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.
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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)
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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
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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
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