Pegvisomant in acromegaly: an update.

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Term Occurence Count Dictionary
Pasireotide 1 endocrinologydiseasesdrugs
acromegaly 50 endocrinologydiseases
cabergoline 2 endocrinologydiseasesdrugs
hyperglycemia 3 endocrinologydiseases
hyperinsulinemia 1 endocrinologydiseases
ovarian dysfunction 1 endocrinologydiseases
Pegvisomant 1 endocrinologydiseasesdrugs
diabetes mellitus 9 endocrinologydiseases
glucose intolerance 1 endocrinologydiseases
hyperprolactinemia 1 endocrinologydiseases
lipodystrophy 8 endocrinologydiseases
Octreotide 1 endocrinologydiseasesdrugs
gigantism 1 endocrinologydiseases
type 2 diabetes mellitus 1 endocrinologydiseases

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Select Drug Character Offset Drug Term Instance
Octreotide 2419 dopamine agonists, and pegvisomant (PEG), a genetically engineered GH-receptor antagonist [[1]–[3]]. Octreotide and lanreotide, especially in their long-acting formulations, are the most widely used SRL to treat
Pasireotide 17578 acromegaly is not biochemically controlled by the treatment and high doses of analogs are administered (70). Pasireotide , a new somatostatin receptor ligand that has been recently approved for the treatment of acromegaly,
Pegvisomant 48 Title: Journal of Endocrinological Investigation Pegvisomant in acromegaly: an updateA. GiustinaG. ArnaldiF. BogazziS. CannavòA. ColaoL. De MarinisE. De MenisE.
cabergoline 21325 series of 42 acromegalic patients treated with PEG alone (19 cases) or in combination with SRL and/or cabergoline (23 cases). The authors showed that 20 ± 16 months after PEG introduction, left ventricular ejection
cabergoline 26883 lipoatrophy. When all possible treatment associations were analyzed, only the triple association of SRL, cabergoline , and PEG was related to a higher incidence of lipodystrophy (42 vs 11%, p = 0.018). Interestingly,
Select Disease Character Offset Disease Term Instance
acromegaly 63 Title: Journal of Endocrinological InvestigationPegvisomant in acromegaly : an updateA. GiustinaG. ArnaldiF. BogazziS. CannavòA. ColaoL. De MarinisE. De MenisE. Degli UbertiF.
acromegaly 454 2007, we published an opinion document to review the role of pegvisomant (PEG) in the treatment of acromegaly . Since then, new evidence emerged on the biochemical and clinical effects of PEG and on its long-term
acromegaly 833 of PEG is still suboptimal, considering that it remains the most powerful tool to control IGF-I in acromegaly allowing to obtain, with a pharmacological treatment, the most important clinical effects in terms of
acromegaly 1029 effects in terms of signs and symptoms, quality of life and comorbidities. The number of patients with acromegaly exposed to PEG worldwide has become quite elevated and the prolonged follow-up allows now to deal quite
acromegaly 1590 of somatostatin receptor ligands (SRL) resistance has been addressed, in order to better define the acromegaly patients to whom the PEG option may be offered.ConclusionsPEG increasingly appears to be an effective
acromegaly 2530 and lanreotide, especially in their long-acting formulations, are the most widely used SRL to treat acromegaly ; they have shown to normalize GH and IGF-I levels in about half of patients and reduce tumor mass in
acromegaly 3148 level and thereby lowering IGF-I production and ameliorating the clinical features associated with acromegaly . In the case of PEG, serum IGF-I is the sole biomarker of drug efficacy [[1], [2], [8]]. PEG has been
acromegaly 3278 PEG, serum IGF-I is the sole biomarker of drug efficacy [[1], [2], [8]]. PEG has been shown to control acromegaly in 60–90% of patients across several clinical trials [[9]–[18]]. In Europe, PEG was approved in
acromegaly 3749 subjects [[20]].In 2007, we published an opinion document to review the role of PEG in the treatment of acromegaly [[21]]. Since then, new evidence emerged on the biochemical and clinical effects of PEG and on its long-term
acromegaly 5230 treatment [[9], [24], [25]]. In more recent studies, in the real life setting, the rate of disease control acromegaly was lower, not exceeding 65–70% [[13], [26]–[28]]. This lower than expected efficacy, observed especially
acromegaly 7897 in combination with SRL [[19], [39]]. A significant role for d3GHR in the biochemical monitoring of acromegaly after surgery is also debated [[40]–[42]].Serum GH levels are not a useful marker of PEG efficacy
acromegaly 10921 on clinical symptoms and signs, and on quality of lifeRecent improvement in the medical treatment of acromegaly has resulted in better biochemical disease control [[49]–[51]]. Normalization of both GH and IGF-I
acromegaly 11094 [[49]–[51]]. Normalization of both GH and IGF-I levels was demonstrated to restore normal life expectancy in acromegaly patients. However, biochemical control does not necessarily relieve all symptoms [[52], [53]]. To quantify
acromegaly 11267 relieve all symptoms [[52], [53]]. To quantify the symptoms and the perceived health in patients with acromegaly , the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) and the Acromegaly Quality of Life Questionnaire
acromegaly 11519 [[52]–[54]]. In particular, the PASQ score is a disease-specific tool that rates five features of acromegaly : headache, excessive perspiration, arthralgia, fatigue, and soft tissue swelling [[52]]. On the other
acromegaly 12033 possibly require further treatment. Both treatments with SRL and PEG showed to be effective in reducing acromegaly signs’ and symptoms’ total scores, and improving health-related quality of life (QoL) [[55]–[57]].
