scholarly journals Diagnosis and Management of Acromegaly in 2012

2011 ◽  
Vol 07 (02) ◽  
pp. 121 ◽  
Author(s):  
Laurence Katznelson ◽  
Keyword(s):  
Tumor Growth ◽  
Medical Therapy ◽  
De Novo ◽  
Therapeutic Option ◽  
Somatostatin Analogs ◽  
Premature Mortality ◽  
Gh Secretion ◽  
Gh Receptor Antagonist ◽  
Failed Surgery ◽  
Multimodality Approach

Acromegaly is an insidious disease that, in most cases, is a result of a pituitary adenoma that hypersecretes growth hormone (GH). The goals of therapy are to control excess GH secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk of premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Medical therapy, including somatostatin analogs, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for de novo patients has been proposed, particularly with somatostatin analogs. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.

Diagnosis and Management of Acromegaly in 2014 (Update from 2012)

2014 ◽  
Vol 10 (02) ◽  
pp. 120
Author(s):  
Laurence Katznelson ◽  
Keyword(s):  
Tumor Growth ◽  
Medical Therapy ◽  
De Novo ◽  
Therapeutic Option ◽  
Somatostatin Receptor ◽  
Premature Mortality ◽  
Gh Secretion ◽  
Gh Receptor Antagonist ◽  
Multimodality Approach ◽  
Somatostatin Receptor Ligand

In this update to the 2012 summary, the current diagnostic and therapeutic approaches to acromegaly are reviewed. The goals of therapy are to control excess growth hormone (GH) secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk for premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Use of a somatostatin receptor ligand (SRL) preoperatively to improve surgical outcomes has not been substantiated. Medical therapy, including SRLs, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for de novo patients has been proposed, particularly with SRLs. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.

Diagnosis and Management of Acromegaly in 2012

2010 ◽  
Vol 8 (1) ◽  
pp. 48
Author(s):  
Laurence Katznelson ◽  
Keyword(s):  
Medical Therapy ◽  
De Novo ◽  
Therapeutic Option ◽  
Premature Mortality ◽  
Somatostatin Analogues ◽  
Gh Secretion ◽  
Gh Receptor Antagonist ◽  
Failed Surgery ◽  
Multimodality Approach

Acromegaly is an insidious disease that, in most cases, is a result of a pituitary adenoma that hypersecretes growth hormone (GH). The goals of therapy are to control excess GH secretion and tumour growth, and to limit, if not reverse, the long-term medical consequences and risk of premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Medical therapy, including somatostatin analogues, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for de novo patients has been proposed, particularly with somatostatin analogues. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.

Diagnosis and Management of Acromegaly in 2014 (Update from 2012)

2015 ◽  
Vol 11 (1) ◽  
pp. 120
Author(s):  
Laurence Katznelson, MD ◽  
Keyword(s):  
Tumor Growth ◽  
Medical Therapy ◽  
De Novo ◽  
Therapeutic Option ◽  
Somatostatin Receptor ◽  
Premature Mortality ◽  
Gh Secretion ◽  
Gh Receptor Antagonist ◽  
Multimodality Approach ◽  
Somatostatin Receptor Ligand

In this update to the 2012 summary, the current diagnostic and therapeutic approaches to acromegaly are reviewed. The goals of therapy are to control excess growth hormone (GH) secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk for premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Use of a somatostatin receptor ligand (SRL) preoperatively to improve surgical outcomes has not been substantiated. Medical therapy, including SRLs, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy forde novopatients has been proposed, particularly with SRLs. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.

scholarly journals Acromegaly: A New Therapy

2002 ◽  
Vol 9 (3) ◽  
pp. 232-235 ◽  
Author(s):  
Keith E. Friend
Keyword(s):  
Dopamine Agonists ◽  
Serum Insulin ◽  
Therapeutic Option ◽  
Somatostatin Analogs ◽  
Treatment Modalities ◽  
Pharmacological Agents ◽  
Gh Receptor ◽  
Igf I ◽  
Gh Receptor Antagonist ◽  
Multimodality Approach

Background The treatment of acromegaly can be challenging. Despite a multimodality approach (surgery, radiation, dopamine agonists, somatostatin analogs), many patients do not achieve normalization of serum insulin-like growth factor I (IGF-I) concentrations. Methods The author discusses the characteristics and indications of pegvisomant therapy for patients with acromegaly and compares the use of this newly developed GH receptor antagonist with other pharmacological agents such as somatostatin and dopamine agonists. Results Therapy with pegvisomant allows serum IGF-I concentrations to be normalized in up to 97% of patients with acromegaly, including those who have failed other treatment modalities. With this agent, circulating GH levels increase as a result of the drop in IGF-I levels. The rise is rapid (within 2 weeks) and does not appear to be progressive over time. Conclusions Published studies have shown pegvisomant to have efficacy in the treatment of acromegaly. As it appears to be well tolerated and safe, this novel compound may be an important therapeutic option for patients with acromegaly. Additional study of this novel agent and its mode of action is warranted.

