhibitor of NO synthase, 30 microM), the inhibitory responses of Rb2 on ACh-evoked CA secretory response was considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of Rb2-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of Rb2 (10 microM) was greatly elevated compared to the corresponding basal released level. Collectively, these results demonstrate that Rb2 inhibits the CA secretory responses evoked by nicotinic stimulation as well as by direct membrane-depolarization from the isolated perfused rat adrenal medulla. It seems that this inhibitory effect of Rb2 is mediated by inhibiting both the influx of Ca2+ and Na+ into the adrenomedullary chromaffin cells and also by suppressing the release of Ca2+ from the cytoplasmic calcium store, at least partly through the increased NO production due to the activation of nitric oxide synthase, which is relevant to neuronal nicotinic receptor blockade.

A New Approach to the Treatment of Metastatic Paraganglioma: Sorafenib / Journal of the Korean Cancer Association, 대한암학회지

Paragangliomas are relatively rare chromaffin cell tumors which may be cured through resection. Patients with paragangliomas may develop metastatic diseases. There is no consensus regarding refractory chemotherapy for treatment of metastatic disease. In this report, we presented a case of a 43-year-old woman who was admitted to the hospital with a history of episodic headaches, diaphoresis, and weakness. Elevated plasma catecholamine levels and a right paraaortic mass were observed on computed tomography. The mass was excised, and a diagnosis of paraganglioma was confirmed. After 20 months of follow-up, local recurrence and metastases were detected in the thorax, abdomen, and skeletal system. Plasma and urinary catecholamine levels were high. Chemotherapy was administered, and no improvement was observed. Therefore, following this palliative conventional chemotherapy, sorafenib was administered for three months, and, finally, positron emission tomography showed that the patient's lesions had completely regressed.

A Case of Functioning Paraganglioma Mimicking Anaphylactic Shock: A Case Report / 대한구급학회지

Paraganglioma is a tumor originating from the extra-adrenal chromaffin cells, and functional paraganglioma causes paroxysmal hypertension, headache and tachycardia, due to excess excretion of catecholamine. However, rarely, ARDS, acute myocardial infarction, heart failure, arrhythmia, and pulmonary edema are also seen in patients with paraganglioma and clinical manifestations are depending on the patient's intravascular volume status. Seventy one-years-old male was presented with hypotension and pulmonary edema after intravenous midazolam injection during colonoscopy under conscious sedation. The patient was initially suspected with anaphylactic shock, due to midazolam injection. However, later, he was diagnosed with paraganglioma, and blood pressure was successfully controlled with alpha adrenergic blockade. We suggest that when we encounter heart failure, pulmonary edema and shock of unknown origin, pheochromocytoma must be taken into consideration.

Influence of PD 123319 (AT2-Receptor Antagonist) on Catecholamine Secretion in the Perfused Rat Adrenal Medulla

BACKGROUND: The aim of this study was to examine whether PD 123319 (an angiotensin II type 2 [AT2] receptor antagonist) can influence the release of catecholamines (CA) from the perfused model of the rat adrenal medulla. METHODS: The adrenal gland was isolated by the modification of Wakade method, and perfused with normal Krebs-bicarbonate solution. The content of CA was measured using the fluorospectrophotometer. RESULTS: During perfusion of PD 123319 (range, 5 to 50 nM) into an adrenal vein for 90 minutes the CA secretory responses evoked by acetylcholine (ACh), high K+, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), and McN-A-343 was dose- and time-dependently inhibited. Furthermore, loading with PD 123319 for 90 minutes also markedly inhibited the CA secretory responses evoked by 4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644), cyclopiazonic acid, veratridine, and angiotensin II (Ang II). PD 123319 did not affect basal CA output. Simultaneous perfusion of PD 123319 and CGP 42112 perfused into an adrenal vein for 90 minutes rather more potently inhibited the CA seretory responses evoked by Ach, high K+, DMPP, Bay-K-8644, veratridine, and Ang II compared to the inhibitory effect by PD123319-treated alone. CONCLUSIONS: Taken together, these results show that PD 123319 inhibits the CA secretion evoked by both cholinergic and Ang II receptor stimulation from the perfused rat adrenal medulla. This inhibitory effect of PD 123319 seems to be exerted by blocking the influx of both Na+ and Ca2+ through their voltage-dependent channels into the rat adrenomedullary chromaffin cells as well as by reducing the Ca2+ release from its cytoplasmic calcium store, which may be relevant to AT2 receptor blockade. Based on these present data, it is thought that PD 123319 has different activity from previously known AT2 antagonist activity in the perfused adrenal medulla, and that AT2 receptors may be involved in the rat adrenomedullary CA secretion.