acromegaly 13101 Subsequently, many other studies [[25], [59]–[61]] have demonstrated a significant improvement in acromegaly -related QoL, and clinical signs and symptoms in patients treated with PEG in monotherapy or in combination
acromegaly 15822 state.Taken altogether, these data suggest that the normalization of IGF-I may induce an improvement in most acromegaly -related symptoms and QoL. However, normalization of clinical picture from the patient’s perspective
acromegaly 16158 combined with SRL in larger series of patients.Effect on comorbiditiesGlucose and lipid metabolismIn acromegaly , abnormal glucose tolerance, hyperinsulinemia, and diabetes mellitus are frequently observed; these
acromegaly 16734 effects have a negative impact on insulin action, reducing insulin sensitivity [[68]]. Treatment of acromegaly may influence glucose metabolism in different ways. It is known that SRL inhibit insulin secretion,
acromegaly 16967 unpredictable impact on glucose homeostasis [[68]]. This effect may potentially impair glucose homeostasis in acromegaly , especially in patients with pre-existing glucose intolerance or type 2 diabetes. Indeed, there is evidence
acromegaly 17470 glycometabolic effect may be observed in some patients treated with conventional SRL, especially when acromegaly is not biochemically controlled by the treatment and high doses of analogs are administered (70).Pasireotide,
acromegaly 17679 (70).Pasireotide, a new somatostatin receptor ligand that has been recently approved for the treatment of acromegaly , binds with higher affinity than octreotide and lanreotide to somatostatin receptor subtype 5, which
acromegaly 18083 response, with minimal inhibition of glucagon secretion and no impact on insulin sensitivity [[72]]. In acromegaly , pasireotide was shown to cause hyperglycemia and diabetes more frequently than octreotide LAR, even
acromegaly 18230 hyperglycemia and diabetes more frequently than octreotide LAR, even in patients with better-controlled acromegaly [[73]]. Conversely, PEG therapy has been reported to have more favorable effects on glucose homeostasis
acromegaly 21998 values, in hypertensive patients [[51]].Respiratory disorders are frequent complications in patients with acromegaly , with a potential impact on both morbidity and mortality [[88]]. The most frequent respiratory complication
acromegaly 22120 potential impact on both morbidity and mortality [[88]]. The most frequent respiratory complication of acromegaly is the obstructive sleep apnoea syndrome (OSAS) with a prevalence up to 80% of patients at diagnosis
acromegaly 22279 with a prevalence up to 80% of patients at diagnosis [[88]–[90]]. The pathogenesis of the OSAS in acromegaly is complex, including systemic as well as local effects of GH and IGF-I excess, such as alterations
acromegaly 22554 airways, and macroglossia. The relationship between activity of the disease and severity of OSAS in acromegaly is controversial: studies have shown either a positive or no correlation between serum GH and IGF-I
acromegaly 22751 GH and IGF-I levels and indices of sleep apnoea [[90]–[93]]. The impact of medical therapies for acromegaly on the prevalence and the severity of OSAS is not clear, although some studies reported an improvement
acromegaly 23002 control of disease was achieved by SRL [[94], [95]].The effect of PEG on respiratory complications of acromegaly has been evaluated in two studies including a small number of patients [[81], [96]]. In one study, twelve
acromegaly 23146 including a small number of patients [[81], [96]]. In one study, twelve subjects with uncontrolled acromegaly under SRL were evaluated using polysomnography and MRI of the tongue before and 6 months after the
acromegaly 24083 with the GH-antagonist, alone or associated with other treatments, on the systemic comorbidities of acromegaly [[81]]. The results of this study were consistent with those of the previous study, showing a significant
acromegaly 24351 of the sleep apnoea after the introduction of PEG and the improvement of the biochemical control of acromegaly .Overall, the results of these two studies suggest a positive impact of PEG therapy on the severity of
acromegaly 24572 larger prospective studies are needed to evaluate the impact of PEG on the incidence of OSAS.BoneIn acromegaly , there is an increase in the risk of vertebral fractures [[97]], which is not necessarily associated
acromegaly 24926 Long-term treatment with PEG also induced a significant increase of bone mineral density in active acromegaly [[101]]. Although PEG use was weakly associated with an increased rate of fractures, this has been attributed
