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Hyperglycemia is a common feature associated with states of increased growth hormone secretion and glucocorticoid levels. The purpose of these guidelines is to assist clinicians and other health care providers to take evidence-based therapeutic decisions for the treatment of hyperglycemia in patients with growth hormone and corticosteroid excess. Both the SID and SIE appointed members to represent each society and to collaborate in Guidelines writing. Members were chosen for their specific knowledge in the field. Each member agreed to produce-and regularly update-conflicts of interest. The authors of these guidelines prepared their contributions following the recommendations for the development of Guidelines, using the standard classes of recommendation shown below. All members of the writing committee provided editing and systematic review of each part of the manuscript, and discussed the grading of evidence. Consensus was guided by a systematic review of all available trials and by interactive discussions.

Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%-70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%-90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to be established. Lastly, novel therapies and new potential delivery modalities (oral octreotide) are summarized.

24 hr monitoring of arterial pressure (AP) in 46 patients with acromegaly in active phase revealed systolic-diastolic arterial hypertension. Analysis of diurnal profile showed the absence of the normal nocturnal fall in AP (non-dipper profile) and the significant rise in the number of patients with elevated nocturnal AP (night-peakers).

Background: Myokines are produced and released by muscle cells in response to muscular contractions. Endogenous Cushing syndrome (CS) and acromegaly cause significant changes in muscle tissue leading to atrophy or hypertrophy. However, there is no data whether these endocrine abnormalities influence myokine secretion., Aims: To evaluate serum levels of myostatin, interleukin-6 (IL6) and irisin in patients with CS and acromegaly., Materials and Methods: Fasting serum samples were taken and stored in aliquot at ≤-20°C from consecutive subjects with clinically evident and biochemically confirmed active CS, acromegaly and healthy volunteers matched by age, sex and body mass index (BMI). Commercially available kits were used to assay serum myokine levels. Grip strength was measured by a dynamometer. Insulin-like growth factor-1 (IGF1) was measured by immunochemiluminescence assay (Liaison), twenty-four hours urine free cortisol (24hUFC) ― by immunochemiluminescence assay (Vitros ECi), salivary free cortisol ― by electrochemiluminescence assay (Cobas). One-way ANOVA was utilized to assess the difference between groups., Results: We enrolled 88 subjects: 30 patients suffered from CS (group 1), 28 ― acromegaly (2) and 30 matched healthy controls (3) with no difference among the groups in sex, age and BMI (p=0.492, 0.062 and 0.174 respectively). Mean 24hUFC in subjects with CS and mean IGF1 in subjects with acromegaly were significantly higher as compared to other groups (p<0.001). Right-hand grip strength was lower in patients with CS as compared to both patients with acromegaly and healthy subjects (p=0.04). However, among these young adults we did not find statistically significant differences in measured myokines levels: irisin ― p=0.15; IL6 ― p=0.34; myostatin ― p=0.50. There was a significant correlation between myostatin and irisin in the whole group of people and in every separately analyzed subset of patients (p<0.001), but no correlation was found between any measured myokines and 24hUFC or IGF1., Conclusions: Hypercortisolism or supraphysiological IGF1 levels do not significantly influence serum levels of myostatin, IL6 and irisin in young adults.

Surgical removal of as much tumor mass as possible is usually considered the first step of treatment in acromegaly, unless the patients are unfit for surgery or refuse an operation. To date, in almost all cases, minimally invasive, transsphenoidal microscopic or endoscopic approaches are used. Whether a curative approach is feasible or a debulking procedure is planned, can be anticipated on the basis of preoperative magnetic resonance imaging. It mostly depends on localization, size, and the invasive character of the lesion. The surgical results depend on tumor-related factors such as size, extension, the presence or absence of invasion, and the magnitude of IGF-1 and growth hormone oversecretion, respectively. However, even surgeon-related factors such as experience and case load of the centers have been shown to strongly affect surgical results and complication rates. A reoperation can be considered at various stages in the treatment algorithm. There are several new technical gadgets which might aid in the surgical procedure: navigation, the Doppler probe, and variants of intraoperative imaging., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To compare hypothalamus-pituitary-adrenal (HPA) axis integrity at diagnosis and recovery after transsphenoidal surgery (TSS), in acromegaly patients, compared with tumor size matched non-functioning adenoma (NFA) patients., Methods: A retrospective 7-year evaluation of acromegaly patients, who underwent TSS with 52 weeks follow-up at a single institution, was undertaken. 50 acromegaly with complete follow-up data at all points and 50 NFA patients were matched for tumor size; HPA axis was similarly assessed pre-operatively and at 6, 12 and 52 weeks post-operatively. Recovery of HPA axis and gender specific prevalence of adrenal insufficiency (AI), were analyzed in both groups. We also studied AI in acromegaly patients requiring medical therapy post-operatively vs those in remission after surgery., Results: AI remained less prevalent in acromegaly vs NFA (acromegaly, p = 0.01; NFA, p = 0.15) at 52 weeks after surgery, although the prevalence of AI decreased in both groups from baseline by 52 weeks. Additionally, recovery from baseline AI was significantly greater by 52 weeks in acromegaly patients over NFA patients (p = 0.001). Recovery of HPA axis in acromegaly patients remained significant (p = 0.03) despite the need for medical therapy. AI at baseline was proportionately more prevalent in acromegalic males at baseline (p = 0.002) but no gender difference was apparent at 52 weeks (p = 0.35). Conversely, in NFA patients, no gender difference was apparent pre-operatively (p = 0.49), but AI was more prevalent in males at 52 weeks (p = 0.001)., Conclusion: In the longest comparative study to date using a standard assessment modality, HPA axis recovery was more frequent in acromegaly compared to NFA patients, independent of tumor size, cavernous sinus invasion (CSI), and body mass index (BMI). HPA axis integrity must be carefully and periodically monitored in acromegaly patients during short- and long-term follow-up to prevent overtreatment with glucocorticoids.

Objective: Our purpose was to compare the findings of CT pulmonary densitovolumetry and pulmonary function in patients with active acromegaly and controlled acromegaly and, secondarily, to correlate these findings., Methods: 11 patients with active acromegaly, 18 patients with controlled acromegaly and 17 control subjects, all non-smokers, underwent quantification of lung volume using multidetector CT (Q-MDCT) and pulmonary function tests., Results: Patients with active acromegaly had larger total lung mass (TLM) values than the controls and larger amounts of non-aerated compartments than the other two groups. Patients with active acromegaly also had larger amounts of poorly aerated compartments than the other two groups, a difference that was observed in both total lung volume (TLV) and TLM. TLV as measured by inspiratory Q-MDCT correlated significantly with total lung capacity, whereas TLV measured using expiratory Q-MDCT correlated significantly with functional residual capacity., Conclusion: Patients with active acromegaly have more lung mass and larger amounts of non-aerated and poorly aerated compartments. There is a relationship between the findings of CT pulmonary densitovolumetry and pulmonary function test parameters., Advances in Knowledge: Although the nature of our results demands further investigation, our data suggest that both CT pulmonary densitovolumetry and pulmonary function tests can be used as useful tools for patients with acromegaly by assisting in the prediction of disease activity.