Influence of Fimasartan (a Novel AT1 Receptor Blocker) on Catecholamine Release in the Adrenal Medulla of Spontaneously Hypertensive Rats

The aim of this study was to determine whether fimasartan, a newly developed AT1 receptor blocker, can affect the CA release in the isolated perfused model of the adrenal medulla of spontaneously hypertensive rats (SHRs). Fimasartan (5~50 microM) perfused into an adrenal vein for 90 min produced dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high K+ (56 mM, a direct membrane depolarizer), DMPP (100 microM) and McN-A-343 (100 microM). Fimasartan failed to affect basal CA output. Furthermore, in adrenal glands loaded with fimasartan (15 microM), the CA secretory responses evoked by Bay-K-8644 (10 microM, an activator of L-type Ca2+ channels), cyclopiazonic acid (10 microM, an inhibitor of cytoplasmic Ca(2+)-ATPase), and veratridine (100 microM, an activator of Na+ channels) as well as by angiotensin II (Ang II, 100 nM), were markedly inhibited. In simultaneous presence of fimasartan (15 microM) and L-NAME (30 microM, an inhibitor of NO synthase), the CA secretory responses evoked by ACh, high K+, DMPP, Ang II, Bay-K-8644, and veratridine was not affected in comparison of data obtained from treatment with fimasartan (15 microM) alone. Also there was no difference in NO release between before and after treatment with fimasartan (15 microM). Collectively, these experimental results suggest that fimasartan inhibits the CA secretion evoked by Ang II, and cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of fimasartan may be mediated by blocking the influx of both Na+ and Ca2+ through their ion channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the Ca2+ release from the cytoplasmic calcium store, which is relevant to AT1 receptor blockade without NO release.

A Case of Pheochromocytoma Associated with Diabetic Ketoacidosis and Infective Endocarditis / 임상당뇨병

Pheochromocytoma is a rare neuroendocrine tumor that is usually derived from adrenal medulla or chromaffin cells along with sympathetic ganglia. In Western countries, the prevalence of pheochromocytoma is estimated to be between 1:6,500 and 1:2,500, compared with an incidence in the United States of 500 to 1,100 cases per year. Despite this low incidence, pheochromocytoma should always be considered for differential diagnoses because previous studies have shown that this condition can be cured in approximately 90% of cases. However, an untreated tumor is likely to be fatal due to catecholamine-induced malignant hypertension, heart failure, myocardial infarction, stroke, ventricular arrhythmias or metastatic disease. Symptoms that result primarily from excess circulating catecholamines and hypertension include severe headaches, generalized inappropriate sweating and palpitations (with tachycardia or occasionally bradycardia). Pheochromocytoma, however, has highly variable and heterogeneous clinical manifestations, including fever, general weakness and dyspepsia, and can be observed in patients who are suffering from infectious diseases. Several of such case reports have been presented, but most of these included infectious patients with high blood pressure and severe fluctuations. In this study, we presented the case of a 53-year-old male who showed normal blood pressure, but had a sustained fever. He was diagnosed with diabetic ketoacidosis, infective endocarditis and asymptomatic adrenal incidentaloma. Despite treatment with antibiotics and valve replacement, the fever persisted. After the patient underwent evaluation for the fever, adrenal incidentaloma was identified as pheochromocytoma. After removal of the abdominal mass, his fever improved.

