scholarly journals Pegvisomant in combination with long-acting somatostatin analogues in acromegaly: the role of the GH receptor deletion of exon 3

2015 ◽  
Vol 173 (5) ◽  
pp. 553-561 ◽  
Author(s):  
S E Franck ◽  
A J van der Lely ◽  
P J D Delhanty ◽  
J O L Jørgensen ◽  
S J C M M Neggers
Keyword(s):  
Somatostatin Receptor ◽  
Serum Levels ◽  
Somatostatin Analogues ◽  
High Dose ◽  
Gh Receptor ◽  
Hardy Weinberg Equilibrium ◽  
Baseline Characteristics ◽  
Long Acting ◽  
Somatostatin Receptor Ligand

BackgroundDoses of the GH receptor (GHR) antagonist pegvisomant (PEGV) that normalize insulin-like growth factor 1 (IGF1) levels vary widely among acromegaly patients. Predictors for PEGV response are baseline IGF1 levels, sex, body weight and previous radiotherapy. A GHR polymorphism lacking exon 3 (d3-GHR) is frequent in the general population. The influence of d3-GHR on PEGV responsiveness in acromegaly is unclear.ObjectiveTo assess the influence of d3-GHR on IGF1 levels and PEGV responsiveness in acromegaly patients using combined PEGV and long-acting somatostatin receptor ligand (LA-SRIF) treatment.DesignData were collected at the Rotterdam Pituitary Centre between 2004 and 2013. Patients with elevated IGF1 levels (>1.2 upper limit of normal; n=112) and over 6 months of high-dose LA-SRIF treatment were co-treated with PEGV. GHR genotype was assessed using genomic DNA in 104 patients.ResultsD3-GHR was observed in 51 (49.0%) of the patients (7.7% homozygous, 41.3% heterozygous) and was in Hardy–Weinberg equilibrium (P=0.859). Baseline characteristics were similar in d3-GHR and full-length (fl)-GHR genotypes. During PEGV/LA-SRIF treatment IGF1 levels were not different between d3-carriers and non-carriers. Similarly, no difference in PEGV dose required to normalize IGF1 (P=0.337) or PEGV serum levels (P=0.433) was observed between the two groups. However, adenoma size decreased significantly (>20% of largest diameter) in 25.6% of the fl-GHR genotype but only in 7.5% of d3-carriers (P=0.034, OR: 4.6 (CI: 1.1–18.9)).ConclusionsGHR genotype does not predict the IGF1 normalizing dose of PEGV in acromegaly patients using combination PEGV/LA-SRIF treatment. However, fewer d3-carriers showed significant reductions in adenoma size.

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.

Hepatoprotective Role of Green Tea, (Camellia senesis) Extract on Paracetamol Induced Hepatic Damage in Guinea-Pigs.

2019 ◽  
Vol 1 (1) ◽  
pp. 44-54
Author(s):  
Rita Oze ◽  
P. Nwankpa ◽  
Gabriel Oze ◽  
Harrison Nwanjo
Keyword(s):  
Green Tea ◽  
Guinea Pigs ◽  
Serum Levels ◽  
Scientific Basis ◽  
Negative Control ◽  
High Dose ◽  
Group I ◽  
Actual Mechanism ◽  
Aspartate Amino Transferase

Aim: Green tea (Camellia senesis) is consumed because of the belief that it protects against liver related ailments. This study aims at finding the possible scientific basis for this claim. Methodology: Twenty guinea pigs of mixed sexes were divided into 4 experimental groups of 5 animals each. Group I served as a negative control for the liver marker-enzymes, aspartate-amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP). Total bilirubin (TB) and its metabolite, conjugated bilirubin (CB), were also estimated. In group II, a high dose of paracetamol was used to induce hepatotoxicity. In groups III and IV, the hepatotoxcity was challenged with the extract of a green tea at 100 and 200 mg/kg. Results: The results showed that the 100 mg/kg attenuated the serum levels of AST, ALT and ALP by 9.20, 7.30. and 5.10 % respectively. The inhibition of ALT was significant (p<0.05). The 200 mg/kg reduced the levels of the enzymes for AST by 12.00, 9.70 and 5.30% respectively (p>0.05). The serum CB was also significantly reduced by the two doses of the extract (p<0.05). The actual mechanism by which these occurred was not known. Conclusion: The extract of the green tea may possess hepatoprotective effects. Key words: Hepatoprotection. Liver enzymes, Green tea. (Camellia senesis). Guinea- pig

scholarly journals Cyclosporine-A induced nephrotoxicity in male and female rats: Is zinc a suitable protective supplement?

