Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues--Observations in two patients with acromegaly and severe headache.

Abstract

BACKGROUND:

Somatotropinomas have unique "fingerprints" of somatostatin receptor (sst) expression, which are targets in treatment of acromegaly with somatostatin analogues (SSAs). However, a significant expression of sst is not always related to the biochemical response to SSAs. Headache is a common complaint in acromegaly and considered a clinical marker of disease activity. SSAs are reported to have an own analgesic effect, but the sst involved are unknown.

PATIENTS AND METHODS:

We investigated sst expression in two acromegalic patients with severe headache and no biochemical effects of octreotide, but a good response to pasireotide. We searched the literature for determinants of biochemical and analgesic effects of SSAs in somatotropinomas.

RESULTS:

Case 1 had no biochemical or analgesic effects of octreotide, a semi-selective SSA, but a rapid and significant effect of pasireotide, a pan-SSA. Case 2 demonstrated discordance between analgesic and biochemical effects of octreotide, in that headache disappeared, but without biochemical improvement. In contrast, pasireotide normalized insulin-like growth factor 1. Both adenomas were sparsely granulated and had strong membranous expressions of sst2a in 50-75% and sst5 in 75-100% of tumor cells. The truncated sst5 variant TMD4 (sst5TMD4) showed expression in 20-57% of tumor cells.

CONCLUSIONS:

A poor biochemical response to octreotide may be associated with tumor expression of a truncated sst5 variant, despite abundant sst2a expression, suggesting an influence from variant sst5 on common sst signaling pathways. Furthermore, unrelated analgesic and biochemical effects of SSAs supported a complex pathogenesis of acromegaly-associated headache. Finally, assessment of truncated sst5 in addition to full length sst could be important for a choice of postoperative SSA treatment in somatotropinomas.

• Authors: Djordje Marina, Pia Burman, Marianne Klose, Olivera Casar-Borota, Raúl M Luque, Justo P Castaño, Ulla Feldt-Rasmussen
• Journal: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society (Growth Horm IGF Res) Vol. 25 Issue 5 Pg. 262-7 (Oct 2015) ISSN: 1532-2238 [Electronic] Scotland
• PMID: 26188991 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Somatostatin
• somatostatin receptor sst2A
• Human Growth Hormone
• Somatostatin
• somatostatin receptor 5
• pasireotide
• pegvisomant
• Octreotide

Topics

• Acromegaly (complications, drug therapy, metabolism)
• Adult
• Female
• Growth Hormone-Secreting Pituitary Adenoma (complications, drug therapy, metabolism)
• Headache (drug therapy, etiology, metabolism)
• Human Growth Hormone (analogs & derivatives, therapeutic use)
• Humans
• Octreotide (therapeutic use)
• Pituitary Neoplasms (complications, drug therapy, metabolism)
• Receptors, Somatostatin (metabolism)
• Somatostatin (analogs & derivatives, therapeutic use)
• Young Adult