Medical Therapy of Acromegaly in Germany 2019 – Data from the German Acromegaly Registry

2020 ◽  
Author(s):  
Marcus Quinkler ◽  
David Petroff ◽  
Ulrich J. Knappe ◽  
Jochen Schopohl ◽  
Anke Tönjes ◽  
...  
Keyword(s):  
Medical Therapy ◽  
Somatostatin Analogs ◽  
Agonist Therapy ◽  
Second Line Therapy ◽  
Gh Secretion ◽  
Gh Receptor ◽  
Dopamine Agonist Therapy ◽  
Line Therapy ◽  
Retrospective Data Analysis ◽  
Medical Regimens

Abstract Context Acromegaly is a rare disease caused by excessive growth hormone (GH) secretion from pituitary adenomas in most cases. If neurosurgical therapy is contraindicated or not sufficient, medical therapy is the second line therapy. Objective To describe current medical therapy in acromegaly. Design & Methods Retrospective data analysis from 2732 patients treated in 69 centers of the German Acromegaly Registry. 749 patients were seen within the recent 18 months, of which 420 were on medical therapy (56.1%). Results 73% of medically treated acromegalic patients had normal/low IGF-1 levels. 57% of patients with non-normalized IGF-1 levels had an IGF-1 value between 1- and 1.25-fold above the upper limit of normal. Most patients (55%) received somatostatin analogs as monotherapy, 12% GH receptor monotherapy, and 9% dopamine agonist therapy. Doses of each medical therapy varied widely, with 120 mg lanreotide LAR every 4 weeks, 30 mg octreotide LAR every 4 weeks, 140 mg pegvisomant per week and 1mg cabergoline per week being the most frequent used regimens. A combination of different medical regimens was used in almost 25% of the patients. Conclusion The majority of German acromegalic patients receiving medical therapy are controlled according to normal IGF-1 levels.

scholarly journals Ghrelin Receptor (GHS-R1a) and Its Constitutive Activity in Somatotroph Adenomas: A New Co-targeting Therapy Using GHS-R1a Inverse Agonists and Somatostatin Analogs

2014 ◽  
Vol 99 (12) ◽  
pp. E2463-E2471 ◽  
Author(s):  
Yves Mear ◽  
Marie-Pierre Blanchard ◽  
Céline Defilles ◽  
Thierry Brue ◽  
Dominique Figarella-Branger ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Inverse Agonist ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Constitutive Activity ◽  
Targeting Therapy ◽  
Ghrelin Receptor ◽  
Gh Secretion

Context: The ghrelin receptor GHS-R1a is highly expressed in human somatotroph adenomas and exhibits unusually high basal signaling activity. In humans, the suppression of this constitutive activity by mutation induces a short stature. Objective: Using a GHS-R1a inverse agonist, modified substance P (MSP), we explored the role of GHS-R1a constitutive activity in GH hypersecretion from somatotroph adenomas and as a putative therapeutic target. Design: The effects of MSP were assessed on GH secretion from 19 human somatotroph tumors in vitro. Moreover, these effects were compared with those of octreotide (somatostatin receptor subtype 2 [sst2] agonist) and with the combination of both drugs. Expression and localization of GHS-R1a and sst2 were studied. Results: For all tumors, MSP inhibited GH secretion in a dose-dependent manner from 13 to 64%. Moreover, MSP enhanced octreotide-induced GH inhibition. For five tumors, the effects of combined MSP plus octreotide treatment were significantly higher than the sum of effects of each drug alone. MSP increased the membrane localization of GHS-R1a and of microdomains colocalizing sst2-GHS-R1a, highlighting the cooperation between the two drugs. Conclusions: The GHS-R1a inverse agonist could open new therapeutic options for acromegalic patients, particularly patients partially sensitive to octreotide whose GH secretion is not completely controlled by the sst2 agonist.

