: A bs trac t A cas e of hypog ly cemia in a patie nt of he mang iopericy toma w ith hepatic metas tas is Sung Il Park, M.D., Nam Su Kim,

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1 : A bs trac t A cas e of hypog ly cemia in a patie nt of he mang iopericy toma w ith hepatic metas tas is Sung Il Park, M.D., Nam Su Kim, M.D., Wan Hee Yoo, M.D., T ae Sun Park, M.D. and Hong Sun Back, M.D. Department of Internal M edicine, College of M edicine, Chonbuk N ational University, Chonju, Korea Tumour-induced hypoglycemia is usually caused by insulinoma or non-islet-cell neoplasm, such as hemangiopericytoma, fibrosarcoma, mesotheliomas. Most of the neoplasms in non- islet- cell tumour- induced hypoglycemia are mesenchymal type, and have a common features, including large- sized, slow- growing and metastatic involvement of the liver. T he mechanisms of hypoglycemia in metastatic liver disease are not clearly defined, and liver failure secondary to hepatic metastasis or insulin or insulin- like mediated process are considered. Glucagon stimulation test has been used to distinguish between insulin- mediated or insulin- like- mediated hypoglycemia and hypoglycemia induced by liver failure. We experinced a case of hypoglycemia in a patient of hemangiopericytoma with liver metastasis in which glucagon stimulation test was used for proper evaluation. We compare this case with previously reported cases, and present here with brief review of literatures.(korean J Med 59: , 2000) Key Words : Hemangiopericytoma; Hypoglycemia; Glucagon,,,,.,, 1, 2), 3).,,.. : : :, , ( ) E- mail : bhs@moak.chonbuk.ac.kr

Korean Journal of Medicine : Vol. 59, No. 3, 2000, 3). 1. :,, 33 : : 18, 7. 1,.. :,,, 11 cm.. 2.. : 4,000/mm3, 10.1 g/dl, 32.4%, 124,000/ mm3. glucose1.5 mmol/l, 8.0 g/dl, 3.6 g/dl, 1.0 mg/dl.

insulin1.8 U/mL( 6-26 U/mL), C- peptide1.0 ng/ml( 1-3.5 ng/ml). Insulin- like growth factor(igf- )60.

2 Korean Journal of Medicine : Vol. 59, No. 3, 2000, 3). 1. :,, 33 : : 18, 7. 1,.. :,,, 11 cm : 4,000/mm3, 10.1 g/dl, 32.4%, 124,000/ mm3. glucose1.5 mmol/l, 8.0 g/dl, 3.6 g/dl, 1.0 mg/dl. alkaline phosphatase 617 IU/L, AST 90 IU/L( : 40 IU/L ), ALT 61 IU/L( : 35 IU/L ), blood urea nitrogen(bun) 9.0 mg/dl, creatinine 0.3 mg/dl,. HBsAg, anti- HBs, alpha- fetoprotein(- FP) 5.6 ng/ml. insulin1.8 U/mL( 6-26 U/mL), C- peptide1.0 ng/ml( ng/ml). Insulin- like growth factor(igf- )60.4 ng/ml( : ng/ml), Insulin growth factor binding protein- (IGF BP- )2,655 ng/ml( 1,730-5,590 ng/ml). ( : 42 mg/dl) Figure 1. Chest X- ray shows multiple nodular and consolidative lesion in both lung. Figure 2. Abdomen CT scan shows multiple, variable sized, round masses in entire liver. Most of small- sized masses were enhanced in arterial phase, but large- sized mass shows peripheral enhancement. (1 mg/ml) 15, 30, 45 87, 105, 115 mg/dl. : X- (Figure 1)., (Figure 2).,,,,,. :. slit- like,

Sung Il Park, et al : A case of hypoglycemia in a patient of hemangiopericytoma with hepatic metastasis, 20,, 3. Figure 3. Sections show highly cellular tumor tissue in cores of liver tissue (A).

