Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma

WALTHER, McCLELLAN M.; REITER, ROBERT; KEISER, HARRY R.; CHOYKE, PETER L.; VENZON, DAVID; HURLEY, KATHY; GNARRA, JAMES R.; REYNOLDS, JAMES C.; GLENN, GLADYS M.; ZBAR, BERTON; LINEHAN, W. MARSTON

doi:10.1097/00005392-199909010-00004

Cited by 255Adrenal and Paraganglionic TumorsEar and Head TumorsNeuroendocrine Tumor Research Advances

Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma

WALTHER, McCLELLAN M., REITER, ROBERT, KEISER, HARRY R., CHOYKE, PETER L., VENZON, DAVID, HURLEY, KATHY, GNARRA, JAMES R., REYNOLDS, JAMES C., GLENN, GLADYS M., ZBAR, BERTON, LINEHAN, W. MARSTON·1999·Journal of Urology

DOI 10.1097/00005392-199909010-00004

Open this paper in CoChat — free account

Abstract

PURPOSE: Families with von Hippel-Lindau disease have variable risk of pheochromocytoma. Patients with von Hippel-Lindau disease and pheochromocytoma identified by screening can have no characteristic signs or symptoms. Families with von Hippel-Lindau disease were screened and followed to describe the natural history of von Hippel-Lindau pheochromocytoma, and to correlate these findings with von Hippel-Lindau germline mutation. MATERIALS AND METHODS: Between 1988 and 1997, 246 individuals with von Hippel-Lindau disease were identified (von Hippel-Lindau group). Between August 1990 and June 1997, 26 consecutive patients with sporadic pheochromocytoma were evaluated (sporadic group). RESULTS: A total of 64 patients with von Hippel-Lindau disease had manifestations of pheochromocytoma, including 33 newly diagnosed during screening at the National Institutes of Health and 31 previously treated (93 adrenal and 13 extra-adrenal pheochromocytomas). 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% (13 of 37) were associated with no symptoms, normal blood pressure and normal catecholamine testing. Comparison of urinary catecholamines in the von Hippel-Lindau and sporadic groups demonstrated increased epinephrine, metanephrines and vanillylmandelic acid in the sporadic group. 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. In 12 patients without signs or symptoms of pheochromocytoma 17 newly diagnosed pheochromocytomas were followed for a median of 34.5 months without morbidity. Median tumor doubling time was 17 months. 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.

Integrity signals

Registry

Crossref · 10.1097/00005392-199909010-00004

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Patients with familial pheochromocytoma may be asymptomatic in 50% of cases, with only a third presenting with hypertension.
“Patients with familial pheochromocytoma may be asymptomatic in 50% of cases, with only a third presenting with hypertension, possibly representing earlier diagnosis and smaller lesions as a result of regular screening in these patients (195,196).”
From Adrenal incidentaloma (2020) · cites this paper as [196]