The aims of this study were to evaluate the forced oscillation technique (FOT) and pulmonary densitovolumetry in acromegalic patients and to examine the correlations between these findings. In this cross-sectional study, 29 non-smoking acromegalic patients and 17 paired controls were subjected to the FOT and quantification of lung volume using multidetector computed tomography (Q-MDCT). Compared with the controls, the acromegalic patients had a higher value for resonance frequency [15.3 (10.9-19.7) vs 11.4 (9.05-17.6) Hz, P=0.023] and a lower value for mean reactance [0.32 (0.21-0.64) vs 0.49 (0.34-0.96) cm H2O/L/s2, P=0.005]. In inspiratory Q-MDCT, the acromegalic patients had higher percentages of total lung volume (TLV) for nonaerated and poorly aerated areas [0.42% (0.30-0.51%) vs 0.25% (0.20-0.32%), P=0.039 and 3.25% (2.48-3.46%) vs 1.70% (1.45-2.15%), P=0.001, respectively]. Furthermore, the acromegalic patients had higher values for total lung mass in both inspiratory and expiratory Q-MDCT [821 (635-923) vs 696 (599-769) g, P=0.021 and 844 (650-945) vs 637 (536-736) g, P=0.009, respectively]. In inspiratory Q-MDCT, TLV showed significant correlations with all FOT parameters. The TLV of hyperaerated areas showed significant correlations with intercept resistance (rs=-0.602, P<0.001) and mean resistance (rs=-0.580, P<0.001). These data showed that acromegalic patients have increased amounts of lung tissue as well as nonaerated and poorly aerated areas. Functionally, there was a loss of homogeneity of the respiratory system. Moreover, there were correlations between the structural and functional findings of the respiratory system, consistent with the pathophysiology of the disease.

Objective: To assess whether sleep apnea-hypopnea syndrome (SAHS) is a risk factor for development of acromegalic cardiomyopathy., Methods: A descriptive, cross-sectional study of 32 patients with acromegaly (15 categorized as non-controlled-NCA and 17 as controlled-CA) compared to 20 matched controls (by sex, age, and BMI) referred to the pulmonology department for suspected SAHS. Polysomnography, echocardiography (M-mode, 2-dimensional, and Doppler), and 12-lead electrocardiography were performed in all participants. Development of cardiac morbidity (ischemia heart disease or heart failure) was evaluated after 7 years., Results: SAHS was diagnosed in 81.3% of patients with acromegaly and 85% of controls. Mild SAHS was more common in CA than in NCA patients (31.3% vs. 0%, p=0.048). There was a trend to greater prevalence of left ventricular diastolic dysfunction (LVDD) in acromegalic patients as compared to controls (58.1% vs. 30%, p=0.05). Presence of severe SAHS in patients with acromegaly was related to greater risk of LVDD (90.9% vs. 40%, p=0.008; OR 2.3 [1.3-4.0]), LV hypertrophy (55.6% vs. 10.5%, p=0.02; OR 5.3 [1.3-22.2]), and cardiac events (87.5% vs. 35.6%; p=0.01; OR 7.53 [1.07-53.24])., Conclusion: SAHS is highly prevalent in patients with acromegaly. Only in these patients was severe SAHS associated to hypertrophy, LV diastolic dysfunction, and cardiac events., (Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Patients with acromegaly can be treated with surgery, radiotherapy and/or medical treatment. In general, patients' beliefs about medication are associated with illness perceptions, a contributory factor of Quality of Life (QoL). At present, there are no quantitative studies on medication beliefs in patients with acromegaly. Here, we aimed to examine possible associations between medication beliefs, illness perceptions, and QoL. Furthermore we aimed to explore whether illness perceptions of patients with remission of acromegaly receiving medical treatment differ from patients without medical treatment., Design: Cross-sectional evaluation of 73 patients with remission of acromegaly (n = 28 patients with medication, n = 45 without medication). The Beliefs about Medicines Questionnaire (BMQ), Illness Perception Questionnaire-Revised (IPQ-R), EuroQoL-5D, and AcroQoL were used for the assessment., Results: Stronger beliefs about the necessity of medical treatment and stronger concerns about the adverse effects were associated with attributing more symptoms to acromegaly, perceiving more negative consequences, and having a stronger belief in a cyclical timeline (BMQ, all P < 0.05). Stronger beliefs about the necessity of medical treatment were associated with a worse disease-specific QoL (BMQ, P < 0.01). Patients with medical treatment perceived a more chronic timeline of their disease, compared to patients without medical treatment (IPQ-R, P = 0.002)., Conclusion: Negative medication beliefs were related to more negative illness perceptions and worse disease-specific QoL. Patients receiving medical treatment for acromegaly tend to perceive a more chronic timeline of their disease, compared to patients with remission without medical treatment. These psychological factors need to be taken into account when treating patients and developing a psychosocial education program aiming to improve QoL., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Context and Objective: Different functional respiratory alterations have been described in acromegaly, but their relationship with pulmonary tissue abnormalities is unknown. The objective of this study was to observe possible changes in lung structure and explain their relationship with gas exchange abnormalities., Design and Setting: Cross-sectional analytical study with a control group, conducted at a university hospital., Methods: The study included 36 patients with acromegaly and 24 controls who were all assessed through high-resolution computed tomography of the thorax (CT). Arterial blood gas, effort oximetry and serum growth hormone (GH) and insulin-like growth factor I (IGF-1) were also assessed in the patients with acromegaly., Results: The abnormalities found in the CT scan were not statistically different between the acromegaly and control groups: mild cylindrical bronchiectasis (P = 0.59), linear opacity (P = 0.29), nodular opacity (P = 0.28), increased attenuation (frosted glass; P = 0.48) and decreased attenuation (emphysema; P = 0.32). Radiographic abnormalities were not associated with serum GH and IGF-1. Hypoxemia was present in seven patients; however, in six of them, the hypoxemia could be explained by underlying clinical conditions other than acromegaly: chronic obstructive pulmonary disease in two, obesity in two, bronchial infection in one and asthma in one., Conclusion: No changes in lung structure were detected through thorax tomography in comparison with the control subjects. The functional respiratory alterations found were largely explained by alternative diagnoses or had subclinical manifestations, without any plausible relationship with lung structural factors.

