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

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@article{fd74cab45ad84759bd14d6364f320abd,
title = "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.",
author = "Djordje Marina and Pia Burman and Marianne Klose and Olivera Casar-Borota and Luque, {Ra{\'u}l M} and Casta{\~n}o, {Justo P} and Ulla Feldt-Rasmussen",
note = "Copyright {\textcopyright} 2015 Elsevier Ltd. All rights reserved.",
year = "2015",
month = oct,
doi = "10.1016/j.ghir.2015.07.003",
language = "English",
volume = "25",
pages = "262--7",
journal = "Growth Regulation",
issn = "1096-6374",
publisher = "Churchill Livingstone",
number = "5",

}

RIS

TY - JOUR

T1 - Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues--Observations in two patients with acromegaly and severe headache

AU - Marina, Djordje

AU - Burman, Pia

AU - Klose, Marianne

AU - Casar-Borota, Olivera

AU - Luque, Raúl M

AU - Castaño, Justo P

AU - Feldt-Rasmussen, Ulla

N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.

PY - 2015/10

Y1 - 2015/10

N2 - 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.

AB - 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.

U2 - 10.1016/j.ghir.2015.07.003

DO - 10.1016/j.ghir.2015.07.003

M3 - Journal article

C2 - 26188991

VL - 25

SP - 262

EP - 267

JO - Growth Regulation

JF - Growth Regulation

SN - 1096-6374

IS - 5

ER -

ID: 46005401