Archives of Dermatological Research

, Volume 303, Issue 5, pp 317–325 | Cite as

Neurofibromatosis type 1 (NF1) and pheochromocytoma: prevalence, clinical and cardiovascular aspects

  • Laura Zinnamosca
  • Luigi Petramala
  • Dario Cotesta
  • Cristiano Marinelli
  • Mauro Schina
  • Rosario Cianci
  • Sandra Giustini
  • Susanna Sciomer
  • Emanuela Anastasi
  • Stefano Calvieri
  • Giorgio De Toma
  • Claudio LetiziaEmail author
Original Paper


The aim of the study was to evaluate the prevalence of pheochromocytoma (PHEO) in patients with neurofibromatosis type 1 (NF1), and to analyze the behavior of some anthropometric and cardiovascular parameters. In 48 consecutive NF1 patients, urinary metanephrines and vanillylmandelic acid excretion were assessed. The body mass index (BMI), waist circumference (WC), ambulatory blood pressure monitoring (ABPM), echocardiography and ultrasound carotid arterial wall evaluation were performed. In NF1 patients, 11 (29.3%) had arterial hypertension, 7 (14.6%) had a PHEO. Four (57%) NF1 patients with PHEO were symptomatic at the diagnosis. In PHEO-NF1 patients, we revealed a lower BMI and WC values with respect to NF1 patients without PHEO and normal subjects (NSs) (p < 0.05), respectively. The nocturnal non-dipping pattern at the ABPM was present in 40.4% of NF1 patients, and in particular this phenomenon was present in PHEO-NF1 patients (71.4%). Left ventricular mass index and intima media thickness were significantly higher in NF1 patients as compared to NS (p < 0.05), particularly in NF1-PHEO patients (p < 0.05). In conclusions, these findings revealed high prevalence of PHEO in NF1 patients and suggest that, in addition to blood pressure, humoral factors (increased sympathetic activity or neurofibromin), influence the pathogenesis of remodeling of cardiovascular system.


