Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes

被引:216
作者
Eisenhofer, G
Walther, MM
Huynh, TT
Li, ST
Bornstein, SR
Vortmeyer, A
Mannelli, M
Goldstein, DS
Linehan, WM
Lenders, JWM
Pacak, K
机构
[1] NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA
[2] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA
[3] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA
[4] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA
[5] Univ Florence, Dept Clin Pathophysiol, Florence, Italy
[6] Univ Nijmegen St Radboud Hosp, Dept Internal Med, NL-6500 HB Nijmegen, Netherlands
关键词
D O I
10.1210/jc.86.5.1999
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This study examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of tyrosine hydroxylase (TR), the rate-limiting enzyme in catecholamine synthesis, and of phenylethanolamine N-methyltransferase (PNMT), the enzyme that converts norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma catecholamines and metanephrines, and tumor cell neurochemistry and expression of TH and PNMT were examined in 19 MEN 2 patients and 30 VHL patients with adrenal pheochromocytomas. MEN 2 patients were more symptomatic and had a higher incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of metanephrines, but paradoxically lower total plasma concentrations of catecholamines, than VHL patients. MEN 2 patients all had elevated plasma concentrations of the epinephrine metabolite, metanephrine, whereas VHL patients showed specific increases in the norepinephrine metabolite, normetanephrine. The above differences in clinical presentation were largely explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT in pheochromocytomas from VHL than from MEN 2 patients. Thus, mutation-dependent differences in the expression of genes controlling catecholamine synthesis represent molecular mechanisms linking the underlying mutation to differences in clinical presentation of pheochromocytoma in patients with MEN 2 and the VHL syndrome.
引用
收藏
页码:1999 / 2008
页数:10
相关论文
共 43 条
[1]   A STUDY OF THE ADRENOTROPIC RECEPTORS [J].
AHLQUIST, RP .
AMERICAN JOURNAL OF PHYSIOLOGY, 1948, 153 (03) :586-600
[2]   A RAPID MICROPREPARATION TECHNIQUE FOR EXTRACTION OF DNA-BINDING PROTEINS FROM LIMITING NUMBERS OF MAMMALIAN-CELLS [J].
ANDREWS, NC ;
FALLER, DV .
NUCLEIC ACIDS RESEARCH, 1991, 19 (09) :2499-2499
[3]   SILENT ADRENAL NODULES IN VON HIPPEL-LINDAU DISEASE SUGGEST PHEOCHROMOCYTOMA [J].
APRILL, BS ;
DRAKE, AJ ;
LASSETER, DH ;
SHAKIR, KMM .
ANNALS OF INTERNAL MEDICINE, 1994, 120 (06) :485-487
[4]   NOREPINEPHRINE AND EPINEPHRINE SECRETION FROM A CLINICALLY EPINEPHRINE-SECRETING PHEOCHROMOCYTOMA [J].
ARONOFF, SL ;
PASSAMANI, E ;
BOROWSKY, BA ;
WEISS, AN ;
ROBERTS, R ;
CRYER, PE .
AMERICAN JOURNAL OF MEDICINE, 1980, 69 (02) :321-324
[5]   Pheochromocytoma in von Hippel-Lindau disease: Clinical presentation and mutation analysis in a large, multigenerational kindred [J].
Atuk, NO ;
Stolle, C ;
Owen, JA ;
Carpenter, JT ;
Vance, ML .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (01) :117-120
[6]  
Aunis D, 1999, ACTA PHYSIOL SCAND, V167, P89
[7]   PHEOCHROMOCYTOMA IN MULTIPLE ENDOCRINE NEOPLASIA TYPE-2A - SURVEY OF 100 CASES [J].
CASANOVA, S ;
ROSENBERGBOURGIN, M ;
FARKAS, D ;
CALMETTES, C ;
FEINGOLD, N ;
HESHMATI, HM ;
COHEN, R ;
CONTEDEVOLX, B ;
GUILLAUSSEAU, PJ ;
HOUDENT, C ;
BIGORGNE, JC ;
BOITEAU, V ;
CARON, J ;
MODIGLIANI, E .
CLINICAL ENDOCRINOLOGY, 1993, 38 (05) :531-537
[8]   MOLECULAR-GENETIC DIAGNOSIS OF VON HIPPEL-LINDAU DISEASE IN FAMILIAL PHEOCHROMOCYTOMA [J].
CROSSEY, PA ;
ENG, C ;
GINALSKAMALINOWSKA, M ;
LENNARD, TWJ ;
WHEELER, DC ;
PONDER, BAJ ;
MAHER, ER .
JOURNAL OF MEDICAL GENETICS, 1995, 32 (11) :885-886
[9]  
EBERT SN, 1994, J BIOL CHEM, V269, P20885
[10]   Plasma normetanephrine and metanephrine for detecting pheochromocytoma in Von Hippel-Lindau disease and multiple endocrine neoplasia type 2 [J].
Eisenhofer, G ;
Lenders, JWM ;
Linehan, WM ;
Walther, MM ;
Goldstein, DS ;
Keiser, HR .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (24) :1872-1879