BACKGROUND: Growth hormone-secreting pituitary adenomas (somatotroph adenoma) predominantly express somatostatin receptors (SSTRs) subtypes 2 and 5. Higher SSTR2 expression on somatotroph adenomas results in a better response to somatostatin analogues (SSAs), which preferentially bind, but also downregulate, SSTR2. The effect of the combined treatment with SSAs and the GH receptor antagonist pegvisomant (PEGV) on SSTR expression in somatotroph adenomas is currently unknown. AIM OF THE STUDY: To assess SSTR2 and SSTR5 expression in three groups of somatotroph adenomas: drug-naive, treated with long-acting (LA) SSA monotherapy, or LA-SSA/PEGV combination therapy before surgery. Additionally, we evaluated the required PEGV dose to achieve insulin-like growth factor I (IGF-I) normalization in relation to the SSTR expression. MATERIALS AND METHODS: At our Pituitary Center Rotterdam, we selected acromegalic patients who underwent transsphenoidal neurosurgery. All patients were eventually treated with LA-SSA/PEGV combination therapy during their medical history. SSTR2 and SSTR5 expression in somatotroph adenoma tissues was determined using immunohistochemistry. RESULTS: Out of 39 somatotroph adenoma tissue samples, 23 were drug-naive, 9 received pretreatment with LA-SSA and 7 LA-SSA/PEGV combined treatment. SSTR2 expression was significantly higher in treatment-naive compared to combined treatment somatotroph adenomas (p = 0.048), while SSTR5 expression did not differ. Noteworthy, SSTR2 expression in naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization during postsurgical medical treatment (ρ = -0.538, p = 0.024). CONCLUSION: In our specific cohort, the SSTR2 expression was lower in patients pretreated with LA-SSA/PEGV compared to the drug-naive acromegalic patients. Additionally, the SSTR2 expression in treatment-naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization.
BACKGROUND: Growth hormone-secreting pituitary adenomas (somatotroph adenoma) predominantly express somatostatin receptors (SSTRs) subtypes 2 and 5. Higher SSTR2 expression on somatotroph adenomas results in a better response to somatostatin analogues (SSAs), which preferentially bind, but also downregulate, SSTR2. The effect of the combined treatment with SSAs and the GH receptor antagonist pegvisomant (PEGV) on SSTR expression in somatotroph adenomas is currently unknown. AIM OF THE STUDY: To assess SSTR2 and SSTR5 expression in three groups of somatotroph adenomas: drug-naive, treated with long-acting (LA) SSA monotherapy, or LA-SSA/PEGV combination therapy before surgery. Additionally, we evaluated the required PEGV dose to achieve insulin-like growth factor I (IGF-I) normalization in relation to the SSTR expression. MATERIALS AND METHODS: At our Pituitary Center Rotterdam, we selected acromegalicpatients who underwent transsphenoidal neurosurgery. All patients were eventually treated with LA-SSA/PEGV combination therapy during their medical history. SSTR2 and SSTR5 expression in somatotroph adenoma tissues was determined using immunohistochemistry. RESULTS: Out of 39 somatotroph adenoma tissue samples, 23 were drug-naive, 9 received pretreatment with LA-SSA and 7 LA-SSA/PEGV combined treatment. SSTR2 expression was significantly higher in treatment-naive compared to combined treatment somatotroph adenomas (p = 0.048), while SSTR5 expression did not differ. Noteworthy, SSTR2 expression in naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization during postsurgical medical treatment (ρ = -0.538, p = 0.024). CONCLUSION: In our specific cohort, the SSTR2 expression was lower in patients pretreated with LA-SSA/PEGV compared to the drug-naive acromegalicpatients. Additionally, the SSTR2 expression in treatment-naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization.
Authors: A Saveanu; G Gunz; H Dufour; P Caron; F Fina; L Ouafik; M D Culler; J P Moreau; A Enjalbert; P Jaquet Journal: J Clin Endocrinol Metab Date: 2001-01 Impact factor: 5.958
Authors: A J van der Lely; R K Hutson; P J Trainer; G M Besser; A L Barkan; L Katznelson; A Klibanski; V Herman-Bonert; S Melmed; M L Vance; P U Freda; P M Stewart; K E Friend; D R Clemmons; G Johannsson; S Stavrou; D M Cook; L S Phillips; C J Strasburger; S Hackett; K A Zib; R J Davis; J A Scarlett; M O Thorner Journal: Lancet Date: 2001-11-24 Impact factor: 79.321
Authors: Diego Ferone; Wouter W de Herder; Rosario Pivonello; Johan M Kros; Peter M van Koetsveld; Ton de Jong; Francesco Minuto; Annamaria Colao; Steven W J Lamberts; Leo J Hofland Journal: J Clin Endocrinol Metab Date: 2008-01-22 Impact factor: 5.958
Authors: S J C M M Neggers; M O van Aken; W W de Herder; R A Feelders; J A M J L Janssen; X Badia; S M Webb; A J van der Lely Journal: J Clin Endocrinol Metab Date: 2008-07-22 Impact factor: 5.958
Authors: Ana Paula M Casarini; Raquel S Jallad; Emília M Pinto; Iberê C Soares; Suely Nonogaki; Daniel Giannella-Neto; Nina R Musolino; Venâncio A F Alves; Marcello D Bronstein Journal: Pituitary Date: 2009 Impact factor: 4.107
Authors: Amy A Swanson; Dana Erickson; Diane Mary Donegan; Sarah M Jenkins; Jamie J Van Gompel; John L D Atkinson; Bradley J Erickson; Caterina Giannini Journal: Pituitary Date: 2020-10-19 Impact factor: 4.107
Authors: Nina Ionovici; Mara Carsote; Dana Cristina Terzea; Anca Mihaela Predescu; Anne Marie Rauten; Mihaela Popescu Journal: Rom J Morphol Embryol Date: 2020 Apr-Jun Impact factor: 1.033
Authors: Lena Rass; Amir-Hossein Rahvar; Jakob Matschke; Wolfgang Saeger; Thomas Renné; Jens Aberle; Jörg Flitsch; Roman Rotermund Journal: Hormones (Athens) Date: 2021-10-21 Impact factor: 2.885
Authors: Claudia Campana; Peter M van Koetsveld; Richard A Feelders; Wouter W de Herder; Anand M Iyer; Marie-Louise F van Velthuysen; Marije J Veenstra; Elisabeth S R van den Dungen; Sanne E Franck; Diego Ferone; Federico Gatto; Leo J Hofland Journal: Eur J Endocrinol Date: 2022-07-21 Impact factor: 6.558