SHORT-TERM GROWTH-HORMONE (GH) TREATMENT OF GH-DEFICIENT ADULTS INCREASES BODY SODIUM AND EXTRACELLULAR WATER, BUT NOT BLOOD-PRESSURE

Initiation of GH treatment in adults is frequently complicated by the development of symptomatic fluid retention. To investigate the mechani sm and extent of fluid retention that occurs with dosages of GH used i n the treatment of GH-deficient adults, we conducted a double blind st udy 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 f actor I, body weight, exchangeable sodium, plasma volume, angiotensino gen, 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 mu g/L during low dose treatment (P = 0.006) and 400 +/- 76 mu g/L du ring 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 exchan geable sodium of 113 +/- 37 mmol (P = 0.02). Plasma volume was not sig nificantly affected by GH treatment. Mean supine angiotensinogen level s were significantly higher during both GH treatments compared to plac ebo (low dose, P = 0.017; high dose, P = 0.028) as were mean supine PR A levels (low dose, P = 0.0002; high dose, P = 0.0025). Supine angiote nsin II, aldosterone, and ANP levels were not significantly affected b y GH treatment. There was no significant change from placebo in any of the sodium-regulating hormones in the erect posture. The mean 24-h he art 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 treatme nt than during placebo (67 +/- 3 beats/min). However, no significant c hange 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 tha t 1) sodium retention is a physiological effect of GH, but does not ca use an acute rise in blood pressure; and 2) the mechanism of sodium an d fluid retention is not primarily due to enhanced aldosterone secreti on or inhibition of ANP release, but more likely to a direct renal tub ular effect.