Altered secretory activity in rat adrenal chromaffin cells after experimentally induced bronchial asthma and dexamethasone treatment: ultrastrucutral and biochemical study

It is generally accepted that chromaffin cells release their contents by both exocytosis and piecemeal degranulaltion [PMD]. Bronchial asthma and dexamethasone treatment might after this secretory activity. This study was designed to shed light on secretory activity in the normal adult rate chromaffin cells, in rats subjected to bronchial asthma and after treatment with dexamethasone. Rats were divided into three equal groups at random:group A[control], group B [asthmatic rats], and group C [dexamethasone-treated asthmatic rats]. In rats of group B, the chronic asthma model was established by an intraperitoneal injection and challenge with ovalbumin. In group C, the rats were pretreated with dexamethasone before each challenge. Serum epinephrine and norepinephrine levels were measured by enzyme-linked immunosorbent assay. Bronchoalveolar lavage fluid was examined for the total leukocytic count and paraffin sections from the lung were stained with H and E. Specimens of the adrenal medulla were examined by transmission electron microscope and were morphometrically analyzed. Significant decreases in serum epinephrine and norepinephrine levels were recorded in asthmatic rats and corrected after dexamethasone treatment. The total numbers of adrenaline and noradrenaline granules were significantly lower in asthmatic rats. Features of PMD manifested as tail-like projections, altered granules with eroded contents, partially empty granules, large completely empty containers, and small cytoplasmic vesicles were observed in control rats and were augmented in rats subjected to chronic asthma. Augmented features of PMD and biochemical changes in the conditions of chronic asthma could be corrected by dexamethasone treatment

A Case of Dopamine-Secreting Pheochromocytoma

A pheochromocytoma is a neuroectodermal tumor that originates from the chromaffin cells of the sympathetic system. It has typical symptoms or signs, such as periodic attacks of paroxysmal hypertension, palpitation, headache, and sweating, related to an increased catecholamine secretion. Types of catecholamine secreted from tumors are usually norepinephrine and epinerphrine. There are a few reports of dopamine-secreting pheochromocytoma with absence of other catecholamines secretion. Here, we report the case of a 59-year-old man with dopamine-secreting pheochromocytoma, with no typical symptoms or signs.

Feocromocitoma bilateral: presentación de un caso / Bilateral pheochromocytoma: presentation of a case

El feocromocitoma como causa de hipertensión arterial secundaria tiene una baja incidencia. La edad de presentación más frecuente es entre 30 y 50 años. Puede tener carácter hereditario autosómico dominante. Sus manifestaciones clínicas no dependen de la topografía ni del tamaño del tumor. Puede debutar con complicaciones graves. Se presenta un paciente de 32 años, cuyo padre hipertenso fallece a los 38 años, sin precisar la causa. El paciente ingresa por el debut de una hipertensión paroxística, se demuestra por ultrasonido y tomografía axial computarizada grandes tumores suprarrenales bilaterales, compatibles con feocromocitoma y el paciente fallece cuatro días después del ingreso por un edema agudo del pulmón, en el curso de una emergencia hipertensiva. Comprobándose por anatomía patológica el diagnóstico tanto macro como microscópico, de feocromocitoma

The pheochromocytoma as a cause of secondary arterial hypertension has low incidence. The most frequent age of presentation is between 30 and 50 years old. It can have dominant autosomyc hereditary character. Its clinical manifestation does not depend on the topography or the size of the tumor. It can debut with serious complications. We present the case of a patient aged 32, whose hypertensive father died at the age of 38, without specified cause. The patient entered the hospital for the debut of a paroxysmal hypertension. By means of ultrasound and on-line axial tomography there were found bilateral suprarenal tumors compatible with pheochromocytoma and the patient dies four days after entering the hospital by acute lung edema, during a hypertensive emergency. It was proven, for pathologic anatomy, the diagnosis so much macroscopic as microscopic, of pheochromocytoma

