Cardiovascular function and glucocorticoid replacement in patients with hypopituitarism.
OBJECTIVE
Retrospective analysis suggests an increased mortality from cardiovascular disease in hypopituitary adults; GH deficiency has been postulated to account for this. However, glucocorticoid replacement doses of 30 mg/day of hydrocortisone (HC) may be excessive, and could therefore be implicated in the increased cardiovascular mortality in this group of patients. The aims of this study were to establish whether patients with hypopituitarism have any abnormalities of the cardiovascular system compared to a control group and whether any of these parameters might be improved by reducing the replacement dose of glucocorticoid.


METHODS
A prospective analysis of cardiovascular function was carried out in 13 patients with hypopituitarism on routine replacement therapy and 20 normal controls who were matched for age and body mass index (BMI). Twenty-four-hour ambulatory blood pressure (BP), erect and supine BP, echocardiography, forearm plethysmography and cardiovascular reflexes in response to tilt, Valsalva and isometric hand grip were performed on controls and on patients taking 30 mg/day of HC and repeated following a reduction in HC dose to 15 mg/day for 3 months. Weight, plasma and urinary electrolytes, 24-hour urinary cortisol excretion, glucose, HbA1C and pituitary function were also assessed on HC 30 mg/day and 15 mg/day.


RESULTS
Mean 24-hour ambulatory BP, in addition to day and night time BP, was lower in patients than in controls (achieving statistical significance in the male subgroup) and did not change significantly with a reduction in HC dose. Erect and supine BP was also lower in patients compared to controls and there was no evidence of postural hypotension following a reduction in HC dose to 15 mg/day. Systolic and diastolic left ventricular dimensions, interventricular septal thickness, ejection fraction and fractional shortening were similar in controls and patients and did not alter with a reduction in HC dose. Systolic and diastolic BP and heart rate responded appropriately to all tests of cardiovascular reflexes (tilt, Valsalva and isometric handgrip) in hypopituitary patients though again measurements of systolic BP were significantly lower in patients during these tests, independent of HC dose. Forearm plethysmography was similar in patients receiving 30 mg of HC and controls but forearm blood flow increased significantly when the HC dose was reduced to 15 mg/day. There was no change in weight, plasma and urinary electrolytes, glucose and HbA1C or pituitary function in the patient group throughout the study.


CONCLUSIONS
In contrast to other studies we have failed to confirm cardiovascular dysfunction in GH deficient hypopituitary adults. Indeed, cardiovascular protection may be conferred on this group by the lower BP levels. Although a reduction in hydrocortisone dose was well tolerated in all patients, it appeared to confer no additional clinical benefit over the 3-month study period. In view of the conflicting data on cardiovascular function in hypopituitary patients, further prospective mortality studies are required in patients with adult GH deficiency.
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, UK.
F P
FP
Dunne
P
P
Elliot
M D
MD
Gammage
T
T
Stallard
T
T
Ryan
M C
MC
Sheppard
P M
PM
Stewart
D000328:Adult; D001794:Blood Pressure; D002319:Cardiovascular System / Q000503:physiopathology*; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D015716:Electrocardiography, Ambulatory; D005260:Female; D005542:Forearm / Q000098:blood supply; D013006:Growth Hormone / Q000172:deficiency; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007018:Hypopituitarism / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011187:Posture; D011446:Prospective Studies; D012039:Regional Blood Flow; D013599:Systole
D013006:Growth Hormone; D006854:Hydrocortisone