Term Octreotide Research Articles

Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR® responsiveness in acromegaly

We present two acromegalic patients in which clinical and molecular data are discussed in regard to their ability to predict long term octreotide LAR therapy response. Patient 1: female, 36 years old at diagnosis. Basal GH and IGF-I at diagnosis were 133 ng/mL and 181% above the upper limit of reference values (ULRV), respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 133 to 13 ng/mL. Patient started on primary octreotide LAR therapy (20mg q28 days) and achieved biochemical parameters of disease control after 6 months. Molecular analysis of tumor fragments: gsp +; quantitative analysis of SSTR (somatostatin receptor) and DR (dopamine receptor) mRNA - SSTR2 23954; SSTR5 2407; DR2 total 17016 copies. Patient 2: male, 38 years old at diagnosis. Basal GH and IGF-I at diagnosis were 120 ng/mL and 114% ULRV, respectively. Patient underwent non-curative trans-sphenoidal surgery. Post-operative GH and IGF-I were 112 ng/mL and 137% ULRV, respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 112 to 7 ng/mL. Octreotide LAR therapy (20 mg q28 days) was then initiated. After 6 months of treatment, patient did not attain biochemical control of disease and displayed increased tumor volume. Molecular analysis of tumor fragments: gsp not done; quantitative analysis of SSTR and DR mRNA - SSTR2 416; SSTR5 3767; DR2 total 3439 copies. In conclusion, these two cases illustrate how laboratory data can be conflicting as predictors of octreotide LAR responsiveness and how molecular analysis of tumor fragments can help explain different behaviors in clinically similar patients.

Extended Octreotide Supression Test To Determine Hormone Responsiveness in a Patient with Multiple Gastric Carcinoid Tumors

Purpose: Type I gastric carcinoid tumors arise from enterochromaffin-like (ECL) cells of gastric fundus under the trophic effect of hypergastrenemia. Histidine decarboxylase (HDC), the enzyme responsible for histamine production in these cells, is regulated by gastrin. Lesions less than 1 cm and fewer than 3–5 in number are typically managed by endoscopic resection. Management of tumors that are larger than 1 cm or more than 5 in number is controversial. Antrectomy has been reported to result in complete regression of tumors. However, in some cases the tumors may become autonomous and no longer gastrin dependent. This has led some authorities to recommend total gastrectomy for tumors that are large or multiple. Methods: A 62 year old asymptomatic male referred for mild anemia, was found to have at least 12 gastric carcinoids 3–10 mm in size in the setting of chronic atrophic gastritis. Biopsies of the intervening mucosa revealed microcarcinoidosis. There was no evidence of local extension or metastasis. We decided to do an extended octreotide supression test to determine if the tumors are still gastrin dependent and would likely regress after antrectomy. The patient was started on octreotide infusion at 12.5–25 mcg/hr for 86 hours after obtaining an informed consent and then started on octreotide depot injections every 4 weeks for five months. Serum fasting gastrin levels and chromogranin A (CGA) levels were measured and an endoscopy with biopsies was performed immediately before and after the infusion and at five months. RNA was extracted from the biopsy specimens and comparative quantitation of HDC mRNA was performed using real-time PCR with FAM-labeled LUX primers after generation of cDNA. Results: Serum fasting gastrin levels decreased from 306 pg/ml pre-treatment to 31 pg/ml at the end of infusion and 112 pg/ml at 5 months. CGA levels decreased from 4–6 times the upper limit of normal to within the normal range at the end of infusion and stayed normal at 5 months. Tissue HDC mRNA decreased 54 fold at the end of infusion and decreased further at five months. There was a decrease in size and number of tumors at five months. Conclusions: Long term octreotide treatment resulted in effective supression of serum gastrin, serum CGA, and tissue HDC mRNA associated with partial tumor regression. These results demonstrate that the carcinoid tumors in this patient are still gastrin dependent and expected to regress after antrectomy.

Dramatic Volume Reduction of a Large GH/TSH Secreting Pituitary Tumor with Short Term Octreotide Therapy

A case is presented of a huge GH/TSH secreting tumor and marked volumetric reduction in size with only one week of Octreotide therapy. To our knowledge, this is the first reported case of such a dramatic volumetric response to short-term Octreotide therapy.

Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for octreotide induced gallstones

BACKGROUNDTreatment of acromegaly with octreotide increases the proportion of deoxycholic acid in, and the cholesterol saturation of, bile and induces the formation of gallstones. Prolongation of intestinal transit has been...

Randomised trial of octreotide for long term management of cirrhosis after variceal haemorrhage

Objective: To assess the efficacy of long term octreotide as adjuvant treatment to programmed endoscopic sclerotherapy after acute variceal haemorrhage in cirrhotic portal hypertension.Design: Randomised clinical trial.Setting: University hospital.Subjects: 32...

Role of intestinal transit in the pathogenesis of gallbladder stones.

