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Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues - Observations in two patients with acromegaly and severe headache
Copenhagen Univ Hosp, Rigshosp, Dept Med Endocrinol, Copenhagen, Denmark..
Skanes Univ Hosp, Dept Endocrinol, Malmo, Sweden..
Copenhagen Univ Hosp, Rigshosp, Dept Med Endocrinol, Copenhagen, Denmark..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2015 (English)In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 25, no 5, 262-267 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 25, no 5, 262-267 p.
Keyword [en]
Acromegaly, Pasireotide, Headache, Analgesic effect, Somatostatin receptors, Truncated sst5
National Category
Endocrinology and Diabetes
URN: urn:nbn:se:uu:diva-265684DOI: 10.1016/j.ghir.2015.07.003ISI: 000362139000009PubMedID: 26188991OAI: oai:DiVA.org:uu-265684DiVA: diva2:866936
Available from: 2015-11-04 Created: 2015-11-02 Last updated: 2015-11-04Bibliographically approved

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Casar-Borota, Olivera
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Department of Immunology, Genetics and Pathology
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