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

Djordje Marina; Pia Burman; Marianne Klose; Olivera Casar-Borota; Raúl M Luque; Justo P Castaño; Ulla Feldt-Rasmussen

doi:10.1016/j.ghir.2015.07.003

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

Djordje Marina, Pia Burman, Marianne Klose, Olivera Casar-Borota, Raúl M Luque, Justo P Castaño, Ulla Feldt-Rasmussen

Department of Clinical Medicine

15 Citations (Scopus)

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.

Original language	English
Journal	Growth Hormone & I G F Research
Volume	25
Issue number	5
Pages (from-to)	262-7
Number of pages	6
ISSN	1096-6374
DOIs	https://doi.org/10.1016/j.ghir.2015.07.003
Publication status	Published - 1 Oct 2015

Keywords

Acromegaly
Adult
Female
Growth Hormone-Secreting Pituitary Adenoma
Headache
Human Growth Hormone
Humans
Octreotide
Pituitary Neoplasms
Receptors, Somatostatin
Somatostatin
Young Adult

Access to Document

10.1016/j.ghir.2015.07.003

Cite this

Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues--Observations in two patients with acromegaly and severe headache. / Marina, Djordje; Burman, Pia; Klose, Marianne et al.

In: Growth Hormone & I G F Research, Vol. 25, No. 5, 01.10.2015, p. 262-7.

Research output: Contribution to journal › Journal article › Research › peer-review

@article{fd3b713f2b1c48ed8ffbd0a66065f21c,

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.",

keywords = "Acromegaly, Adult, Female, Growth Hormone-Secreting Pituitary Adenoma, Headache, Human Growth Hormone, Humans, Octreotide, Pituitary Neoplasms, Receptors, Somatostatin, Somatostatin, Young Adult",

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",

year = "2015",

month = oct,

day = "1",

doi = "10.1016/j.ghir.2015.07.003",

language = "English",

volume = "25",

pages = "262--7",

journal = "Growth Hormone & I G F Research",

issn = "1096-6374",

publisher = "Churchill Livingstone",

number = "5",

}

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

PY - 2015/10/1

Y1 - 2015/10/1

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.

KW - Acromegaly

KW - Adult

KW - Female

KW - Growth Hormone-Secreting Pituitary Adenoma

KW - Headache

KW - Human Growth Hormone

KW - Humans

KW - Octreotide

KW - Pituitary Neoplasms

KW - Receptors, Somatostatin

KW - Somatostatin

KW - Young Adult

U2 - 10.1016/j.ghir.2015.07.003

DO - 10.1016/j.ghir.2015.07.003

M3 - Journal article

C2 - 26188991

SN - 1096-6374

VL - 25

SP - 262

EP - 267

JO - Growth Hormone & I G F Research

JF - Growth Hormone & I G F Research

IS - 5

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this