Neurofibromatosis type 1 Pheochromocytoma Cardiovascular diseases 


  1. 1.
    Bausch B, Borozdin W, Mautner VF et al (2007) Germline NF1 mutational spectra and loss-of-heterozygosity analyses in patients with pheochromocytoma and neurofibromatosis type 1. J Clin Endocrinol Metab 92(7):2784–2792PubMedCrossRefGoogle Scholar
  2. 2.
    Bravo EL, Tagle R (2003) Pheochromocytoma: state-of-the-art and future prospects. Endocr Rev 24:539–553PubMedCrossRefGoogle Scholar
  3. 3.
    Ceruti M, Petramala L, Cotesta D et al (2006) Ambulatory blood pressure monitoring in secondary arterial hypertension due to adrenal diseases. J Clin Hypertens 8:642–648CrossRefGoogle Scholar
  4. 4.
    Cichowski K, Jacks T (2001) NF1 tumor suppressor gene function: narrowing the GAP. Cell 104:593–604PubMedCrossRefGoogle Scholar
  5. 5.
    Cotesta D, Erlic Z, Petramala L et al (2008) Coincidence of neurofibromatosis Type 1 and multiple endocrine neoplasia type 2. Endocrinologist 18:277–281CrossRefGoogle Scholar
  6. 6.
    Denolle T, Chatellier G, Julien J et al (1993) Left ventricular mass and geometry before and after etiologic treatment in renovascular hypertension, aldosterone-producing adenoma, and pheochromocytoma. Am J Hypertens 6:907–913PubMedGoogle Scholar
  7. 7.
    Ferner RE, Huson SM, Thomas N et al (2007) Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet 44(2):81–88PubMedCrossRefGoogle Scholar
  8. 8.
    Friedman JM (1999) Epidemiology of neurofibromatosis type 1. Am J Med Genet 89:1–6PubMedCrossRefGoogle Scholar
  9. 9.
    Gabriel KR (1997) Neurofibromatosis. Curr Opin Pediatr 9:89–93PubMedCrossRefGoogle Scholar
  10. 10.
    Goldberg NS, Roenigk RK (1996) Neurofibromatosis, tuberous sclerosis, and other neurocutaneous discorde. In: Wintronb BU (ed) Cutaneous medicine and surgery: an interpretated program in dermatology. WB Saunders, Philadelpfia, pp 1729–1741Google Scholar
  11. 11.
    Goldstein DS, Eisenhofer G, Flynn JA et al (2004) Diagnosis and localization of pheochromocytoma. Hypertension 43:907–910PubMedCrossRefGoogle Scholar
  12. 12.
    Gutmann DH, Aylsworth A, Carey JC et al (1997) The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 278:51–57PubMedCrossRefGoogle Scholar
  13. 13.
    Hansen TW, Jeppesen J, Rasmussen S, Ibsen H, Torp-Pedersen C (2006) Ambulatory blood pressure monitoring and risk of cardiovascular disease: a population based study. Am J Hypertens 19(3):243–250PubMedCrossRefGoogle Scholar
  14. 14.
    Heineke J, Molkentin JD (2006) Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol 7:589–600PubMedCrossRefGoogle Scholar
  15. 15.
    Heniford BT, Arca MJ, Walsh RM, Gill IS (1999) Laparoscopic adrenalectomy for cancer. Semin Surg Oncol 16(4):293–306PubMedCrossRefGoogle Scholar
  16. 16.
    Huson SM, Compston DA, Clark P et al (1989) A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet 26:704–711PubMedCrossRefGoogle Scholar
  17. 17.
    Ito Y, Fujimoto Y, Obara T (1992) The role of epinephrine, norepinephrine, and dopamine in blood pressure disturbances in patients with pheochromocytoma. World J Surg 16:759–763PubMedCrossRefGoogle Scholar
  18. 18.
    Jenne DE, Tinschert S, Reimann H et al (2001) Molecular characterization and gene content of breakpoint boundaries in patients with neurofibromatosis type 1 with 17q11.2 microdeletions. Am J Hum Genet 69:516–527PubMedCrossRefGoogle Scholar
  19. 19.
    Kurpad AV, Khan K, Calder AG, Elia M (1994) Muscle and whole body metabolism after norepinephrine. Am J Physiol 266:E877–E884PubMedGoogle Scholar
  20. 20.
    La Batide-Alanore A, Chatellier G, Plouin PF (2003) Diabetes as a marker of pheochromocytoma in hypertensive patients. J Hypertension 21:1703–1707CrossRefGoogle Scholar
  21. 21.
    Lakkis MM, Epstein JA (1998) Neurofibromin modulation of Ras activity is required for normal endocardial-mesenchymal transformation in the developing heart. Development 125:4359–4367PubMedGoogle Scholar
  22. 22.
    Lenders JW, Eisenhofer G, Mannelli M et al (2005) Phaeochromocytoma. Lancet 366:665–675PubMedCrossRefGoogle Scholar
  23. 23.
    Mancia G, Ferrari A, Gregorini L et al (1983) Blood pressure and heart rate variabilities in normotensive and hypertensive human beings. Circ Res 53:96–104PubMedGoogle Scholar
  24. 24.
    Mannelli M, Ianni L, Cilotti A et al (1999) Pheochromocytoma in Italy: a multicentric retrospective study. Eur J Endocrinol 141:619–624PubMedCrossRefGoogle Scholar
  25. 25.
    Millar-Craig MW, Bishop CN, Raftery EB (1978) Circadian variation of blood-pressure. Lancet 1:795–797PubMedCrossRefGoogle Scholar
  26. 26.
    Norton KK, Xu J, Gutmann DH (1995) Expression of the neurofibromatosis I gene product, neurofibromin, in blood vessel endothelial cells and smooth muscle. Neurobiol Dis 2:13–21PubMedCrossRefGoogle Scholar
  27. 27.
    O’Brien E, Sheridan J, O’Malley K (1988) Dippers and non-dippers. Lancet 2:397PubMedCrossRefGoogle Scholar
  28. 28.
    Pacak K, Linehan WM, Eisenhofer G et al (2001) Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med 134:315–329PubMedGoogle Scholar
  29. 29.
    Palatini P, Penzo M, Racioppa A et al (1992) Clinical relevance of nighttime blood pressure and of daytime blood pressure variability. Arch Intern Med 152:1855–1860PubMedCrossRefGoogle Scholar
  30. 30.
    Rizzoni D, Muiesan ML, Porteri E et al (1998) Relations between cardiac and vascular structure in patients with primary and secondary hypertension. J Am Coll Cardiol 32:985–992PubMedCrossRefGoogle Scholar
  31. 31.
    Routledge F, McFetridge-Durdle J (2007) Non-dipping blood pressure patterns among individuals with essential hypertension: a review of the literature. Eur J Cardiovasc Nurs 6:9–26PubMedCrossRefGoogle Scholar
  32. 32.
    Shub C, Cueto-Garcia L, Sheps SG et al (1986) Echocardiographic findings in pheochromocytoma. Am J Cardiol 57:971–975PubMedCrossRefGoogle Scholar
  33. 33.
    Tedesco MA, Di Salvo G, Natale F, Pergola V, Calabrese E, Grassia C, Ratti G, Iarussi D, Iacono A, Calabrò R, Lama G (2002) The heart in neurofibromatosis type 1: an echocardiographic study. Heart J. 143:883–888CrossRefGoogle Scholar
  34. 34.
    Walther MM, Herring J, Enquist E et al (1999) von Recklinghausen’s disease and pheochromocytomas. J Urol 162:1582–1586PubMedCrossRefGoogle Scholar
  35. 35.
    Xu J, Ismat FA, Wang T et al (2009) Cardiomyocyte-specific loss of neurofibromin promotes cardiac hypertrophy and dysfunction. Circ Res 105:304–311PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Laura Zinnamosca
    • 1
  • Luigi Petramala
    • 1
  • Dario Cotesta
    • 1
  • Cristiano Marinelli
    • 1
  • Mauro Schina
    • 3
  • Rosario Cianci
    • 1
  • Sandra Giustini
    • 2
  • Susanna Sciomer
    • 3
  • Emanuela Anastasi
    • 4
  • Stefano Calvieri
    • 2
  • Giorgio De Toma
    • 5
  • Claudio Letizia
    • 1
    Email author
  1. 1.Department of Clinical Sciences, Secondary Hypertension UnitUniversity “Sapienza”RomeItaly
  2. 2.Department of DermatologyUniversity “Sapienza”RomeItaly
  3. 3.Department of CardiologyUniversity “Sapienza”RomeItaly
  4. 4.Department of Experimental MedicineUniversity “Sapienza”RomeItaly
  5. 5.Department of Surgery “Pietro Valdoni”University “Sapienza”RomeItaly

Personalised recommendations