Subcutaneous Octreotide Infusion Research Articles

Health-related quality of life in patients with inoperable malignant bowel obstruction: secondary outcome from a double-blind, parallel, placebo-controlled randomised trial of octreotide

BackgroundThis analysis aims to evaluate health-related quality of life (HrQoL) (primary outcome for this analysis), nausea and vomiting, and pain in patients with inoperable malignant bowel obstruction (IMBO) due to cancer or its treatments randomised to standardised therapies plus octreotide or placebo over a maximum of 72 h in a double-blind clinical trial.MethodsAdults with IMBO and vomiting recruited through 12 services spanning inpatient, consultative and community settings in Australia were randomised to subcutaneous octreotide infusion or saline. HrQoL was measured at baseline and treatment cessation (EORTC QLQ-C15-PAL). Mean within-group paired differences between baseline and post-treatment scores were analysed using Wilcoxon Signed Rank test and between group differences estimated using linear mixed models, adjusted for baseline score, sex, age, time, and study arm.ResultsOne hundred six of the 112 randomised participants were included in the analysis (n = 52 octreotide, n = 54 placebo); 6 participants were excluded due to major protocol violations. Mean baseline HrQoL scores were low (octreotide 22.1, 95% CI 14.3, 29.9; placebo 31.5, 95% CI 22.3, 40.7). There was no statistically significant within-group improvement in the mean HrQoL scores in the octreotide (p = 0.21) or placebo groups (p = 0.78), although both groups reported reductions in mean nausea and vomiting (octreotide p < 0.01; placebo p = 0.02) and pain scores (octreotide p < 0.01; placebo p = 0.03). Although no statistically significant difference in changes in HrQoL scores between octreotide and placebo were seen, an adequately powered study is required to fully assess any differences in HrQoL scores.ConclusionThe HrQoL of patients with IMBO and vomiting is poor. Further research to formally evaluate the effects of standard therapies for IMBO is therefore warranted.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12608000211369 (date registered 18/04/2008)

Метод непрерывной подкожной инфузии аналогов соматостатина в терапии пациентов с врожденным гиперинсулинизмом

BACKGROUND: Congenital hyperinsulinism (CHI) is a severe disease with a high risk of development of neurological complications due to persistent hypoglycemia. The use of an analog of somatostatin (octreotide) in patients with the resistance to the first-line drug allows to avoid surgical intervention. However, the octreotide is currently used in the form of frequent fractional injections due to the short duration of it’s effect. We present in this article our own experience of using octreotide in continuous subcutaneous infusion in pediatric patients in order to improve the quality of life. AIM To evaluate the efficiency and safety of the regime of continuous subcutaneous infusion of octreotide with the use of micro-dispensers (pumps) in children with diazoxide-resistant course of CHI. MATERIALS AND METHODS: An observational single-centre dynamic research was carried out on the basis of the Federal State Budgetary Institution «Endocrinology Research Centre» of the Ministry of Health of the Russian Federation. The study included pediatric patients with CHI and proven diazoxide-resistant course who were initially treated with octreotide in the form of intermittent subcutaneous injections. The researches compared the indicants of efficiency and safety of therapy on treatment of intermittent injections and after transfer to continuous subcutaneous infusion of the drug. The duration of each method of administration was at least 2 weeks. RESULTS: 16 patients took part in the research. The median for the total duration of octreotide usage in the examined patients was 3 months. According to the results of the work, the use of micro-dispensers for continuous subcutaneous administration of octreotide allowed to reduce the number of patients with episodes of hypoglycemia for more than 4 times (13/16 vs. 3/16); p=0,001). Also, there was a significant decrease in the number of patients with hyperglycemic episodes (4/16 vs. 0/16); p=0.000) and reduced dose of intravenous glucose (6.8 vs 5.2 mg/kg/min; p=0.042) as a result of continuous therapy, which indicates the advantages of smooth continuous administration comparing to single injections. We have not detected any significant side effects of the treatment. Elevated liver enzyme levels, dyspeptic symptoms and gallstone formation in some patients did not require cancellation of therapy. There were no hormonal disorders in the form of hypothyroidism and somatotropic hormone deficiency against the background of continuous octreotide infusion. CONCLUSIONS: Thus, the use of octreotide in patients with diazoxide-resistant course of СHI in continuous subcutaneous infusion using pumps has a number of advantages over the standard method of intermittent subcutaneous injection. This method of administration allows to achieve better glycemic control and reduce the risks from infusion therapy with highly concentrated glucose solutions, which undoubtedly improves the quality of life of patients.

