Clinical and pathophysiological aspects of somatostatin and the gastrointestinal tract

1987 ◽  
Vol 116 (4_Suppla) ◽  
pp. S19-S25 ◽  
Author(s):  
C. B.H.W. Lamers
Keyword(s):  
Gastrointestinal Tract ◽  
Gastrointestinal Haemorrhage ◽  
Somatostatin Analogues ◽  
Exocrine Secretion ◽  
Somatostatin Analogue ◽  
Cell Hyperplasia ◽  
Secretory Diarrhoea ◽  
D Cell ◽  
Long Acting ◽  
Clinical Conditions

Abstract. Somatostatin is present in the gastrointestinal tract in appreciable amounts. The highest concentrations of the polypeptide are found in the stomach, the upper small intestine, and the pancreas. Within the gastrointestinal tract, somatostatin inhibits various functions, including endocrine and exocrine secretion, motility, blood flow, absorption, and growth. The polypeptide regulates these functions by endocrine, paracrine, neurocrine or luminal mechanisms. Abnormalities of endogenous somatostatin have been implicated in several gastrointestinal disorders, including the somatostatinoma syndrome, antroduodenal D-cell hyperplasia, peptic ulcer, obesity, and liver cirrhosis. Because of its potent inhibitory effects, somatostatin or somatostatin-analogues have been used as therapeutic agents in various clinical conditions, such as upper gastrointestinal haemorrhage, endocrine pancreatic tumours, gastrointestinal and pancreatic fistulas, pancreatitis, secretory diarrhoea, and dumping syndrome. The recent availability of the synthetic long-acting somatostatin-analogue SMS 201-995 (Sandostatin) has greatly facilitated the therapeutical application of somatostatin-polypeptides.

scholarly journals Somatostatin and gastrointestinal tract. Clinical experiences

2013 ◽  
Vol 154 (39) ◽  
pp. 1535-1540 ◽  
Author(s):  
László Herszényi ◽  
Emese Mihály ◽  
Zsolt Tulassay
Keyword(s):  
Gastrointestinal Tract ◽  
Gastrointestinal Hormones ◽  
Gastrointestinal Diseases ◽  
Somatostatin Analogues ◽  
Therapeutic Modality ◽  
Exocrine Function ◽  
Somatostatin Analogue ◽  
Clinical Experiences ◽  
Pancreatic Fistulas ◽  
Long Acting

The effect of somatostatin on the gastrointestinal tract is complex; it inhibits the release of gastrointestinal hormones, the exocrine function of the stomach, pancreas and bile, decreases motility and influences absorption as well. Based on these diverse effects there was an increased expectation towards the success of somatostatin therapy in various gastrointestinal disorders. The preconditions for somatostatin treatment was created by the development of long acting somatostatin analogues (octreotide, lanreotide). During the last twenty-five years large trials clarified the role of somatostatin analogues in the treatment of various gastrointestinal diseases. This study summarizes shortly these results. Somatostatin analogue treatment could be effective in various pathological conditions of the gastrointestinal tract, however, this therapeutic modality became a part of the clinical routine only in neuroendocrine tumours and adjuvant treatment of oesophageal variceal bleeding and pancreatic fistulas. Orv. Hetil., 2013, 154, 1535–1540.

scholarly journals Long Acting Somatostatin Analogue: Clinical Potential for Gastrointestinal Disease

1989 ◽  
Vol 3 (2) ◽  
pp. 77-81 ◽  
Author(s):  
Richard N. Fedorak
Keyword(s):  
Gastrointestinal Tract ◽  
Gastrointestinal Hemorrhage ◽  
Neuroendocrine Tumours ◽  
Gastrointestinal Disease ◽  
Somatostatin Analogues ◽  
Somatostatin Analogue ◽  
Short Bowel ◽  
Long Acting ◽  
Clinical Potential ◽  
Biological Actions