Background: We aimed to evaluate whether atrial electromechanical delay (AEMD) measured by tissue Doppler imaging (TDI), which is an indicator for structural and electrical remodelling of the atria, is prolonged in patients with active or inactive acromegaly, or both, compared with a control group., Methods: A total of 34 patients with acromegaly (18 active/16 inactive) and 35 patients as a control group were enrolled. Both intra- and inter-AEMD were calculated by TDI. The correlation between clinical variables and AEMD were analyzed., Results: Both inter-AEMD and right and left intra-AEMD were prolonged in patients with acromegaly compared with the control group (P < 0.001, P < 0.001, and P = 0.004, respectively). Also, patients with active acromegaly showed higher inter-AEMD and right intra-AEMD compared with patients with inactive acromegaly (P < 0.05). There was no significant difference in left intra-AEMD between patients with active acromegaly and those with inactive acromegaly (P = 0.977). The growth hormone and insulin-like growth factor (IGF-1) levels positively correlated with inter-AEMD (r = 0.577; P < 0.001; r = 0.614; P < 0.001, respectively). Additionally, we found that inter-AEMD was significantly and positively correlated with relationship between maximal values of passive mitral inflow (E, PW-Doppler) and lateral early diastolic mitral annular velocities (e', TDI) (r = 0.316; P = 0.008). Only the serum IGF-1 level was independently associated with inter-AEMD in multivariate linear regression analysis (β = 0.500; P = 0.011)., Conclusions: Our study findings showed that both inter- and intra-AEMD are prolonged in patients with acromegaly. Also, AEMD was observed to be more prolonged in patients with active acromegaly than in those with inactive acromegaly. IGF-1 was an independent predictor of inter- AEMD in patients with acromegaly. Being a noninvasive, inexpensive, and simple technique, AEMD may be used as an indicator for atrial electrical and structural remodelling in patients with acromegaly., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular complications, including arrhythmias and cardiac sudden death, are the most common causes of enhanced mortality in acromegaly. However, few data are available on cardiac autonomic functions and sympathovagal balance in acromegalic patients., Objective: The aim of this study was to investigate both the time and frequency domain parameters of Heart Rate Variability (HRV), in order to characterize the cardiac autonomic functions in patients affected by acromegaly. This study correlated anthropometric, metabolic, echocardiographic parameters and blood pressure with those relating to HRV, to identify the main factors responsible for the HRV related alterations possibly present. We also aimed to analyze the effects of the treatment with somatostatin analogues (SSAs) on HRV., Materials and Methods: This study enrolled 47 acromegalic patients (23 males, age 49.1 ± 13.5 years) and 37 (13 males) age matched (52.3 ± 13.3 years) healthy subjects. All participants underwent 12-lead 24 h ECG Holter recordings and a HRV analysis of the ECG tracings was performed. The parameters obtained from the time domain analysis of HRV included pNN50, SDNN, SDNN index, SDANN and RMSSD. The power spectral analysis of HRV was obtained by summing powers of the LF (low frequency) and the HF (high frequency) band. Sympathovagal balance was estimated by calculating the LF/HF ratio during 24 h and 15 min of clinostatism. The HRV of 28 acromegalic patients was studied before and after SSAs treatment., Results: Acromegalic patients showed significantly lower SDNN and SDANN compared to controls. Diabetic and non-diabetic acromegalic patients showed decreased SDNN and SDANN, when compared to healthy subjects. Diabetic acromegalic patients had a lower LF/HF ratio during 24 h when compared to non-diabetic acromegalic patients. Similar results were obtained analyzing patients affected by acromegaly and impaired glucose tolerance. SDNN and SDANN were lowered by hypertension in the acromegalic population, when compared to controls, and hypertensive acromegalic patients also displayed a decreased LF/HF ratio during 24 h when compared to normotensive acromegalic subjects. Patients with ventricular arrhythmias in Lown classes 3-5 showed a decreased SDANN compared to patients in Lown class 0-2. The treatment with SSAs was able to ameliorate all the time domain parameters of HRV, without altering the 24 h LF/HF ratio., Conclusion: Cardiac autonomic functions and sympathovagal balance are altered in patients affected by acromegaly and could be ameliorated by SSAs therapy. HRV analysis allows an estimation of the autonomic sympathovagal balance and may be a useful clinical tool for the cardiac risk stratification in acromegalic patients.

In this double case report, we present two special cases of pituitary apoplexy. First, we describe a patient with growth hormone deficiency despite clinical suspicion of acromegaly. Imaging showed evidence of a recent pituitary apoplexy, which might have caused spontaneous remission of the acromegaly before presentation at our outpatient clinic. Second, we describe a patient who presented with spontaneous remission of Cushing's disease after pituitary apoplexy, followed by a spontaneous remission of a relapse of the Cushing's disease due to a second pituitary apoplexy. These cases show that patients in spontaneous remission of hormonally active pituitary adenomas should be suspected of a pituitary apoplexy. Furthermore, even after spontaneous remission following pituitary apoplexy, careful long-term follow-up of these patients is mandatory, as relapses of hormonal hypersecretion can occur.

Introduction: The prevalence of erectile dysfunction (ED) and its correlates in men with acromegaly has never been investigated., Aim: The aim of this study was to evaluate sexual function in men with acromegaly., Methods: Multicenter-based, retrospective analysis of a nonselected series of 57 acromegalic subjects (mean age: 52.7 ± 14.2 years) was performed. Acromegalic subjects reporting ED (n = 24) were compared with matched ED patients without acromegaly or pituitary disease (controls), selected from a cohort of more than 4,000 subjects enrolled in the Florence Sexual Medicine and Andrology Unit., Main Outcome Measures: Patients were interviewed using Structured Interview on Erectile Dysfunction (SIEDY) structured interview, a 13-item tool for the assessment of ED-related morbidities. Several clinical and biochemical parameters were taken. Penile color Doppler ultrasound (PCDU) was performed in a subgroup of 37 acromegalic subjects., Results: ED was reported by 42.1% of acromegalic subjects. After adjusting for age and testosterone, acromegalic subjects with ED had a higher prevalence of hypertension and more often reported an impairment of sleep-related erections and a longer smoking habit. Accordingly, acromegaly-associated ED was characterized by a higher organic component and worse PCDU parameters. No relationship between ED and testosterone levels or other acromegaly-related parameters was found. However, acromegalic subjects with severe ED reported a longer disease duration. In a case-control analysis, comparing acromegalic subjects with ED-matched controls free from acromegaly (1:5 ratio), acromegalic men had a worse ED problem and a higher organic component of ED, as derived from SIEDY score. In line with these data, acromegalic patients with ED had a higher prevalence of major adverse cardiovascular events history at enrollment and lower PCDU parameters., Conclusions: Subjects with complicated acromegaly are at an increased risk of developing ED, especially those with cardiovascular morbidities. Our data suggest including a sexual function evaluation in routine acromegaly follow-up., (© 2015 International Society for Sexual Medicine.)

Cardiovascular diseases, including ventricular arrhythmias are responsible for increased mortality in patients with acromegaly. Acromegaly may cause repolarization abnormalities such as QT prolongation and impairment of repolarization reserve enhancing liability to arrhythmia. The aim of this study was to determine the short-term beat-to-beat QT variability in patients with acromegaly. Thirty acromegalic patients (23 women and 7 men, mean age±SD: 55.7±10.4 years) were compared with age- and sex-matched volunteers (mean age 51.3±7.6 years). Cardiac repolarization parameters including frequency corrected QT interval, PQ and QRS intervals, duration of terminal part of T waves (Tpeak-Tend) and short-term variability of QT interval were evaluated. All acromegalic patients and controls underwent transthoracic echocardiographic examination. Autonomic function was assessed by means of five standard cardiovascular reflex tests. Comparison of the two groups revealed no significant differences in the conventional ECG parameters of repolarization (QT: 401.1±30.6 ms vs 389.3±16.5 ms, corrected QT interval: 430.1±18.6 ms vs 425.6±17.3 ms, QT dispersion: 38.2±13.2 ms vs 36.6±10.2 ms; acromegaly vs control, respectively). However, short-term beat-to-beat QT variability was significantly increased in acromegalic patients (4.23±1.03 ms vs 3.02±0.80, P<0.0001). There were significant differences between the two groups in the echocardiographic dimensions (left ventricular end diastolic diameter: 52.6±5.4 mm vs 48.0±3.9 mm, left ventricular end systolic diameter: 32.3±5.2 mm vs 29.1±4.4 mm, interventricular septum: 11.1±2.2 mm vs 8.8±0.7 mm, posterior wall of left ventricle: 10.8±1.4 mm vs 8.9±0.7 mm, P<0.05, respectively). Short-term beat-to-beat QT variability was elevated in patients with acromegaly in spite of unchanged conventional parameters of ventricular repolarization. This enhanced temporal QT variability may be an early indicator of increased liability to arrhythmia.

