Multiple facets in the control of acromegaly

Vilar, Lúcio; Valenzuela, Alex; Ribeiro‐Oliveira, Antônio; Giraldo, Claudia Milena Gómez; Pantoja, Doly; Bronstein, Marcello D.

doi:10.1007/s11102-013-0536-7

Cited by 9 publications

(7 citation statements)

References 46 publications

(91 reference statements)

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“…Metabolic abnormalities, including impaired glucose tolerance and insulin resistance, are increased in acromegaly, contributing to greater risks of diabetes . Furthermore, dyslipidaemia and hypertension are more frequent than in the general population and are associated with an increased incidence of cardiovascular morbidity and mortality . Medical management therefore should correct hormone levels and reduce tumour size without contributing to metabolic impairment.…”

Section: Introductionmentioning

confidence: 99%

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Glucose and lipid levels with lanreotide autogel 120 mg in treatment‐naïve patients with acromegaly: data from the PRIMARYS study

Caron

Petersenn²,

Houchard

et al. 2016

Clinical Endocrinology

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SummaryObjective Impaired glycaemic control, characteristic of acromegaly, can be exacerbated by treatment with somatostatin analogues (SSAs), particularly those with multireceptor activity. We present data from the PRIMARYS study on the impact of the SSA lanreotide, associated with tumour volume and hormonal improvements, on glucose and other metabolic parameters in acromegaly. Design PRIMARYS was a 48-week open-label single-arm phase 3b study of lanreotide autogel 120 mg/4 weeks. A priori and post hoc metabolic profile data are reported for the overall population, patients with/without diabetes and patients achieving/not achieving hormonal control. Patients Treatment-na€ ıve adults with pituitary macroadenoma, mean growth hormone >1 lg/l and elevated insulin-like growth factor-1 levels (n = 90). Measurements Glycaemic parameters [glycated haemoglobin (HbA 1c ) and fasting plasma glucose (FPG) levels] assessed at baseline and weeks 12, 24 and 48. Lipid-profile data (triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) collected at baseline and study end. Results In patients with diabetes (n = 24), HbA 1c showed a clinically relevant decrease during treatment [mean change from baseline to week 48, À1Á44% (95% CI: À2Á52, À0Á36)]. In the overall population, in patients without diabetes, or in patients with/without hormonal control, HbA 1c did not significantly change by week 48. Mean FPG levels showed no significant change by week 48 in all populations. Individually, increases and decreases in glycaemic parameters affected some patients in all populations. Glycaemic status as a composite measure of HbA 1c and FPG (classification as normal, mild or diabetic) was stable from baseline to study end in most patients (overall, 70%; patients with diabetes, 50%; patients without diabetes, 76%), but worsened by week 48 in nine (15%) patients [seven (50%) with diabetes at baseline] and improved in nine (15%) patients (none with diabetes). Changes in lipid profiles were not considered clinically meaningful. Conclusions Glucose and lipid levels were not detrimentally affected in most patients, while only a relatively small proportion showed deterioration in glucose control.

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Section: Introductionmentioning

confidence: 99%

“…2,3 Furthermore, dyslipidaemia and hypertension are more frequent than in the general population and are associated with an increased incidence of cardiovascular morbidity and mortality. [4][5][6] Medical management therefore should correct hormone levels and reduce tumour size without contributing to metabolic impairment.…”

Section: Introductionmentioning

confidence: 99%

Glucose and lipid levels with lanreotide autogel 120 mg in treatment‐naïve patients with acromegaly: data from the PRIMARYS study

Caron

Petersenn²,

Houchard

et al. 2016

Clinical Endocrinology

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“…In a meta-analysis study, patients with acromegaly who achieved at least a 50% decrease in GH or IGF1 levels with octreotide or lanreotide showed significant improvements in interventricular septum thickness, left ventricular posterior wall thickness, and left ventricular mass (50) . Additionally, normalization of shoulder thickening (61%) and knee thickening (89%) were observed in patients who achieved disease control after SSA treatment for 12 months, while 61% of patients also demonstrated improvements in sleep apnea (18) . However, there remains a high prevalence of comorbidities in many patients who achieve control of GH and IGF1 levels.…”