Cancer: Principles and Practice of Oncology.
(1991) · Annals of Internal Medicine · doi:10.7326/0003-4819-114-9-819_4 · Cited by 8,524 · see citing works
Identification of the von Hippel-Lindau Disease Tumor Suppressor Gene
Latif, F., Tory, K., Gnarra, J. R., Yao, M., Duh, F.-M. C., Orcutt, M. L., Stackhouse, T. M., Kuzmin, I., Modi, W. S., Geil, L., et al. (1993) · Science · doi:10.1126/science.8493574 · Cited by 2,971 · see citing works
Self-citation
The Relationship Between Specific RET Proto-oncogene Mutations and Disease Phenotype in Multiple Endocrine Neoplasia Type 2
Eng, C. (1996) · JAMA · doi:10.1001/jama.276.19.1575 · Cited by 1,180 · see citing works
Clinical Features and Natural History of von Hippel-Lindau Disease
Maher, E. R., Yates, J. R. W., Harries, R. W. J., et al. (1990) · QJM · doi:10.1093/qjmed/77.2.1151 · Cited by 950 · see citing works
Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: Correlations with phenotype
Chen, F., Kishida, T., Yao, M., Hustad, T., Glavač, D., Dean, M. C., Gnarra, J. R., Orcutt, M. L., Duh, F.-M. C., Glenn, G. M., et al. (1995) · Human Mutation · doi:10.1002/humu.1380050109 · Cited by 551 · see citing works
Self-citation
von Hippel-Lindau disease: genetic, clinical, and imaging features.
Choyke, P. L., Glenn, G. M., Walther, M. M., Patronas, N. J., Linehan, W. M., & Zbar, B. (1995) · Radiology · doi:10.1148/radiology.194.3.7862955 · Cited by 544 · see citing works
Self-citation
Pheochromocytomas, Multiple Endocrine Neoplasia Type 2, and von Hippel-Lindau Disease
Neumann, H. P. H., Berger, D. P., Sigmund, G., Blum, U. C. H., Schmidt, D., Parmer, R. J., Volk, B., & Kirste, G. R. (1993) · New England Journal of Medicine · doi:10.1056/nejm199311183292103 · Cited by 463 · see citing works
Identification of intragenic mutations in the Von Hippel — Lindau disease tumour suppressor gene andcorrelation with disease phenotype
Crossey, P. A., Richards, F. M., Foster, K., reen, J. S., Prowse, A. H., Latlf, F., Lerman, M. I., Zbar, B., Atfara, N. A., Ferguson-Smith, M. A., et al. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.8.1303 · Cited by 382 · see citing works
Self-citation
Plasma Metanephrines in the Diagnosis of Pheochromocytoma
Lenders, J. W. M., Keiser, H. R., Goldstein, D. S., Willemsen, J. J., Friberg, P., Jacobs, M.-C., Kloppenborg, P. W. C., Thien, T., & Eisenhofer, G. (1995) · Annals of Internal Medicine · doi:10.7326/0003-4819-123-2-199507150-00004 · Cited by 242 · see citing works
Self-citation
Pheochromocytoma: New concepts and future trends
Bravo, E. L. (1991) · Kidney International · doi:10.1038/ki.1991.244 · Cited by 219 · see citing works
Turnover and Metabolism of Catecholamines in Patients with Pheochromocytoma*
Crout, J. R., & Sjoerdsma, A. (1964) · Journal of Clinical Investigation · doi:10.1172/jci104898 · Cited by 201 · see citing works
Genetic predisposition to phaeochromocytoma: analysis of candidate genes GDNF, RET and VHL
Woodward, E. R. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.7.1051 · Cited by 125 · see citing works
Differences between sporadic and multiple endocrine neoplasia type 2A phaeochromocytoma
Pomares, F. J., Canas, R., Rodriguez, J. M., Hernandez, A. M., Parrilla, P., & Tebar, F. J. (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.3751208.x · Cited by 124 · see citing works
Glucagon and clonidine testing in the diagnosis of pheochromocytoma.
Grossman, E., Goldstein, D. S., Hoffman, A., et al. (1991) · Hypertension · doi:10.1161/01.hyp.17.6.733 · Cited by 108 · see citing works
MANAGEMENT OF HEREDITARY PHEOCHROMOCYTOMA IN VON HIPPEL-LINDAU KINDREDS WITH PARTIAL ADRENALECTOMY
Walther, M. M., Keiser, H. R., Choyke, P. L., et al. (1999) · The Journal of Urology · doi:10.1016/s0022-5347(01)61900-1 · Cited by 105 · see citing works
Self-citation
Consequences of Direct Genetic Testing for Germline Mutations in the Clinical Management of Families With Multiple Endocrine Neoplasia, Type II
Neumann, H. P. H. (1995) · JAMA · doi:10.1001/jama.1995.03530140061033 · Cited by 100 · see citing works
Pheochromocytoma as the first manifestation of von Hippel-Lindau disease.
Richard, S., Beigelman‐Aubry, C., Duclos, J. M., Fendler, J. P., Plauchu, H., Plouin, P., Resche, F., Schlumberger, M. J., Vermesse, B., & Proye, C. (1994) · PubMed · Cited by 85 · see citing works
German medullary thyroid carcinoma/multiple endocrine neoplasia registry
Raue, F. (1998) · Langenbeck s Archives of Surgery · doi:10.1007/s004230050143 · Cited by 85 · see citing works
Pathology of the Adrenal Glands
Mendelsohn, G. (1991) · The American Journal of Surgical Pathology · doi:10.1097/00000478-199106000-00010 · Cited by 73 · see citing works
Familial Pheochromocytoma, Hypercalcemia, and Von Hippel-Lindau Disease
Atuk, N. O., McDONALD, T., WOOD, T., Carpenter, J. T., Walzak, M. P., Donaldson, M. H., Gillenwater, J. Y., TURNER, S. M., & WESTFALL, V. K. (1979) · Medicine · doi:10.1097/00005792-197905000-00001 · Cited by 67 · see citing works
Sporadic phaeochromocytomas are rarely associated with germline mutations in the von Hippel‐Lindau and RET genes
Bar, M., Friedman, E., Jakobovitz-Picard, O., Leibowitz, G., Lerer, I., Abeliovich, D., & Gross, D. J. (1997) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1997.3251150.x · Cited by 59 · see citing works
Bilateral Adrenalectomy with Autotransplantation of Adrenocortical Tissue or Unilateral Adrenalectomy: Treatment Options for Pheochromocytomas in Multiple Endocrine Neoplasia Type 2A.
Okamoto, T., Obara, T., Ito, Y., et al. (1996) · Endocrine Journal · doi:10.1507/endocrj.43.169 · Cited by 43 · see citing works
Silent Adrenal Nodules in von Hippel-Lindau Disease Suggest Pheochromocytoma
Aprill, B. S., Drake, A. J., Lasseter, D. H., et al. (1994) · Annals of Internal Medicine · doi:10.7326/0003-4819-120-6-199403150-00006 · Cited by 42 · see citing works
Pathology of the adrenal glands
Lack, E. E. (1990) · Churchill Livingstone eBooks · Cited by 38 · see citing works
Consequences of direct genetic testing for germline mutations in the clinical management of families with multiple endocrine neoplasia, type II
Neumann, H. P. H. (1995) · JAMA · doi:10.1001/jama.274.14.1149 · Cited by 34 · see citing works
Three-decade investigation of familial pheochromocytoma. An allele of von Hippel-Lindau disease?
Tisherman, S. (1993) · Archives of Internal Medicine · doi:10.1001/archinte.153.22.2550 · Cited by 34 · see citing works
Total bilateral laparoscopic adrenalectomy in patients with Cushing's syndrome and multiple endocrine neoplasia (IIa)
Fernández‐Cruz, L., Sáenz, A., Benarroch, G., et al. (1997) · Surgical Endoscopy · doi:10.1007/s004649900307 · Cited by 30 · see citing works
Genotype--Phenotype Correlation of Patients with Multiple Endocrine Neoplasia Type 2 in Japan
Egawa, S., Futami, H., Takasaki, K., et al. (1998) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/28.10.590 · Cited by 27 · see citing works
Glucagon-blood catecholamine test: use in isolated and familial pheochromocytoma
Siqueira-Filho, A. G. (1975) · Archives of Internal Medicine · doi:10.1001/archinte.135.9.1227 · Cited by 22 · see citing works
Cancer of the Endocrine System
Schneider, D. F., Mazeh, H., Lubner, S. J., Jaume, J. C., & Chen, H. (2014) · Elsevier eBooks · doi:10.1016/b978-1-4557-2865-7.00071-0 · Cited by 18 · see citing works
Von Hippel-Lindau Disease and Pheochromocytoma
Walther, M. M. (1996) · JAMA · doi:10.1001/jama.1996.03530350021025 · Cited by 17 · see citing works
Self-citation
Plasma norepinephrine and epinephrine responses to glucagon in patients with suspected pheochromocytomas
Levinson, P. D., Hamilton, B. P. M., Mersey, J. H., et al. (1983) · Metabolism · doi:10.1016/0026-0495(83)90142-7 · Cited by 16 · see citing works
Evaluation of Clonidine suppression and various provocation tests in the diagnosis of pheochromocytoma
Koshida, H., Miyamori, I., Soma, R., et al. (1990) · Journal of Endocrinological Investigation · doi:10.1007/bf03349626 · Cited by 11 · see citing works
The Relationship of the Pattern of Hypertension to Biochemical Findings in Patients with Pheochromocytoma
Sato, T., YOSHINAGA, K., & DeQuattro, V. L. (1970) · Japanese Heart Journal · doi:10.1536/ihj.11.423 · Cited by 7 · see citing works
Von Hippel-Lindau disease and pheochromocytoma
Walther, M. M. (1996) · JAMA · doi:10.1001/jama.275.11.839 · Cited by 5 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors
Fassnacht, M., Arlt, W., Bancos, I., Dralle, H., Newell-Price, J., Sahdev, A., Tabarin, A., Terzolo, M., Tsagarakis, S., & Dekkers, O. M. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0467 · Cited by 1,566 · see citing works
Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma
Pacak, K., Linehan, W. M., Eisenhofer, G., Walther, M. M., & Goldstein, D. S. (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-134-4-200102200-00016 · Cited by 618 · see citing works
Self-citation
Adrenal incidentaloma
Sherlock, M., Scarsbrook, A., Abbas, A., Fraser, S., Limumpornpetch, P., Dineen, R., & Stewart, P. M. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa008 · Cited by 347 · see citing works
“Patients with familial pheochromocytoma may be asymptomatic in 50% of cases, with only a third presenting with hypertension, possibly representing earlier diagnosis and smaller lesions as a result of regular screening in these patients (195,196).”
Background
Pheochromocytoma: The expanding genetic differential diagnosis.
Bryant, J., Farmer, J., Kessler, L. J., Townsend, R. R., & Nathanson, K. L. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djg024 · Cited by 250 · see citing works
The molecular pathogenesis of hereditary and sporadic adrenocortical and adrenomedullary tumors
Koch, C. A., Pacak, K., & Chrousos, G. P. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021069 · Cited by 177 · see citing works
<p>Von Hippel-Lindau Disease: Current Challenges and Future Prospects</p>
Gläsker, S., Vergauwen, E., Koch, C. A., Kutikov, A., & Vortmeyer, A. O. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s190753 · Cited by 99 · see citing works

