Erectile function and androgen and estrogen beta receptor gene polymorphisms in acromegalic men.

PURPOSE: Sexual dysfunctions are often experienced by male patients with acromegaly, due to a combination of hypogonadism and other comorbidities, but are a scarcely investigated complication. Erectile dysfunction is also closely related to cardiovascular diseases through endothelial dysfunction. Therefore, this project aimed to assess the prevalence of erectile dysfunction in a population of acromegalic men and evaluate its association with cardio-metabolic disorders, also exploring associations with androgen and estrogen receptor gene polymorphisms. METHODS: Sexually active men aged 18-65 with previous diagnosis of acromegaly were recruited. Clinical and laboratory data were retrospectively collected. Each patient also provided a blood sample for AR and ERß gene polymorphisms analyses and filled out the IIEF-15 questionnaire. RESULTS: Twenty men with previous diagnosis of acromegaly (mean age 48.4 ± 10.0 years) were recruited. 13/20 subjects (65%) had erectile dysfunction, but only four had a concurrent biochemical hypogonadism, with no significant correlation with IIEF-15 scores. Total testosterone negatively correlated with sexual intercourse satisfaction domain (ρ = - 0.595; p = 0.019) and general satisfaction domain (ρ = - 0.651; p = 0.009). IGF-1 levels negatively correlated with biochemical hypogonadism (ρ = - 0.585; p = 0.028). The number of CAG and CA repeats in AR and ERß receptors genes was not significantly associated with IIEF-15 scores or with GH/IGF-1 levels, but a negative correlation between CA repeats and the presence of cardiomyopathy (ρ = - 0.846; p = 0.002) was present. CONCLUSIONS: Men with acromegaly have a high prevalence of erectile dysfunction, but it does not appear to be correlated with treatments, testosterone levels and AR/ER-beta signaling. Nonetheless, a shorter CA polymorphic trait (ERbeta) is associated with the presence of cardiomyopathy. If confirmed, these data may suggest an association between an incorrect hormonal balance and increased cardiovascular risk in acromegaly subjects.

Acromegalic cardiomyopathy: a neglected cause of cardiomyopathy.

ABSTRACT: Acromegaly represents a rare endocrine condition characterized by an excessive secretion of the growth hormone (GH) and the insulin-like growth factor-1 (IGF-1), mostly subsequent to a pituitary adenoma. Acromegaly affects 40-60 people per million without significant dif-ference between men and women, with an average age of onset of 44. The slow progression of the disease leads to a delay in diagnosis of 4 to 10 years from the onset of the hormonal imbalance. The increase of the GH and IFG-1 levels is associated with cardiac, respiratory, metabolic and rheumatic disorders. The cardiac involvement, also called acromegalic cardiomyopathy, causes a serious deterioration of the prognosis quoad vitam. An early diagnosis and a targeted treatment at the initial stage of the myocardial damage can enable the revers-ibility of the structural alterations.

Specific FSTL1 polymorphism may determine the risk of cardiomyopathy in patients with acromegaly.

BACKGROUND: We have investigated the role of a cardiomyokine, follistatin-like 1 (FSTL1), and its single nucleotide polymorphism on acromegalic cardiomyopathy. METHODS: The study was performed as a cross-sectional case research in a Tertiary Referral Centre. Forty-six patients with acromegaly (29 F-17 M, mean age: 50.3 ± 12.1 years) were included. FSTL1 levels were measured and the rs1259293 region of the FSTL1 gene was subjected to polymorphism analysis. 1.5 Tesla MRI was used to obtain cardiac images. RESULTS: There were 15 active (6 F-9M) and 31 (22 F-9M) controlled patients. Active patients had a higher left ventricular mass (LVM) and left ventricular mass index (LVMi). GH levels were positively correlated with left ventricular end-diastolic volume index (LVEDVi), stroke volume index (SVi), cardiac index (Ci), LVM and LVMi; r = 0.35, 0.38, 0.34, 0.39 and 0.39, respectively. IGF-1 index was positively correlated with LVEDVi, left ventricular end-systolic volume index (LVESVi), SVi, Ci, LVM and LVMi; r = 0.36, 0.34, 0.32, 0.31, 0.42 and 0.42, respectively. Twenty out of 46 patients with acromegaly (43.5%) had myocardial fibrosis. FSTL1 levels were neither correlated with disease activity nor with any functional and structural cardiac parameter. Multivariate linear regression analysis revealed no association between FSTL1 and any study parameters. The rs1259293 variant genotype CC was significantly associated with low left ventricular mass. CONCLUSIONS: Serum FSTL1 levels are not associated with functional and structural measures of myocardium in patients with acromegaly. However, the risk of left ventricular hypertrophy is reduced in CC genotyped individuals of FSTL1.

