Individualized growth hormone substitution with normalized IGF-I levels does not stimulate the renin-angiotensin-aldosterone system.
OBJECTIVE
To study the effects of individualized recombinant GH substitution, aiming at normal circulating IGF-I levels, in GH-deficient adults on blood pressure, the renin-angiotensin-aldosterone system (RAAS), natriuretic peptides and urine free cortisol.


METHODS
Open study with control group. The patients were titrated in dose steps of 0.17 mg GH/day every 6-8 weeks until an IGF-I level around the mean + 1 SD was attained (T(max)). After another month the dose was reduced by 0.17 mg (minimum dose 0.17 mg/day) to produce IGF-I levels at or slightly below the age-related mean (T(end)), and this maintenance dose was held constant for 6 months.


METHODS
Eighteen patients (11 males and seven females) with GH deficiency participated. For comparison we also prospectively evaluated 17 matched control subjects.


METHODS
Blood pressure and heart rate, circulating levels of IGF-I, plasma renin activity (PRA), immunoreactive active renin (IRR), angiotensin II, aldosterone, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and 24-h urine aldosterone and urine free cortisol levels.


RESULTS
Blood pressure was unchanged by GH substitution but heart rate increased significantly (P < 0.03). PRA was elevated on the highest GH dose (T(max)) compared to baseline (P < 0.01), but returned to baseline and levels of controls at (T(end)). Four patients developed transient oedema and tended to have higher PRA levels than the rest of the subjects (P = 0.09). The circulating levels of IRR, angiotensin II, aldosterone, BNP and 24-h urine aldosterone and urine free cortisol levels were unchanged by GH substitution, and did not differ from the levels in the control subjects. Baseline ANP levels in the patients were lower than in the controls (P < 0.01), but increased after GH substitution (P < 0.01) to levels found in with the controls.


CONCLUSIONS
We found no major changes of the variables in the circulating renin-angiotensin-aldosterone system and a normalization of atrial natriuretic peptide when an individualized dose of GH was titrated to near-normal IGF-I levels.
D000328:Adult; D000886:Anthropometry; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000187:drug effects*
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D009320:Atrial Natriuretic Factor; D006854:Hydrocortisone