1. Asymptomatic paraganglioma
Kyunghee University College of Medicine
Department of Internal Medicine
R3 Ha Sung Hyung

2. Clinical characteristics
Sustained or paroxysmal hypertension is the most common sign.
Classic triad — ‘episodic headache, sweating, palpitation’
- Headche: mild or severe, and variable in duration, occurs in
up to 90%.
- Sweating: occurs in up to 60 to 70%.
- Other symptoms include dyspnea, generalized weakness, and panic attack-type symptoms….
A simplified diagnostic approach to pheochromocytoma.
Medicine (Baltimore) 1991; 70:46.

3. Less common symptoms Pallor, Constipation, Orthostatic hypotension,
Visual blurring,
Papilledema,
Weight loss,
Polyuria,
Polydipsia,
..may reflect the toxic effect of excess catecholamines
Pheochromocytoma: New concepts and future trends.
Kidney Int 1991; 40:544.
Constipation,
Increased ESR,
Hyperglycemia,
Leukocytosis,
Psychiatric disorders,
Dilated cardiomyopathy

4. There were no statistically significant differences in tumor size,
ORIGINAL ARTICLE NIPPON ACTA RADIOLOGICA 2001; 61: 33-38
Significance of CT Findings and Catecholamine Determination in Peripheral Blood of Asymptomatic Pheochromocytoma and Paraganglioma 
SUMMARY The purpose of this study was to assess the CT findings and significance of hormone determination in the peripheral blood of asymptomatic patients with pheochromocytoma and paraganglioma. CT findings in 29 patients with surgically proven pheochromocytoma(n = 19)and paraganglioma(n = 10)were reviewed. Nine patients(31%)were symptomatic and 20 (69%)were asymptomatic. Tumor size ranged from 39 mm to 114 mm(mean: 60 mm)in symptomatic patients and 11 mm to 100 mm(mean: 50 mm)in asymptomatic ones. Of the 9 symptomatic patients and 18 asymptomatic patients, a homogeneous solid pattern was seen in 4 and 4, mixed pattern in 2 and 6, and massive necrotic pattern in 3 and 8 patients, respectively, on CT scans. The CT attenuation values in symptomatic cases ranged from 30 HU to 50 HU(mean: 41 HU)on precontrast CT scans and 60 HU to 111 HU(mean: 77 HU)on postcontrast CT scans, while those in asymptomatic cases ranged from 15 HU to 48 HU(mean: 33 HU)on precontrast CT scans and 66 HU to 133 HU(mean: 95 HU)on postcontrast CT scans. There were no statistically significant differences in tumor size, homogeneity, or CT attenuation values between symptomatic and asymptomatic patients. All symptomatic patients and 17(89%)of 19 asymptomatic cases showed elevated levels of catecholamine(epinephrine)or norepinephrine in the peripheral blood. Our study showed that the CT findings in asymptomatic patients were similar to those in symptomatic patients, and 89% of asymptomatic patients showed elevation of catecholamine in the peripheral blood. Determination of catecholamine level in the peripheral blood is recommended for preoperative diagnosis in patients suspected of having asymptomatic pheochromocytoma or paraganglioma on CT scans.
Received Jul. 14, 2000; revision accepted Dec. 9, 2000
There were no statistically significant differences in tumor size,
homogeneity, or CT attenuation values between symptomatic and
asymptomatic patients.
All symptomatic patients and 17(89%)of 19 asymptomatic cases
showed elevated levels of catecholamine(epinephrine)or norepinephrine
in the peripheral blood.
Our study showed that the CT findings in asymptomatic patients were
similar to those in symptomatic patients.

5. 1995년 6월 ~ 1999년 10월, 수술적 절제 후 병리조직학적 소견상 갈색세포종으로
진단된 34명의 환자.
특이 증상 없이 다른 질환으로 CT촬영이나 초음파상 우연히 발견된 예14예(41%) ;
MEN 선별검사상 발견된 예가 2예
건진 복부 초음파상 발견된 예가 4예
복부동통, 설사, 혈변, 등의 증상으로 시행한 복부 CT상 발견된 예가 5예
고혈압 선별 검사상 발견된 예가 2예

6. PHEOCHROMOCYTOMA IN GENETIC DISORDERS
Most catecholamine-secreting tumors are sporadic.
Some patients (15 to 20%) have the disease as part of a familial disorder.
; in these patients the catecholamine-secreting tumors are more likely to be bilateral adrenal pheochromocytomas or paragangliomas.
Familial pheochromocytoma
There are two primary familial disorders associated with pheochromocytoma, both of which have autosomal dominant inheritance:
von Hippel-Lindau (vHL) syndrome & MEN2

7. Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes.
J Clin Endocrinol Metab 2001; 86:1999.
- Tyrosine hydroxylase (TH) : the rate-limiting enzyme in catecholamine syn.
- Phenylethanolamine N-methyltransferase (PNMT) : the enzyme that converts norepinephrine to epinephrine.
MEN 2 patients :
- more symptomatic and higher incidence of hypertension and higher plasma concentrations of metanephrines,
- but paradoxically lower total plasma concentrations of catecholamines
VHL patients :
- specific increases in the norepinephrine metabolite, normetanephrine.
- explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT

8. Pheochromocytomas and paragangliomas in von Hippel-Lindau disease: a role for laparoscopic and cortical-sparing surgery Arch Surg 2002; 137:682.
A total of 109 patients identified at the Mayo Clinic, Rochester, Minn, with VHL (60 males and 49 females) between January 1, 1975, and June 30, Seventeen patients (16%) had an identifiable adrenal mass and 3 patients had paragangliomas. Follow-up was complete in all but 2 patients.
RESULTS: Three patients with paragangliomas and 13 of 17 patients with adrenal masses underwent surgical resection. Median age at time of diagnosis was 30 years (range, years);
‘ 8 (40%) were asymptomatic’. Fractionated urinary catecholamine and metanephrine concentrations were normal in one third of patients. Computed tomographic scanning identified 20 (83%) of 24 tumors. Adrenalectomies were performed as unilateral or bilateral, open or laparoscopic, and, finally, total or cortical-sparing. Seven (50%) of the patients underwent other concurrent abdominal procedures. There were no deaths, with an overall operative morbidity of 2 patients (14%). Only the 2 patients in whom bilateral total adrenalectomies were performed became corticosteroid dependent. No recurrences have been noted to date.
CONCLUSIONS: A multidisciplinary approach is imperative for proper examination and monitoring of patients with VHL. Evaluation should begin early in life and always before elective surgery and childbirth. All adrenal masses in patients with VHL should be thoroughly evaluated and most should be resected. Early intervention and advanced surgical techniques better allow for cortical-sparing and laparoscopic procedures. With low recurrence rates, corticosteroid independence can be maintained for prolonged periods.

9. Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families
J Urol 1999; 162:659.
MATERIALS AND METHODS: Between 1988 and 1997, 246 individuals with von Hippel-Lindau disease were identified. Between August 1990 and June 1997, 26 consecutive patients with sporadic pheochromocytoma were evaluated.
RESULTS: A total of 64 patients with von Hippel-Lindau disease had manifestations of pheochromocytoma,
Germline von Hippel-Lindau gene missense mutation was associated with extra-adrenal pheochromocytoma, younger age at presentation and the only patient with metastases. Of the 33 newly diagnosed patients with von Hippel-Lindau disease 4 had pheochromocytoma 2 times (37 pheochromocytomas) during followup. Of these pheochromocytomas 35% were associated with no symptoms, normal blood pressure and normal catecholamine testing. Analysis of urinary catecholamine excretion in the von Hippel-Lindau and sporadic groups together demonstrated a correlation between tumor size, and urinary metanephrines, vanillylmandelic acid, norepinephrine, epinephrine and dopamine.
CONCLUSIONS: Von Hippel-Lindau gene missense mutation correlated with the risk of pheochromocytoma in patients with von Hippel-Lindau disease. These findings support a von Hippel-Lindau disease clinical classification, wherein some families are at high risk for manifestations of pheochromocytoma. Von Hippel-Lindau disease pheochromocytomas identified by screening were smaller and less functional than sporadic pheochromocytomas.

10. von Hippel-Lindau disease
Hemangioblastomas, including retinal angiomas
Clear cell renal cell carcinomas (RCCs)
Pheochromocytomas
Endolymphatic sac tumors of the middle ear
Serous cystadenomas and neuroendocrine tumors of the pancreas
Papillary cystadenomas of the epididymis and broad ligament
DIAGNOSIS
Clinical criteria were developed for the diagnosis of VHL primarily based on the finding of more then one VHL-associated tumor. With the advent of genetic testing, detection of a germline mutation in the VHL gene is typically used to establish the diagnosis of VHL disease

11. The specific criteria used at the Massachusetts General
Hospital VHL Clinic