High prevalence of prolonged QT interval duration in male patients with Cushing's disease.

UNLABELLED: 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.

Increased prevalence of prolonged QT interval in males with primary or secondary hypogonadism: a pilot study.

Symptoms and signs of male hypogonadism span all organ systems, including the cardiovascular apparatus. The electrocardiographic QT interval reflects cardiac ventricular repolarization and, if prolonged, increases the risk of malignant arrhythmias. QT interval duration is similar in boys and girls during childhood, but shortens in males after puberty and experimental studies suggest that testosterone is a major contributor to shortening of QT interval in men. The aim of the present pilot study was to assess the duration of ventricular repolarization in adult males with primary or secondary hypogonadism. Standard ECG recordings were performed in 26 men (mean age 39.2 +/- 2.17 years) with pituitary or testicular hypogonadism and repeated in 15 patients during testosterone replacement. Twenty-six age-matched control men were also analysed. Measured QT intervals were corrected for heart rate according to Bazzett's formula (QTc = QT/radical RR interval). The prevalence of prolonged QTc was considerably higher in hypogonadal patients (four of 26 men) than in control men (none, p < 0.05) and in the general, healthy population (<2.5%). QTc interval normalized on hormone replacement therapy in the four patients presenting prolonged QTc in the hypogonadal state. Heart rate and left ventricular mass did not differ among the two groups and no known QT-prolonging factor was apparent in patients with abnormal QTc interval. In conclusion, a high number prolonged QT interval measurements was observed in hypogonadal men who may therefore be at increased risk for cardiac arrhythmias. This observation reveals an additional feature of male hypogonadism, which may benefit from testosterone replacement therapy.

Circadian blood pressure profile in patients with active Cushing's disease and after long-term cure.

Hypertension is a major feature of Cushing's disease, with the attendant increase in the rate of cardiovascular events. The circadian blood pressure profile also impacts cardiovascular risk and a few studies have shown that patients with Cushing's syndrome do not present the expected nocturnal blood pressure decrease and, further, that this alteration persists in short-range disease remission. These studies were performed by conventional discontinuous ambulatory pressure monitoring, a technique not devoid of limitations. Aim of our study was the assessment of blood pressure and heart rate profile by beat-to-beat noninvasive monitoring in twelve patients with active Cushing's disease (9 women and 3 men, age 33.3+/-2.36 years) and the assessment of its possible changes at short- (<1 year) and long-term (2-3 years) follow-up after curative surgery. No nocturnal blood pressure dipping (i.e., decrease by 10% of daytime values) was observed in 50% of patients both during active hypercortisolism and within 1 year from surgery. Recovery of blood pressure dipping profile was detected at long-term follow-up in a minority of patients. Daytime heart rate was higher in patients with active Cushing's disease and decreased over time after cure. In conclusion, patients with Cushing's disease present absent nocturnal blood pressure dipping and abnormal heart rate values which do not resolve after short-term remission of hypercortisolism and show only partial improvement in the long run. These findings identify additional cardiovascular risk factors for patients cured of Cushing's disease.