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Although sodium retention and volume expansion occur during GH administration, blood pressure is decreased or unchanged. The aim was to study the effect of short- and long-term GH replacement in adults on sodium balance, renal hemodynamics, and blood pressure. Ten adults with severe GH deficiency were included into a 7-d, randomized, placebo-controlled, cross-over trial followed by 12 months of open GH replacement. All measurements were performed under metabolic ward conditions. Extracellular water (ECW) was determined using multifrequency bioelectrical impedance analysis. Renal plasma flow and glomerular filtration rate were assessed using renal paraminohippurate and Cr(51) EDTA clearances, respectively. Renal tubular sodium reabsorption was assessed using lithium clearance. Plasma renin activity (PRA), plasma concentrations of angiotensin II, aldosterone, atrial natriuretic peptides and brain natriuretic peptides (BNP) and 24-h urinary norepinephrine excretion were measured. Seven days of GH treatment decreased urinary sodium excretion. Lithium clearance as a marker of proximal renal tubular sodium reabsorption was unaffected by GH treatment. ECW was increased after both short- and long-term treatment. This increase was inversely correlated to the decrease in diastolic blood pressure (r = -0.70, P = 0.02) between baseline and 12 months. Short-term treatment increased PRA and decreased BNP. The increase in PRA correlated with an increase in 24-h urinary norepinephrine excretion (r = 0.77, P &lt; 0.01). Glomerular filtration rate and renal plasma flow did not change during treatment. The sodium- and water-retaining effect of GH takes place in the distal nephron. The sustained increase in ECW in response to GH is associated with an unchanged or decreased blood pressure. This together with unchanged or decreased atrial natriuretic peptides and BNP may prevent pressure-induced escape of sodium.

GH Increases Extracellular Volume by Stimulating Sodium Reabsorption in the Distal Nephron and Preventing Pressure Natriuresis