scholarly journals Acromegaly: recent progress in diagnostics and treatment

2011 ◽  
Vol 57 (1) ◽  
pp. 46-59 ◽  
Author(s):  
N N Molitvoslovova
Keyword(s):  
Recent Progress ◽  
New Technologies ◽  
Somatostatin Analogs ◽  
Normal Range ◽  
Gh Receptor ◽  
Modern Methods ◽  
Igf I ◽  
Gh Receptor Antagonist ◽  
Serious Disease ◽  
Long Acting

Acromegaly is a serious disease with different complications leads to reduced life expectancy and increase mortality. Only early diagnosis and modern methods of management of disease lead to remission. According to consensus on criteria for cure of acromegaly (2010) the measurement of GH and age-matched total IGF-I concentrations are the most important biochemical variables for the diagnosis of acromegaly and for monitoring progression or treatment response. The optimal disease control is now defined as IGF-I level in the age – adjusted normal range, random GH levels less than 1,0 µg/liter and nadir GH level during OGTT less than 0,4 µg/liter. MRI with use a contract substance is the best method of adenoma visualization. The trassphenoidal surgery with new technologies (endoscope, intraoperative blood sampling, neuronavigation, intraoperative MRI), radiosurgery, modern medical treatment (multiligand long-acting somatostatin analogs, GH receptor antagonist) are effective modalities for treatment of acromegaly, which elaborated last decades.

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.

scholarly journals A comparison between octreotide-LAR and lanreotide-SR in the chronic treatment of acromegaly

1999 ◽  
pp. 267-271 ◽  
Author(s):  
R Cozzi ◽  
D Dallabonzana ◽  
R Attanasio ◽  
M Barausse ◽  
G Oppizzi
Keyword(s):  
Chronic Treatment ◽  
Somatostatin Analogs ◽  
Somatostatin Analog ◽  
Normal Range ◽  
First Line ◽  
Hormonal Change ◽  
Upper Limit ◽  
Igf I ◽  
Long Acting ◽  
Active Disease

BACKGROUND: At present long-acting somatostatin analogs represent the first-line medical treatment of acromegaly. These drugs produce stable suppression of GH in most sensitive patients and IGF-I normalization in many; they also increase the compliance of acromegalic patients. The recent availability of octreotide (OC)-LAR, a somatostatin analog to be administered at 28-day intervals, has prompted us to compare, in the same group of patients, its effects and those of another somatostatin analog already available, lanreotide-SR (LSR, to be administered at 14-day intervals). PATIENTS: Twelve somatostatin analog-sensitive acromegalic patients with active disease were enrolled in a prospective open sequential study after giving their informed consent. After chronic treatment with LSR (6-24 months), the patients were changed to treatment with OC-LAR, without wash-out. LSR had been administered at individually tailored dosages (30 mg i.m. at 7-21-day intervals, median 10 days - every 7 days in seven patients, 10 days in two patients, 14 days in two patients and 21 days in one patient) according to GH and IGF-I responses. Disease stability was obtained, as shown by maximal GH/IGF-I suppression without any significant hormonal change between the last two control measurements. OC-LAR was administered i.m. at 28-day intervals six times at the dosage of 20 mg for the first three times and 10 or 30 mg for the last three times (according to individual GH/IGF-I responses). GH (mean of three, hourly samples) and IGF-I concentrations were evaluated on the same day as each administration of the drug, before its injection. RESULTS: GH and IGF-I values were significantly decreased by LSR treatment. GH decreased from 41.6 +/- 14.6 microg/l (mean +/- s.e.) to 7.2 +/- 1.5 microg/l (P < 0.02), whereas IGF-I values declined from 959 +/- 95 microg/l to 460 +/- 61 microg/l (P < 0.00001), expressed as absolute values, and from 287 +/- 30% to 137 +/- 19% expressed as percentage of the upper limit of normal range (% ULNR). At the end of the last cycle, OC-LAR treatment achieved a significant further suppression both in GH (to 5.1 +/- 1.1 microg/l, P < 0.05 compared with LSR) and in IGF-I concentrations (to 374 +/- 60 microg/l, P<0.05 compared with LSR, and to 112 +/- 19% as % ULNR). LSR decreased GH concentrations to less than 2.5 microg/l in one patient and normalized IGF-I concentrations in four patients. OC-LAR decreased GH concentrations to less than 2.5 microg/l in four patients and normalized or near-normalized IGF-I concentrations (i.e. to < 110% ULNR) in eight patients. CONCLUSIONS: These preliminary results show that the once-monthly OC-LAR administration schedule proved more efficacious than LSR given every 7-21 days, in a greater number of acromegalic patients.

