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.

Biological Characteristics of Growth Hormone-Producing Pituitary Adenomas Are Different According to Responsiveness to Thyrotropin-Releasing Hormone

“…The smaller volume but higher GH levels per volume in the TRH responders would indicate that adenomas in this group are characterized by slower growth with higher GH production. One limitation of this study is that we could not use the Ki-67 labeling index for evaluating tumor proliferation because more than half of the patients received preoperative octreotide treatment (29). The overlap between the TRH responders and the octreotide responders has been previously pointed out (30).…”

Short-term Preoperative Octreotide Treatment of GH-secreting Pituitary Adenoma: Predictors of Tumor Shrinkage

“…Previous studies have indicated that octreotide treatment induces various degrees of tumor shrinkage in 23-60% of patients using different criteria for tumor shrinkage as well as different doses and treatment periods [9][10][11][12][13][14][15][16][17]. However, octreotide-induced tumor shrinkage is unpredictable, and does not correlate with the endocrinologic effect [9,10,18,20].…”

“…Octreotide has also been applied preoperatively in the hope of favorable effects on the surgical outcome. Several reports have shown the benefits of preoperative oct-reotide treatment in tumor shrinkage, tumor softening, and improvement of the patient's general condition by reducing the serum GH level, which also reduces perioperative morbidity [9][10][11][12][13][14][15][16][17]. However, whether this treatment improves surgical results in cases of the GH-secreting macroadenoma remains controversial [18,19].…”

Pituitary Cell Turnover: From Adult Stem Cell Recruitment through Differentiation to Death

“…In general, the index of apoptosis in normal human pituitary was difficult to determine, and secretory adenomas presented higher rates of apoptosis than NFPAs did. Bromocriptine could increase the apoptosis index in responsive adenomas [107,108]. …”