Section: Current Recommendations For Monitoringmentioning

confidence: 96%

“…Cardiovascular disease, diabetes mellitus, hypertension, sleep apnea, and arthritis are common comorbidities associated with acromegaly (18) . Improvements in several comorbidities have been reported in patients with acromegaly who achieved biochemical control.…”

Section: Current Recommendations For Monitoringmentioning

confidence: 99%

Need for improved monitoring in patients with acromegaly

Silverstein¹

2015

Endocrine Connections

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Acromegaly is a rare and insidious disease characterized by the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF1) and is most commonly due to a pituitary adenoma. Patients with acromegaly who experience prolonged exposure to elevated levels of GH and IGF1 have an increased mortality risk and progressive worsening of disease-related comorbidities. Multimodal treatment with surgery, medical therapy, and radiotherapy provides biochemical control, defined by recent acromegaly clinical guidelines from the Endocrine Society as a reduction of GH levels to <1.0 ng/ml and normalization of IGF1 levels, to a substantial proportion of patients and is associated with improved clinical outcomes. Patients with acromegaly, even those without clinical symptoms of disease, require long-term monitoring of GH and IGF1 levels if the benefits associated with biochemical control are to be maintained and the risk of developing recurrent disease is to be abated. However, suboptimal monitoring is common in patients with acromegaly, and this can have negative health effects due to delays in detection of recurrent disease and implementation of appropriate treatment. Because of the significant health consequences associated with prolonged exposure to elevated levels of GH and IGF1, optimal monitoring in patients with acromegaly is needed. This review article will discuss the biochemical assessments used for therapeutic monitoring in acromegaly, the importance of monitoring after surgery and medical therapy or radiotherapy, the consequences of suboptimal monitoring, and the need for improved monitoring algorithms for patients with acromegaly.

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“…These comorbidities are usually due to local mass effects of the tumour or the consequence of long term GH and and IGF‐I excess. Overall, acromegaly treatment goals should include the management of these comorbidities because effective biochemical control of acromegaly can usually improve several of the comorbidities; however, this is not always the case, as some comorbidities may have reached the point of irreversibility and maybe considered as a sequel of the disease . In these cases, additional standard‐of‐care measures should be employed to manage uncontrolled comorbidities .…”

Section: Personalized Treatment Of Comorbidities Of Acromegalymentioning

confidence: 99%

Treatment of acromegaly in the era of personalized and predictive medicine

Puig-Domingo

2015

Clinical Endocrinology

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Summary Acromegaly is a chronic disorder usually diagnosed late in the disease evolution. Such delayed diagnosis, together with the inability to achieve the treatment goals of normalizing biochemical disease markers and controlling tumour mass may result in substantial morbidity and mortality. Somatostatin analogues (SSA) are accepted as first‐line medical therapy or as second‐line therapy in patients undergoing unsuccessful surgery and are considered a cornerstone in the treatment of acromegaly. However, because a high percentage of patients experience SSA medical treatment failure, the identification of biomarkers associated with a successful or unsuccessful response to all classes of medical therapy would help in the choice of treatment and potentially allow for a quicker normalization of biochemical parameters. The current treatment algorithms for acromegaly are based upon a “trial‐and‐error” approach with additional treatment options provided when disease is not controlled. In many other diseases, therapeutic algorithms have been evolving towards personalized treatment with the medication that best matches individual disease characteristics, using biomarkers that identify therapeutic response. Additionally, a personalized approach to complementary treatment of comorbidities present in the acromegalic patient is also required. This review will discuss the development of a potential treatment algorithm for acromegaly addressing the biochemical control of the disease as well of its associated comorbidities, under a personalized approach based upon markers of prognostic and predictive significance, such as tumour size, MRI adenoma signal, GH value after acute octreotide test, granular adenoma pattern, Ki‐67, somatostatin receptor phenotype, aryl hydrocarbon‐interacting protein expression, gsp mutations, RAF kinase activity, E‐cadherin and beta‐arrestin‐1.

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Multiple facets in the control of acromegaly

Cited by 9 publications

References 46 publications

Glucose and lipid levels with lanreotide autogel 120 mg in treatment‐naïve patients with acromegaly: data from the PRIMARYS study

Glucose and lipid levels with lanreotide autogel 120 mg in treatment‐naïve patients with acromegaly: data from the PRIMARYS study

Need for improved monitoring in patients with acromegaly

Treatment of acromegaly in the era of personalized and predictive medicine

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