ABSTRACT
OBJECTIVE: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1-5), within and between pituitary tumor types. DESIGN AND METHODS: Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA. RESULTS: Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2>SSTR3>>SSTR1>>>SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2. CONCLUSIONS: The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide.
Subject(s)
Adenoma/metabolism , Human Growth Hormone/metabolism , Pituitary Neoplasms/metabolism , Receptors, Somatostatin/genetics , Acromegaly/etiology , Adenoma/surgery , Adult , Antisense Elements (Genetics) , DNA Primers , Female , Follow-Up Studies , Gene Dosage , Gene Expression , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Middle Aged , Molecular Sequence Data , Octreotide/therapeutic use , Pituitary Neoplasms/surgery , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Os análogos da somatostatina são muito utilizados no tratamento da acromegalia. Com o objetivo de determinar o valor do teste agudo (TA) com octreotide subcutâneo (SC) como preditor da resposta ao tratamento com octreotide LAR®, analisamos os dados de 20 pacientes. Para o TA, amostras de sangue foram colhidas antes e duas horas após a administração de octreotide SC para a dosagem de GH. Os níveis de GH antes e após o TA foram 21,9 (2,3-143,4) e 3,1ng/mL (0,3-61,3), respectivamente. Foi considerado controle de doença: GH< 2,5ng/mL e IGF-I normal em algum momento durante o tratamento. A sensibilidade, especificidade e os valores preditivos positivo e negativo do TA foram 0,9, 0,6, 0,69 e 0,86 para redução de 75 por cento do GH no teste. Concluímos que, em nossa casuística, um decréscimo de 75 por cento dos níveis de GH no TA teve um bom poder discriminatório entre pacientes com maior e menor chance de resposta ao tratamento.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Acromegaly/drug therapy , Antineoplastic Agents, Hormonal/administration & dosage , Human Growth Hormone/blood , Insulin-Like Growth Factor I/metabolism , Octreotide/administration & dosage , Acromegaly/diagnosis , Drug Tolerance , Injections, Subcutaneous , Predictive Value of Tests , ROC CurveABSTRACT
Somatostatin analogues are frequently used to treat acromegaly. To determine the value of the acute test (AT) with subcutaneous (SC) octreotide as a predictor of the response to treatment with octreotide LAR, we analyzed data from 20 patients. For the AT, blood was drawn before and two hours after the SC administration of octreotide for measuring GH. GH levels before and after the AT were 21.9 ng/mL (2.3-143.4) and 3.1 ng/mL (0.3-61.3), respectively. Control of the disease was defined as: GH< 2.5 ng/mL and normal IGF-I anytime during treatment. Sensitivity, specificity, positive and negative predictive values of the AT were 0.9, 0.6, 0.69 and 0.86 for a reduction of 75% of the GH on the test. From our sample we conclude that a 75% reduction of the GH levels during the acute test was able to discriminate patients with a higher or lower chance of responding to treatment.
