Download PDF
Horm Metab Res 2006; 38(6): 405-410
DOI: 10.1055/s-2006-944545
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Patients with Cushing’s Syndrome Have Increased Intimal Media Thickness at Different Vascular Levels: Comparison with a Population Matched for Similar Cardiovascular Risk Factors

N.  Albiger1 , R.  M.  Testa1 , B.  Almoto1 , M.  Ferrari1 , F.  Bilora2 , F.  Petrobelli2 , A.  Pagnan2 , F.  Mantero1 , C.  Scaroni1
  • 1Division of Endocrinology, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy
  • 2Second Chair of Internal Medicine, Department of Medical and Surgical Sciences, University of Padua Medical School, Padua, Italy
Further Information

Publication History

Received 24 August 2005

Accepted after revision 3 January 2006

Publication Date:
06 July 2006 (online)

Also available at
    Permissions and Reprints

Abstract

Cushing’s syndrome (CS) is associated with high cardiovascular risk. The aim of this study was to analyze intimal media thickness (IMT) in patients with CS and compare them with subjects matched for similar conventional and independent cardiovascular risk factors. Twenty eight patients with CS (mean age: 40.7 ± 2.5 y) and 28 subjects (mean age: 41.1 ± 14 y) matched for sex, age, smoking habit, body mass index, blood pressure levels, glucose and lipid metabolism were evaluated. IMT was measured at right and left common carotid (CC), carotid bulb (BC), aorta (Ao) and femoral (F) levels by B-echo-Doppler ultrasonography. Although parameters of cardiovascular risk factors did not differ statistically between patients and controls, IMT was significantly increased (right and left CC-IMT, p < 0.05; right and left BC-IMT, p < 0.01, Ao-IMT p < 0.05) and wall plaques were more common (14.2 % vs. 7.1 %) in patients. In CS patients, CC-IMT and F-IMT correlated positively and significantly with fasting glucose (right CC-IMT: r2 = 0.37, p = 0.05; left CC-IMT: r2 = 0.43, p = 0.02; right F-IMT: r2 = 0.57; p < 0.01; left F-IMT: r2 = 0.47, p = 0.01) and HOMA index (left CC-IMT: r2 = 0.64, p < 0.01 and left F-IMT: r2 = 0.48, p < 0.05). The CS patients’ waist-to-hip ratio (WHR) was evaluated and correlated positively and significantly with CC-IMT (right: r2 = 0.53, p = 0.01 and left: r2 = 0.44, p = 0.05). No correlation was found between IMT and cortisol levels, however. In conclusion, patients with CS have more severe atherosclerotic damage than a population matched for similar cardiovascular risk factors. Multiple events related to long-term cortisol effects on metabolism and at vascular and endothelial sites may increase the risk of cardiovascular damage in patients with CS.

