A single-dose comparison of the acute effects between the new somatostatin analog SOM230 and octreotide in acromegalic patients.

Treatment with the somatostatin receptor (sst) subtype 2 predominant analogs octreotide and lanreotide induces clinical and biochemical cure in approximately 65% of acromegalic patients. GH-secreting pituitary adenomas, which are not controlled, also express sst(5). We compared the acute effects of octreotide and SOM230, a new somatostatin analog with high affinity for sst(1,2,3,5) on hormone release in acromegalic patients. In a single-dose, proof-of-concept study, 100 microg octreotide and 100 and 250 microg SOM230 were given s.c. to 12 patients with active acromegaly. Doses of 100 and 250 microg SOM230 dose-dependently suppressed GH levels from 2-8 h after administration (-38 +/- 7.7 vs. -61 +/- 6.7%, respectively; P < 0.01). A comparable suppression of GH levels by octreotide and 250 microg SOM230 was observed in eight patients (-65 +/- 7 vs. -72 +/- 7%, respectively). In three patients, the acute GH-lowering effect of 250 microg SOM230 was significantly superior to that of octreotide (-70 +/- 2 vs. -17 +/- 15%, respectively; P < 0.01). In one patient, the GH-lowering effect of octreotide was better than that of SOM230. Tolerability for SOM230 was good. Glucose levels were initially slightly elevated after octreotide and SOM230, compared with control day, whereas insulin levels were only significantly suppressed by octreotide. We conclude that SOM230 is an effective GH-lowering drug in acromegalic patients with the potential to increase the number of patients controlled during long-term medical treatment.

[1]  C. Bruns,et al.  A novel somatostatin mimic with broad somatotropin release inhibitory factor receptor binding and superior therapeutic potential. , 2003, Journal of medicinal chemistry.

[2]  S. Lamberts,et al.  The pathophysiological consequences of somatostatin receptor internalization and resistance. , 2003, Endocrine reviews.

[3]  S. Lamberts,et al.  Quantitative and functional expression of somatostatin receptor subtypes in human thymocytes. , 2002, American journal of physiology. Endocrinology and metabolism.

[4]  M. Culler,et al.  Somatostatin receptor subtype 1-selective activation reduces cell growth and calcitonin secretion in a human medullary thyroid carcinoma cell line. , 2002, Biochemical and biophysical research communications.

[5]  C. Bruns,et al.  SOM230: a new somatostatin peptidomimetic with potent inhibitory effects on the growth hormone/insulin-like growth factor-I axis in rats, primates, and dogs. , 2002, Endocrinology.

[6]  P M Stewart,et al.  Primary medical therapy for acromegaly: an open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size. , 2002, The Journal of clinical endocrinology and metabolism.

[7]  P. Freda Somatostatin analogs in acromegaly. , 2002, The Journal of clinical endocrinology and metabolism.

[8]  G. Meno-Tetang,et al.  SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. , 2002, European journal of endocrinology.

[9]  P. Cappabianca,et al.  Long-term effects of depot long-acting somatostatin analog octreotide on hormone levels and tumor mass in acromegaly. , 2001, The Journal of clinical endocrinology and metabolism.

[10]  S. Schulz,et al.  Homo- and Heterodimerization of Somatostatin Receptor Subtypes , 2001, The Journal of Biological Chemistry.

[11]  G. Sassolas,et al.  Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly , 2000, Clinical endocrinology.

[12]  L. Buscail,et al.  Somatostatin Receptors , 2000, Digestion.

[13]  U. Kumar,et al.  Subtypes of the Somatostatin Receptor Assemble as Functional Homo- and Heterodimers* , 2000, The Journal of Biological Chemistry.

[14]  M. Culler,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2000 by The Endocrine Society Human Somatostatin Receptor Subtypes in Acromegaly: Distinct Patterns of Messenger Ribonucleic Acid Expression and Hormone Suppression Identify , 2022 .