Continuous subcutaneous infusion of somatostatin analogues in the treatment of congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is a severe disease with a high risk of development of neurological complications due to persistent hypoglycemia. The use of an analog of somatostatin (octreotide) in patients with the resistance to the first-line drug allows to avoid surgical intervention. However, the octreotide is currently used in the form of frequent fractional injections due to the short duration of it&rsquo;s effect. We present in this article our own experience of using octreotide in continuous subcutaneous infusion in pediatric patients in order to improve the quality of life. AIM To evaluate the efficiency and safety of the regime of continuous subcutaneous infusion of octreotide with the use of micro-dispensers (pumps) in children with diazoxide-resistant course of CHI. An observational single-centre dynamic research was carried out on the basis of the Federal State Budgetary Institution &laquo;Endocrinology Research Centre&raquo; of the Ministry of Health of the Russian Federation. The study included pediatric patients with CHI and proven diazoxide-resistant course who were initially treated with octreotide in the form of intermittent subcutaneous injections. The researches compared the indicants of efficiency and safety of therapy on treatment of intermittent injections and after transfer to continuous subcutaneous infusion of the drug. The duration of each method of administration was at least 2 weeks. 16 patients took part in the research. The median for the total duration of octreotide usage in the examined patients was 3 months. According to the results of the work, the use of micro-dispensers for continuous subcutaneous administration of octreotide allowed to reduce the number of patients with episodes of hypoglycemia for more than 4 times (13/16 vs. 3/16); p=0,001). Also, there was a significant decrease in the number of patients with hyperglycemic episodes (4/16 vs. 0/16); p=0.000) and reduced dose of intravenous glucose (6.8 vs 5.2 mg/kg/min; p=0.042) as a result of continuous therapy, which indicates the advantages of smooth continuous administration comparing to single injections. We have not detected any significant side effects of the treatment. Elevated liver enzyme levels, dyspeptic symptoms and gallstone formation in some patients did not require cancellation of therapy. There were no hormonal disorders in the form of hypothyroidism and somatotropic hormone deficiency against the background of continuous octreotide infusion. Thus, the use of octreotide in patients with diazoxide-resistant course of СHI in continuous subcutaneous infusion using pumps has a number of advantages over the standard method of intermittent subcutaneous injection. This method of administration allows to achieve better glycemic control and reduce the risks from infusion therapy with highly concentrated glucose solutions, which undoubtedly improves the quality of life of patients.

Partial diazoxide responsiveness in a neonate with hyperinsulinism due to homozygous ABCC8 mutation.

