Endocrine Abstracts

Adult Growth Hormone Deficiency (AGHD) is associated with relative phosphate deficiency. Phosphate is an important determinant of serum PTH concentration. PTH target-organ sensitivity is reduced in AGHD and may underlie the pathogenesis of AGHD-related osteopaenia. We examined the effect of phosphate supplementation on change in PTH target-organ sensitivity when given simultaneously with Growth Hormone Replacement (GHR) in AGHD patients.

24 AGHD patients were consented to the study. Patients were randomised to receive either GHR alone or GHR plus 1g phosphate-sandoz. 1/2-hourly blood and 3-hourly urine samples were collected for 24h before and 1, 3, 6 and 12 months following treatment. Samples were analysed for PTH, calcium, phosphate and nephrogenous cyclic AMP (NcAMP, marker of renal PTH activity). Serum calcium was adjusted for albumin (ACa).

Following 1 month, 24-hour mean NcAMP (14.3plus/minus1.6nmol/LGFR versus 17.7plus/minus1.8nmol/LGFR, p=0.007) and ACa concentrations (2.28plus/minus0.001mmol/L versus 2.31plus/minus0.001mmol/L, p<0.001) increased significantly, while PTH concentration (4.78plus/minus0.01pmol/L versus 4.46plus/minus0.01pmol/L, p<0.001) decreased significantly in patients receiving GHR alone, indicating an increase in PTH target-organ sensitivity. Adjunctive phosphate supplementation resulted in significant increases in 24-hour mean NcAMP (15.1plus/minus1.7nmol/LGFR versus 21.9plus/minus1.7nmol/LGFR, p<0.001), ACa (2.27plus/minus0.001mmol/L versus 2.30plus/minus0.001mmol/L, p<0.001) and PTH concentrations (4.71plus/minus0.01pmol/L versus 5.29plus/minus0.01pmol/L, p<0.01) at 1 month. The higher phosphate load in the phosphate group may have resulted in increased PTH concentration, thereby masking changes in PTH target-organ sensitivity. NcAMP peaked at 1 month, decreasing below baseline by 12 months in patients receiving GHR alone, but peaked at 3 months and remained above baseline at 12 months in patients receiving phosphate. Mean % increase in NcAMP was significantly higher in the phosphate group (113.4% versus 29.4%, p<0.001).

Phosphate supplement as an adjunct to GHR resulted in increased and maintained renal PTH activity compared with GHR alone. Further studies are required to determine whether such benefits confer advantage in terms of improvement in BMD.