Increasing evidence implicates prolonged intestinal transit (slow transit constipation) in the pathogenesis of conventional gallbladder stones (GBS), and that of gallstones induced by long term octreotide (OT) treatment. Both groups of GBS patients have multiple abnormalities in the lipid composition and physical chemistry of their gallbladder bile-associated with, and possibly due to, an increased proportion of deoxycholic acid (DCA) (percentage of total bile acids). In turn, this increase in the percentage of DCA seems to be a consequence of prolonged colonic transit. Thus, in acromegalic patients OT treatment significantly prolongs large bowel transit time (LBTT) and leads to an associated increase of the percentage of DCA in fasting serum (and, by implication, in gallbladder bile). LBTT is linearly related to the percentage of DCA in fasting serum and correlates significantly with DCA input (into the enterohepatic circulation) and DCA pool size. However, these adverse effects of OT can be overcome by the concomitant use of the prokinetic drug cisapride, which normalizes LBTT and prevents the rise in the percentage of serum DCA. Therefore, in OT-treated patients and other groups at high risk of developing stones, it may be possible to prevent GBS formation with the use of intestinal prokinetic drugs.

Long term octreotide treatment of gastric carcinoid tumors in two patients with zollinger-ellison syndrome (ZES) associated with multiple endocrine neoplasia type I (men 1)

Long term octreotide treatment of gastric carcinoid tumors in two patients with zollinger-ellison syndrome (ZES) associated with multiple endocrine neoplasia type I (men 1)

Octreotide long term treatment of acromegaly: effect of drug withdrawal on serum growth hormone/insulin-like growth factor-I concentrations and on serum gastrin/24-hour intragastric pH values.

We studied a possible persistence of low GH concentrations after drug withdrawal in eight acromegalic patients who had been receiving octreotide treatment continuously for 42 months. Since octreotide induces chronic active gastritis, intragastric pH and serum gastrin were also determined before and during drug withdrawal. Results were compared to the respective pretreatment (pre-Tx) values. GH and insulin-like growth factor-I (IGF-I) increased after 4 weeks of octreotide withdrawal to pre-Tx values (GH, 12-h profile, 4.5 +/- 0.6, 2.6 +/- 0.7, and 5.6 +/- 1.1 micrograms/L; IGF-I, three samples, 3.4 +/- 0.4, 0.8 +/- 0.1, and 2.5 +/- 1.0 IU x 10(3)/L; means +/- SE, pre-Tx, on and off octreotide). A reduced insulin and augmented glucose response to oral glucose during therapy normalized after octreotide withdrawal (insulin, 527 +/- 84, 289 +/- 62, and 733 +/- 110 pmol/L; glucose, 6.2 +/- 0.3, 8.5 +/- 0.4, and 6.8 +/- 0.2 mmol/L; pre-Tx, on and off octreotide, means +/- SE). During octreotide treatment, the median 24-h intragastric pH value was 2.8 (pre-Tx pH not determined), and the median serum gastrin concentration (areas under the curve of 12-h profiles) was 1275 +/- 153 ng/L.12 h (n = 7). During octreotide withdrawal, pH decreased to 1.4, while serum gastrin increased to a median of 2937 +/- 472 ng/L.12 h. We conclude that GH and IGF-I suppression by long term octreotide therapy does not persist after drug withdrawal, indicating a need for life-long treatment. Octreotide-induced insulin suppression and glucose elevation are reversible. A high gastric pH during treatment may facilitate the development of octreotide-related gastritis. The gastrin increase during octreotide withdrawal probably reflects a response to chronic active gastritis after release from octreotide-induced gastrin inhibition.

Effects of long term octreotide on gall stone formation and gall bladder function.

Effects of long term octreotide on gall stone formation and gall bladder function.

Effective Clinical Response to Long Term Octreotide Treatment, with Reduced Serum Concentrations of Growth Hormone, Insulin-Like Growth Factor-I, and the Amino-Terminal Propeptide of Type III Procollagen in Acromegaly

Ten patients with active acromegaly, six with a poor response to previous therapies and four newly diagnosed, were treated with the long-acting somatostatin analog octreotide (Sandostatin; 200-500 micrograms/day, sc, twice or three times daily) for 6-15 months. There was rapid clinical improvement in all patients. The mean daily serum GH concentration was reduced by 64% and was normalized (all GH values less than 2 micrograms/L) in three patients. Serum insulin-like growth factor-I (IGF-I) concentrations were lowered by 40% and were normalized in eight patients. Serum concentrations of the amino-terminal propeptide of type III procollagen (PIIINP), an index of tissue collagen metabolism, were reduced by 40% and were normalized in all patients with initially elevated values. There was a statistically significant positive correlation between the mean serum GH and IGF-I levels (r = 0.47; P less than 0.001) as well as between serum GH and PIIINP levels (r = 0.34; P less than 0.05) and between serum IGF-I and PIIINP (r = 0.50; P less than 0.001). The effects of octreotide on pituitary tumor size and pathology were evaluated in one patient. The therapy did not seem to be associated with significant changes in sellar computed tomographic scans or light microscopic findings. The drug was generally well tolerated. However, indications of significant hepato-biliary dysfunction were noted in one patient after 5 months of therapy. This was reversible upon discontinuation of therapy and did not occur later during the rechallenge with a lower dose of the drug. However, there was probably newly formed cholelithiasis in four patients during the therapy. Our study suggests that octreotide is an effective and relatively safe new approach for treating active acromegaly. Further studies are needed to investigate long term effects on the hepatobiliary system.