Name somatostatin is found throughout the gastrointestinal tract and has a wide variety of biological actions. Nevertheless, its short biological half-life and limited stability necessitate its use via continuous parenteral infusion and, thus, limits its therapeutic usefulness The development of long acting somatostatin analogues have lead to a re-examination of the therapeutic usefulness of somatostatin in gastrointestinal disease. Somatostatin analogues appear most beneficial tn preventing symptoms associated with neuroendocrine tumours. In addition, case controlled studies exist to demonstrate somatostatin analogue effectiveness in treatment of gastrointestinal hemorrhage, pancreatic fistula, pancreatitis, short bowel syndrome and dumping syndrome.

Aggravation of hypoglycemia in insulinoma patients by the long-acting somatostatin analogue octreotide (Sandostatin®)

1989 ◽  
Vol 121 (1) ◽  
pp. 34-40 ◽  
Author(s):  
C. D. A. Stehouwer ◽  
W. F. Lems ◽  
H. R. A. Fischer ◽  
W. H. L. Hackeng ◽  
M. A. B. Naafs
Keyword(s):  
Blood Glucose ◽  
Hormone Secretion ◽  
Somatostatin Analogues ◽  
Serum Glucose ◽  
Somatostatin Analogue ◽  
Transient Decrease ◽  
Glucoregulatory Hormones ◽  
Octreotide Therapy ◽  
Long Acting ◽  
Analogue Octreotide

Abstract. Recently somatostatin analogues were successfully used to control insulin-induced hypoglycemia in patients with insulinoma. We observed a transient decrease in glucose levels and symptomatic hypoglycemia after administration of the long-acting somatostatin analogue octreotide (Sandostatin®) in two insulinoma patients. We studied the acute effects of octreotide (administered before breakfast) on blood glucose and glucoregulatory hormones in these patients. In one patient, we studied the effects of glucagon replacement and changing the time of breakfast (relative to octreotide administration) on octreotide-associated changes in blood glucose and glucoregulatory hormones. Compared with control levels, octreotide therapy reduced insulin levels. During hypoglycemia glucagon and growth hormone levels were suppressed, but cortisol levels appropriately increased. The increase in catecholamine levels was normal in one patient, but markedly attenuated in the other. A transient decrease in serum glucose after octreotide was absent after glucagon replacement, but present when breakfast was taken before administration of octreotide. We conclude that in patients with insulinoma, octreotide therapy may be associated with clinically important hypoglycemia, during which counterregulatory hormone secretion may be attenuated.

scholarly journals Self-Administration of Long-Acting Somatostatin Analogues in NET Patients—Does It Affect the Clinical Outcome?

Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1287
Author(s):  
Anna Sowa-Staszczak ◽  
Marta Opalińska ◽  
Anna Kurzyńska ◽  
Karolina Morawiec-Sławek ◽  
Aleksandra Gilis-Januszewska ◽  
...  
Keyword(s):  
Medical Staff ◽  
Somatostatin Receptor ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Somatostatin Analogue ◽  
Self Administration ◽  
Good Expression ◽  
Well Differentiated ◽  
Long Acting

Background and Objectives: Long-acting somatostatin analogues (SSA) (octreotide LAR and lanreotide Autogel) are recommended as first line treatment of locally advanced or metastatic well-differentiated neuroendocrine tumors (NETs) with a good expression of somatostatin receptor (SSTR). Both of these SSAs are usually administered via injections repeated every 4 weeks. The purpose of the study was to compare the route of SSA administration (injection performed by professional medical staff and self-administration of the drug) with progression-free survival. Materials and methods: 88 patients in 2019 and 96 patients in 2020 with locally advanced or metastatic well-differentiated NETs were included in the study. All patients had a good expression of SSTR type 2 and had been treated for at least 3 months with a stable dose of long-acting somatostatin analogue every 4 weeks. All of them had received training on drug self-injections from professional NET nurses at the beginning of the COVID-19 epidemic. Results: The rate of NET progression in the study group in 2020 was higher than in 2019 29.1% vs. 18.1% (28 vs. 16 cases), p = 0.081. Conclusions: The method of administration of long-acting SSA injection performed by professional medical staff vs. self-injection of the drug may significantly affect the risk of NET progression. The unequivocal confirmation of such a relationship requires further observation.