Role of Cardiac Magnetic Resonance (CMR) in Determining Implantable Cardioverter-Defibrillator (ICD) Indication in Acromegalic Cardiomyopathy: A Case Report.

Potentially fatal arrhythmia is one of the causes of premature death in acromegalic cardiomyopathy patients who are not properly treated. Implantable cardioverter-defibrillator (ICD) is one of the most effective and established treatments to prevent sudden cardiac death due to potentially fatal tachyarrhythmia. However, since the indication of ICD changes depending on whether it is ischemic cardiomyopathy or non-ischemic cardiomyopathy, proper diagnosis is important in patients with these diseases. Cardiac magnetic resonance (CMR) is a convenient and useful tool for diagnosing these. Both potentially fatal arrhythmias and coronary artery disease (CAD) are known to be important complications of acromegaly. Herein, we present a case of potentially fatal tachyarrhythmia due to acromegalic cardiomyopathy with the acute coronary syndrome. Furthermore, we mention the usefulness of CMR in the case which is difficult to determine the indication for an ICD.

Undiagnosed acromegaly as an underlying cause of sudden death.

We report a case of sudden death in a 31-year-old male diagnosed at autopsy with clinical undiagnosed acromegaly. The purpose of this report is to underline the importance of health professionals reacting to phenotypic acromegaly, such as acral enlargement and/or unexplained hypertension, including a range of severe comorbidities, to avoid a fatal outcome. Recent studies have shown that the increased mortality seen in acromegaly patients can be reversed with modern treatment aimed at normalizing GH and IGF-I levels. One year before death, the presented case was diagnosed with hypertension, but was otherwise described as healthy. The forensic autopsy, including post-mortem CT, showed phenotypic facial and body characteristics for acromegaly, general visceromegaly, and a pituitary tumor. The cause of death was heart failure due to end-stage acromegalic cardiopathy. Because the disease is slowly progressive, the individual himself, and the people close to him, might not have considered the acromegaly-related facial changes as abnormal.

[Heart arrhythmias and conduction disorders in patients with acromegaly: the role of cardiac magnetic resonance imaging].

Cardiovascular complications including arrhythmias and cardiac conduction disorders are one of the main reasons of high mortality rate in acromegaly, while they have not been well explored. AIM: To estimate arrhythmias frequency in acromegaly, identify risk factors leading to the development of arrhythmia and cardiac conduction disorder, to determine the role of cardiac MRI in detecting structural and functional changes. MATERIALS AND METHODS: A single-center prospective cohort study, which included 461 patients (151 men and 310 women) with acromegaly, was conducted. All the patients underwent a standard medical examination, including hormonal blood test, electrocardiogram, echocardiography, electrocardiogram daily monitoring. 18 patients with arrhythmias (11 men and 7 women) had cardiac MRI with gadolinium-based contrast. RESULTS: The results of our research show high frequency of arrhythmias and cardiac conduction disorders in patients with acromegaly 42%. Most frequent kinds of arrhythmias and cardiac conduction disorders were sinus bradycardia 19.1% of the cases and conduction disorders of bundle branch blocks 14.5%. Men were more likely to suffer from arrhythmias and cardiac conduction disorders than women (54.2% and 37.4%, respectively,p=0.0005). Not acromegaly activity but duration of the disease was a main risk factor of arrhythmias and cardiac conduction disorders. Patients with arrhythmias had a long anamnesis of acromegaly (10 and 7 years, respectively, p=0.04). Meanwhile, cardiac conduction disorders were commonly observed in the patients who were treated with somatostatin analogs comparing to the patients who didnt undergo this therapy (50% and 38.6% respectively,p=0.004). We showed that 61% of patients with acromegaly and cardiac conduction disorders who underwent magnetic resonance imaging (MRI) had the signs of myocardial fibrosis. The value of the ejection fraction of the left ventricle according to MRI was higher than with echocardiography (p=0.04). CONCLUSION: Arrhythmias and cardiac conduction disorders are often observed in patients with acromegaly even with remission of the disease. High risk group need careful diagnostic and monitoring approaches. Cardiac MRI is the gold standard for visualization of structural and morphological changes in the heart. Use of cardiac MRI in acromegalic patients expands our understanding of arrhythmias and cardiac conduction disorders in this disease. There are no specific laboratory markers of diffuse myocardial fibrosis, and the role of myocardial fibrosis in the occurrence of cardiac arrhythmias and conduction disorders needs further studying.