SummaryWe report a case of partial diazoxide responsiveness in a child with severe congenital hyperinsulinaemic hypoglycaemia (CHI) due to a homozygous ABCC8 mutation. A term baby, with birth weight 3.8 kg, born to consanguineous parents presented on day 1 of life with hypoglycaemia. Hypoglycaemia screen confirmed CHI. Diazoxide was commenced on day 7 due to ongoing elevated glucose requirements (15 mg/kg/min), but despite escalation to a maximum dose (15 mg/kg/day), intravenous (i.v.) glucose requirement remained high (13 mg/kg/min). Genetic testing demonstrated a homozygous ABCC8 splicing mutation (c.2041-1G>C), consistent with a diffuse form of CHI. Diazoxide treatment was therefore stopped and subcutaneous (s.c.) octreotide infusion commenced. Despite this, s.c. glucagon and i.v. glucose were required to prevent hypoglycaemia. A trial of sirolimus and near-total pancreatectomy were considered, however due to the significant morbidity potentially associated with these, a further trial of diazoxide was commenced at 1.5 months of age. At a dose of 10 mg/kg/day of diazoxide and 40 µg/kg/day of octreotide, both i.v. glucose and s.c. glucagon were stopped as normoglycaemia was achieved. CHI due to homozygous ABCC8 mutation poses management difficulties if the somatostatin analogue octreotide is insufficient to prevent hypoglycaemia. Diazoxide unresponsiveness is often thought to be a hallmark of recessively inherited ABCC8 mutations. This patient was initially thought to be non-responsive, but this case highlights that a further trial of diazoxide is warranted, where other available treatments are associated with significant risk of morbidity.Learning points:Homozygous ABCC8 mutations are commonly thought to cause diazoxide non-responsive hyperinsulinaemic hypoglycaemia.This case highlights that partial diazoxide responsiveness in homozygous ABCC8 mutations may be present.Trial of diazoxide treatment in combination with octreotide is warranted prior to considering alternative treatments, such as sirolimus or near-total pancreatectomy, which are associated with more significant side effects.

Sirolimus treatment of severe congenital hyperinsulinism

Sirolimus treatment reduced dependence on octreotide and frequent feeding in 4 infants with CHI in a recent study [1]. We report our experience in a 1 year-old boy with presumed diffuse disease due to a de novo heterozygous ABCC8 missense mutation (p.D1506E). This macrosomic infant (term birth weight 5.676kg) presented with hypoglycaemia in the first hours of life. Critical sample results were consistent with CHI (blood glucose 0.9mmol/L, insulin 41mU/L, free fatty acids 0.2mmol/L[RR 0.1-0.6]). The family history was significant for type 2 diabetes in both grandmothers, and CHI in his maternal second cousin. No ABCC8 missense mutation was identified in either parent or his second cousin. Initial management included intravenous glucose (12mg/kg/min) and glucagon infusions. Maximal dose diazoxide (20mg/kg/day for 5 days) was ineffective so subcutaneous octreotide infusion was initiated (26mcg/kg/day). At discharge from hospital (age 10 weeks) he was overweight (height SDS 1.11, weight SDS 3.1), receiving octreotide 27mcg/kg/day, nocturnal gastrostomy Polyjoule® feeds (equivalent to 11mg/kg/min glucose) plus 3-hourly daytime bolus feeds. Sirolimus (0.5mg/m2/day) was added at age 7 months because of continued weight gain and intermittent mild hypoglycaemia while receiving octreotide 37mcg/kg/day. The dose was increased to 6mg/m2/day, aiming for trough levels 15-20ng/ml. After 3 months, the octreotide dose has stabilised (36mcg/kg/day) and the intensity of feeds has been reduced (3.5mg/kg/minute glucose overnight), resulting in weight loss; however, he has also developed linear growth failure (height velocity 6cm/year over 3 months). At 1 year of age his length and weight SDS are 0.48 and 1.21 respectively, and he is developmentally appropriate for age. Apart from one mild episode of respiratory syncytial virus, he has had no significant illnesses during sirolimus treatment. In conclusion, treatment with sirolimus has improved our patient’s blood glucose concentrations, decreased his dependence on hypercaloric nocturnal continuous feeds and decreased his weight gain; however the burden of care remains more significant than reported in the 4 published cases, 2 of whom had heterozygous mutations in ABCC8. The combination of high-dose octreotide and sirolimus may not be sustainable long-term in view of their likely combined contribution to his growth failure and the potential for immunosuppression due to sirolimus. Written informed consent was obtained from the patient's parent or guardian for publication of this Case report (and any accompanying images). A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Diazoxide-unresponsive congenital hyperinsulinism associated with ABCC8 nonsense mutation

Case presentation A baby boy with birth weight of 2.4kg at 35 weeks was born via Caesarian section. The boy was allowed feeding on demands, however he had the first onset of hypoglycemia at 2 hours of life. His blood sugar ranged from low reading to 2.5 mmol/L. The patient was treated with boluses of intravenous dextrose D10% followed by maintenance dextrose with its increasing strength in order to treat the refractory hypoglycemia. In addition to that intravenous hydrocortisone and glucagon infusion were started. The patient’s blood sugar could only be maintained > 3.0mmol/L after a glucose load of 30mg/kg/min and a glucagon infusion of 50mcg/kg/hour. During hypoglycemia, the insulin level was 19.6 pmol/L (17.8-173.0) and blood ketone was negative. Oral diazoxide was started at 5.0mg/kg/day in divided doses combined with chlorothiazide 7.0 mg/kg/day. Diazoxide was titrated up to 20.0mg/kg/day as he had a poor response even after 1 week of the treatment. Apart from that oral nifidipine 2.5 mg/kg/day in divided doses was also started after a few days with the combination therapy. Only after starting octreotide infusion a good rise of blood sugar was seen within 1 hour and the glucose load could be brought down and the other drugs were off. The boy was discharged with subcutaneous octreotide infusion at 2mcg/ hour via portable insulin pump. Results The boy is heterozygous for an ABCC8 nonsense mutation, p.R934*. A second ABCC8 mutation has not been found and sequencing of the KCNJ11 gene failed to detect a change from the normal sequence. He has inherited the mutation from his father; a focal lesion is therefore possible. 18F-DOPA PET-CT scanning is recommended and if a focal lesion is identified and surgically resected, microsatellite analysis of the DNA can be undertaken to confirm loss of heterozygosity.

Congenital hyperinsulinism: current status and future perspectives.

The diagnosis and treatment of congenital hyperinsulinism (CHI) have made a remarkable progress over the past 20 years and, currently, it is relatively rare to see patients who are left with severe psychomotor delay. The improvement was made possible by the recent developments in the understanding of the molecular and pathological basis of CHI. Known etiologies include inactivating mutations of the KATP channel genes (ABCC8 and KCNJ11) and HNF4A, HNF1A, HADH, and UCP2 or activating mutations of GLUD1, GCK, and SLC16A1. The understanding of the focal form of KATP channel CHI and its detection by 18F-fluoro-L-DOPA positron emission tomography have revolutionized the management of CHI, and many patients can be cured without postoperative diabetes mellitus. The incidence of the focal form appears to be higher in Asian countries; therefore, the establishment of treatment systems is even more important in this population. In addition to diazoxide or long-term subcutaneous infusion of octreotide or glucagon, long-acting octreotide or lanreotide have also been used successfully until spontaneous remission. Because of these medications, near-total pancreatectomy is less often performed even for the diazoxide-unresponsive diffuse form of CHI. Other promising medications include pasireotide, small-molecule correctors such as sulfonylurea or carbamazepine, GLP1 receptor antagonists, or mammalian target of rapamycin inhibitors. Unsolved questions in this field include the identification of the remaining genes responsible for CHI, the mechanisms leading to transient CHI, and the mechanisms responsible for the spontaneous remission of CHI. This article reviews recent developments and hypothesis regarding these questions.

Efficacy and safety of long‐term, continuous subcutaneous octreotide infusion for patients with different subtypes of KATP‐channel hyperinsulinism

To evaluate the efficacy of long-term, continuous, subcutaneous octreotide infusion for congenital hyperinsulinism caused by mutations in the KATP-channel genes, KCNJ11 and ABCC8. Fifteen Japanese patients with diazoxide-unresponsive, KATP-channel hyperinsulinism. Molecular diagnoses were made by sequencing and multiple ligation-dependent probe amplification analysis. In patients with paternally inherited, monoallelic mutations, 18F-DOPA PET scans were performed to determine the location of the lesion. The patients were treated with continuous, subcutaneous octreotide infusion at a dosage of up to 25 μg/kg/day, using an insulin pump to maintain blood glucose levels higher than 3.33 mmol/l. Additional treatments (IV glucose, glucagon or enteral feeding) were administered as needed. The efficacy of the treatment was assessed in patients who received octreotide for 4 months to 5.9 years. Three patients had biallelic mutations, and 12 had monoallelic, paternally inherited mutations. Four patients with monoallelic mutations showed diffuse 18F-DOPA uptake, whereas seven patients showed focal uptake. Octreotide was effective in all the patients. The patients with biallelic mutations required a higher dosage (17-25 μg/kg/day), and two patients required additional treatments. By contrast, the patients with monoallelic mutations required a lower dosage (0.5-21 μg/kg/day) irrespective of the PET results and mostly without additional treatments. Treatment was discontinued in three patients at 2.5, 3.3 and 5.9 years of age, without psychomotor delay. Except for growth deceleration at a higher dosage, no significant adverse effects were noted. Long-term, continuous, subcutaneous octreotide infusion is a feasible alternative to surgery especially for patients with monoallelic KATP-channel mutations.

Clinical observation of continuously subcutaneous-pumped octreotide infusion in palliative treatment of malignant bowel obstruction

The aim of the study was to observe the effectiveness of continuously subcutaneous-pumped octreotide infusion in palliative treatment of malignant bowel obstruction (MBO). Clinical data were retrospectively analyzed in 26 carcinoma patients complicated with MBO, in the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China, from March 2007 to April 2009. All 26 carcinoma patients with MBO were divided into two groups: the controlling group (CG, routine therapy, 15 patients) and the octreotide group (OG, 11 patients). The octreotide group received routine therapy combined with octreotide (0.3 mg/d) by 24 hours continuously subcutaneous octreotide infusion. The changes of curative effectiveness related to symptoms, the times of recovering exsufflation and defecation, the average drain of gastrointestinal drainage tube, the duration of gastrointestinal drainage tube and the rate of extubation, were observed and compared between the two groups. After treatment, remarkable changing rates of MBO related symptoms were 81.8% (9/11) in OG, and 46.7% (7/15) in CG (P < 0.05). The 78% of SG and 30% of CG recovered the exsufflation and defecation, and the mean times they needed were 3.2 d and 5.8 d, respectively (P < 0.05). The durations of gastrointestinal drainage tube of OG and CG were (5 ± 1.2) d and (10 ± 2.3) d, respectively, and the rates of extubation were 54.5% and 20%, respectively. The improvement rate in the octreotide group was better than that in the controlling group and the difference was significant (72.7% and 26.7%, P < 0.05). The administration of octreotide in combination with routine treatment can be very effective in the treatment of MBO. It can relieve the symptoms of MBO effectively and improve the quality of life of the end-stage patients. It has provided one kind of new treating thought and method for treatment of malignant bowel obstruction.

Generation of growth hormone pulsatility in women: evidence against somatostatin withdrawal as pulse initiator.

To test whether endogenous hypothalamic somatostatin (SRIH) fluctuations are playing a role in the generation of growth hormone (GH) pulses, continuous subcutaneous octreotide infusion (16 microg/h) was used to create constant supraphysiological somatostatinergic tone. Six healthy postmenopausal women (age 67 +/- 3 yr, body mass index 24.7 +/- 1.2 kg/m(2)) were studied during normal saline and octreotide infusion providing stable plasma octreotide levels of 2,567 +/- 37 pg/ml. Blood samples were obtained every 10 min for 24 h, and plasma GH was measured with a sensitive chemiluminometric assay. Octreotide infusion suppressed 24-h mean GH by 84 +/- 3% (P = 0.00026), GH pulse amplitude by 90 +/- 3% (P = 0.00031), and trough GH by 54 +/- 5% (P = 0.0012), whereas GH pulse frequency remained unchanged. The response of GH to GH-releasing hormone (GHRH) was not suppressed, and the GH response to GH-releasing peptide-6 (GHRP-6) was unaffected. We conclude that, in women, periodic declines in hypothalamic SRIH secretion are not the driving force of endogenous GH pulses, which are most likely due to episodic release of GHRH and/or the endogenous GHRP-like ligand.

Combination of continuous subcutaneous infusion of insulin and octreotide in Type 1 diabetic patients

The effect of 7 day continuous subcutaneous infusion of octreotide (200 μg day −1) was evaluated in seven insulin-pump treated Type 1 diabetic patients (age 43±1.5 year; BMI 25.1±0.7 kg m −2; HbA 1c 7.4±0.3%). A 24-h metabolic and hormonal profile, and a euglycaemic hyperinsulinaemic clamp (0.25, 0.5, 1.0 mg kg −1 min −1), with [ 3H]glucose infusion and indirect calorimetry, were performed before and after a 7-day octreotide infusion. Mean 24-h plasma glucose was similar before and after octreotide (9.7±0.8 vs. 9.1±1.0 mmol l −1) but insulin requirement dropped by 45% (49±4 vs. 27±2 U day −1; P<0.01). Both 24-h plasma hGH and glucagon were suppressed by octreotide (1.85±0.35 vs. 0.52±0.04 μg l −1, and 117±23 vs. 102±14 ng l −1, respectively). Glucose utilisation increased after octreotide (insulin 0.5 mU kg −1 min −1 clamp 3.09±0.23 vs. 4.19±0.19 mg kg −1 min −1; 1 mU kg −1 min −1 clamp 5.64±0.61 vs. 7.93±0.57 mg kg −1 min −1; both P<0.05) and endogenous glucose production was similarly suppressed. Glucose oxidation was not affected by octreotide, while the improvement in glucose storage (insulin 1.0 mU kg −1 min −1 clamp 3.89±0.60 vs. 5.64±0.67 mg kg −1 min −1, P<0.05) entirely accounted for the increase in glucose disposal. Endogenous glucose production was more effectively suppressed at the two lower insulin infusion rates ( P>0.05). Energy expenditure declined after octreotide. Continuous subcutaneous octreotide infusion suppresses counterregulatory hormones, increases insulin-mediated glucose metabolism by enhancing glucose storage, and reduces energy expenditure. These results support a role for counterregulatory hormones in the genesis of insulin resistance and the catabolic state of Type 1 diabetes.

Preoperative treatment of growth hormone-producing pituitary adenoma with continuous subcutaneous infusion of octreotide.

Preoperative therapy with octreotide, a long-acting somatostatin analog, suppresses GH hypersecretion, shrinks GH-producing tumors and leads to an improvement in subsequent surgical remission in acromegalic patients. A continuous infusion of octreotide has demonstrated more persistent suppression of GH secretion than intermittent injections, and only a few studies were reported on the effect of the tumor shrinkage with a continuous infusion of a small dose of octreotide. We therefore investigated the preoperative effects of small doses of octreotide (120-240 micrograms/day) administered continuously (with a subcutaneous infusion pump) over a short period (2 or 4 weeks) in nine untreated acromegalic patients. Octreotide therapy resulted in suppression of serum GH and IGF-1 concentrations in 8 out of 9 patients and reduction in pituitary tumor size measured by MRI in all patients (by 7.9 to 38.5%). In particular, considerable reduction in tumor size (more than 20%) occurred in 6 of 9 patients. In three patients assessed serially throughout the preoperative period, reduction in tumor size was noted within only one week after the start of octreotide therapy and reduction rate more than 20% was obtained within the first two weeks. In one patient, suprasellar tumor expansion totally disappeared after such therapy. Our results indicate that short-term continuous subcutaneous infusion of a small dose of octreotide results in not only inhibition of GH hypersecretion but also shrinkage of tumor size prior to surgery.

Effects of octreotide on glycaemic control, glucose disposal, hepatic glucose production and counterregulatory hormones secretion in type 1 and type 2 insulin treated diabetic patients

We studied the effects of continuous subcutaneous infusion of octreotide (100 μg/day for 5 days) on glycaemic values, counterregulatory hormones secretion, hepatic glucose production (HGP) and glucose disposal during an euglycaemic clamp in 7 C-peptide-negative type 1 diabetic patients and 7 C-peptide positive insulin-treated type 2 diabetic patients. In type 1, but not type 2 diabetic patients, octreotide significantly reduced glycaemic values ( P<0.005) and also diminished HGP during an euglycaemic clamp ( P<0.05). However, insulin stimulated global glucose uptake remained unchanged. GH, glucagon, IGF-I, IGFBP-3 levels, were significantly lowered by octreotide in both type 1 and type 2 diabetic patients whereas cortisol and epinephrine remained unmodified. Moreover in type 2 diabetic patients both basal ( P<0.05) and after-meal ( P<0.01) C-peptide secretion was reduced by octreotide. These data point to different metabolic effects of octreotide in type 1 versus type 2 diabetic patients with the drug only being able to reduce glycaemic values and HGP in the former but not in the latter subjects. The failure of octreotide to diminish glycaemic values and HGP in type 2 diabetic patients in spite of its ability to lower GH and glucagon may probably depend on temporary blockage of residual endogenous insulin secretion induced by octreotide administration.

Histopathological Improvement of Acromegalic Cardiomyopathy by Intermittent Subcutaneous Infusion of Octreotide.

We studied functional and histopathological changes in acromegalic cardiomyopathy following intermittent subcutaneous infusion of octreotide. A 68-year-old female patient with acromegaly associated with congestive heart failure due to dilated cardiomyopathy was initially treated with cardioactive medication for three months, but it was not effective in correcting echocardiographic abnormalities. Further treatment with intermittent subcutaneous infusion of octreotide (20 microg/2 h) for 12 months not only reduced circulating GH and insulin-like growth factor-I (IGF-I) levels but also considerably improved histopathological changes in the myocardial specimen biopsied. These findings provide the first evidence of the favorable effect of octreotide on histopathological changes in acromegalic cardiomyopathy.

Tolerability of Continuous Subcutaneous Octreotide Used in Combination with Other Drugs

Continuous subcutaneous infusion of octreotide combined with other drugs has proved to be useful in some circumstances in palliative care setting when theoral route is no longer available. Forty-four patients were administered octreotide alone or in combination with other drugs in the same syringe driver for symptom control in advanced cancer patients. Good tolerability and compatibility were observed without visual drug precipitation for a period of 48 hours at room temperature, the standard clinical situation in patients' homes. Such a combination of drugs administered by the subcutaneous route makes possible the adequate control of symptoms in the final days of life.

The impact of continuous subcutaneous infusion of octreotide on gallstone formation in acromegalic patients

The impact of continuous subcutaneous infusion of octreotide on gallstone formation in acromegalic patients

Stimulation of muscle glucose disposal by insulin in humans is a function of the preexisting plasma insulin level.

To examine whether tissue sensitivity to insulin is dependent upon the prevailing plasma insulin concentration, the ability of acute hyperinsulinemia to stimulate glucose disposal was investigated in six normal subjects before and after prolonged reduction of the plasma insulin concentration. Glucose turnover ([6,6-2H2]glucose), whole body glucose oxidation and nonoxidative glucose disposal (indirect calorimetry), and glycogen synthase activity in muscle were determined in the postabsorptive and in the insulin-stimulated states (euglycemic hyperinsulinemic clamp: 3 mU.kg-1.min-1) before and after a 4-day subcutaneous infusion of the somatostatin analogue octreotide (200 micrograms/24 h). Constant octreotide infusion 1) decreased postabsorptive and meal-stimulated plasma insulin levels by approximately 30-40% but did not significantly alter overall glucose tolerance, free fatty acid, growth hormone, and glucagon levels and 2) was associated with significant increases in insulin-mediated whole body glucose disposal (pre-drug: 10.29 +/- 0.49 vs. postdrug: 11.42 +/- 0.72 mg.kg-1.min-1, P < 0.04), nonoxidative glucose disposal (6.82 +/- 0.57 vs. 7.68 +/- 0.62, P < 0.03), and fractional glycogen synthase activity (0.14 +/- 0.03 vs. 0.20 +/- 0.04 mU/mg protein, P < 0.02). In contrast, infusion of saline instead of octreotide for 4 days to control subjects did not alter any of the metabolic parameters. We conclude that lowering the plasma insulin concentration over a prolonged period of time increases insulin sensitivity. The effects of insulin to stimulate whole body glucose utilization, nonoxidative glucose disposal, and glycogen synthase activity in muscle are therefore functions of the preexisting plasma insulin concentration.

Intramuscular injections of slow-release lanreotide (BIM 23014) in acromegalic patients previously treated with continuous subcutaneous infusion of octreotide (SMS 201-995)

Nine acromegalic patients (five females and four males), mean age 50 +/- 4 years, presented macroadenomas (N = 7), microadenoma (N = 1) or normal computed tomography scans (N = 1). Patients were treated with continuous subcutaneous infusion of octreotide (range 200-600 micrograms/day). Following a washout period of 7 days, the patients were injected im with 30 mg slow-release lanreotide every 10 days for the first month and then twice monthly. In case of elevated growth hormone (GH) levels at 3 months, the patients were injected every 10 days for the next three months. Plasma GH and insulin-like growth factor I (IGH-I) decreased in all patients during octreotide treatment. After 6 months of octreotide treatment, seven patients were considered as well controlled (mean 8 h GH < 5 micrograms/l, IGF-I normal) whereas in two patients the mean 8-h GH and/or IGF-I levels remained increased. Serum GH and IGH-I increased after octreotide withdrawal. In one patient, serum GH and IGF-I increased during slow-release lanreotide administration and injections were stopped after 45 days. After 3 months of lanreotide, three patients were well controlled while in five patients GH or IGF-I levels were not normalized. At 6 months, five patients were injected twice monthly and three patients had one injection every 10 days. Six patients were well controlled and in two patients the mean 8-h GH level remained increased. The pituitary tumor volume decreased by 20-30% in two patients during octreotide, as well as in one other during slow-release lanreotide therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous Versus Intermittent Subcutaneous Infusion of Octreotide in the Treatment of Acromegaly

This review evaluates the efficacy, tolerability, and safety of continuous subcutaneous infusion (CSI) relative to intermittent subcutaneous injection (ISI) of the somatostatin analog, octreotide in the treatment of acromegaly. Data was extracted from five clinical series using CSI octreotide in acromegaly, six reports comparing CSI to ISI, and three studies comparing pulsatile subcutaneous infusion (PSI) to ISI. Effects of each drug regimen on the control of growth hormone (GH), insulin-like growth factor (IGF-1), clinical symptomatology, pituitary tumor size, and adverse effects were evaluated. Normalization of serum GH or IGF-1 levels, as well as improvement in clinical symptoms was reported in the majority of the patients studied. Cases in which pituitary adenomas decreased in size were also documented during the study period. When the effects of CSI were compared with ISI, a more pronounced control of GH and IGF-1 was observed. In addition, diurnal GH fluctuation during CSI was significantly reduced relative to ISI in two reports. Moreover, in two patients, CSI achieved similar clinical and biochemical effects at lower doses than when the drug was given by ISI. Finally, adverse effects with CSI may be less severe than with ISI. Continuous subcutaneous infusion of octreotide produced biochemical improvement in 67 of the 88 patients reviewed. When compared with ISI, CSI induced more pronounced biochemical control, often with less fluctuation in GH and IGF-1 levels. Because of a lack of data, definite conclusions regarding the differences between regimens on clinical symptomatology and tolerability could not be discerned. A large prospective, long-term randomized crossover study is recommended to make these determinations.

Palliation of malignant intestinal obstruction using octreotide

Vomiting due to malignant intestinal obstruction is an unpleasant terminal event in many cancer patients, which responds poorly to conventional therapies. Somatostatin and its long-acting analogues reduce intestinal secretion. For this reason, octreotide was used in a phase I/II study of patients with intractable vomiting secondary to intestinal obstruction due to malignant disease. Vomiting was controlled or the volume of nasogastric aspirate was markedly reduced in 18 of 24 (75%) patients receiving a subcutaneous infusion of octreotide (median initial dose 300, range 100-600 micrograms/day) for a median of 9.4 (range 1-38) days. A further 2 patients had partial relief of their symptoms. Octreotide is an effective treatment of nausea and vomiting due to malignant bowel obstruction.