acromegaly 25596 mellitus, the common polymorphism (UGT1A1) of Gilbert’s syndrome, and male sex [[47]]. Of the 341 acromegaly patients included in the Italian ACROSTUDY, liver test abnormalities (>3 × ULN of ALT and AST,
acromegaly 27904 be trained to frequently change the site of injection.Reproductive system and pregnancyIn women with acromegaly , reproductive disorders, including menstrual abnormalities, galactorrhoea, and decreased libido, are
acromegaly 28112 are commonly reported, occurring in 40–80% of patients [[107]–[110]]. In particular, women with acromegaly often present with menstrual irregularity, mainly oligo-amenorrhea, associated with anovularity and
acromegaly 29126 approximately 100 pregnancies have been described in literature [[112]]. Consequently, the management of acromegaly during pregnancy has to be precisely defined and the benefit-to-risk profile of the different treatment
acromegaly 31121 [[120]] reported the first case in the literature of a 29-year-old woman with previously uncontrolled acromegaly , that conceived at her first cycle of in vitro fertilization and intra-cytoplasmic sperm injection,
acromegaly 31661 delivered. Subsequently, Brian et al. [[121]] reported a case of a 26-year-old female with uncontrolled acromegaly , despite surgery, DA, and SRL therapy. After IGF-I normalization with PEG monotherapy, the patient conceived
acromegaly 32701 data available to date, which seem not to suggest adverse consequences of PEG on pregnancy outcome in acromegaly . In particular, they reviewed data on 35 pregnancy outcomes of acromegalic patients exposed to PEG included
acromegaly 33968 the use of PEG during pregnancy is not recommended unless absolutely clinical necessary (i.e., severe acromegaly -related diabetes, or cardio-respiratory complications in SRL-resistant patients). The potential fetal
acromegaly 36417 aspect turns out to be particularly important because the delay between the onset and the diagnosis of acromegaly has not been reduced in the last decades [[132]], and such a diagnostic delay requires rapid normalization
acromegaly 40700 with diabetes mellitus.ConclusionsThis review focuses on some emerging aspects of the management of acromegaly with particular reference to their impact on the clinical use of PEG which may be considered still suboptimal.
acromegaly 40886 may be considered still suboptimal. In fact, PEG remains the most powerful tool to control IGF-I in acromegaly and therefore the medical treatment through which we can obtain the most important clinical effects
acromegaly 41350 effects. From the review of the most current literature, it appears that the number of patients with acromegaly exposed to PEG worldwide has become quite elevated and their prolonged follow-up allows us to deal quite
acromegaly 42007 PEG on glucose metabolism has been highlighted as it may indicate PEG as the best medical option in acromegaly patients with diabetes mellitus. We have also reviewed some aspects of the treatment with PEG which
acromegaly 42346 case, although the very limited published material is reassuring, PEG use remains not indicated in acromegaly patients undergoing pregnancy. Finally, in an attempt to adequately define all the patients to whom
diabetes mellitus 2936 than octreotide LAR, but to be associated with a greater frequency and degree of hyperglycemia and diabetes mellitus [[6], [7]].PEG has a unique mechanism of action, antagonizing endogenous GH at the GH receptor level
diabetes mellitus 7038 exhibits a favorable effect on the glycemic profile and can be useful in acromegalic patients with diabetes mellitus [[21]]. However, the rate of IGF-I normalization is reduced in patients with diabetes mellitus (64%
diabetes mellitus 7133 with diabetes mellitus [[21]]. However, the rate of IGF-I normalization is reduced in patients with diabetes mellitus (64% in diabetic vs 75% in non-diabetic patients), and higher PEG doses are necessary to control the
diabetes mellitus 16220 comorbiditiesGlucose and lipid metabolismIn acromegaly, abnormal glucose tolerance, hyperinsulinemia, and diabetes mellitus are frequently observed; these abnormalities contribute to the increase in cardiovascular morbidity
diabetes mellitus 18705 monotherapy, induces a significant decrease in fasting glucose levels also in patients with diagnosed diabetes mellitus and impaired glucose tolerance (IGT); there is also evidence of an improvement in glucose tolerance
diabetes mellitus 19833 SRL on insulin secretion.These findings suggest that in patients resistant to SRL with uncontrolled diabetes mellitus or worsening hyperglycemia, PEG monotherapy may be the first medical option, since it may allow to reach
diabetes mellitus 25487 combined with SRL. Different risk factors for developing LTLE have been hypothesized, such as type 2 diabetes mellitus , the common polymorphism (UGT1A1) of Gilbert’s syndrome, and male sex [[47]]. Of the 341 acromegaly
