Short-term growth hormone (GH) treatment of GH-deficient adults increases body sodium and extracellular water, but not blood pressure
DM Hoffman, L Crampton, C Sernia, TV Nguyen and KK Ho
Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia.
Initiation of GH treatment in adults is frequently complicated by the
development of symptomatic fluid retention. To investigate the mechanism
and extent of fluid retention that occurs with dosages of GH used in the
treatment of GH-deficient adults, we conducted a double blind study in
which seven GH-deficient patients (aged 24-74 yr) each received in random
order daily sc injections of placebo, a physiological dose of GH (0.04
U/kg, low dose), and a supraphysiological dose of GH (0.08 U/kg, high dose)
for 7 days, separated by 21-day washout periods. On the seventh day,
measurements were made of serum insulin-like growth factor I, body weight,
exchangeable sodium, plasma volume, angiotensinogen, PRA, aldosterone,
atrial natriuretic peptide (ANP), and mean 24-h ambulatory heart rate and
blood pressure. GH significantly increased mean insulin-like growth factor
I levels from 105 +/- 11 to 304 +/- 45 micrograms/L during low dose
treatment (P = 0.006) and 400 +/- 76 micrograms/L during high dose
treatment (P = 0.004). High dose GH caused a 1.2 +/- 0.3 kg increase in
body weight (P = 0.01) and a 193 +/- 65 mmol increase in exchangeable
sodium (P = 0.008). Low dose GH had a lesser effect, with no significant
increase in body weight, but an increase in exchangeable sodium of 113 +/-
37 mmol (P = 0.02). Plasma volume was not significantly affected by GH
treatment. Mean supine angiotensinogen levels were significantly higher
during both GH treatments compared to placebo (low dose, P = 0.017; high
dose, P = 0.028) as were mean supine PRA levels (low dose, P = 0.0002; high
dose, P = 0.0025). Supine angiotensin II, aldosterone, and ANP levels were
not significantly affected by GH treatment. There was no significant change
from placebo in any of the sodium-regulating hormones in the erect posture.
The mean 24-h heart rate was significantly higher during low dose (82 +/- 2
beats/min; P = 0.0001) and high dose (88 +/- 3 beats/min; P = 0.0001) GH
treatment than during placebo (67 +/- 3 beats/min). However, no significant
change in mean 24-h systolic or diastolic blood pressure was observed. In
summary, acute GH administration using doses currently employed in treating
adults causes a dose-related increase in body weight and body sodium, but
no associated increase in blood pressure. We conclude that 1) sodium
retention is a physiological effect of GH, but does not cause an acute rise
in blood pressure; and 2) the mechanism of sodium and fluid retention is
not primarily due to enhanced aldosterone secretion or inhibition of ANP
release, but more likely to a direct renal tubular effect.
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