Hyperthyroidism due to non-tumoural inappropriate TSH secretion

1986 ◽  
Vol 113 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Gareth Williams ◽  
Marius Kraenzlin ◽  
Laurence Sandier ◽  
Jacky Burrin ◽  
Adam Law ◽  
...  
Keyword(s):  
Pituitary Tumour ◽  
Somatostatin Analogues ◽  
Molar Ratio ◽  
Somatostatin Analogue ◽  
Axial Tomography ◽  
Α Subunit ◽  
Tsh Secretion ◽  
Long Acting ◽  
Inappropriate Tsh Secretion ◽  
Tsh Levels

Abstract. Inappropriate hypersecretion of TSH was investigated in a 25 year old man whose hyperthyroidism had relapsed 4 years after subtotal thyroidectomy. Serum TSH levels were further increased by both TRH and metoclopramide and were partially suppressed by triiodothyronine (120 μ/day). The serum α-subunit: TSH molar ratio was < 1.0, and computerised axial tomography showed no evidence of a pituitary tumour. These features are characteristic of inappropriate TSH secretion due to thyrotroph resistance to thyroid hormones. A long-acting somatostatin analogue (SMS 201-995), 50 μg injected sc twice-daily for three days, suppressed TSH levels and nearly normalised thyroid hormone levels. Somatostatin analogues may be therapeutically useful in thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion.

scholarly journals Long-acting somatostatin analogue treatments in autosomal dominant polycystic kidney disease and polycystic liver disease: a systematic review and meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e032620 ◽  
Author(s):  
Joshua Griffiths ◽  
Mark T Mills ◽  
Albert CM Ong
Keyword(s):  
Autosomal Dominant ◽  
Data Extraction ◽  
Meta Analysis ◽  
Somatostatin Analogues ◽  
Mean Difference ◽  
Somatostatin Analogue ◽  
Polycystic Kidney ◽  
Polycystic Liver ◽  
Autosomal Dominant Polycystic Kidney ◽  
Long Acting

ObjectivesA number of randomised control trials (RCTs) investigating the effects of long-acting somatostatin analogues in autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD) have been recently reported. We sought to evaluate all available RCTs investigating the efficacy of somatostatin analogues treatment in ADPKD and PLD.Data sourcesElectronic databases; Pubmed, Clincaltrials.gov and Cochrane Central Register of Controlled TrialsEligibility criteria for selecting studiesRCTs and randomised cross-over trials comparing the effects of somatostatin analogue treatment with controls in patients with ADPKD or PLD.Data extraction and synthesisData extraction and bias assessments were performed by two independent reviewers between January and May 2019. Outcomes assessed included estimated glomerular filtration rate (eGFR), total kidney volume (TKV), total liver volume (TLV), progression to end stage renal failure (ESRF) and adverse effects. Data were pooled using a random-effects model and reported as relative risk or mean difference with 95% CIs.ResultsMeta-analysis was performed of six RCTs or randomised cross-over trials and three secondary analyses. A total of 592 patients were included. Compared with controls, somatostatin analogue treatment significantly reduced TLV (mean difference −0.15 L, 95% CI −0.26 to −0.03, p=0.01). There was no significant effect on TKV (mean difference −0.19 L, 95% CI −0.50 to 0.12, p=0.23) or eGFR (mean difference 0.27 mL/min/1.73 m2, 95% CI −2.03 to 2.57, p=0.82). There was no effect on progression to ESRF. Somatostatin analogues were associated with known adverse effects such as gastrointestinal symptoms.ConclusionsThe available RCT data show improvement in TLV with somatostatin analogue treatment. There was no benefit to TKV or eGFR in patients with ADPKD, while being associated with various side effects. Further studies are needed to assess potential benefit in reducing cyst burden in patients with PLD.

