Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Lower levels of placental growth hormone in early pregnancy in women with type 1 diabetes and large for gestational age infants

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The insulin like growth factor system in cirrhosis. Relation to changes in body composition following adrenoreceptor blockade

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Pregnancy-induced increase in circulating IGF-I is associated with progression of diabetic retinopathy in women with type 1 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Sex differences in acromegaly at diagnosis: A nationwide cohort study and meta-analysis of the literature

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Adrenal insufficiency in kidney transplant patients during low-dose prednisolone therapy: a cross-sectional case-control study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Limited diagnostic utility of Chromogranin A measurements in workup of neuroendocrine tumors

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Corticotroph aggressive pituitary tumours and carcinomas frequently harbour ATRX mutations

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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 languageEnglish
JournalGrowth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society
Volume25
Issue number5
Pages (from-to)262-7
Number of pages6
ISSN1096-6374
DOIs
Publication statusPublished - Oct 2015

ID: 46005401