The aim of this study was to evaluate atrial electromechanical delay (EMD), P wave dispersion (Pwd), and left atrial (LA) mechanical functions in patients with active acromegaly. Twenty-three patients with active acromegaly and 27 age- and sex-matched controls were included in this study. All atrial electromechanical interval parameters (PA lateral, PA septum, PA tricuspid, interatrial EMD, intra-LA EMD, and intra-right atrial EMD) were measured from mitral lateral annulus, mitral septal annulus, and right ventricular tricuspid annulus by tissue Doppler imaging. LA volumes were measured by the disk method in the apical four-chamber view and were indexed to the body surface area. Mechanical function parameters of LA were calculated. Pwd was performed by 12-lead electrocardiograms. Atrial electromechanical intervals (PA lateral, PA septum, PA tricuspid, interatrial EMD, intra-LA EMD, and intra-right atrial EMD) and Pwd were similar between patients with acromegaly and control subjects (all p > 0.05). LA volumes (maximum, minimum, and presystolic) and LA mechanical functions were not significantly different between the groups (all p > 0.05). Additionally, serum levels of growth hormone and insulin-like growth factor-1 were not correlated with atrial electromechanical parameters and LA mechanical functions. Atrial electrical conduction times were not prolonged and LA mechanical functions were not impaired in patients with active acromegaly compared with controls. And the prevalence of supraventricular arrhythmia risk may not increase in this population.

Objective: To evaluate use of pegvisomant, a growth hormone (GH) receptor antagonist, as monotherapy in ACROSTUDY, a global safety surveillance study set in 14 countries (373 sites)., Methods: A descriptive analysis of safety, magnetic resonance imaging (MRI) reading, and treatment outcomes in 710 subjects who received at least 1 pegvisomant dose as monotherapy during and up to 5 years follow-up in ACROSTUDY., Results: Subjects received a mean of 5.4 years of pegvisomant and were followed in ACROSTUDY for a mean of 3.8 years. A total of 1,255 adverse events (AEs) were reported in 345 subjects (48.6%). Serious AEs (SAEs) were reported in 133 (18.7%) subjects, including 22 deaths, none of which were attributed to pegvisomant use. Of 670 (94%) subjects with at least 1 liver function test (LFT) reported in ACROSTUDY, 8 (1.2%) had reported increases in transaminases >3 times the upper limit of normal (ULN). No liver failure was reported. Based on central MRI reading, 12 of 542 subjects (2.2%) had a confirmed increase or increase/decrease in tumor size. Injection-site reactions were reported in 2.3%. At 5 years of therapy, insulin-like growth factor 1 (IGF-1) level was reported normal in 67.5% (mean dose 17.2 mg/day) and elevated in 29.9% (mean dose 19.8 mg/day). Subjects on 20 mg per day or more rose from 36% at 3 years to 41% at 5 years of therapy., Conclusions: ACROSTUDY data indicate that pegvisomant used as sole medical therapy is safe and effective for patients with acromegaly. The reported low incidence of pituitary tumor size increase and liver enzyme elevations are reassuring and support the positive benefit-risk of pegvisomant therapy.

Background: Previous studies report impaired health-related quality of life (HRQoL) in patients with functional pituitary adenomas (FPA). We assessed HRQoL in FPA patients having undergone surgery at our University Central Hospital between 2000 and 2010, with combined adjuvant treatment given to achieve strict hormonal control., Design: A cross-sectional study including a large control population., Patients and Methods: HRQoL was assessed by the 15D in 100 FPA patients (acromegaly n = 47, Cushing's disease n = 21, prolactinoma n = 26, TSH-adenoma n = 2, gonadotropinoma n = 4), operated on a mean 7·4 (range 2·1-13·0) years earlier. An age- and gender-standardized sample of the general population (n = 4924) served as controls. HRQoL determinants were assessed by independent samples t-test and multiple regression analysis., Results: Hormonal remission rate was 90·9% and 43·9% of the patients received replacement therapy. The mean 15D scores were similar in patients and controls (0·917 vs 0·922, P = 0·568). On single dimensions, patients were worse off regarding speech and sexual activity (both P < 0·05) and better off regarding discomfort and symptoms (P < 0·05). Age (P = 0·001), co-morbidities (P = 0·009), Cushing's disease (P = 0·034), and thyroxine dose (P = 0·002) predicted impaired HRQoL, but not hypopituitarism, hydrocortisone replacement, radiotherapy, or time after surgery., Conclusions: It is possible to achieve near-normal HRQoL in surgically treated FPA patients given adjuvant treatment to achieve strict hormonal remission. However, in addition to age and co-morbidities, Cushing's disease and need for thyroxine replacement therapy predict impaired HRQoL., (© 2014 John Wiley & Sons Ltd.)

Purpose: Patients treated for pituitary adenomas generally report a reduced quality of life (QoL). At present, the patient's perspective of QoL has not been fully addressed and this, and further insight in potential determinants of QoL in pituitary diseases is required to design strategies to improve QoL. We aimed to define patients' perceived QoL and to identify potential factors they perceive to contribute to QoL., Methods: We conducted four independent focus groups of six patients each, per specific pituitary disease (Cushing's disease, Non-functioning pituitary macroadenoma, acromegaly, prolactinoma). In two sessions these focus groups discussed aspects of QoL. Verbatim transcripts were analyzed using a grounded theory approach., Results: The issues raised by the patient groups were compatible with statements and items of available QoL questionnaires. In addition, other QoL aspects emerged, such as visual limitations (physical problems); issues with a desire to have children/family planning, fear of collapsing, fear of recurrence, panic, persisting thoughts, problems with an altered personality, anger, jealousy, sadness, frustration (psychological problems); and difficulties communicating about the disease, lack of sympathy and understanding by others, and a reduced social network (social problems). Next, this study uncovered factors which might contribute to a decreased QoL (e.g. less effective coping strategies, negative illness perceptions, negative beliefs about medicines, unmet needs regarding care)., Conclusions: This focus group study demonstrated that important disease-specific aspects of QoL are neglected in current pituitary disease-specific questionnaires and elucidated potential factors that contribute to a decreased QoL. Information provided in this study can (and will) be used for developing additional items for disease-specific QoL questionnaires and for the development of a self-management intervention aiming to improve QoL in patients treated for pituitary diseases.