Bringing Cardiovascular Comorbidities in Acromegaly to an Update. How Should We Diagnose and Manage Them?

Patients with acromegaly frequently develop cardiovascular comorbidities, which significantly affect their morbidity and contribute to an increased all-cause mortality. In this regard, the most frequent complications that these patients may encounter include hypertension, cardiomyopathy, heart valve disease, arrhythmias, atherosclerosis, and coronary artery disease. The specific underlying mechanisms involved in the pathophysiology of these comorbidities are not always fully understood, but uncontrolled GH/IGF-I excess, age, prolonged disease duration, and coexistence of other cardio-vascular risk factors have been identified as significant influencing predisposing factors. It is important that clinicians bear in mind the potential development of cardiovascular comorbidities in acromegalic patients, in order to promptly tackle them, and avoid the progression of cardiac abnormalities. In many cases, this approach may be performed using straightforward screening tools, which will guide us for further diagnosis and management of cardiovascular complications. This article focuses on those cardiovascular comorbidities that are most frequently encountered in acromegalic patients, describes their pathophysiology, and suggests some recommendations for an early and optimal diagnosis, management and treatment.

Cardiac resynchronization therapy improves heart failure in one patient with acromegaly-induced cardiomyopathy: a case report.

BACKGROUND: Congestive heart failure is rarely observed in patients with acromegaly. Excessive growth hormone secretion and elevation of insulin-like growth factor 1 contribute to pathological changes in myocyte growth and structure, cardiac contractility, vascular function, and in later stage may progress to cardiac dysfunction. Early recognition of the condition is paramount, though the insidious progression of the disease commonly results in late diagnosis. Current standard regimens of pharmacological therapy, surgical treatment, radiotherapy are designed to normalize serum levels of both insulin-like growth factor 1 and growth hormone. In patients with late-stage heart failure due to acromegalic cardiomyopathy, cardiac resynchronization therapy might be a desirable treatment to help cardiac synchronization, improve symptoms, and eventually reduce hospital admissions together with mortality rates. CASE PRESENTATION: We describe a case of a 49-year-old man with a history of acromegaly who presented to our hospital with a diagnosis of decompensated systolic heart failure. Serial electrocardiograms showed wide (160-200 ms) QRS duration with left bundle branch block. Echocardiography showed severe left ventricular dysfunction that simultaneously achieved a left ventricular ejection fraction of 16%. Surgical indication was rarely assessed by neurosurgeons. Given that the stereotactic radiosurgery together with pharmacotherapy produced infinitesimal effects, cardiac resynchronization therapy was performed. Owing to biventricular synchronization and holding back reverse remodeling, the patient's symptoms were successfully alleviated, and he was discharged from the hospital. CONCLUSIONS: Congestive heart failure is a rare complication in acromegaly-induced cardiomyopathy (occurs in only 3% of patients). Early diagnosis and treatment with curative drugs more than cardiovascular implantable electronic devices might lead to better surgical outcomes in this group of patients.

Acromegalic cardiomyopathy: Epidemiology, diagnosis, and management.