scholarly journals Sunitinib achieved fast and sustained control of VIPoma symptoms

2015 ◽  
Vol 172 (1) ◽  
pp. K1-K3 ◽  
Author(s):  
Louis de Mestier ◽  
Thomas Walter ◽  
Hedia Brixi ◽  
Catherine Lombard-Bohas ◽  
Guillaume Cadiot
Keyword(s):  
Quality Of Life ◽  
Tyrosine Kinase ◽  
Targeted Therapies ◽  
Therapeutic Option ◽  
Somatostatin Analogs ◽  
Watery Diarrhea ◽  
Tyrosine Kinase Receptors ◽  
Secretory Pathways ◽  
Discharge From Hospital

VIPomas are rare-functioning neuroendocrine tumors (NETs). Overproduction of vasointestinal peptide (VIP) leads to the Verner–Morrison syndrome, whose management is challenging when refractory to somatostatin analogs. Two patients with progressive metastatic pancreatic NETs and refractory VIPoma symptoms were treated with sunitinib. This led to fast and sustained total relief of VIPoma symptoms, enabling earlier discharge from hospital and improvement in their quality of life. In both cases, sunitinib discontinuation led to the quick recurrence of watery diarrhea, which resolved within a few days after reintroducing sunitinib. The anti-secretory effect of sunitinib on VIPoma syndrome was probably not related to any anti-tumor effect. These observations agree with the rare reported cases of anti-secretory effects with targeted therapies. The sunitinib-driven inhibition of multiple-tyrosine kinase receptors might act on secretory pathways and describe sunitinib's ability to improve VIPoma symptoms. Sunitinib could be a therapeutic option to control refractory VIPoma symptoms in patients with NETs.

572 Fibroblast activating protein (FAP)-targeting IL-12 (anti-FAP/IL-12) TMEkine™ potentiates anti-cancer effects in preclinical cancer models

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A606-A606
Author(s):  
Donggeon Kim ◽  
Dahea Lee ◽  
Soomin Ryu ◽  
Yeongseon Byeon ◽  
Kyoung-Ho Pyo ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Solid Tumor ◽  
Immune Modulation ◽  
Therapeutic Option ◽  
Complete Response ◽  
Tumor Burden ◽  
Tumor Growth Inhibition ◽  
Durable Response ◽  
Anti Cancer ◽  
Nih 3T3

BackgroundAlthough cancer immunotherapy showed promising results in hematological malignancies, it has come up with relatively low tumor response for many solid tumors partly due to immune-suppressive tumor microenvironment (TME). Because of the immune-suppressive nature of TME, TME has been an active area of research and therapeutic target for restoring immune system and subsequent tumor growth inhibition. Among the many components in TME, cancer-associated fibroblasts (CAFs) are one of the key cell components of TME where one of the promising solid-tumor TME marker, fibroblast-activating protein (FAP) is highly expressed. Here we have developed an antibody-cytokine fusion protein from our TMEkine™ platform containing anti-FAP and IL-12. Our TMEkine™ (anti-FAP-IL-12) molecule induced strong anti-cancer effects in preclinical solid tumor models by immune-modulation.MethodsIL-12 cytokine was mutated in TMEkine™ (anti-FAP-IL-12) to reduce systemic toxicity and its binding affinity was tested to FAP and IL-12 receptor. The anti-tumor activity of anti-FAP-IL-12 was investigated on CT26 (murine colorectal cancer) syngeneic mouse models with/without NIH-3T3 (murine fibroblast). Additionally, mice showing complete response after anti-FAP-IL-12 administration were re-injected CT26 with/without 4T1 cells for re-challenge study to monitor long-term durable response generated from the initial immune activation.ResultsWe showed that TMEkine™ (anti-FAP-IL-12) interacts with FAP and IL-12 receptor. IL-12 activity was attenuated by our IL-12 mutants. We also showed that TMEkine™ (anti-FAP-IL-12) induced IFN-γ from primary human T cells and NK cells. TMEkine™ (anti-FAP-IL-12) administration resulted in significant reduction of the tumor burden in both CT26+NIH-3T3/FAP+ and CT26/FAP+ models. In the re-challenge experiments, CT26 tumor growth was inhibited significantly compared to 4T1 tumor suggesting memory immune response was generated in TMEkine™ (anti-FAP-IL-12) treated mice.ConclusionsThese findings provide evidences that the treatment of anti-FAP/IL-12 TMEkine™ induced anti-cancer effects without serious adverse effects. Anti-FAP/IL-12 has a strong potential to provide a therapeutic option for cancer-specific immunomodulator and cancer cell eradication.

