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Absence of apoptosis in somatotropinomas treated with octreotide
Abstract:
Octreotide is a potent agonist of somatostatin that lowers the serum level of growth hormone (GH), and reduces the size of somatotropinomas. However, the detailed mechanism of shrinkage of this tumour is not known. We, therefore, evaluated 11 patients with somatotropinomas who were treated with octreotide 300 micrograms/day for 2-5 weeks to observe the morphological changes in the tumour using electron microscopy and the immunocytochemical study of apoptosis using polyclonal anti-single stranded DNA. Findings were compared with those obtained with bromocriptine treatment (10 mg/day, 2 weeks) of 5 patients with somatotropinomas, and 11 patients who received no preoperative treatment (control group). The octreotide group showed neither increase in stromal tissue nor cell death. The size of tumour cells appeared to be slightly reduced. No typical apoptotic bodies were seen on the electron micrographs. The apoptotic index in the octreotide group (0.40 +/- 0.60%; mean +/- SD) resembled that in the control group (0.81 +/- 0.79%). In contrast, the bromocriptine group showed some cell death and an increase in stromal tissue. The bromocriptine group also showed the apoptotic index which (20.1 +/- 14.8%) was significantly higher than that of the control group (0.81 +/- 0.79%). Thus, octreotide did not induce apoptosis in somatotropinomas despite the presence of tumour shrinkage. Because of the lack of fibrosis observed in the octreotide-treated tumours, the preoperative administration of octreotide may help to improve the outcome of the transsphenoidal operation.
Insights
Octreotide shrinks somatotropinomas without inducing apoptosis, unlike bromocriptine. This lack of fibrosis suggests octreotide may improve surgical outcomes for growth hormone (GH)-secreting tumors.
Area of Science:
- Endocrinology
- Oncology
- Cell Biology
Background:
- Somatotropinomas, tumors secreting growth hormone (GH), are often treated with somatostatin analogs like octreotide.
- Octreotide reduces GH levels and tumor size, but the mechanism of tumor shrinkage is not fully understood.
- Apoptosis, or programmed cell death, is a potential mechanism for tumor size reduction.
Purpose of the Study:
- To investigate the mechanism of tumor shrinkage induced by octreotide in somatotropinomas.
- To compare the effects of octreotide and bromocriptine on tumor cell apoptosis and morphology.
- To evaluate the potential of preoperative octreotide administration to improve surgical outcomes.
Main Methods:
- Electron microscopy and immunocytochemical studies of apoptosis (using anti-single stranded DNA) were performed on somatotropinoma tissue from 11 patients treated with octreotide.
- Findings were compared to 5 patients treated with bromocriptine and 11 untreated controls.
- Tumor cell size, stromal tissue, cell death, and apoptotic index were assessed.
Main Results:
- Octreotide treatment led to slight tumor cell size reduction but did not increase stromal tissue or induce significant cell death.
- No typical apoptotic bodies were observed, and the apoptotic index in the octreotide group was similar to the control group.
- Bromocriptine treatment resulted in increased cell death, stromal tissue, and a significantly higher apoptotic index compared to controls.
Conclusions:
- Octreotide reduces somatotropinoma size through a mechanism other than apoptosis.
- The lack of observed fibrosis suggests that preoperative octreotide may be beneficial for transsphenoidal surgery.
- Bromocriptine, in contrast, appears to induce apoptosis in somatotropinomas.