Acromegalic cardiomyopathy is the leading cause of morbidity and all-cause mortality in patients with acromegaly. Though acromegaly is a rare condition, the associated derangements are vast and severe. Stemming from an increase in circulating growth hormone (GH) and insulin-like growth factor-1 levels (IGF-1), acromegalic cardiomyopathy results in pathological changes in myocyte growth and structure, cardiac contractility, and vascular function. These molecular changes manifest commonly as biventricular hypertrophy, diastolic and systolic dysfunction, and valvular regurgitation. Early recognition of the condition is paramount, though the insidious progression of the disease commonly results in a late diagnosis. Biochemical testing, based on IGF-1 measurements, is the gold standard of diagnosis. Management should be centered on normalizing serum levels of both IGF-1 and GH. Transsphenoidal resection remains the most cost-effective and permanent treatment for acromegaly, though medical therapy possesses benefit for those who are not surgical candidates. Ultimately, achieving control of hormone levels results in a severe reduction in mortality rate, underscoring the importance of early recognition and treatment.

Endoscopic therapy and curative effect in pituitary adenoma patients complicated by acromegalic cardiomyopathy.

The study aimed to retrospectively analyze the clinical characteristics of patients with pituitary adenomas complicated by acromegalic cardiomyopathy and to evaluate the effect of endoscopic surgery. Eighty-six pituitary adenoma patients complicated by acromegalic cardiomyopathy who were treated with endoscopic surgery in the First Affiliated Hospital of Soochow University from January 2010 to December 2016 were enrolled. We noted patient clinical characteristics and explored the relationships with surgical treatment. Before and after surgery, all patients underwent an examination of pituitary endocrinology, brain magnetic resonance (MR), and echocardiography. The serum levels of growth hormone (GH), left ventricular end-diastolic diameter (LVIDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular ejection fraction (EF), and mitral valve (E/A ratio) were examined with non-invasive methods, and the results were compared. Of the 86 patients, there were 23 with microadenomas, 27 with large adenomas, and 36 with giant adenomas. There were 28 patients with invasive adenomas and 58 with non-invasive adenomas. The pre-operative mean GH level was 71.23 ± 3.29 µg/L, which was positively correlated with tumor volume (r = 0.751, P < 0.01). Via trans-sphenoidal endoscopic pituitary adenoma resection, 51 patients underwent total tumor resections, 25 underwent subtotal resections, 8 underwent major part resections, and 2 underwent partial resections. After surgery, the GH mean level was 3.81 ± 1.03 µg/L, which was significantly different (t = 3.72, P < 0.01) from the pre-operative level. Cardiac function indices, including LVIDd, IVST, LVPWT, E/A, and EF, were significantly improved. The long-term curative rate was 39.17% and the remission rate was 77.29%. For pituitary adenoma patients complicated by acromegalic cardiomyopathy, endoscopic surgery resulted in a good curative effect and the growth hormone levels were maintained, which can significantly improve cardiac structure and function.

Cardiovascular comorbidities in acromegaly: an update on their diagnosis and management.

Comorbidities related to the cardiovascular system are one of the most prevalent in patients with acromegaly, and contribute to an increased risk of morbidity and all-cause mortality. Specifically, hypertension, cardiomyopathy, heart valve disease, arrhythmias, atherosclerosis, coronary artery disease, and cardiac dysfunction may be frequent findings. Although the underlying physiopathology for each comorbidity may not be fully elucidated, uncontrolled growth hormone/insulin-like growth factor 1 excess, age, prolonged disease duration, and coexistence of other cardio-vascular risk factors are significant influencing variables. A simple diagnostic approach to screen for the presence of these comorbidities may allow prompt treatment and arrest the progression of cardiac abnormalities. In this article, we revise the most prevalent cardiovascular comorbidities and their pathophysiology in acromegalic patients, and we address some recommendations for their prompt diagnosis, management and treatment. Strengths and pitfalls of different diagnostic techniques that are currently being used and how different treatments can affect these complications will be further discussed.

Effects of long-term combined treatment with somatostatin analogues and pegvisomant on cardiac structure and performance in acromegaly.