scholarly journals Increasing frequency of combination medical therapy in the treatment of acromegaly with the GH receptor antagonist pegvisomant

2018 ◽  
Vol 178 (4) ◽  
pp. 321-329 ◽  
Author(s):  
Christian J Strasburger ◽  
Anders Mattsson ◽  
Patrick Wilton ◽  
Ferah Aydin ◽  
Judith Hey-Hadavi ◽  
...  
Keyword(s):  
Clinical Care ◽  
Somatostatin Analogues ◽  
Treatment Modalities ◽  
Gh Receptor ◽  
Igf I ◽  
Gh Receptor Antagonist ◽  
Long Acting ◽  
Combination Regimens ◽  
To Receive

Pegvisomant monotherapy is effective and safe in treatment of acromegaly. However, some clinicians combine pegvisomant with somatostatin analogues (SSA) or dopamine agonist (DA). In this analysis of ACROSTUDY, a long-term non-interventional study, the use of combination regimens was evaluated. Based on their baseline treatment, 2043 patients were retrospectively categorized as: long-acting SSA combined with pegvisomant, ‘Combo SSA’ 768 patients (38%); DA combined with pegvisomant, ‘Combo DA’ 123 (6%); pegvisomant monotherapy, ‘Peg mono’ 1128 (55%). Treatment patterns changed over the 10-year period, with recent patients more likely to receive any combination (20% in 2003 vs 54% in 2012). Combo SSA use varied widely among countries from 22% to 78%. Exposure periods of the three treatment modalities were defined from pegvisomant start until the last visit in ACROSTUDY; patients could switch treatment categories. At year 4, IGF-I was normal in 62% of Combo SSA, 63% of Combo DA and 65% of Peg mono groups. Pegvisomant was initiated as daily injections in 94% of patients in the Peg mono group, 66% of Combo SSA and 91% of Combo DA patients. During 6169 years of treatment exposure, 3424 adverse events (AEs) were reported in 946 (51%) patients, of which 617 (18%) were serious and 401 (12%) were considered treatment related. The reported incidence of serious AEs and treatment-related non-serious AEs were similar among the three treatment modalities. This analysis describes real-world clinical care and shows favorable efficacy and safety for Peg mono and combinations. Novel findings include an increased use of combination therapy over time and variability in treatment modalities between countries.

scholarly journals Hypothesis: Extra-hepatic acromegaly: a new paradigm?

2011 ◽  
Vol 164 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Sebastian J Neggers ◽  
John J Kopchick ◽  
Jens O L Jørgensen ◽  
Aart J van der Lely
Keyword(s):  
Medical Treatment ◽  
Therapeutic Response ◽  
Somatostatin Analogs ◽  
Normal Serum ◽  
New Paradigm ◽  
Gh Receptor ◽  
Gh Receptor Antagonist ◽  
Long Acting ◽  
Biochemical Assessment ◽  
Serum Gh