Resistant Paediatric Somatotropinomas due to AIP Mutations: Role of Pegvisomant

2018 ◽  
Vol 90 (3) ◽  
pp. 196-202 ◽  
Author(s):  
Kriti Joshi ◽  
Adrian F. Daly ◽  
Albert Beckers ◽  
Margaret Zacharin
Keyword(s):  
Combined Therapy ◽  
Somatostatin Analogues ◽  
Somatostatin Analogue ◽  
Tumour Mass ◽  
Residual Tumour ◽  
Control Disease ◽  
Long Acting ◽  
Analogue Octreotide

Background: Somatotropinomas are rare in childhood and frequently associated with genetic mutations. AIP mutations are found in 20–25% cases and cause aggressive somatotropinomas, often resistant to somatostatin analogues. Aims: To assess responses to multimodal therapy including pegvisomant in 2 children with sporadic somatotropinomas due to AIP mutations. Case Description: We report 2 children, a boy aged 13 and a girl aged 10, with rapid growth, visual impairment, and growth hormone hypersecretion. Magnetic resonance imaging confirmed a pituitary macroadenoma with parasellar extension in both. Despite multiple surgical attempts to debulk tumour mass, residual tumour persisted. Genetic analysis showed two different AIP mutations (patient 1: c.562delC [p.Arg188Glyfs*8]; patient 2: c.140_ 163del24 [p.Gly47_Arg54del8]). They were initially treated with a long-acting somatostatin analogue (octreotide LAR 30 mg/month) and cabergoline as a dopamine agonist, with the later addition of pegvisomant titrated up to 20 mg/day and with radiotherapy for long-term control. Somatostatin analogue was ceased due to patient intolerance and lack of control. Patient 1 had normalization of insulin-like growth factor-1 (IGF-1) after 5 months of combined therapy with pegvisomant and cabergoline. For patient 2, normalization of IGF-1 was achieved after 2 months of cabergoline and pegvisomant. Conclusion: AIP-associated tumours can be resistant to management with somatostatin analogues. Pegvisomant can safely be used, to normalize IGF-1 levels and help control disease.

Lanreotide Autogel Therapy in Patients with Acromegaly –Current Role and Perspectives for the Future

2010 ◽  
Vol 6 (2) ◽  
pp. 36
Author(s):  
Josef Marek ◽  
Keyword(s):  
Healthcare Professionals ◽  
Single Injection ◽  
Somatostatin Analogues ◽  
Hormonal Control ◽  
Somatostatin Analogue ◽  
Octreotide Lar ◽  
Care Givers ◽  
Active Release ◽  
Long Acting ◽  
Lanreotide Autogel

Lanreotide Autogel is a long-acting (effective for four to six weeks after a single injection) somatostatin analogue that normalises growth hormone (GH) and insulin-like growth factor I levels in about 50% of patients. It causes tumour volumes to shrink by more than 20% in 72–85% of patients. These effects are similar to those with octreotide long active release (LAR). Similarly, there are no differences between octreotide LAR and lanreotide Autogel in improvement of cardiac function, glycometabolic effects or occurrence of side effects, including cholelithiasis. In comparison to octreotide LAR, lanreotide Autogel has the advantage of being available in a convenient pre-filled syringe and it can be injected subcutaneously by patients or their care-givers/partners, omitting the necessity of injections by healthcare professionals. The efficacy of lanreotide can be increased by combination with dopamine agonists. Co-administration of lanreotide Autogel with pegvisomant appears to be safe and to improve hormonal control in a majority of patients with acromegaly partially controlled by somatostatin analogues alone.

scholarly journals A Multicenter Experience with Long-Acting Somatostatin Analogues in Patients with Congenital Hyperinsulinism