Context: GH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of studies dealing with this topic., Objective: We conducted a meta-analysis of studies examining the effects of acromegaly on bone turnover, bone mineral density (BMD), and fractures. Furthermore, we evaluated the effects of sex, gonadal status, and activity of disease on skeletal end-points in acromegaly., Data Sources: We conducted MEDLINE and EMBASE systematic searches up to December 31, 2013., Study Eligibility Criteria: Studies conducted in patients with acromegaly and reporting at least one determinant of skeletal fragility., Data Extraction and Analysis: Study design, patient characteristics, interventions, and outcomes were independently extracted by two authors. We calculated the standardized mean difference (SMD) of bone turnover and BMD differences, whereas fractures were presented as relative frequencies in acromegaly and odds ratios between patients and controls., Results: Forty-one studies fulfilled eligibility criteria and were therefore selected for data extraction and analysis. A total of 1935 patients were included (eight to 206 per study). Acromegaly patients had higher bone formation (SMD, 1.49; 95% confidence interval [CI], 0.97-2.01; P < .0001) and bone resorption (SMD, 1.57; 95% CI, 1.03-2.10; P < .0001) as compared to control subjects, without significant differences in lumbar spine BMD. BMD at the femoral neck tended to be higher in acromegaly patients vs control subjects (SMD, 0.67; 95% CI, 0.07-1.27; P = .03). Patients with acromegaly had high frequency of vertebral fractures (odds ratio, 8.26; 95% CI, 2.91-23.39; P < .0001), in close relationship with male gender, hypogonadism, and active acromegaly., Limitations: LIMITATIONS included heterogeneous study protocols with possible variability in the assessment of skeletal end-points., Conclusions: Skeletal fragility is an emerging complication of acromegaly.

Purpose: The aim of this study was to compare topographic and biomechanical properties of corneas in patients with acromegaly with those of healthy individuals., Methods: Thirty-five patients with acromegaly (study group) and 35 healthy individuals (control group) were enrolled in this prospective study. Topographic measurements, including central corneal thickness (CCT), mean keratometry (K) value, K1, K2, surface asymmetry index, corneal volume (CV), and anterior chamber depth in the right eye of each participant were obtained using a Scheimpflug camera with a Placido disc topographer (Sirius; Costruzione Strumenti Oftalmici). Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOP), and Goldmann-corelated intraocular pressure (IOPg) were measured using Reichert Ocular Response Analyzer (Reichert Ophthalmic Instruments)., Results: Mean CCT, CV, CH, CRF, and IOPg values were higher in acromegalic eyes (549.3 ± 30.2 μm, 59.1 ± 3.1 μm, 11.3 ± 1.2 mm Hg, 11.3 ± 1.2 mm Hg, and 17.5 ± 2.9 mm Hg, respectively) than in healthy eyes (531.4 ± 33.6 μm, 57.4 ± 2.7 μm, 10.4 ± 1.2 mm Hg, 10.2 ± 1.6 mm Hg, and 14.8 ± 3.1 mm Hg, respectively; CCT, P = 0.042; CV, P = 0.032; CH, P = 0.044; CRF, P = 0.035; IOPg, P < 0.001)., Conclusions: CCT, CV, CH, CRF, IOPg, and IOP with Goldmann applanation tonometry were significantly higher in acromegalic eyes. These corneal topographic and biomechanical properties, disease duration, and disease status should be considered when planning corneal refractive surgery and determining accurate intraocular pressure in patients with acromegaly.

Introduction: Although prolonged small intestine and colonic transit time has been demonstrated in acromegaly patients, the influence of acromegaly on oesophagus motility and the pathological mechanisms involved are still not clarified. We aimed to investigate manometric measurements to ascertain whether oesophagus motility is affected in active acromegaly patients., Material and Methods: The study was performed in an institutional referral centre at a tertiary care hospital. Twenty-three acromegaly patients (mean age 43.2 ± 13.2 years) and 25 sex- and age-matched healthy control subjects (mean age 48.6 ± 7.9 years) were recruited to a case-control study. Oesophageal manometry was performed using MMS (Medical Measurement Systems, Netherlands) Solar GI - Air Charged Intelligent Gastrointestinal Conventional Manometry., Results: In manometric measurements the lower oesophageal sphincter pressure was 18 ± 7 mmHg in acromegaly patients and 15.6 ± 4.4 mm Hg in controls, and there was no significant difference (p = 0.17). The percentage of relaxation was 64.8% and 81.8%, respectively, and it was significantly lower in acromegaly patients than in controls (p < 0.001). Additionally, the duration of relaxation was found to be 4 ± 1.9 seconds and 5 ± 1.7 seconds in patients and controls, respectively (p = 0.049)., Conclusions: Our study has demonstrated a significant reduction in the percentage and duration of lower oesophageal sphincter relaxation in oesophagus motility even in acromegaly patients without any gastrointestinal symptoms. Further clinical and pathophysiological studies are required to clarify the underlying mechanisms of gastrointestinal motility disorders in acromegaly.

Background: Obese, non-acromegalic persons show lower growth hormone (GH) concentrations at fasting and reduced GH nadir during an oral glucose tolerance test (OGTT). However, this finding has never been studied with regard to whole-body insulin-sensitivity as a possible regulator., Methods: In this retrospective analysis, non-acromegalic (NonACRO, n = 161) and acromegalic (ACRO, n = 35), non-diabetic subjects were subdivided into insulin-sensitive (IS) and -resistant (IR) groups according to the Clamp-like Index (CLIX)-threshold of 5 mg · kg(-1) · min(-1) from the OGTT., Results: Non-acromegalic IS (CLIX: 8.8 ± 0.4 mg · kg(-1) · min(-1)) persons with similar age and sex distribution, but lower (p < 0.001) body-mass-index (BMI = 25 ± 0 kg/m2, 84% females, 56 ± 1 years) had 59% and 70%, respectively, higher (p < 0.03) fasting GH and OGTT GH area under the curve concentrations than IR (CLIX: 3.5 ± 0.1 mg · kg(-1) · min(-1), p < 0.001) subjects (BMI = 29 ± 1 kg/m2, 73% females, 58 ± 1 years). When comparing on average overweight non-acromegalic IS and IR with similar anthropometry (IS: BMI: 27 ± 0 kg/m2, 82% females, 58 ± 2 years; IR: BMI: 27 ± 0 kg/m2, 71% females, 60 ± 1 years), but different CLIX (IS: 8.7 ± 0.9 vs. IR: 3.8 ± 0.1 mg · kg(-1) · min(-1), p < 0.001), the results remained almost the same. In addition, when adjusted for OGTT-mediated glucose rise, GH fall was less pronounced in IR. In contrast, in acromegalic subjects, no difference was found between IS and IR patients with regard to fasting and post-glucose-load GH concentrations., Conclusions: Circulating GH concentrations at fasting and during the OGTT are lower in non-acromegalic insulin-resistant subjects. This study seems the first to demonstrate that insulin sensitivity rather than body-mass modulates fasting and post-glucose-load GH concentrations in non-diabetic non-acromegalic subjects.

Purpose of Review: To provide an update on current understanding of osteoporosis associated with acromegaly., Recent Findings: Patients with acromegaly have an increased risk of morphometric vertebral fractures. This seems to correlate with acromegaly activity and its duration, but it persists after biochemical control is achieved. Coexistent hypogonadism, diabetes mellitus and over-replacement with glucocorticoids have additional detrimental effects. Bone mineral density can be normal, increased or decreased, and is usually discordant with occurrence of fractures. However, a decrease in the hip bone mineral density during follow-up has been associated with development of new vertebral fractures. Bone turnover markers are increased and tend to normalize after biochemical control of acromegaly. Hypercalcemia rarely occurs in acromegaly and may be parathyroid hormone-dependent or 1,25 dihydroxy-vitamin D dependent. The latter improves with biochemical control of acromegaly., Summary: Screening with thoracic and lumbar vertebral radiographs is indicated in patients with acromegaly. We recommend biochemical control of acromegaly, treatment of hypogonadism and other risk factors of osteoporosis and avoiding supraphysiologic doses of glucocorticoids. Further studies are needed to understand mechanisms of skeletal fragility in acromegaly and clinical impact of vertebral fractures. Further studies of tailored therapy for patients with acromegaly and osteoporosis are also needed.