Study on relationship of dose-effect and time-effect of APA microencapsulated bovine chromaffin cells on pain treatment / 生物医学工程学杂志

This study was to investigate the relationship of dose-effect and time-effect of Alginate-Polylysine-Alginate (APA) microencapsulated bovine chromaffin cells on the treatment of pain model rats. Using a rat model of painful peripheral neuropathy, the antinociceptive effects of APA microencapsulated bovine cells transplanted into the subarachnoid space was evaluated by cold allodynia test and hot hyperalgesia test. Compared with control group, the withdrawal difference with cell number 50 thousands groups, 100 thousands groups and 200 thousands groups was reduced (P < 0.05), and the difference decreased with the cells increases, indicating a significant analgesic effect. There was no significant difference between 400 thousands groups and 200 thousands groups. This analgesic effect maintained longer than 12 weeks. There was a positive correlation between the analgesic effect and the quantity of APA microencapsulated bovine chromaffin cells which were transplanted to treat pain model rats, and the effective antinociception remained longer than 12 weeks.

Case of Pheochromocytoma Presenting as a Seizure in the Emergency Department

Pheochromocytomas are catecholamine-producing tumors that originate from chromaffin cells of adrenal medulla. Typical symptoms are paroxysmal hypertension, headache, hyperhidrosis, and hypermetabolism. But, the clinical presentation is sometimes quite variable. Atypical clinical presentations can complicate diagnosis. Seizure as a presenting symptom is very rare in pheochromocytoma. We report the case of a 58-year-old female transferred to our emergency department with seizure and transient stuporous mentality. Incidentally, we diagnosed pheochromocytoma by femoral artery computed tomography because of puncture complication in the femoral artery.

Case of Pheochromocytoma Presenting as a Seizure in the Emergency Department

Pheochromocytomas are catecholamine-producing tumors that originate from chromaffin cells of adrenal medulla. Typical symptoms are paroxysmal hypertension, headache, hyperhidrosis, and hypermetabolism. But, the clinical presentation is sometimes quite variable. Atypical clinical presentations can complicate diagnosis. Seizure as a presenting symptom is very rare in pheochromocytoma. We report the case of a 58-year-old female transferred to our emergency department with seizure and transient stuporous mentality. Incidentally, we diagnosed pheochromocytoma by femoral artery computed tomography because of puncture complication in the femoral artery.

Laparoscopically Resected Composite Pheochromocytoma-Ganglioneuroma

Composite pheochromocytoma-ganglioneuroma is one of the mixed neuroendocrine-neural tumors composed of pheochromocytoma and other neural crest derivatives. To date, less than 50 cases of composite pheochromocytoma have been reported, and about 70% of the accompanying tumors were ganglioneuromas. Here, we describe six cases of composite pheochromocytoma-ganglioneuromas in five men and one woman, aged 33 to 64. The size of the tumors ranged from 3.0 to 11.0 cm, and four out of the six presented with intermittent onset of hypertension, palpitation, or dizziness. Microscopically, each tumor was composed of large pleomorphic shaped chromaffin cells arranged in the Zellballen patterns characteristic of pheochromocytoma, and they were mixed with clusters of mature ganglion cells and bundles of spindle-shaped Schwann cells characteristic of ganglioneuroma of variable proportions. All were successfully treated laparoscopically, and none were associated with multiple endocrine neoplasm syndrome or neurofibromatosis. Preoperative diagnosis of a composite pheochromocytoma-ganglioneuroma is impossible because of the low incidence rate, and the radiological findings and symptoms are similar to those of typical pheochromocytomas. Although the significance of microscopic detection of the nonpheochromocytoma component from pheochromocytoma has not yet been clarified, microscopic identification of the composite pheochromocytoma-ganglioneuroma is important because cumulative cases are used in an effort to predict the behavior of this composite tumor.