High Prevalence of Prolonged QT Interval Duration in Male Patients with Cushing's Disease

 

 Buy Article Permissions and Reprints

Abstract

Hypogonadal males have recently been shown to present prolonged QT interval, an electrocardiographic measure indicative of risk for fatal cardiac arrhythmias. Excess cortisol secretion induces low testosterone levels in male patients with Cushing's disease but no study has yet evaluated if this is accompanied by changes in QT interval duration. We therefore decided to evaluate whether male patients with Cushing's disease present changes in QT interval duration. QT interval was measured in electrocardiographic readings from 19 men and 35 women with Cushing's disease and age- and sex-matched controls were used for comparison. QT interval was corrected for heart rate according to Bazett's formula (QTc) and QTc >440 msec and >460 msec were taken as indicative of increased risk for torsade de pointes in men and women, respectively. Mean QTc was significantly longer in male patients compared with healthy controls (426.9±9.27 vs. 389.7±8.31, p<0.05) and 5 men with Cushing's disease presented prolonged QTc (prevalence 26%). By comparison, none of the women with Cushing's disease presented prolonged QTc. Hypokalemia and low testosterone appeared associated with long QTc.

Conclusions: Male patients with Cushing's disease present prolongation of QT interval which may lead to measurements associated with high risk for ventricular arrhythmias. Both low testosterone levels and hypokalemia appear to contribute to long QT in men with Cushing's disease.

References

• 1 The University of Arizona center for Education and Resarch on Therapeutics . Drugs that prolong the QT interval and/or induce torsade de pointes ventricular arrhythmia (updated 8/9/2010).  Available from http://www.azcert.org/medical-pros/drug-lists/drug-lists.htm
  Google Scholar
• 2 Abi-Gerges N, Philp K, Pollard C. et al . Sex differences in ventricular repolarization: from cardiac electrophysiology to torsades de pointes.  Fundam Clin Pharmacol. 2004;  18 139-151
  Google Scholar
• 3 Al-Khatib SM, LaPointe NM, Kramer JM. et al . What clinicians should know about the QT interval.  JAMA. 2003;  289 2120-2127
  Google Scholar
• 4 Casale PN, Devereux RB, Alonso DR. et al . Improved sex-specific criteria of left ventricular hypertrophy for clinical and computer interpretation of electrocardiograms: validation with autopsy findings.  Circulation. 1987;  75 565-572
  Google Scholar
• 5 Fazio S, Biondi B, Lupoli G. et al . Evaluation, by noninvasive methods, of the effects of acute loss of thyroid hormones on the heart.  Angiology. 1992;  43 287-293
  Google Scholar
• 6 Fraley MA, Birchem JA, Senkottaiyan N. et al . Obesity and the electrocardiogram.  Obes Res. 2005;  6 275-281
  Google Scholar
• 7 Invitti C, Pecori Giraldi F, De Martin M. et al the Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study.  J Clin Endocrinol Metab. 1999;  84 440-448
  Google Scholar
• 8 James AF, Choisy SCM, Hancox JC. Recent advances in understanding sex differences in cardiac repolarization.  Prog Biophys Mol Biol. 2007;  94 265-319
  Google Scholar
• 9 Mancia G, De Backer G, Dominiczak A. et al . 2007 Guidelines for the management of arterial hypertension.  Eur Heart J. 2007;  28 1462-1536
  Google Scholar
• 10 Matsumura K, Fujii K, Kansui Y. et al . Prolongation of the QT interval in primary aldosteronism.  Clin Exp Pharmacol Physiol. 2005;  32 66-69
  Google Scholar
• 11 Muiesan ML, Lupia M, Salvetti M. et al . Left ventricular structural and functional characteristics in Cushing's syndrome.  J Am Coll Cardiol. 2003;  41 2275-2279
  Google Scholar
• 12 Oikarinen L, Nieminen MS, Viitasalo M. et al . Relation of QT interval and QT dispersion to echocardigraphic left ventricular hypertrophy and geometric pattern in hypertensive patients. The LIFE study.  J Hypertension. 2001;  19 1883-1891
  Google Scholar
• 13 Pecori Giraldi F, Andrioli M, De Marinis L. et al . Significant GH deficiency after long-term cure by surgery in adult patients with Cushing's disease.  Eur J Endocrinol. 2007;  156 235-241
  Google Scholar
• 14 Pecori Giraldi F, Moro M, Cavagnini F. the Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis . Gender-related differences in the presentation and course of Cushing's disease.  J Clin Endocrinol Metab. 2003;  88 1554-1558
  Google Scholar
• 15 Pecori Giraldi F, Toja PM, Filippini B. et al . Increased prevalence of prolonged QT interval in males with primary or secondary hypogonadism. A pilot study.  Int J Androl. 2010;  33 e132-e138
  Google Scholar
• 16 Pham TV, Rosen MR. Sex, hormones, and repolarization.  Cardiovasc Res. 2002;  53 740-751
  Google Scholar
• 17 Rautaharju PM, Zhou SH, Wong S. et al . Sex differences in the evolution of the electrocardiographic QT interval with age.  Can J Cardiol. 1992;  8 690-695
  Google Scholar
• 18 Roden DM. Drug-induced prolongation of the QT interval.  N Engl J Med. 2004;  350 1013-1022
  Google Scholar
• 19 Schwartz PJ, Moss AJ, Vincent GM. et al . Diagnostic criteria for the long QT syndrome.  Circulation. 1993;  88 782-784
  Google Scholar
• 20 Ryzhikov VD. ECG changes in the active form of Itsenko-Cushing disease and in a state of clinical remission.  Zdravookhr Kirg. 1978;  6 22-26
  Google Scholar
• 21 Savel’ev AA, Stepanov MA. On rhythm disorders in Itsenko-Cushing syndrome.  Ter Arkh. 1962;  34 124-129
  Google Scholar
• 22 Scott BD, Friday KJ. Cushing's syndrome presenting as sudden death.  Am Heart J. 1988;  115 487-488
  Google Scholar
• 23 Stramba-Badiale M, Spagnolo D, Bosi G. et al . Are gender differences in QTc present at birth?.  Am J Cardiol. 1995;  75 1277-1278
  Google Scholar
• 24 Sugihara N, Shimizu M, Kita Y. et al . Cardiac characteristics and postoperative courses in Cushing's syndrome.  Am J Cardiol. 1992;  69 1475-1480
  Google Scholar
• 25 Tsuda K, Saikawa T, Yonemochi H. et al . Electrocardiographic abnormalities in patients with Cushing's syndrome.  Jpn Heart J. 1995;  36 333-339
  Google Scholar

Correspondence

Dr. F. Pecori Giraldi

University of Milan

Ospedale San Luca

Istituto Auxologico Italiano IRCCS

via Spagnoletto 3

20149 Milan

Italy

Email: fpg@auxologico.it