Objective: To evaluate gynecological problems of female patients with acromegaly and the relationship of these problems with the activity of the disease., Study Design: Thirty-four women with acromegaly and 27 age- and body mass index-matched female healthy controls (HC) were included in the study. Demographic features, medical history, hormonal status and disease activity were obtained. A detailed gynecological examination was performed., Results: The incidence of pelvic organ prolapse (POP) was higher in patients with acromegaly (53%, n=18) compared to the HC (15%, n=4) (p=0.003). Limiting the analysis to only cases with previous pregnancy, POP was seen in 18 (60%) of 30 cases with acromegaly and in 4 (20%) of 20 of the HC (p=0.005). Additionally, in cases with prior vaginal delivery, POP was present in 18 (60%) of 30 cases with acromegaly and in 4 (24%) of 17 of the HC (p=0.02). The frequency of POP was similar in patients with controlled and uncontrolled acromegaly (p=0.3)., Conclusion: Acromegaly may facilitate occurrence of pelvic organ prolapse and may cause additional health issues in female cases., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aim of the Study: To describe morphological and functional cardiovascular changes in acromegaly (ACM) patients, as well as to investigate the ability of Doppler-based myocardial deformation imaging (DMI) to characterize subtle dysfunction in ACM., Methods: 69 patients (pts) with ACM (mean age 47 ± 10 years, 27 men) and 31 controls (mean age 43 ± 16 years, matched for age and gender) were recruited. Standard echocardiography and DMI data were obtained for all patients. Peak systolic longitudinal strain values (S) were determined for the left and right ventricles. Radial S was measured at the level of the mid inferolateral segment. Using a high-resolution echo-tracking system, the main indices of arterial stiffness were measured., Results: Of the ACM subjects, 57 had active disease (group A), and 12 controlled ACM (group B). All pts with ACM presented structural changes: a higher LV indexed mass (112 ± 36, 118 ± 23 vs 74 ± 18 g/m(2), p < 0.001) and a higher relative wall thickness (0.45 ± 0.09, 0.50 ± 0.07 vs 0.40 ± 0.07, p = 0.003) compared to controls. Also, ACM pts had functional changes: reduced LV ejection fraction (57 ± 5, 55 ± 5 vs 64 ± 4%, p < 0.001) and altered diastolic function (E/A 1.0 ± 0.4, 1.1 ± 0.1 vs 1.3 ± 0.3, p = 0.005) compared to controls. Both longitudinal and radial LV S values were lower in ACM compared to controls: -16.5 ± 3.5, -16.8 ± 4.3 vs -21.5 ± 3.8%, p < 0.001 for longitudinal and 38.3 ± 12.3, 35.6 ± 11.8 vs 52.2 ± 11.7%, p = 0.002 for radial strain., Conclusions: ACM pts present LV concentric hypertrophy and LV systolic and diastolic dysfunction, even in controlled disease. Altered global LV systolic function appears to be due both to longitudinal and radial dysfunction.

Objective: Control of acromegaly may ameliorate blood pressure (BP) in hypertensive (HT) patients. We evaluated the impact of acromegaly control on BP values of normotensive (NT) acromegalics., Design: Retrospective cohort study., Patients: Fifty-eight naïve patients with acromegaly (39 F; age range, 30-69 years), including 28 NT and 30 HT subjects, participated in the study., Measurements: Blood pressure was measured by clinical measurement and 24-h ambulatory monitoring at diagnosis and after 24 months of medical therapy for acromegaly., Results: Acromegaly was controlled by medical therapy in 15 NT and 17 HT patients at 24 months. In the NT group, systolic (SBP) or diastolic (DBP) BP significantly increased (all P < 0·005) when acromegaly was uncontrolled, but did not change when the disease was controlled. Changes in SBP and DBP were also significantly different between uncontrolled and controlled NT patients. At 24 months, clinical hypertension was detected only in uncontrolled NT patients (46% vs 0%, P < 0·001), whereas ambulatory hypertension was found in 38% of uncontrolled and in 7% of controlled NT subjects (P = 0·035). In the HT group, ambulatory SBP increased in patients with uncontrolled acromegaly (24-h SBP P = 0·046, day SBP P = 0·005, night SBP P = 0·005), whereas ambulatory DBP decreased in subjects with controlled disease (24-h DBP P = 0·008, day DBP P = 0·026)., Conclusions: Control of acromegaly has a beneficial effect on BP regulation either in HT or NT subjects; in the latter, it may prevent progression towards hypertension., (© 2014 John Wiley & Sons Ltd.)

Purpose: To investigate the effect of acromegaly on corneal biomechanical parameters., Methods: This cross-sectional, comparative clinical study included 34 acromegalic patients and 30 age-matched and sex-matched healthy controls. Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated and corneal-compensated intraocular pressure (IOPg and IOPcc, respectively) were measured using the Ocular Response Analyzer. Central corneal thickness (CCT) was determined with the ultrasonic pachymeter., Results: The mean duration of disease for the acromegalic patients was 5.3 years. There was no significant difference between the groups regarding mean CH, CRF, IOPg and IOPcc values. The respective mean values in patients with acromegaly and controls were 10.3 ± 2.2 and 9.5 ± 1.5 mmHg (p = 0.13) for CH; 10.5 ± 2.4 and 9.7 ± 1.7 mmHg (p = 0.16) for CRF, 16.1 ± 3.6 and 15.5 ± 2.9 mmHg (p = 0.49) for IOPg, 16.8 ± 3.4 and 17.0 ± 2.8 mmHg (p = 0.82) for IOPcc, and 544.8 ± 32.2 and 530.7 ± 22.9 μm (p = 0.05) for CCT. A significant moderate correlation was detected between the duration of acromegaly and IOPg OD (r = 0.430, p = 0.01). There was no significant correlation between other ocular parameters and levels of GH and IGF-1 at the time of diagnosis, the status of control, adenoma type, radiotherapy treatment, and drug usage., Conclusions: In acromegalic patients, the duration of disease was correlated with IOPg OD level. Corneal biomechanical parameters and CCT values were not significantly different than those in age-matched and sex-matched healthy individuals.