3 Sung Il Park, et al : A case of hypoglycemia in a patient of hemangiopericytoma with hepatic metastasis, 20,, 3. Figure 3. Sections show highly cellular tumor tissue in cores of liver tissue (A). T he tumor has a turbulent pattern and composed of oval to elongated cells with inconspicuous nucleoli, abundant cytoplasm and slit- like vessels (B) (H&E satin 200) (Figure 3). :. 11,,,,,. 1923Zimmermann, 1942StoutMurray4)., 45.5),, (36.4%), (21.4%), (13.3%), (13.3%), (12.1%), parasternal (3.5%) 6). Table 1. Summary of clinical and biochemical data in patients of hemangiopericytoma with hepatic metastasis and hypoglycemia No. References Anatomic site Patient Glucoseb Insulinc C- peptided IGF- Ie IGF- IIf big IGF- IIg Glucagon Sex Agea (mmol/l) (U/mL) (nmol/l) (ng/ml) (ng/ml) (nmol/l) testh 1. Paullada et al (1968) Retroperitoneum M positive 2. Bell & Buist (1981) Retroperitoneum M Arimasa et al (1986) Maxillary sinus M Low 4. Hoekmann et al (1994) Cerebellum M % positive 5. W egmann et al (1994) Meninges F Low elevated 6. Sohda & Yun (1996) Meninges F Normal Chung & Henry (1996) Abdomen M Low < positive 8. Hoff et al (1998) Chest F < 3 < < positive 9. Adams et al. (1999) Retroperitoneum M Present case (1999) Meninges M positive a: Age at primary operation/tumour diagnosis. b: Blood glucose level during hypoglycemic attack. Normal range: Normal range for each datas; c:6-26, d: , e: , f: , g: (10-20%). h: Positive: an increase in plasma glucose of 25 mg/dl (1.4 mmol/l) or more after the administration of 1mg of IV glucagon in patients who become hypoglycemia during a prolonged fast

4 : Paullada 7) Parker 8),,,,,, 6). Hoog 1), (T able 1).,. (insulin- like growth factor- I, IGFs)70 IGF- I67IGF- II, IGF- II 9, 10). IGF- II mrna big IGF- II 1, 11), big IGF- II 12). IGF- II pro- IGF- II7.5kDa IGF- II (O- glycosylation). Yang 13,14) big IGF- II. big IGF- II. big IGF- II, big IGF- II. IGFs, IGF, IGFBP- 3, ALS (acid- labile subunit) 150kDaIGFs70-80%. IGF IGFBP- 2 50kDa IGFs20-30% IGFs 14)., big IGF- II IGF- I, ALS, IGFBP kda. IGFBP kdaigfs 1, 12, 14). Frystyk 12) IGF- II. IGF- II IGF- 3), Daughaday 15)- (big IGF- ) E , 16).,., 3). IGF- I, IGF- II, big IGF- II (T able 1).,, big IGF- II. big IGF- II,.. 9, 14, 17),

