A Comparison among the Effectiveness of Growth Hormone Suppression in Active Acromegaly of Bromocriptine and Long Acting Somatostatin Analogue (SMS 201–995)

Abstract. Twelve patients with active acromegaly were treated with the long-acting somatostatin analogue SMS 201-995 at a dose of 50 μg sc twice daily in the first 2 weeks of treatment and 100 μg twice daily thereafter. Four hours after the first injection of SMS, GH levels became normal in 8 of the 12 patients. The GH response after hpGRF administration was strongly suppressed by SMS. Paradoxical GH responses to TRH disappeared in 6 out of 7 patients during SMS. Paradoxical GH responses to LHR, however, persisted in 4 out of 4 patients. Paradoxical responses of GH after glucose loading disappeared in 2 out of 2 patients. We conclude that SMS normalizes most anomalous growth hormone kinetics in acromegaly. This drug offers a new tool in the treatment of this disease.

Download Full-text

Central effects of growth hormone-releasing hexapeptide (GHRP-6) on growth hormone release are inhibited by central somatostatin action

Journal of Endocrinology ◽

10.1677/joe.0.1440555 ◽

1995 ◽

Vol 144 (3) ◽

pp. 555-560 ◽

Cited By ~ 56

Author(s):

K M Fairhall ◽

A Mynett ◽

I C A F Robinson

Keyword(s):

Growth Hormone ◽

Somatostatin Analogue ◽

Hormone Release ◽

Growth Hormone Release ◽

Central Action ◽

Central Effects ◽

Central Actions ◽

Long Acting ◽

Major Target

Abstract Growth hormone (GH) release is stimulated by a variety of synthetic secretagogues, of which growth hormone-releasing hexapeptide (GHRP-6) has been most thoroughly studied; it is thought to have actions at both pituitary and hypothalamic sites. To evaluate the central actions of this peptide, we have studied GH release in response to direct i.c.v. injections in anaesthetized guinea pigs. GHRP-6 (0·04–1 μg) stimulated GH release >10-fold 30–40 min after i.c.v. injection. The same GH response required >20-fold more GHRP-6 when given by i.v. injection. GH release could also be elicited by a non-peptide GHRP analogue (L-692,585, 1 μg i.c.v.), whereas a growth hormone-releasing factor (GRF) analogue (human GRF 27Nle(1–29)NH2, 2 μg, i.c.v.) was ineffective. A long acting somatostatin analogue (Sandostatin, SMS 201–995, 10 μg i.c.v.) (SMS) given 20 min before 200 ng GHRP-6 blocked GH release. This was unlikely to be due to a direct effect of SMS leaking out to the pituitary, since central SMS injections did not affect basal GH release, nor did they block GH release in response to i.v. GRF injections. We conclude that the hypothalamus is a major target for GHRP-6 in vivo. Since the GH release induced by central GHRP-6 injections can be inhibited by a central action of somatostatin, and other data indicate that GHRP-6 activates GRF neurones, we suggest that somatostatin may block this activation via receptors known to be located on or near the GRF cells themselves. Somatostatin may therefore be a functional antagonist of GHRP-6 acting centrally, as well as at the pituitary gland. Journal of Endocrinology (1995) 144, 555–560

Download Full-text

Disappearance half-life times of exogenous and growth hormone-releasing factor-stimulated endogenous growth hormone in normal rats

Journal of Endocrinology ◽

10.1677/joe.0.1280369 ◽

1991 ◽

Vol 128 (3) ◽

pp. 369-374 ◽

Cited By ~ 15

Author(s):

I. M. Chapman ◽

A. Helfgott ◽

J. O. Willoughby

Keyword(s):

Growth Hormone ◽

Endogenous Growth ◽

Half Life ◽

Somatostatin Analogue ◽

Blood Samples ◽

Growth Hormone Releasing Factor ◽

Hypothalamic Hormones ◽

Significant Difference ◽

Long Acting ◽

Analogue Octreotide

ABSTRACT This study was performed to determine the disappearance half-life times of endogenous and exogenous rat GH in conscious normal rats and to compare these with the decay characteristics of GH at the end of spontaneous normal bursts. The endogenous half-life was determined in five rats by giving an i.v. injection of rat GH-releasing factor followed after 10 min by an i.v. injection of long-acting somatostatin analogue (octreotide) and taking blood samples for 85 min. The half-lives (mean ± s.e.m.) were 3·4±0·4 min and 13·2±1·1 min for the first and second exponential respectively as determined by bi-exponential analysis. The exogenous GH half-life was determined in ten rats by giving i.v. octreotide followed after 10 min by i.v. rat GH and sampling for 85 min. The half-lives of exogenous GH were 3·3±0·2 min and 17·5±1·4 min by bi-exponential analysis and there was no significant difference between the half-lives of endogenous and exogenous GH. The half-life of the decline of GH levels at the end of spontaneous bursts in nine rats was 14·4±0·9 min, not different from the half-life of endogenous GH, the secretion of which was terminated by octreotide. This suggests that the end of spontaneous GH bursts is marked by sudden cessation of GH release and may provide an indication of the rapidity of change in the levels of the underlying hypothalamic hormones which control GH release. Journal of Endocrinology (1991) 128, 369–374

Download Full-text

Octreotide long-acting repeatable and lanreotide Autogel are equally effective in controlling growth hormone secretion in acromegalic patients

Acta Endocrinologica ◽

10.1530/eje.0.1500489 ◽

2004 ◽

pp. 489-495 ◽

Cited By ~ 57

Author(s):

SW van Thiel ◽

JA Romijn ◽

NR Biermasz ◽

BE Ballieux ◽

M Frolich ◽

...

Keyword(s):

Growth Hormone ◽

Binding Affinity ◽

Receptor Subtype ◽

Somatostatin Analogue ◽

Deconvolution Analysis ◽

Octreotide Lar ◽

Gh Secretion ◽

Igf I ◽

Long Acting ◽

Lanreotide Autogel

OBJECTIVE: Recently a new depot preparation of the long-acting somatostatin analogue, lanreotide Autogel was introduced for the treatment of acromegaly. Like octreotide long-acting repeatable (LAR), it has high binding affinity for the somatostatin receptor subtype SSTR 2 and less binding affinity for SSTR 5. We hypothesized that the ability to suppress growth hormone (GH) secretion in patients with acromegaly would be similar for these depot preparations. PATIENTS AND STUDY DESIGN: Seven patients (mean age+/-S.E.M. 48.4+/-7 years) on long-term octreotide LAR treatment at a monthly injection interval for a mean of 2.8 years were enrolled in the study. They underwent a GH secretory profile study with 10 min sampling for 24 h, 28 days after an injection. At 2, 4 and 6 weeks after the next injection fasting GH profiles (every 30 min for 3.5 h) and serum IGF-I measurements were measured. These investigations were repeated 12 months later, when the patients were on an individually titrated stable dose of lanreotide Autogel. RESULTS: Secretory characteristics and total 24 h GH secretion, estimated by deconvolution analysis of the 10 min 24 h plasma GH concentrations, did not show differences between these two long-acting somatostatin analogues. Both drugs were equally effective in GH and IGF-I suppression as measured at 2, 4 and also at 6 weeks following an injection. CONCLUSION: The efficacy of lanreotide Autogel and octreotide LAR was equal, notwithstanding that these drugs are administered in a different way and have different pharmacokinetics.

Download Full-text