2018 ◽  
Vol 5 (12) ◽  
pp. 2888-2897
Author(s):  
Samira Choopani ◽  
Sayyedehnikta Kasaei ◽  
Ardeshir Talebi ◽  
Mojgan Mortazavi ◽  
Yousef Gheisari ◽  
...  
Keyword(s):  
Kidney Tissue ◽  
Serum Levels ◽  
Female Rats ◽  
Histological Evaluation ◽  
High Dose ◽  
Kidney Transplant Patient ◽  
Male And Female ◽  
Male And Female Rats ◽  
Tissue Damages

Background: Cyclosporine (CYC) is an immunosuppressant drug used widely in kidney transplant patient. The major side effect of CYC is nephrotoxicity. In this study, three different doses of CYC alone or accompanied with zinc (Zn) supplement were administrated in male and female rats to determine the kidney tissue damages and functions. Methods: Male and female rats were treated with 10, 50 or 100 mg/kg/day of CYC alone or accompanied with 10 mg /kg/day of Zn sulfate for 10 days. The parameters related to renal function were determined and the kidney tissues were subjected to histological evaluation. Results: All male and female animals were treated with high dose CYC (100 mg/kg/day) alone or accompanied with Zn supplement during the experiment. The data obtained for the serum levels of creatinine (Cr) and blood urea nitrogen/Cr ratio, clearance of Cr, kidney weight (KW), sodium (Na) filtration rate, Na excretion rate and Na excretion fraction (%) in surviving animals suggest a role of gender in the variation of these factors. The kidney tissue damage score (KTDS) was increased as the dosage of CYC was elevated, and the Zn supplement attenuated the KTDS in animals treated with low dose CYC (10 mg/kg/day). Conclusion: The CYC-induced nephrotoxicity may be gender-related, and the 10 mg/kg dose of Zn sulphate as a supplement may possibly prevent the induced nephrotoxicity in males due to its antioxidant effects.  

scholarly journals Excellent response to pasireotide therapy in an aggressive and dopamine-resistant prolactinoma

2019 ◽  
Vol 181 (2) ◽  
pp. K21-K27 ◽  
Author(s):  
Eva C Coopmans ◽  
Sebastiaan W F van Meyel ◽  
Kay J Pieterman ◽  
Jolique A van Ipenburg ◽  
Leo J Hofland ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Somatostatin Receptor ◽  
Cystic Degeneration ◽  
Tumor Control ◽  
Receptor Subtype ◽  
Cell Necrosis ◽  
New Treatment ◽  
Long Acting ◽  
Somatostatin Receptor Ligand ◽  
Tumor Cell Necrosis

Prolactinomas are the most commonly encountered pituitary adenomas in the clinical setting. While most can be controlled by dopamine agonists, a subset of prolactinomas are dopamine-resistant and very aggressive. In such tumors, the treatment of choice is neurosurgery and radiotherapy, with or without temozolomide. Here, we report a patient with an highly aggressive, dopamine-resistant prolactinoma, who only achieved biochemical and tumor control during pasireotide long-acting release (PAS-LAR) therapy, a second-generation somatostatin receptor ligand (SRL). Interestingly, cystic degeneration, tumor cell necrosis or both was observed after PAS-LAR administration suggesting an antitumor effect. This case shows that PAS-LAR therapy holds clinical potential in selective aggressive, dopamine-resistant prolactinomas that express somatostatin (SST) receptor subtype 5 and appears to be a potential new treatment option before starting temozolomide. In addition, PAS-LAR therapy may induce cystic degeneration, tumor cell necrosis or both in prolactinomas.

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.

scholarly journals Pasireotide: A Novel Treatment for Tumor-Induced Hypoglycemia Due to Insulinoma and Non-Islet Cell Tumor Hypoglycemia

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Mahwash Siddiqui ◽  
Amy Vora ◽  
Sadia Ali ◽  
Jessica Abramowitz ◽  
Sasan Mirfakhraee
Keyword(s):  
Successful Treatment ◽  
Islet Cell ◽  
Somatostatin Receptor ◽  
Islet Cell Tumor ◽  
Somatostatin Analogues ◽  
Cell Tumor ◽  
Novel Treatment ◽  
Tumor Hypoglycemia ◽  
Somatostatin Receptor Ligand ◽  
Biochemical Features

Abstract Tumor-induced hypoglycemia is a serious disorder most commonly caused by insulinoma or non-islet cell tumor hypoglycemia (NICTH). The hypoglycemia can be severe and refractory to conventional therapy, leading to significant morbidity and mortality. The objective of this work is to describe a series of challenging cases in which refractory, tumor-induced hypoglycemia was shown to respond to the use of pasireotide, a second-generation somatostatin receptor ligand. We describe the clinical and biochemical features of 3 patients with tumor-induced hypoglycemia due to an occult insulinoma, malignant insulinoma, and non-islet cell tumor hypoglycemia. In these 3 individuals, the hypoglycemia remained refractory to guideline-recommended medical therapy, such as diazoxide, nonpasireotide somatostatin analogues, and glucocorticoids. Pasireotide was substituted to attenuate the refractory hypoglycemia for each patient. The addition of pasireotide led to prompt improvement in the frequency and severity of hypoglycemic episodes for each tumor-induced hypoglycemia patient. We demonstrate the successful treatment of 3 individuals with refractory, tumor-induced hypoglycemia with pasireotide. We offer the first reported use of pasireotide for the successful treatment of nonmalignant insulinoma and non-islet cell tumor hypoglycemia.

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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