To date, no data are available on the effects of long-term combined treatment with somatostatin analogues (SA) and pegvisomant (PEG) on cardiovascular complications in acromegaly. The current study aimed at investigating the effects of long-term SA + PEG on cardiac structure and performance. Thirty-six patients (14 M, 22 F, aged 52.3 ± 10.2 years) entered this study. Weight, BMI, systolic (SBP) and diastolic (DBP) blood pressure, IGF-I, fasting glucose (FG), fasting insulin (FI), HOMA-IR, HbA1c, and lipids were evaluated at baseline (T0), after long-term (median 36 months) SA (T1), after 12 (T12) and 60 (T60) months of SA + PEG, and at last follow-up (LFU, median 78 months). At each time point, all patients underwent echocardiography. At T1, induced a slight but not significant decrease in IGF-I (p = 0.077), whereas FI (p = 0.004), HOMA-IR (p = 0.013), ejection fraction (EF, p = 0.013), early (E) to late (A) ventricular filling velocities (E/A, p = 0.001), and isovolumetric relaxation time (IVRT, p = 0.000) significantly improved. At T12, IGF-I (p = 0.000) significantly reduced compared to T0, and FI (p = 0.001), HOMA-IR (p = 0.000), LVMI (p = 0.000), and E/A (p = 0.006) further improved compared to T1. At T60, FI (p = 0.027), HOMA-IR (p = 0.049), and E/A (p = 0.005) significantly improved as compared to T1. At LFU IGF-I normalized in 83.3 %, FI (p = 0.000), HOMA-IR (p = 0.000), LVMi (p = 0.000), and E/A (p = 0.005) further improved as compared to T1. PEG dose significantly correlated with LVMi at T12 (r = 0.575, p = 0.000) and T60 (r = 0.403, p = 0.037). Long-term PEG addition to SA improves cardiac structure and performance, particularly diastolic dysfunction, in acromegalic patients resistant to SA.

Cardiovascular involvement in patients affected by acromegaly: an appraisal.

Cardiovascular complications are frequent in acromegalic patients. Several studies reported increased prevalence of traditional cardiovascular risk factors and early development of endothelial dysfunction and of structural vascular alterations, with subsequent increased risk of coronary artery disease. Furthermore, chronic exposure to high levels of GH and IGF-I leads to the development of the so called "acromegalic cardiomyopathy", characterized by concentric biventricular hypertrophy, diastolic dysfunction and, additionally, by progressive impairment of systolic performance leading to overt heart failure. Cardiac valvulopathies and arrhythmias have also been documented and may concur to the deterioration of cardiac function. Together with strict control of cardiovascular risk factors, early control of GH and IGF-I excess, by surgical or pharmacological therapy, has been reported to ameliorate cardiac and metabolic abnormalities, leading to a significant reduction of left ventricular hypertrophy and to a consistent improvement of cardiac performance.

Distúrbios cardiovasculares na acromegalia: [revisão] / Cardiovascular disturbances in acromegaly: [review]

A acromegalia acarreta uma série de distúrbios ao sistema cardiovascular, decorrentes da exposição crônica a níveis elevados de GH e IGF-1. Estes distúrbios são os principais responsáveis pelo aumento da mortalidade de acromegálicos. Entre as várias formas de acometimento cardiovascular, destaca-se a miocardiopatia acromegálica, entidade caracterizada, inicialmente, pelo estado hiperdinâmico, seguido de hipertrofia ventricular esquerda concêntrica e disfunção diastólica por déficit de relaxamento, culminando com disfunção sistólica e, por vezes, insuficiência cardíaca franca. Além disso, são também relevantes as arritmias, as valvulopatias, sobretudo mitral e aórtica, a cardiopatia isquêmica, a hipertensão e os distúrbios dos metabolismos glicêmico e lipídico. Nesta revisão são abordados os principais aspectos clínicos e prognósticos destas entidades, os efeitos do tratamento da acromegalia sobre elas e as repercussões correspondentes sobre a sobrevida dos pacientes.

Acromegaly causes a number of disorders in the cardiovascular system, resulting from chronic exposure to high levels of GH and IGF-1. Such disorders are the main responsible for increased mortality rates among acromegalic patients. Among several forms of cardiovascular impairment is acromegalic cardiomyopathy, an entity that is initially characterized by a hyperdynamic state, followed by concentric left ventricular hypertrophy and diastolic dysfunction due to relaxation deficit, culminating in systolic dysfunction and sometimes heart failure. In addition, arrhythmias and heart valve diseases are also relevant, especially mitral and aortic, ischemic heart disease, hypertension, and glucose and lipid metabolism disorders. This review approaches the main clinical and prognostic aspects of these entities, the effects of acromegaly treatment on them, and the respective consequences on patient survival.