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

Abstract Objective: In the medical treatment of acromegaly different factors are influencial; 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 μg/l at baseline to 1·97 ± 0·20 μg/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 μg/l and 1·90 ± 0·20 μg/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 μg/l (P < 0·05) during the 2-week wash-out period and decreased to 290 ± 35 μg/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. European Journal of Endocrinology 136 61–66

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Differential effects of octreotide treatment and transsphenoidal surgery on growth hormone—binding protein levels in patients with acromegaly

Journal of Neurosurgery ◽

10.3171/jns.1999.90.4.0647 ◽

1999 ◽

Vol 90 (4) ◽

pp. 647-650 ◽

Cited By ~ 1

Author(s):

Irma Hernandez ◽

Daniela Soderlund ◽

Ana Laura Espinosa-de-los-Monteros ◽

Raquel Ochoa ◽

Arturo Zarate ◽

...

Keyword(s):

Growth Hormone ◽

Transsphenoidal Surgery ◽

Binding Protein ◽

Hormone Binding ◽

Content Type ◽

Growth Hormone Binding Protein ◽

Igf I ◽

Octreotide Treatment ◽

Hormone Binding Protein ◽

Fine Print

Object. The high-affinity growth hormone—binding protein (GHBP) represents the extracellular portion of the growth hormone (GH) receptor, and its serum levels are a reflection of the tissue receptor status. Levels of GHBP are decreased in patients with active acromegaly, probably because of downregulation of GH receptors. However, there are no studies of patients with acromegaly in which the effects of medical (that is, administration of somatostatin analogs) and surgical therapy on GHBP levels have been compared. That is the task the authors set out to accomplish in this study.Methods. The authors studied seven patients in whom acromegaly had been recently diagnosed. They examined these patients at baseline, 2 months after octreotide treatment (subcutaneous administration of 100 µg octreotide three times per day), and 1 month after transsphenoidal surgery. Growth hormone—binding activity was measured, as well as the following biochemical markers of the somatotropic axis: GH suppression induced by oral administration of glucose, insulin-like growth factor-I (IGF-I), and insulin-like growth factor—binding protein-3 (IGFBP3). Although octreotide treatment induced a decrease in the levels of GH, IGF-I, and IGFBP3, as well as an increase in the level of GHBP, these biochemical markers did not reach normal levels. On the other hand, after transsphenoidal surgery, GHBP levels became normal, particularly in those patients in whom serum GH could be suppressed to an undetectable level after glucose loading.Conclusions. The authors conclude that persistently low GHBP levels in patients with acromegaly are normalized by successful pituitary surgery and correlate well with disease activity.

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Growth hormone-binding protein-related immunoreactivity in the serum of patients with acromegaly is regulated inversely by growth hormone concentration

Acta Endocrinologica ◽

10.1530/eje.0.1320306 ◽

1995 ◽

Vol 132 (3) ◽

pp. 306-312 ◽

Cited By ~ 12

Author(s):

Jürgen Kratzsch ◽

Werner F Blum ◽

Manfred Ventz ◽

Thomas Selisko ◽

Gerd Birkenmeyer ◽

...

Keyword(s):

Growth Hormone ◽

Binding Protein ◽

Receptor Density ◽

Hormone Concentration ◽

Hormone Binding ◽

Gh Receptor ◽

Growth Hormone Binding Protein ◽

Igf I ◽

Hormone Binding Protein ◽

Igfbp 3

Kratzsch J. Blum WF, Ventz M, Selisko T, Birkenmeyer G, Keller E. Growth hormone-binding proteinrelated immunoreactivity in the serum of patients with acromegaly is regulated inversely by growth hormone concentration. Eur J Endocrinol 1994;132:306–12. ISSN 0804–4643 In this report we describe a newly developed radioimmunoassay (RIA) for the determination of the high-affinity growth hormone-binding protein (GHBP) in human blood. Using this RIA for the measurement of GHBP in serum of 29 patients with acromegaly, decreased concentrations were found compared to the normal range, depending on the activity of the disease. Growth hormonebinding protein was correlated inversely to log GH (r = −0.7, p < 0.001). A weaker relationship was shown between the GHBP activity determined in a functional assay based on charcoal separation and log GH (r = −0.51, p< 0.01). While insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) were correlated directly to log GH (r = 0.77 and r = 0.66, p < 0.001), an inverse and weaker relationship was evident between GHBP measured by RIA and IGF-I or IGFBP-3 (r = −0.61 and r = −0.57,p < 0.01). In contrast, no correlation could be detected between data of the functional GHBP assay and IGF-I or IGFBP-3, These results suggest, that: (1) in patients with acromegaly the GH receptor density in tissue reflected by the GHBP serum levels seems to be down-regulated, depending on the increased GH level; (2) low GHBP concentrations indicate an active disease in acromegaly and may be of diagnostic interest; (3) presuming that the GH receptor density is related to GH sensitivity, the variation of GH sensitivity is less important for IGF-I and IGFBP-3 production than the circulating GH concentration, at least in the situation of acromegaly; (4) because endogenous GH does not interfere in that assay, the RIA provides a valuable tool for the investigation of regulations between GH, GHBP and the GH receptor, especially in patients with acromegaly. The GHBP levels may be used as a sensitive parameter of GH oversecretion and tissue sensitivity to this hormone. Jürgen Kratzsch, Inst. Clin. Chem., University of Leipzig, Paul-List-Str. 13–15, D-04103 Leipzig, Germany

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