Growth hormone binding protein and growth hormone availability in acromegalic patients treated with long-acting octreotide (Sandostatin-LAR)

Medical Department M (Endocrinology and Diabetes), University Hospital, Aarhus, Denmark.

OBJECTIVE: In the medical treatment of acromegaly different factors are influential; among these the impact on growth hormone binding protein (GHBP) has not been clarified. DESIGN: Twenty acromegalic patients and nineteen age- and gender-matched normal subjects participated in this study. The patients were treated for 21 months with depot long-acting microsphere-enclosed octreotide (Sandostatin-LAR). Previously, all the patients were treated s.c. with octreotide t.i.d. After a 2-week wash-out period (baseline) the patients received the first i.m. injection of the long-acting octreotide. The first two injections were administered at 60-day intervals; thereafter the injections were at 28-day intervals. METHODS: The levels of GHBP, complexed GHBP, growth hormone (GH) and insulin-like growth factor-I (IGF-I) were determined in fasting serum samples. RESULTS: In the 2-week wash-out period GHBP levels decreased from 1.13 +/- 0.17 to 0.92 +/- 0.15 nmol/l (P < 0.05). During the 21-months treatment, GHBP increased again to 1.10 +/- 0.16 nmol/l. In the age- and gender-matched control group GHBP levels were significantly higher at all times (1.95 +/- 0.21 nmol/l. P(all) < 0.02). Mean levels of 8-h GH decreased from 12.6 +/- 2.58 microg/l at baseline to 1.97 +/- 0.20 microg/l after 21 months of treatment (P < 0.05). Mean 8-h GH levels were unchanged during long-acting octreotide treatment compared with levels during s.c. treatment (1.97 +/- 0.20 microg/l and 1.90 +/- 0.20 microg/l respectively). In fasting blood samples GH-complexed GHBP ranged from 13.8 +/- 2.4% (9 months) to 25.4 +/- 4.5% (baseline) of total GHBP. Serum IGF-I increased from 367 +/- 45 to 764 +/- 80 microg/l (P < 0.05) during the 2-week wash-out period and decreased to 290 +/- 35 microg/l (P < 0.05) after 21 months of treatment with long-acting octreotide. IGF-I levels after 21 months were significantly lower than during s.c. octreotide treatment (P < 0.05). CONCLUSION: Serum GHBP levels are similar during treatment with long-acting octreotide as compared with regular octreotide. Furthermore, significant changes in GHBP can occur within 2 weeks. Finally, in addition to the lowering effect on GH levels, the induced increase in GHBP levels may imply a further advantage in octreotide treatment of acromegaly. circulating GH bound to GHBP may less readily reach the tissues.