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OCTREOTIDE STIMULATES INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-1 (IGFBP-1) LEVELS IN ACROMEGALY

Division of Endocrinology & Metabolism, Cedars-Sinai Medical Center-UCLA School of Medicine Los Angeles, CA

Address all correspondence to: Dr. S. Melmed, B-131 Division of Endocrinology & Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, 90048.

Insulin-like growth factors (IGFs) circulate in a complexed state with several binding proteins (BPs). Of these, IGFBP-1 is regulated by hormonal and nutritional factors. The somatostatin analogue, octreotide, has been used to effectively control hypersomaototropism in acromegaly. IGFBP-1 levels were measured by RIA in 17 acromegalic patients receiving octreotide. Serum hormone sampling was conducted hourly for 8 hr periods. Among 13 octreotide responders, mean pre-treatment basal GH, IGF-1, and IGFBP-1 levels were 19 ± 5 ug/L, 1021 ± 168 ug/L, and 36 ± 8 ug/L respectively. One month following octreotide treatment, an acute subcutaneous injection (100 ug) maximally attenuated GH to 3 ± 0.6 ug/L (18% of control, P < 0.03) and IGF-1 to 467 ± 75 ug/L (46% of control, P < 0.008) after 4 hrs. IGFBP-1 levels, however, were stimulated to 95 ± 16 ug/L (297% of control, P < 0.003) during the same time period. A significant increase in IGFBP-1 levels occured within 2 hrs (158% of baseline, P < 0.03), and was sustained until the 7 th hr following injection. Insulin, a known suppressor of IGFBP-1, did not change during this time. Among the 4 octreotide non-responders, mean basal IGFBP-1 levels were 42 ± 4 ug/L, and 4 hrs following octreotide administration IGFBP-1 was 40 ± 7 ug/L. Octreotide induced a dynamic inverse relationship between circulating GH and IGFBP-1 levels (r = – 0.73, P < 0.001). The absence of IGFBP-1 changes in octreotide non-responders and the non-suppression of insulin in octreotide responsive patients, suggest a direct GH-mediated mechanism of IGFBP-1 regulation in octreotide treated patients with acromegaly. IGFBP-1 may be another useful marker in evaluating the response of acromegaly to octreotide treatment in patients who experience clinical benefit but equivocal GH and IGF-1 attenuation.

Received April 17, 1991.

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