Key words

Cushing’s syndrome - intimal media thickness

References

  • 1 Aron D C, Flinding J W, Tyrrel J B. Cushing’s disease.  Endocrinol Metab Clin North Am. 1987;  16 705-730
    PubMedGoogle Scholar
  • 2 Terzolo M, Pia A, Ali A, Osella G, Reimondo G, Bovio S, Daffara F, Procopio M, Paccotti P, Borretta G, Angeli A. Adrenal incidentaloma: a new cause of the metabolic syndrome?.  J Clin Endocrinol Metab. 2002;  87 998-1003
    CrossrefPubMedGoogle Scholar
  • 3 Findling J W, Raff H. Diagnosis and differential diagnosis of Cushing’s syndrome.  Endocrinol Metab Clin North Am. 2001;  30 729-747
    CrossrefPubMedGoogle Scholar
  • 4 Leibowitz G, Tsur A, Chayen S D, Salameh M, Raz I, Cerasi E, Gross D J. Pre-clinical Cushing’s syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients.  Clin Endocrinol (Oxf). 1996;  44 717-722
    CrossrefPubMedGoogle Scholar
  • 5 Contreras L N, Cardoso E, Lozano M P, Pozzo J, Pagano P, Claus-Hermbeg H. Detección de sindrome de Cushing preclínico en pacientes con sobrepeso y diabetes mellitus tipo 2.  Medicina. 2000;  60 326-330
    PubMedGoogle Scholar
  • 6 Etxabe J, Vazquez J A. Morbidity and mortality in Cushing’s disease: an epidemiological approach.  Clin Endocrinol (Oxf). 1994;  40 479-484
    CrossrefPubMedGoogle Scholar
  • 7 Pivonello R, Faggiano A, Lombardi G, Colao A. The metabolic syndrome and cardiovascular risk in Cushing’s syndrome.  Endocrinol Metab Clin N Am. 2005;  34 327-339
    CrossrefPubMedGoogle Scholar
  • 8 O'Leary D H, Polak J F, Kronmal R A, Savage P J, Borhani N O, Kittner S J, Tracy R, Gardin J M, Price T R, Furberg C D. Thickening of the carotid wall. A marker for atherosclerosis in the elderly? Cardiovascular Health Study Collaborative Research Group.  Stroke. 1996;  Feb 27 224-231
    CrossrefPubMedGoogle Scholar
  • 9 Lekakis J P, Papamichael C M, Cimponeriu A T, Lekakis J P, Papamichael C M, Cimponeriu A T, Stamatelopoulos K S, Papaioannou T G, Kanakakis J, Alevizaki M K, Papapanagiotou A, Kalofoutis A T, Stamatelopoulos S F. Atherosclerotic changes of extracoronary arteries are associated with the extent of coronary atherosclerosis.  Am J Cardiol. 2000;  85 949-952
    CrossrefPubMedGoogle Scholar
  • 10 Faggiano A, Pivonello R, Spiezia S, De Martino M C, Filippella M G, Di Somma C, Lombardi G, Colao A. Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing’s disease during active disease and 1 year after disease remission.  J Clin Endocrinol Metab. 2003;  88 2527-2533
    CrossrefPubMedGoogle Scholar
  • 11 Colao A, Pivonello R, Spiezia S, Faggiano A, Ferone D, Filippella M, Marzullo P, Cerbone G, Siciliani M, Lombardi G. Persistence of increased cardiovascular risk in patients with Cushing's disease after five years of successful cure.  J Clin Endocrinol Metab. 1999;  84 2664-2672
    CrossrefPubMedGoogle Scholar
  • 12 Chalmers J. WHO-ISH Hypertension Guidelines Committee 1999. World Health Organization - International Society of Hypertension Guidelines for the Management of Hypertension.  J Hypertension. 1999;  17 151-185
    PubMedGoogle Scholar
  • 13 Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assessment: insulin resistance and β cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 2000;  28 412-419
    PubMedGoogle Scholar
  • 14 Emoto M, Nishizawa Y, Maekawa K, Hiura Y, Kanda H, Kawagishi T, Shoji T, Okuno Y, Morii H. Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas.  Diabetes care. 1999;  22 818-822
    PubMedGoogle Scholar
  • 15 Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging.  Circulation. 1986;  74 1399-1406
    CrossrefPubMedGoogle Scholar
  • 16 Barnett H J, Taylor D W, Eliasziw M, Fox A J, Ferguson G G, Haynes R B, Rankin R N, Clagett G P, Hachinski V C, Sacket D L, Thorpe K E, Meldrum H E, Spence J D. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.  N Engl J Med. 1998;  339 1415-1425
    CrossrefPubMedGoogle Scholar
  • 17 RebuffeŽ-Scrive M, Lundholm K, Björntorp P. Glucocorticoid hormone binding to human adipose tissue.  Eur J Clin Invest. 1985;  15 267-271
    PubMedGoogle Scholar
  • 18 Bujalska I J, Kumar S, Stewart P M. Does central obesity reflect “Cushing’s disease of the omentum”?.  Lancet. 1997;  349 1210-1213
    CrossrefPubMedGoogle Scholar
  • 19 Steinberg H O, Shaker H, Leaming R, Johnson A, Brechtel G, Baron A D. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance.  J Clin Invest. 1996;  97 2601-2610
    CrossrefPubMedGoogle Scholar
  • 20 Denis C V. Von Willebrand factor in vascular pathophysiology.  Pathologie Biologie. 2003;  51 395-396
    CrossrefPubMedGoogle Scholar
  • 21 Ambrosi B, Sartorio A, Pizzocaro A, Passini E, Bottasso B, Federici A. Evaluation of haemostatic and fibrinolytic markers in patients with Cushing's syndrome and in patients with adrenal incidentaloma.  Exp Clin Endocrinol Diabetes. 2000;  108 294-298
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Kirilov G, Tomova A, Dakovska L, Kumanov P h, Shinkov A, Alexandrov A S. Elevated plasma endothelin as an additional cardiovascular risk factor in patients with Cushing’s syndrome.  European J Endocrinol. 2003;  149 549-553
    PubMedGoogle Scholar
  • 23 Kelly J J, Mangos G, Williamson P M, Whitworth J A. Cortisol and hypertension.  Clin Exp Pharmacol Physiol. 1998;  25 (Suppl) S51-S56
    PubMedGoogle Scholar
  • 24 Healey B. Endothelial cell dysfunction: an emerging endocrinopathy linked to coronary disease.  J Am Coll Cardiol. 1990;  16 357-358
    PubMedGoogle Scholar
  • 25 Zacharieva S, Atanassova I, Nachev E, Orbetzova M, Kirilov G, Kalinov K, Shigarminova R. Markers of vascular function in hypertension due to Cushing’s syndrome.  Horm Metab Res. 2005;  37 36-39
    Article in Thieme ConnectPubMedGoogle Scholar

Carla Scaroni

Division of Endocrinology, Department of Medical and Surgical Sciences

University of Padua · Via Ospedale 105 · Padua · Italy 35128

Phone: +39 (049) 821 13 23

Fax: +39 (049) 65 73 91 ·

Email: carla.scaroni@unipd.it

      >