Medical treatment of acromegaly with long-acting somatostatin analogs (LA-SMSA) and the GH receptor antagonist, pegvisomant (PEGV), has made it possible to achieve normal serum IGF1 concentrations in a majority of patients with acromegaly. These two compounds, however, impact the GH–IGF1 axis differently, which challenges the traditional biochemical assessment of the therapeutic response. We postulate that LA-SMSA in certain patients normalizes serum IGF1 levels in the presence of elevated GH actions in extra-hepatic tissues. This may result in persistent disease activity for which we propose the term extra-hepatic acromegaly. PEGV, on the other hand, blocks systemic GH actions, which are not necessarily reliably reflected by serum IGF1 levels, and this treatment causes a further elevation of serum GH levels. Medical treatment is therefore difficult to monitor with the traditional biomarkers. Moreover, the different modes of actions of LA-SMSA and PEGV make it attractive to use the two drugs in combination. We believe that it is time to challenge the existing concepts of treatment and monitoring of patients with acromegaly.

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 Pharmacological approach to the treatment of acromegaly

2004 ◽  
Vol 16 (4) ◽  
pp. 1-4 ◽  
Author(s):  
Shereen Ezzat
Keyword(s):  
Somatostatin Analogs ◽  
Serum Levels ◽  
Clinical Effects ◽  
Pharmacological Agents ◽  
The Past ◽  
Gh Receptor ◽  
Naturally Occurring ◽  
Igf I ◽  
Extended Duration ◽  
Line Of Therapy

The treatment of patients with persistently active acromegaly has been facilitated over the past decade by the advent of highly specific and selective pharmacological agents. Somatostatin analogs, derived from the native inhibitory hormone somatostatin, are available in extended-duration preparations and are effective in reducing serum levels of growth hormone (GH) and insulin-like growth factor–I (IGF-I) as well as in improving the adverse clinical effects of acromegaly. Cabergoline, an agonist with a specificity for the dopamine D-2 receptor, has been shown to suppress IGF-I levels and induce tumor shrinkage in 35 and 50% of patients, respectively. The GH receptor antagonists compete with naturally occurring GH for binding with the GH receptor. As such, pegvisomant normalizes circulating IGF-I levels in 80 to 90% of patients with acromegaly. This last line of therapy should be considered for use in patients in whom surgery and medical therapy with somatostatin and/or dopamine agonists are either ineffective or poorly tolerated.

Growth Hormone Receptor Antagonist Therapy in Acromegalic Patients Resistant to Somatostatin Analogs*

2000 ◽  
Vol 85 (8) ◽  
pp. 2958-2961 ◽  
Author(s):  
Vivien S. Herman-Bonert ◽  
Kenneth Zib ◽  
John A. Scarlett ◽  
Shlomo Melmed
Keyword(s):  
Growth Hormone ◽  
Receptor Antagonist ◽  
Growth Hormone Receptor ◽  
Hormone Secretion ◽  
Somatostatin Analogs ◽  
Growth Hormone Secretion ◽  
Primary Therapy ◽  
Gh Receptor ◽  
Gh Receptor Antagonist ◽  
Octreotide Therapy

Transsphenoidal surgical resection is the primary therapy for acromegaly caused by GH secreting pituitary adenomas. Medical therapy for patients not controlled by surgery includes primarily somatostatin analogs and secondarily dopamine agonists, both of which inhibit pituitary growth hormone secretion. A novel GH receptor antagonist (pegvisomant) binds to hepatic GH receptors and inhibits peripheral insulin-like growth factor-1 generation. Six patients resistant to maximal doses of octreotide therapy received pegvisomant—three received placebo or pegvisomant 30 mg or 80 mg weekly for 6 weeks and three received placebo and pegvisomant 10–20 mg/d for 12 weeks. Thereafter, all patients received daily pegvisomant injections of doses determined by titrating IGF-1 levels. Serum total IGF-1 levels were normalized in all six acromegalic patients previously shown to be resistant to somatostatin analogs via a novel mechanism of peripheral GH receptor antagonism. The GH receptor antagonist is a useful treatment for patients harboring GH-secreting tumors who are resistant to octreotide.