Aims: The aim was to compare the intraocular pressure (IOP), central corneal thickness (CCT), and optic disc topography findings of biochemically controlled acromegalic patients and the control group and to evaluate the effect of the duration of acromegaly and serum growth hormone and insulin-like growth factor-1 (IGF-1) levels on these ocular parameters., Materials and Methods: IOP measurement with Goldmann applanation tonometry, CCT measurement with ultrasonic pachymetry, and topographic analysis with Heidelberg retinal tomograph III were performed on 35 biochemically controlled acromegalic patients and 36 age- and gender-matched controls., Results: Mean IOP and CCT were 14.7 ± 2.9 mmHg and 559.5 ± 44.9 μm in the acromegaly patients and 13.0 ± 1.6 mmHg and 547.1 ± 26.7 μm in controls (P = 0.006 and P = 0.15, respectively). A significant moderate correlation was found between the duration of acromegaly and CCT (r = 0.391) and IOP (r = 0.367). Mean retinal nerve fiber layer (RNFL) thickness was significantly lower in the acromegalic patients (0.25 ± 0.05 mm) as compared to controls (0.31 ± 0.09 mm) (P = 0.01). A significant moderate correlation was detected between IGF-1 level and disc area (r = 0.362), cup area (r = 0.389) and cup volume (r = 0.491)., Conclusion: Biochemically controlled acromegalic patients showed significantly higher CCT and IOP levels and lower RNFL thickness compared to healthy controls and the duration of disease was correlated with CCT and IOP levels.

Introduction: Acromegaly is a disorder with increased morbidity which can involve many organs and the eye can be one of them which was investigated in few reports. Herein, we aimed to evaluate CCT, IOP and retinal thickness (RT), and their relationships with serum GH and IGF-1 levels and disease duration, in acromegaly patients. We compared the ocular parameters with those of a control group. This study included the largest number of patients of any comparable investigation to date., Material and Method: We enrolled 30 acromegaly patients (15 male, 15 female and age: 48.4 ± 12.8 years) and 21 age and gender matched controls. All participants underwent complete hormonal and ophtalmological evaluation including central corneal thickness (CCT), retinal thickness (RT) and intraocular pressure (IOP) values., Results: There were no significant differences in median right and left CCTs and mean CCT (p = 0.646, p = 0.667 and p = 0.384, respectively). Nor were there statistically significant differences in median right and left RT, or mean central RT, between the acromegaly and control groups (p = 0.977, p = 0.738 and p = 0.811, respectively). However median right, left and mean IOPs were found to be significantly higher in the acromegaly group, despite there being no difference in the CCT values (p = 0.011, p = 0.028 and p = 0.047, respectively). When we analyzed two subgroups of acromegaly patients (active/inactive), we found that the median right, left and mean CCTs and RTs, were not significantly different between the groups. Although there was a significant difference in IOP between the acromegaly and control groups, the two subgroups of acromegaly patients had similar IOPs (p = 0.400, p = 0.621 and p = 0.451 for right, left and mean IOPs, respectively). IOP was not found to be correlated with serum IGF-I, GH or disease duration in acromegaly patients., Conclusion: Our study results suggest that acromegaly is associated with increased ocular pressures irrespective of disease activity. Therefore detailed ocular evaluation should be a routine component of the follow up visits of acromegaly patients.

Objective: There are still contradictory data in the literature whether patients with acromegaly are under risk in terms of atherosclerotic heart disease. Increased arterial stiffness develops before atherosclerosis and is evaluated to be a risk factor for atherosclerosis. Mean platelet volume (MPV) is currently gaining interest as a new independent cardiovascular risk factor. There are contrasting views about arterial stiffness in patients with acromegaly. There is no report in literature studying MPV in acromegaly patients. The aim of this study was to evaluate MPV and arterial stiffness in patients with acromegaly., Methods: This study was designed as an observational cross-sectional, case-controlled study. Twenty-eight patients with acromegaly and 22 healthy volunteers were recruited for the study. The arteriography device Mobil-O-Graph® (IEM GmbH. Stolberg, Germany) which can perform oscillometric measurements was used to measure arterial stiffness. The Mann-Whitney U test, Student's t-test, Spearman's nonparametric correlation analysis and the chi-square test were used to statistical analyze., Results: Aortic pulse wave velocity (PWV) value was found to be 6.41 ± 2.12 m/s in the patient group with active acromegaly and 5.24 ± 1.04 m/s in the healthy control group. The difference was statistically significant (p=0.03). The mean MPV value was found to be 9.68 ± 1.11 in the patient group with active acromegaly and 8.53 ± 1.18 in the healthy control group. There was a statistically significant difference between the two groups (p=0.004). In patients with acromegaly, a positive correlation was found between MPV and insulin-like growth hormone-I (IGF-1) level (p=0.021, r=0.434)., Conclusion: We determined an increase in aortic PWV and MPV in patients with acromegaly. In conclusion, evaluation of MPV and arterial stiffness in future studies could be beneficial in determining the risks for cardiovascular disease in patients with acromegaly.

Purpose: To evaluate central corneal thickness (CCT) and intraocular pressure (IOP) in a cohort of acromegalic patients, and to correlate CCT with serum levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1)., Methods: Consecutive patients affected by acromegaly underwent a comprehensive endocrinological and ophthalmological evaluation, including serum GH and IGF-1 levels, CCT measured with ultrasonic pachymetry and IOP assessed with Goldmann applanation tonometry., Results: Fourteen patients with acromegaly and 28 healthy controls were included in the study. Acromegalic patients had a statistically higher median CCT (570 μm [range 551.5-638] vs 542.7 μm [range 461.5-610]; p < 0.01) and higher median IOP (17.2 mm Hg [range 14-21] vs 13.7 mm Hg [range 10.5-19]; p < 0.01) than healthy controls. No statistically significant correlation was found among CCT and GH, CCT and IGF-1, IOP and GH, IOP and IGF-1 in the acromegalic group, whereas a statistically significant correlation was documented between CCT and IOP in the entire cohort (Spearman's correlation coefficient: 0.56, p < 0.01). However, when IOP was corrected for CCT no significant difference was found between the two study groups (p = 0.07)., Conclusions: Our results suggest that acromegaly is associated with an increased CCT, which could lead to an overestimation of IOP readings as determined with Goldmann applanation tonometry.

This article, the last in the life sciences series, is the second of two articles on the endocrine system. It discusses human growth hormone, the pancreas and adrenal glands. The relationships between hormones and their unique functions are also explored. It is important that nurses understand how the endocrine system works and its role in maintaining health to provide effective care to patients. Several disorders caused by human growth hormone or that affect the pancreas and adrenal glands are examined.

Purpose: Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess in acromegaly have various effects on many organs. The ophthalmologic effects of GH and IGF-1 excess have not yet been investigated in detail. The aim of the current study is to compare the corneal biomechanical properties of patients with acromegaly and those of healthy subjects., Methods: 45 patients with acromegaly (F/M=27/18) and 42 age-matched and gender-matched healthy individuals (F/M=24/18) were enrolled in this cross-sectional study. Central corneal thickness (CCT), corneal resistance factor (CRF), corneal hysteresis (CH), corneal compensated intraocular pressure (IOPcc) and Goldmann correlated IOPG were measured in patients with acromegaly and in healthy individuals using the Ocular Response Analyser (ORA). GH and IGF1 values were also determined in the study group., Results: The mean CH and CRF values were higher in acromegalic patients (12.1±2.2 and 12.3±2.4, respectively) than in healthy subjects (11.0±1.6 and 10.8±1.5, respectively; for CH, p=0.014; for CRF, p=0.001). Mean IOPG measurement was higher in the acromegaly group than in the control group (p=0.017). There was no statistically significant difference in measured CCT (p=0.117) and IOPcc (p=0.594) values between acromegalic patients and healthy subjects., Conclusions: These findings indicate that acromegaly has target organ effects on the eye. Consequently, it can change corneal biomechanical properties such as corneal hysteresis and the CRF. Corneal biomechanical properties are known to affect the accuracy of IOP measurements. These findings should be taken into account when measuring IOP values in acromegaly patients, as IOP readings may be overestimated.