[15]  D. Torigian,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1998 by The Endocrine Society Octreotide as Primary Therapy for Acromegaly* , 2022 .

[16]  S. Melmed,et al.  Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. , 1997, The Journal of clinical investigation.

[17]  G. Mengod,et al.  Somatostatin receptor subtypes sst1, sst2, sst3 and sst5expression in human pituitary, gastroentero‐pancreatic and mammary tumors , 1997 .

[18]  S. Melmed,et al.  Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation. , 1997, The Journal of clinical investigation.

[19]  G. Bell,et al.  Molecular biology of somatostatin receptors. , 1995, Endocrine reviews.

[20]  A. Harris,et al.  A prospective multicenter octreotide dose response study in the treatment of acromegaly , 1995, Journal of endocrinological investigation.

[21]  Y. Patel,et al.  Expression of mRNA for all five human somatostatin receptors (hSSTR1-5) in pituitary tumors. , 1994, Life sciences.

[22]  A. Harris,et al.  Long-term treatment of 189 acromegalic patients with the somatostatin analog octreotide. Results of the International Multicenter Acromegaly Study Group. , 1991, Archives of internal medicine.

[23]  S. Lamberts,et al.  SMS 201-995 induces a continuous decline in circulating growth hormone and somatomedin-C levels during therapy of acromegalic patients for over two years. , 1987, The Journal of clinical endocrinology and metabolism.

[24]  S. Lamberts,et al.  Long-term treatment of acromegaly with the somatostatin analogue SMS 201-995. , 1985, The New England journal of medicine.

[25]  S. Lamberts,et al.  The somatostatin analog SMS 201-995 induces long-acting inhibition of growth hormone secretion without rebound hypersecretion in acromegalic patients. , 1985, The Journal of clinical endocrinology and metabolism.

[26]  S. Lamberts,et al.  Isolation of large numbers of dispersed human pituitary adenoma cells obtained by aspiration , 1984, Journal of endocrinological investigation.

[27]  N. Ling,et al.  Hypothalamic Polypeptide That Inhibits the Secretion of Immunoreactive Pituitary Growth Hormone , 1973, Science.

[28]  I. Lancranjan,et al.  Results of a European Multicentre Study with Sandostatin® LAR® in Acromegalic Patients , 2004, Pituitary.

[29]  H. Wilkinson,et al.  Somatostatin receptor subtype 5 regulates insulin secretion and glucose homeostasis. , 2003, Molecular endocrinology.

[30]  P. Laurberg,et al.  Efficacy of the new long-acting formulation of lanreotide (lanreotide Autogel) in the management of acromegaly. , 2002, The Journal of clinical endocrinology and metabolism.

[31]  P. Caron,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society BIM-23244, a Somatostatin Receptor Subtype 2- and 5- Selective Analog with Enhanced Efficacy in Suppressing Growth Hormone (GH) from Octreotide- , 2022 .

[32]  J. Schaeffer,et al.  Somatostatin inhibits insulin and glucagon secretion via two receptors subtypes: an in vitro study of pancreatic islets from somatostatin receptor 2 knockout mice. , 2000, Endocrinology.

[33]  S. Lamberts,et al.  Somatostatin receptor subtypes in human thymoma and inhibition of cell proliferation by octreotide in vitro. , 2000, The Journal of clinical endocrinology and metabolism.

[34]  É. Mezey,et al.  Colocalization of somatostatin receptor sst5 and insulin in rat pancreatic beta-cells. , 1999, Endocrinology.

[35]  M. Thangaraju,et al.  Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis. , 1999, Diabetes.

[36]  G. Mengod,et al.  Somatostatin receptor subtypes sst1, sst2, sst3 and sst5 expression in human pituitary, gastroentero-pancreatic and mammary tumors: comparison of mRNA analysis with receptor autoradiography. , 1997, International journal of cancer.