5 4: ) 19)., diazoxide,,, somatostatin, 2). 20) somatostatin 14). Hoff 3) 4 2.,. 1. R E F E R E N C E S 1) Hoog A, Sandberg NAC, Hulting AL, Falkmer UG. High- molecular weight IGF- 2 expression in a haemangiopericytoma associated with hypoglycemia. APM IS 105: , ) Wegmann W, Vonesch HJ, Kamber J, Kiss D. Rezidivierendes und metastsierendes Hamangioperizytom der M eningen mit paraneoplastischer Hypoglykamie. Schweiz M ed W ochenscher 124: , ) Hoff AO, Vassilopoulou- sellin R. The role of glucagon administration in the diagnosis and treatment of patients with tumor hypoglycemia. Cancer 82: , ) Stout A, Murray M. Hemangiopericytoma. A vascular tumor features Z immerman, pericytes. A nn Surg 166:26, ) Enzinger FM, Smith BH. Hemangiopericytoma. An analysis of 106 cases. Hum Pathol 7:61-82, ),,,, : , ) Paullada JJ, Lisci- Garmilla A, Gonzales- Angulo A, Jurado- Mendoza J, Quijano- Narezo M, Gomez- Peralta L, Doria- Medina M. Hemangiopericytoma associated with hypoglycemia. Metabolic and electron microscopic studies of a case. Am J M ed 44: , ) Parker LA, Vincent LM, Mauro MA. Hemangiopericytoma metastatic to liver: sonographic appearance, J Clin Ultrasound 13: , ) Hoekman K, van Doorn J, Gloudemans T, Hoekstra OS, Maassen JA, Vermorken JB, Wagstaff J, Pinedo HM. Tumour- induced hypoglycemia. A case report. Ann Oncol 5: , ) Daughaday WH, T rivedi B, Baxter RC. Serum "big insulin- like growth factor II" from patients with tumor hypoglycemia lacks normal E- domain O- linked glycosylation, a possible determinant of normal propeptide processing. Proc N atl Acad Sci USA 90: , ) Sohda T, Yun K. Insulin- like growth factor II expression in primary meningeal hemangiopericytoma and its metastasis to the liver accompanied by hypoglycemia. Hum Pathol 27: , ) Frystyk J, Skjaerbaek C, Zapf J, Orskov H. Increased levels of circulating free insulin- like growth factors in patients with non- islet cell tumor hypoglycemia. Diabetologia 41: , ) Yang C, Zhan XH, Perdue JF. Investigating the function of the E domain during the processing of human proinsulin-like growth factor-ii. Programme of the Annual M eeting of the Endocrine Society p.80, ) Chung J, Henry RR. M echanisms of tumor- induced hypoglycemia with intra- abdominal hemangiopericytoma. J Clin Endocrinol M etab 81: , ) Daughaday WH, Trivedi B. M easurements of deriatives of pro- insulin- like growth factor by a radioimmunoassay directed against the E- domain in normal subjects and patients with non- islet cell tumor hypoglycemia. J Clin Endocrinol M etab 75: , ) Silbert CK, Rossini AA, Ghazvinian S, Wildrich WC, Marks LJ, Sawin CT. T umor hypoglycemia: deficient splanchnic glucose output and deficient glucagon secretion. Diabetes 25: , ) Arimasa N, Kobayashi T, Yoshilka K, Taketa K, Oka Y. M alignant hemangiopericytoma associated with huge metastasis in the liver and hypoglycemia. A case report. K nanzo A cta Hepat 27: , ) Bell GM, Buist T AS. Arterial embolization in the management of liver tumour with recurrent

6 Korean Journal of Medicine : Vol. 59, No. 3, 2000 hypoglycemia. Prostagrad M ed J 57: , ) Adams J, Peter J, Parker D. Liver transplantation for metastatic hemangiopericytoma associated with hypoglycemia. T ransplantation 67: , ) Katz LEL, Liu F, Baker B, Agus MSD, Nuun SE. T he effect of growth hormone treatment on the insulinlike growth factor axis in a child with nonlslet cell tumor hypoglycemia. J Clin Endocrinol M etab 81: ,

Seok Joo Kim, et al. Hepatocellular Carcinoma with Severe Hypoglycemia : Involvement of Insulin- like Growth Fa ctor I & II a nd Insulin- like Growth

Seok Joo Kim, et al. Hepatocellular Carcinoma with Severe Hypoglycemia : Involvement of Insulin- like Growth Fa ctor I & II a nd Insulin- like Growth 5 4 1999 ; 332 337 1 : (IGF) (IGFBP), Abstract Hepatocellular Carcinoma with Severe Hypoglycemia : Involvement of Insulin-like Growth Factor I, II and Insulin-like Growth Factor Binding Proteins Seok Joo