scholarly journals Extra-hepatic Acromegaly

2013 ◽  
Vol 09 (01) ◽  
pp. 66
Author(s):  
Sanne E Franck ◽  
Aart Jan van der Lely ◽  
Sebastian Neggers ◽  
◽  
◽  
...  
Keyword(s):  
Growth Hormone ◽  
Serum Insulin ◽  
Somatostatin Analogs ◽  
Normal Serum ◽  
Gh Receptor ◽  
Level Increase ◽  
Gh Receptor Antagonist ◽  
Extrahepatic Tissues ◽  
High Doses ◽  
The Impact

After the introduction of somatostatin analogs (LA-SMSA) and the growth hormone (GH) receptor antagonist, pegvisomant (Peg-v) normal serum insulin-like growth factor-1 (IGF-1) concentrations in virtually every patients with acromegaly is possible. The impact of these products on the GH–IGF1 axis is completely different. We advocate that LA-SMSA may normalize serum IGF1 levels in the presence of elevated GH actions in extrahepatic tissues. This results in persistent peripheral disease activity that we call ‘extra-hepatic acromegaly’. Peg-v competitively blocks systemic GH action and results in a GH serum level increase. Therefore high doses of Peg-v are necessary to control IGF-1. Since the mode of action differs between these products, it is questionable if identical IGF-1 levels, during Peg-v or LA-SMSA are really identical representations of the biochemical situation. With the traditional biomarkers medical treatment is therefore difficult to monitor with the traditional biomarkers. Additionally, Peg-v and LA-SMSA could be ideal combination since they have different mode of actions. We believe that the time has come to challenge the existing concepts of treatment and monitoring of patients with acromegaly.

scholarly journals Differential gene expression in patients with anal fistula reveals high levels of prolactin recepetor

2017 ◽  
Vol 74 (5) ◽  
pp. 456-462
Author(s):  
Yi-Huan Song ◽  
Jian-Ming Qiu ◽  
Guan-Gen Yang ◽  
Dong Wang ◽  
A-Li Lin ◽  
...  
Keyword(s):  
Anal Fistula ◽  
De Novo ◽  
Therapeutic Option ◽  
Differentially Expressed Gene ◽  
Staining Intensity ◽  
Independent Effect ◽  
Anal Fistulas ◽  
Mediators Of Inflammation ◽  
Differential Expression Profile ◽  
Complex Cases

Background/Aim. There are limited data examining variations in the local expression of inflammatory mediators in anal fistulas where it is anticipated that an improved understanding of the inflammatory milieu might lead to the potential therapeutic option of instillation therapy in complicated cases. The aim of the present study was to examine prolactin receptors (PRLR) as inflammatory markers and to correlate their expression with both the complexity of anal fistulas and the likelihood of fistula recurrence. Methods. Microarray was used to screen the differentially expressed gene profile of anal fistula using anal mucosa samples with hemorrhoids with ageand sex-matched patients as controls and then a prospective analysis of 65 patients was conducted with anal fistulas. PRLR immunohistochemistry was performed to define expression in simple, complex and recurrent anal fistula cases. The quantitative image comparison was performed combining staining intensity with cellular distribution in order to create high and low score PRLR immunohistochemical groupings. Results. A differential expression profile of 190 genes was found. PRLR expression was 2.91 times lower in anal fistula compared with control. Sixty-five patients were assessed (35 simple, 30 complex cases). Simple fistulas showed significantly higher PRLR expression than complex cases with recurrent fistulae showing overall lower PRLR expression than de novo cases (p = 0.001). These findings were reflected in measurable integrated optical density for complex and recurrent cases (complex cases, 8.31 ? 4.91 x 104 vs simple cases, 12.30 ? 6.91 x 104; p < 0.01; recurrent cases, 7.21 ? 3.51 x 104 vs primarily healing cases, 8.31 ? 4.91 x 104; p < 0.05). In univariate regression analysis, low PRLR expression correlated with fistula complexity; a significant independent effect maintained in multivariate analysis odds ratio [(OR) low to high PRLR expression = 9.52; p = 0.001)]. Conclusion. PRLR expression inversely correlates with anal fistula complexity. Further work must define the specificity of this finding and its relationship to other conventional mediators of inflammation.

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