Pheochromocytoma with elevated metanephrines as the only biochemical finding.
Shawar, L., & Svec, F. A. (1996) · PubMed · Cited by 17 · see citing works
Discriminating Pheochromocytomas from Other Adrenal Lesions: The Dilemma of Elevated Catecholamines
Carr, J. C., Spanheimer, P. M., Rajput, M., Dahdaleh, F. S., Lal, G., Weigel, R. J., Sugg, S. L., Liao, J., & Howe, J. R. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-013-3142-z · Cited by 16 · see citing works
Lessons from an unpleasant surprise: a biochemical strategy for the diagnosis of pheochromocytoma
Gardet, V., Gatta‐Cherifi, B., Simonnet, G., et al. (2001) · Journal of Hypertension · doi:10.1097/00004872-200106000-00006 · Cited by 62 · see citing works
Increased catecholamine excretion after labetalol therapy: A spurious effect of drug metabolites
Miano, L., Kolloch, R. E., & Quattro, V. D. (1979) · Clinica Chimica Acta · doi:10.1016/0009-8981(79)90361-9 · Cited by 24 · see citing works
Circulating and Urinary Catecholamines in Pheochromocytoma
Bravo, E. L., Tarazi, R. C., Gifford, R. W., et al. (1979) · New England Journal of Medicine · doi:10.1056/nejm197909273011302 · Cited by 361 · see citing works