scholarly journals Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: Safety and efficacy evaluation from the German Pegvisomant Observational Study

2007 ◽  
Vol 156 (1) ◽  
pp. 75-82 ◽  
Author(s):  
I Schreiber ◽  
M Buchfelder ◽  
M Droste ◽  
K Forssmann ◽  
K Mann ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Receptor Antagonist ◽  
Signs And Symptoms ◽  
Efficacy Evaluation ◽  
Safety And Efficacy ◽  
Gh Receptor ◽  
Elevated Liver Enzymes ◽  
Igf I ◽  
Gh Receptor Antagonist

Objective: The GH receptor antagonist pegvisomant is a highly effective new treatment option in acromegaly. The German Pegvisomant Observational Study (GPOS) was started to monitor long-term safety and efficacy of pegvisomant as prescribed in clinical practice. Design: GPOS is an observational, multi-center, surveillance study, which comprises non-interventional data collection. Methods: Of the 229 patients included in the study, 90.4% had previous pituitary surgery, 43.2% were treated by radiation therapy, and 94.3% had previous medical therapy for acromegaly that had been discontinued mainly due to persistent IGF-I elevation or side effects. The intention-to-treat population included 177 patients with at least one post-baseline efficacy measurement. Results: IGF-I levels decreased from 1.75±0.91-fold the upper limit of normal at baseline to 1.05± 0.62 at the 6-month visit, 0.96±0.60 at the 12-month visit, and to 0.89±0.41-fold after 24 months (P<0.0001). Mean duration of pegvisomant therapy was 51.8±35.8 weeks (median=51.9 weeks). IGF-I was normalized in 64.4% at 6 months with a median dose of 15.0 mg/day, in 70.9% at 12 months, and in 76.3% at 24 months. Fasting glucose levels improved from 114.4±45.9 to 101.5± 42.8 mg/dl after 6 months (P<0.01) and to 100.6±33.2 mg/ml after 12 months (P<0.01). General physical condition measured by specific signs and symptoms score improved significantly. Adverse events occurring in >1% were injection site reactions in 7.4%, elevated liver enzymes (>3 times of normal) in 5.2% (3.1% spontaneously normalized during continued treatment), reported increase of pituitary tumor volume in 5.2% (which was verified in 3.1%), and headache in 1.7%. Conclusions: Pegvisomant is generally well tolerated with a safety profile similar to that reported in clinical trials and can effectively reduce IGF-I in patients with acromegaly refractory to conventional therapy.

scholarly journals Drug-induced hepatitis in an acromegalic patient during combined treatment with pegvisomant and octreotide long-acting repeatable attributed to the use of pegvisomant

2006 ◽  
Vol 154 (6) ◽  
pp. 805-806 ◽  
Author(s):  
J Feenstra ◽  
M O van Aken ◽  
W W de Herder ◽  
R A Feelders ◽  
A J van der Lely
Keyword(s):  
Adverse Drug Reaction ◽  
Combined Treatment ◽  
Somatostatin Analog ◽  
Acromegalic Patient ◽  
Hepatic Enzyme ◽  
Hepatic Enzymes ◽  
Drug Induced ◽  
Gh Receptor ◽  
Gh Receptor Antagonist ◽  
Long Acting

We report on a patient with acromegaly who developed severe drug-induced hepatitis during combined treatment with the long-acting somatostatin-analog octreotide and the GH receptor antagonist pegvisomant. The hepatic enzyme disturbances normalized after discontinuation of pegvisomant. After rechallenge with monotherapy pegvisomant, however, the hepatic enzyme disturbances reappeared within a few weeks, indicating that most likely pegvisomant alone and not the long-acting somatostatin analog or the combination of these two drugs was responsible for this case of drug-induced hepatitis. Clinicians should be aware of this potential severe adverse drug reaction and therefore frequent control of hepatic enzymes is mandatory during treatment with pegvisomant.

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