2017 ◽  
Vol 89 (2) ◽  
pp. 82-89 ◽  
Author(s):  
Ivo van der Steen ◽  
Mirjam E. van Albada ◽  
Klaus Mohnike ◽  
Henrik Thybo Christesen ◽  
Susann Empting ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Side Effects ◽  
Liver Enzymes ◽  
Blood Glucose Control ◽  
Severe Hypoglycemia ◽  
Somatostatin Analogues ◽  
Somatostatin Analogue ◽  
Congenital Hyperinsulinism ◽  
Elevated Liver Enzymes ◽  
Long Acting

Background/Aims: Congenital hyperinsulinism (CHI) is a rare disease characterized by recurrent severe hypoglycemia. In the diffuse form of CHI, pharmacotherapy is the preferred choice of treatment. Long-acting somatostatin analogues have been used in children as off-label medication. However, the efficacy, outcomes, and adverse effect profiles of long-acting somatostatin analogues have not been described in multicentered studies. The aim of this retrospective study is to summarize the experience with long-acting somatostatin analogues in a large group of children with CHI. Methods: Data were obtained retrospectively from 27 patients with CHI who received long-acting somatostatin analogues in 6 different centers in Europe. These included information on glycemic stability, auxology, and adverse effect profile in clinical follow-up assessments. Results: Blood glucose control improved in most patients (89%). No life-threatening side effects occurred. Thirteen patients (48%) experienced side effects; in 3 patients (11%), the side effects were the main reason for discontinuation of the treatment. The most frequent side effect was elevated liver enzymes (n = 10, 37%). Conclusion: Long-acting somatostatin analogues are effective in glycemic control of patients with CHI. However, in 37% of all patients increased liver enzymes were observed. It is important to monitor liver function in all patients receiving long-acting somatostatin analogue therapy.

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE: GH excess: diagnosis and medical therapy

2014 ◽  
Vol 170 (1) ◽  
pp. R31-R41 ◽  
Author(s):  
Marianne Andersen
Keyword(s):  
Polyclonal Antibodies ◽  
Somatostatin Analogues ◽  
Somatostatin Analogue ◽  
Primary Therapy ◽  
Α Subunit ◽  
Endocrine Disease ◽  
Increased Risk ◽  
Gh Receptor Antagonist ◽  
Long Acting

Acromegaly is predominantly caused by a pituitary adenoma, which secretes an excess of GH resulting in increased IGF1 levels. Most of the GH assays used currently measure only the levels of the 22 kDa form of GH. In theory, the diagnostic sensitivity may be lower compared with the previous assays, which have used polyclonal antibodies. Many GH-secreting adenomas are plurihormonal and may co-secrete prolactin, TSH and α-subunit. Hyperprolactinaemia is found in 30–40% of patients with acromegaly, and hyperprolactinaemia may occasionally be diagnosed before acromegaly is apparent. Although trans-sphenoidal surgery of a GH-secreting adenoma remains the first treatment at most centres, the role of somatostatin analogues, octreotide long-acting repeatable and lanreotide Autogel as primary therapy is still the subject of some debate. Although the normalisation of GH and IGF1 levels is the main objective in all patients with acromegaly, GH and IGF1 levels may be discordant, especially during somatostatin analogue therapy. This discordance usually takes the form of high GH levels and an IGF1 level towards the upper limit of the normal range. Pasireotide, a new somatostatin analogue, may be more efficacious in some patients, but the drug has not yet been registered for acromegaly. Papers published on pasireotide have reported an increased risk of diabetes mellitus due to a reduction in insulin levels. Pegvisomant, the GH receptor antagonist, is indicated – alone or in combination with a somatostatin analogue – in most patients who fail to enter remission on a somatostatin analogue. Dopamine-D2-agonists may be effective as monotherapy in a few patients, but it may prove necessary to apply combination therapy involving a somatostatin analogue and/or pegvisomant.

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