Authors: WALTHER, M. M., REITER, R., KEISER, H. R., CHOYKE, P. L., VENZON, D., HURLEY, K., GNARRA, J. R., REYNOLDS, J. C., GLENN, G. M., ZBAR, B., & LINEHAN, W. M.
Affiliations: National Institutes of Health (US)
ORCID: REITER, ROBERT
CHOYKE, PETER L.
VENZON, DAVID
GNARRA, JAMES R.
REYNOLDS, JAMES C.
LINEHAN, W. MARSTON
Venue: Journal of Urology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1999-09
Volume: 162
Issue: 3 Part 1
Pages: 659-664
ISSN: 0022-5347 (ISSN-L)
1527-3792
DOI: 10.1097/00005392-199909010-00004
OpenAlex: W2054639131
Cited by: 255
References: 35
Citations by year: 2026: 4 · 2025: 5 · 2024: 6 · 2023: 1 · 2022: 7 · 2021: 10 · 2020: 12 · 2019: 9 · 2018: 6 · 2017: 9 · 2016: 4 · 2015: 9 · 2014: 9 · 2013: 9 · 2012: 26
FWCI: 12.62
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Journal of Urology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
Health Sciences › Medicine › Oncology › Ear and Head Tumors
Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
Keywords: von Hippel-Lindau disease, pheochromocytoma, sporadic pheochromocytoma, natural history (disease), missense mutations, extra-adrenal pheochromocytoma, urinary catecholamines, metanephrine, vanillylmandelic acid, tumor size
MeSH terms: Adrenal Gland Neoplasms, von Hippel-Lindau Disease, Humans, Mutation, Pheochromocytoma

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks