scholarly journals The use of long-acting somatostatin analogs in congenital hyperinsulinism

2020 ◽  
Vol 66 (5) ◽  
pp. 70-78
Author(s):  
E. E. Novokreshhennyx ◽  
D. N. Gubaeva ◽  
M. A. Melikyan
Keyword(s):  
Pediatric Patients ◽  
Somatostatin Analogs ◽  
Drug Dose ◽  
Effective Dosage ◽  
Research Centre ◽  
Congenital Hyperinsulinism ◽  
Subcutaneous Injections ◽  
Subcutaneous Infusion ◽  
Long Acting ◽  
Single Center Observational Study

BACKGROUND: Children with congenital hyperinsulinism (CHI), a severe orphan disease, are still one of the most demanding patients in the endocrinology practice. The use of first- and second-line drugs is not always effective and has a number of restrictions. Lanreotide — long-acting somatostatin — represents an alternative insulinostatic therapy. The main advantage of lanreotide is stable concentration of the drug in the blood that enables minimizing the number of injections. However, the experience of using lanreotide in the treatment of CHI is limited to small groups of patients. There is also a problem of the absence of a standardized regimen in clinical practice; and the calculator for evaluating the initial effective drug dose is needed.AIM of the study is to evaluate the effectiveness and safety of lanreotide therapy in the treatment of CHI in children.MATERIALS AND METHODS: An open single-center observational study was conducted on the basis of Endocrinology Research Centre. The study included diazoxide-unresponsive pediatric patients with CHI who were initially treated with octreotide in different modes: multiple daily subcutaneous injections or continuous subcutaneous infusion via pumps. The indicators of the effectiveness and safety of the lanreotide therapy were evaluated shortly after the first injection and lately on a regular visit after further injections.RESULTS: The study group included 12 patients. Persistent euglycaemia was achieved in 67% of the subjects (8/12). Complete effectiveness of the therapy was observed in 8/12 patients (67%), partial — in 3/12 (25%), and lack of effectiveness — in 1/12 of the patient (8%). The age of the patients at the time of lanreotide administration was 6 months (5; 15). According to the study, the most effective dose of lanreotide is 3.5-5.5 mg/ kg/ month. There were no significant side effects observed.CONCLUSIONS: The use of lanreotide in patients with diazoxide-resistant congenital hyperinsulinism was effective and safe in the vast majority of the patients. Moreover, we were able to calculate the effective dosage of lanreotide in CHI patients which fulfilled the clinical demand.

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

2020 ◽  
Vol 66 (3) ◽  
pp. 81-87
Author(s):  
Maria A. Melikyan ◽  
Diliara N. Gubaeva ◽  
Maria A. Kareva
Keyword(s):  
Quality Of Life ◽  
Pediatric Patients ◽  
Research Centre ◽  
Infusion Therapy ◽  
Congenital Hyperinsulinism ◽  
Intravenous Glucose ◽  
Subcutaneous Infusion ◽  
Number Of Patients ◽  
Continuous Subcutaneous Infusion

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 its 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.

The effect of subcutaneous infusion versus subcutaneous injections of a somatostatin analogue (SMS 201-995) on the diurnal GH profile in acromegaly

1987 ◽  
Vol 116 (1) ◽  
pp. 108-112 ◽  
Author(s):  
José Timsit ◽  
Philippe Chanson ◽  
Etienne Larger ◽  
Michèle Duet ◽  
Arlette Mosse ◽  
...  
Keyword(s):  
Somatostatin Analogue ◽  
Short Term ◽  
Subcutaneous Injections ◽  
Subcutaneous Infusion ◽  
Long Term Study ◽  
Term Trial ◽  
Diurnal Profile ◽  
Long Acting ◽  
Plasma Gh

Abstract. Multiple sc injections of a long-acting somatostatin analogue (SMS 201-995) are currently used in the treatment of acromegaly. However, plasma GH concentration often reaches a pathological level (> 5 μg/l) between two injections. In seven patients with active acromegaly we compared, in a short-term trial, the effect of SMS 201-995 administered by continuous sc infusion (50 μg and 100 μg a day) and by three scinjections (100 μg each). In six patients, plasma GH levels were significantly reduced regardless of the mode and dose of treatment (P < 0.05). However, comparing diurnal profiles, 100 μg continuous sc infusion was more effective than discontinuous administration in reducing the number of GH levels above 5 μg/l (P < 0.01). In two patients, continuous infusion was the only way to decrease all plasma GH values below 5 μg/l during the diurnal profile determination. Moreover, even when, in a long-term study, the dose of multiple injections was progressively increased to 500 μg three times a day, GH levels remained consistently elevated in one of these patients. Thus, in some acromegalic patients continuous sc injection seems currently the most efficient way of treatment with SMS 201-995.

scholarly journals Successful treatment of congenital hyperinsulinism with long-acting release octreotide

2012 ◽  
Vol 166 (2) ◽  
pp. 333-339 ◽  
Author(s):  
Kim-Hanh Le Quan Sang ◽  
Jean-Baptiste Arnoux ◽  
Asmaa Mamoune ◽  
Cécile Saint-Martin ◽  
Christine Bellanné-Chantelot ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Pediatric Patients ◽  
Somatostatin Analogue ◽  
Congenital Hyperinsulinism ◽  
Common Cause ◽  
The Third ◽  
Long Acting ◽  
Monthly Visit

ContextCongenital hyperinsulinism (HI) is a common cause of hypoglycemia in infancy. The medical treatment of diazoxide-unresponsive HI is based on a somatostatin analogue.ObjectiveThis study aims at replacing three daily s.c. octreotide (Sandostatin, Novartis) injections by a single and monthly i.m. injection of long-acting release (LAR) octreotide (Sandostatin LP, Novartis) in HI patients.Subjects and methodLAR octreotide was injected every 4 weeks during 6 months and s.c. octreotide injections were stopped after the third injection of LAR octreotide. After this 6-month study, LAR octreotide was continued, with an average follow-up of 17 months. Ten HI pediatric patients unresponsive to diazoxide and currently treated with s.c. octreotide were included in the trial. Glycemias and other parameters (HbA1c, IGF1, height, weight, quality of life (QoL), and satisfaction) were monitored at each monthly visit.ResultsFor all ten patients, glycemias were maintained in the usual range, HbAlc (mean 5.5%; 95% CI: 4.6–6.2) and IGF1 (mean 89.7 ng/ml; 95% CI: 26–153) were unchanged. Patients gained height significantly (mean 2.7 cm; 95% CI: 1.9–3.4) and no side effect was noted during the study and the later follow-up. Plasma octreotide levels were stable under LAR octreotide. Parents' questionnaires of general satisfaction were highly positive whereas children's QoL evaluation remained unchanged.ConclusionIn these diazoxide-unresponsive HI patients, LAR octreotide was efficient, well tolerated and contributed to a clear simplification of the medical care.

scholarly journals Retrospective Analysis of the Effectiveness and Reversibility of Long-Acting Contraception Etonogestrel (Implanon®) in Common Marmosets (Callithrix jacchus)

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 963
Author(s):  
Sandra Roubos ◽  
Annet L. Louwerse ◽  
Jan A. M. Langermans ◽  
Jaco Bakker
Keyword(s):  
Control Method ◽  
Population Control ◽  
Callithrix Jacchus ◽  
Research Centre ◽  
Primate Research ◽  
Common Marmosets ◽  
Neonatal Deaths ◽  
Unintended Pregnancies ◽  
Colony Management ◽  
Long Acting

Contraception is an important population control method for the colony management of primates housed in captivity. Etonogestrel (ENG) implants (i.e., Implanon®) are a widely used progestin-based contraceptive in common marmosets (Callithrix jacchus) with the theoretical advantages of being reversible and long-acting. However, no dose and efficacy data are available yet. Therefore, data from 52 adult female marmosets contracepted with ENG (one-fourth or one-third of an implant) housed at the Biomedical Primate Research Centre (BPRC, Rijswijk, The Netherlands) over the past 18 years were analyzed. Using an electronic database, a retrospective longitudinal cohort study was conducted to calculate the reproductive data before, during and after ENG use. The data show an effectiveness in preventing pregnancy of 99%. The implant was effective within one week after insertion. Unintended pregnancies did occur, but in 60% of these cases, the animals were already pregnant at the time of implant insertion. In these cases, healthy offspring were born despite the use of the implant. No stillbirths, neonatal deaths or maternal deaths could be linked to ENG use. After implant removal, 83% of the animals delivered healthy offspring. No difference in contraception efficacy was observed between the use of one-fourth or one-third of an implant. ENG achieved a contraceptive protection exceeding 99% and was shown to be reversible concerning fertility. To our knowledge, this is the first detailed analysis on the use of ENG in marmosets.

scholarly journals Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2

2006 ◽  
Vol 13 (3) ◽  
pp. 955-962 ◽  
Author(s):  
E Ferrante ◽  
C Pellegrini ◽  
S Bondioni ◽  
E Peverelli ◽  
M Locatelli ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cultured Cells ◽  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Somatostatin Analogs ◽  
Receptor Type ◽  
Apoptotic Activity ◽  
Long Acting ◽  
Induced Apoptosis

Somatostatin analogs currently used in the treatment of acromegaly and other neuroendocrine tumors inhibit hormone secretion and cell proliferation by binding to somatostatin receptor type (SST) 2 and 5. The antiproliferative pathways coupled to these receptors have been only partially characterized. The aim of this study was to evaluate the effect of octreotide and super selective SST2 (BIM23120) and SST5 (BIM23206) analogs on apoptotic activity and apoptotic gene expression in human somatotroph tumor cells. Eight somatotroph tumors expressing similar levels of SST2 and SST5 evaluated by real-time PCR and western blot analyses were included in the study. In cultured cells obtained from these tumors, octreotide induced a dose-dependent increase of caspase-3 activity (160 ± 20% vs basal at 10 nM) and cleaved cytokeratin 18 levels (172 ± 25% vs basal) at concentrations higher than 0.1 nM. This effect was due to SST2 activation since BIM23120 elicited comparable responses, while BIM23206 was ineffective. BIM23120-stimulated apoptosis was dependent on phosphatases, since it was abrogated by the inhibitor orthovanadate, and independent from the induction of apoptosis-related genes, such as p53, p63, p73, Bcl-2, Bax, BID, BIK, TNFSF8, and FADD. In somatotroph tumors, both BIM23120 and BIM2306 caused growth arrest as indicated by the increase in p27 and decrease in cyclin D1 expression. In conclusion, the present study showed that octreotide-induced apoptosis in human somatotroph tumor cells by activating SST2. This effect, together with the cytostatic action exerted by both SST2 and SST5 analogs, might account for the tumor shrinkage observed in acromegalic patients treated with long-acting somatostatin analogs.

scholarly journals Combined treatment for acromegaly with long-acting somatostatin analogs and pegvisomant: long-term safety for up to 4.5 years (median 2.2 years) of follow-up in 86 patients

2009 ◽  
Vol 160 (4) ◽  
pp. 529-533 ◽  
Author(s):  
SJCMM Neggers ◽  
WW de Herder ◽  
JAMJL Janssen ◽  
RA Feelders ◽  
AJ van der Lely
Keyword(s):  
Combined Therapy ◽  
Combined Treatment ◽  
Somatostatin Analogs ◽  
Pituitary Surgery ◽  
Median Dosage ◽  
Previously Treated ◽  
Long Acting

BackgroundWe previously reported on the efficacy, safety, and quality of life (QoL) of long-acting somatostatin analogs (SSA) and (twice) weekly pegvisomant (PEG-V) in acromegaly and improvement after the addition of PEG-V to long-acting SSA.ObjectiveTo assess the long-term safety in a larger group of acromegalic patients over a larger period of time: 29.2 (1.2–57.4) months (mean (range)).DesignPegvisomant was added to SSA monotherapy in 86 subjects (37 females), to normalize serum IGF1 concentrations (n=63) or to increase the QoL. The median dosage was 60.0 (20–200) mg weekly.ResultsAfter a mean treatment period of 29.2 months, 23 patients showed dose-independent PEG-V related transient liver enzyme elevations (TLEE). TLEE occurred only once during the continuation of combination therapy, but discontinuation and re-challenge induced a second episode of TLEE. Ten of these patients with TLEE also suffered from diabetes mellitus (DM). In our present series, DM had a 2.28 odds ratio (CI 1.16–9.22; p=0.03) higher risk for developing TLEE. During the combined therapy, a clinical significant decrease in tumor size by more than 20% was observed in 14 patients. Two of these patients were previously treated by pituitary surgery, 1 with additional radiotherapy and all other patients received primary medical treatment.ConclusionLong-term combined treatment with SSA and twice weekly PEG-V up to more than 4 years seems to be safe. Patients with both acromegaly and DM have a 2.28 higher risk of developing TLEE. Clinical significant tumor shrinkage was observed in 14 patients during combined treatment.

scholarly journals Somatostatin Analogs in Clinical Practice: A Review

2020 ◽  
Vol 21 (5) ◽  
pp. 1682 ◽  
Author(s):  
Mariana Gomes-Porras ◽  
Jersy Cárdenas-Salas ◽  
Cristina Álvarez-Escolá
Keyword(s):  
Dopamine Agonists ◽  
Therapeutic Option ◽  
Somatostatin Analogs ◽  
Intestinal Fistula ◽  
Endocrine Tumors ◽  
Congenital Hyperinsulinism ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Endocrine Diseases ◽  
Digestive Diseases ◽  
Graves Orbitopathy

Somatostatin analogs are an invaluable therapeutic option in the diagnosis and treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. They should also be considered an effective and safe therapeutic alternative to corticotropinomas, gonadotropinomas, and prolactinomas resistant to dopamine agonists. Somatostatin analogs have also shown to be useful in the treatment of other endocrine diseases (congenital hyperinsulinism, Graves’ orbitopathy, diabetic retinopathy, diabetic macular edema), non-endocrine tumors (breast, colon, prostate, lung, and hepatocellular), and digestive diseases (chronic refractory diarrhea, hepatorenal polycystosis, gastrointestinal hemorrhage, dumping syndrome, and intestinal fistula).

scholarly journals Living With Neuroendocrine Tumors: Assessment of Quality of Life Through a Mobile Application

2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jared R. Adams ◽  
David Ray ◽  
Renee Willmon ◽  
Sonia Pulgar ◽  
Arvind Dasari
Keyword(s):  
Quality Of Life ◽  
Neuroendocrine Tumors ◽  
Mobile Application ◽  
Somatostatin Analogs ◽  
Physical Symptoms ◽  
Measurement Information ◽  
Treatment Change ◽  
Patient Reported ◽  
Long Acting

PURPOSE To understand the quality of life (QoL) for patients with neuroendocrine tumors (NETs) through comparison of QoL questionnaires and symptom tracking as well as journaling via the Carcinoid NETs Health Storylines mobile application (app). PATIENTS AND METHODS This was a 12-week prospective, observational study of US patients with NET who were taking long-acting somatostatin analogs. National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) and European Organisation for Research and Treatment of Cancer (EORTC) questionnaires were administered three times. Patients also monitored symptoms, mood, bowel movements, food, activity, and sleep, and they journaled in their app, which was coded by theme and sentiment for qualitative analysis. RESULTS Of the 120 patients with NET, 78% were women (mean age, 57 years); 76% had gastroenteropancreatic NETs, and 88% had metastases. Lanreotide depot and octreotide long-acting release (LAR) were used by 41% and 59%, respectively. The most common symptoms at baseline were fatigue (76.7%), diarrhea (62.5%), abdominal discomfort (64.1%), and trouble sleeping (57.5%). The majority completed five of six survey assessments (median, 5; mean, 5.1) and tracked four symptoms in the app (median, 4; mean, 5.5); the average frequency was 41.6 days for each symptom (median, 43; mean, 41.6; range, 1 to 84 days [12 weeks]). Without treatment change, most EORTC-assessed physical symptoms decreased from baseline to midpoint (eg, 59.3% at baseline v 33% at midpoint reported “quite a bit” or “very much” diarrhea; P = .002). App-based symptom tracking revealed large day-to-day variation, but weekly averages correlated well with survey scores. Journal entries showed that more patients made predominantly negative unsolicited entries about their injection experience with octreotide LAR compared with lanreotide (13 of 17 v two of 13; P < .001). CONCLUSION Patients with NET experience a large symptom burden that varies daily. A decrease in physical symptoms on QoL surveys suggests an effect from daily app-based monitoring or journaling, which may reduce recall bias and benefit the patient’s experience of symptoms.

scholarly journals Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients

Pituitary ◽  
2011 ◽  
Vol 14 (3) ◽  
pp. 253-258 ◽  
Author(s):  
Sebastian J. C. M. M. Neggers ◽  
Wouter W. de Herder ◽  
Richard A. Feelders ◽  
A. J. van der Lely
Keyword(s):  
Somatostatin Analogs ◽  
Long Acting
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