How cardiac auscultation and a routine ECG can rule out a diagnosis of Cushing's Syndrome and Addison's Disease

Download Tribute to a Teacher: Clinical Pearls by Dr. Lown.

This pearl derives from work on the Lown Ganong Levine Syndrome (LGL) carried out in 1950. The study characterized patients with abbreviated A-V conduction and paroxysms of atrial tachyarrhythmias (1). Unlike the closely related WPW syndrome, these patients lacked the characteristic delta wave. During the scanning of thousands of electrocardiograms for this project, we segregated two groups: one with a P-R interval of 0.12 seconds or less, the short P-R group, and a control group of 0.16 seconds or more. Impressive was the fact that we found large numbers of patients with Addison's disease in the control group, but none in the short P-R group. At the time the Peter Bent Brigham Hospital in Boston was a world center for Addison's disease, but this factor did not explain the odd concentration of patients in the longer P-R group.

In an extensive investigation of this anomalous observation, we discovered that adrenal corticosteroids facilitate A-V conduction (2).

In an analysis of 388 electrocardiograms, we found the mean P-R duration was 0.176 seconds among 54 patients with Addison's disease while it was only 0.136 seconds among 34 patients with Cushing's syndrome (p<0.001). Nearly 20% of Addison patients had first degree A-V block. We also found that administration of cortisone abbreviated A-V conduction, while the P-R prolonged among Cushing patients who underwent adrenalectomy. Furthermore, the P-R duration varied with urinary ketosteroid excretion. Thus we discovered that endocrine factors modulate atrio-ventricular conduction.

Now for an elegant pearl: It has long been known that the intensity of the first heart sound at the apex correlates with the duration of A-V conduction. The longer this interval, the softer the first heart sound. It should therefore follow that those with Addison's disease, having a prolonged P-R interval, will have a soft first heart sound, while in Cushing's syndrome, the P-R being short, one would note a first sound that is loud or even snapping.

The clinical value is straightforward. Without extensive work, except for mere cardiac auscultation, judging by the intensity of the first sound one could deduce the absence of either of these endocrinological disorders.
- Originally published on 9 September 1997

Further reflections
When this tidbit of a finding was presented at medical grand rounds at the Peter Bent Brigham Hospital, Dr. Levine was elated beyond measure. One would have imagined that we had discovered a cure for cancer. As a clinician he sparkled at an astute clinical association that led to a correct diagnosis. He was persuaded that with a carefully obtained history and an attentive listening through a stethoscope, few were the maladies that could not be identified at the bedside expeditiously and with little cost or burden. He would have marveled at our new scientific era wherein nothing remains hidden, but would have expressed nostalgia for the loss of intimacy between physician and patient.
- 13 September 2008

Citations:

1. Lown B, Ganong FW, Levine SA. The syndrome of short P-R interval, normal QRS complex and paroxysmal rapid heart action. Circulation. 1952;5:693.
2. Lown B, Arons W, Ganong FW, Levine SA. Adrenal steroids in auriculo-ventricular conduction. Am Heart J. 1955;50:61.

Clinical Pearl
Date Posted: 13 September 2008