diabetes mellitus 40605 pasireotide might be an alternative option, though high-dose SRL should be preferred in those with diabetes mellitus .ConclusionsThis review focuses on some emerging aspects of the management of acromegaly with particular
diabetes mellitus 42032 has been highlighted as it may indicate PEG as the best medical option in acromegaly patients with diabetes mellitus . We have also reviewed some aspects of the treatment with PEG which are less frequently dealt with,
gigantism 35234 alterations as observed in patients bearing AIP gene mutations or the newly discovered X-linked acro gigantism [[127]].To define the therapeutic efficacy of SRL treatment, the effects on both GH/IGF-1 secretion
glucose intolerance 17020 may potentially impair glucose homeostasis in acromegaly, especially in patients with pre-existing glucose intolerance or type 2 diabetes. Indeed, there is evidence that currently available SRL, lanreotide autogel (ATG),
hyperglycemia 2918 biochemical disease control than octreotide LAR, but to be associated with a greater frequency and degree of hyperglycemia and diabetes mellitus [[6], [7]].PEG has a unique mechanism of action, antagonizing endogenous GH at
hyperglycemia 18126 secretion and no impact on insulin sensitivity [[72]]. In acromegaly, pasireotide was shown to cause hyperglycemia and diabetes more frequently than octreotide LAR, even in patients with better-controlled acromegaly
hyperglycemia 19864 findings suggest that in patients resistant to SRL with uncontrolled diabetes mellitus or worsening hyperglycemia , PEG monotherapy may be the first medical option, since it may allow to reach the combined objective
hyperinsulinemia 16198 patients.Effect on comorbiditiesGlucose and lipid metabolismIn acromegaly, abnormal glucose tolerance, hyperinsulinemia , and diabetes mellitus are frequently observed; these abnormalities contribute to the increase in cardiovascular
hyperprolactinemia 28349 Hypopituitarism or a direct action of GH and IGF-I excess on the pituitary–gonadal axis or the co-existence of hyperprolactinemia due to mass effect or to prolactin hypersecretion by the tumor have been proposed as potential mechanisms
lipodystrophy 26475 due to local GH lipolysis inhibition [[18], [26], [103]–[106]].In 1288 patients of the ACROSTUDY, lipodystrophy was reported as a minor side effect with a very low prevalence (1.4%) [[26]]. However, a recent multicentre
lipodystrophy 26662 [[26]]. However, a recent multicentre retrospective study involving 19 Spanish centers [[18]] reported lipodystrophy development in 15% of patients (15/97), mostly females. Fourteen patients had lipohypertrophy and one
lipodystrophy 26941 analyzed, only the triple association of SRL, cabergoline, and PEG was related to a higher incidence of lipodystrophy (42 vs 11%, p = 0.018). Interestingly, lipodystrophy did not depend on PEG dose, but there was a
lipodystrophy 26998 and PEG was related to a higher incidence of lipodystrophy (42 vs 11%, p = 0.018). Interestingly, lipodystrophy did not depend on PEG dose, but there was a significant relationship between the grade of lipodystrophy
lipodystrophy 27102 lipodystrophy did not depend on PEG dose, but there was a significant relationship between the grade of lipodystrophy and escape from PEG, defined as loss of biochemical control in a patient who was previously controlled
lipodystrophy 27283 patient who was previously controlled (p = 0.019). This observation suggests that the presence of lipodystrophy might influence the response to treatment. The female prevalence, observed also in previous studies
lipodystrophy 27576 tissue or to a gender-specific adipocyte response. Only few patients discontinued treatment due to lipodystrophy . Generally, lipohypertrophy regressed in all patients after medication was discontinued.Overall, in
lipodystrophy 27769 discontinued.Overall, in patients receiving PEG, injection sites should be monitored for early signs of lipodystrophy and patients should be trained to frequently change the site of injection.Reproductive system and pregnancyIn
ovarian dysfunction 28531 have been proposed as potential mechanisms for the impairment in gonadotropin secretion, leading to ovarian dysfunction and consequent infertility [[108]–[110]]. Moreover, IGF-I excess was found to be associated with polycystic
type 2 diabetes mellitus 25480 PEG was combined with SRL. Different risk factors for developing LTLE have been hypothesized, such as type 2 diabetes mellitus , the common polymorphism (UGT1A1) of Gilbert’s syndrome, and male sex [[47]]. Of the 341 acromegaly

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