Cutis verticis gyrata (CVG) is a descriptive term for a dermal sign in which deep furrows and convoluted ridges are seen upon the scalp. They are formed due to thickening of the skin folds of the scalp and produce an appearance that resembles the gyri of the brain. The condition is classified primary when the etiology is unknown or neurologically based. CVG will be considered secondary when a definite cause, systemic or localized, is responsible for the sign. We describe a 34 year-old male who was presented with a one-month history of arthralgia in his interphalangeal joints. His physical examination revealed scalp changes compatible with CVG, which appeared 3 years earlier. Following a thorough investigation of the patient, acromegaly was diagnosed. Although CVG is a rare condition, it has been described in patients with acromegaly. The appearance of SVG as an early sign of acromegaly makes this case unique and important. In a patient developing CVG, acromegaly and other treatable disorders should always be excluded.

Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with acromegaly.

Objectives: Acromegaly is a metabolic disorder caused by increased growth hormone secretion. As a consequence of acromegaly some typical craniofacial morphology changes appear. This pilot study was conducted to compare the bite force and the characteristic size and shape of the craniofacial components of acromegalic patients with the healthy Turkish individuals. In addition, the correlations between bite force and craniofacial morphology of patients with acromegaly and control individuals were evaluated., Study Design: The maximum bite force of the participants was recorded with strain-gage transducer. Lateral x-ray scans were made under standard conditions, in centric occlusion. On cephalograms, the linear and angular measurements was performed., Results: Patients with acromegaly showed increased anterior and posterior total face height, ramus length, width of frontal sinuses, gonial angle and a negative difference between maxillary and mandibular protrusions. In addition, females with acromegaly showed larger lower anterior face height and sella turcica, decreased facial angle, increased mandibular plane angle. The cephalometric measurements, except one did not showed correlation with the bite force in acromegalic patients. In control group, significant correlations were observed between anterior total face height and anterior lower face height, mandibular plane angle and gonial angle., Conclusions: The greater changes were observed in the mandible. The maximum bite force of patients with acromegaly showed no difference from healthy individuals. The non-significant difference of bite force between healthy participants and acromegalic patients provide important information for dental treatment and prosthetic rehabilitation of acromegalic patients.

Acromegaly is a chronic debilitating disease that presents with multiple systemic manifestations, including changes in body composition, joint abnormalities, muscular impairment and visual disturbances. This study aimed to assess posture and body balance in acromegalic patients and to establish the correlation between these measures. Twenty-eight acromegalic patients and a similar number of control subjects matched for sex, age, weight, height and body mass index underwent postural evaluation using the photogrammetry and measurement of balance using the stabilometry in two tasks: feet apart, eyes open and feet together, eyes closed. In comparison with the control group, the acromegalic group presented postural deviations in lateral views in the vertical alignment of the trunk (P=0.001 for the right side and P=0.021 for the left), the hip angle (P=0001 for the right side and P=0.016 for the left side) and horizontal alignment of the pelvis (P=0.017 for the right and P<0.001 for the left side). Compared with healthy subjects, the acromegalic patients presented displacement of the centre of pressure in both the anterior-posterior direction and the medial-lateral direction in both evaluated tasks. We observed significant correlations between balance measures and the following posture evaluation variables: distance between the lower limbs, horizontal alignment of the head and vertical alignment of the head. Our results suggest that posture and balance need to be evaluated for acromegalic patients in clinical practice, as there are significant postural imbalances and deviations in these patients., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Context and Objective: The interaction between pregnancy and acromegaly has been studied only retrospectively. We used prospective data to assess those interactions., Design: Prospective, interventional, multicentric study., Patients: TEN PREGNANCIES IN EIGHT ACROMEGALIC PATIENTS WERE INCLUDED ACCORDING TO THE FOLLOWING CRITERIA: previous diagnosis of acromegaly; and active acromegaly before pregnancy. Sellar magnetic resonance image (MRI), GH, and IGF1 measurements were carried out before pregnancy. The exclusion criterion was radiotherapy., Intervention: Withdrawal of pharmacological treatment (octreotide and/or cabergoline and/or pegvisomant) following pregnancy diagnosis., Main Outcome Measures: Clinical/biochemical evaluations throughout pregnancy/puerperium and sellar MRI after delivery; and GH and IGF1 measurements before pregnancy. GH was measured by an interference-free IFMA assay during pregnancy and IGF1 by measured by Immulite 2000 assay in patients and 64 control pregnancies., Results: No tumor growth was observed. Nine deliveries were at term and one at 35 weeks (preeclampsia). All newborns were healthy. Mean IGF1 levels before and during pregnancy were similar, but increased significantly during puerperium. As IGF1 in controls increased after midgestation, the prevalence of controlled IGF1 rose significantly from 2/10 (<20 weeks) to 9/10 (>30 weeks). Diabetes mellitus and hypertension/preeclampsia developed in one patient in each group; both complications were nonsignificantly (P=0.06) associated with IGF1 >1.3 ULN before pregnancy., Conclusions: Acromegaly control usually improved and tumor growth was not stimulated during pregnancy in spite of withdrawal of drug treatment. Drug treatment can be discontinued in most patients. Uncontrolled disease before pregnancy may pose a higher risk for diabetes and hypertension.

The aim of this study was to systematically assess health care utilisation, diagnostic delay and psychosocial impairment in patients with acromegaly in rural versus urban health care environments. 41 patients with acromegaly were questioned to time lapse of symptom onset, first seeking medical advice and time of acromegaly diagnosis. Quality of life (QoL), and psychosocial impairment (depression, daytime sleepiness, sleep disturbances, disturbances of body image) were measured by self-assessment questionnaires. Patients were grouped into living in rural health care environments (RHCE, n = 22 patients) or urban health care environments (UHCE, n = 19 patients) using data on population density from the German Federal Statistical Office. RHCE patients waited significantly longer (2.5 vs. 0.89 years; p = .025) after symptom onset before seeking medical advice, but diagnosis of acromegaly was established at least as quickly as in UHCE (1.45 vs. 2.74 years; n.s.). There was a consistent trend toward more psychosocial impairment in UHCE which reached significance for sleep disturbances (p = .004). For all patients significant correlations between time delay of diagnostic process (defined as first visit to the doctor because of acromegaly-related symptoms and establishment of acromegaly diagnosis) and psychological QoL, depression, daytime sleepiness, sleep disorders and body image emerged. Patients with acromegaly in UHCE experienced more psychosocial impairment than patients in RHCE. The correlation of significantly increased psychosocial impairment and delay of diagnosis by the physician may reflect long-lasting embitterment in patients with acromegaly and should be considered during psychosocial counselling.

Background: In active acromegaly, pathologically elevated GH and IGF-1 levels are associated with increased bone turnover and a high bone mass, the latter being sustained after normalization of GH values. In a cross-sectional study design, we have previously reported a high prevalence of vertebral fractures (VFs) of about 60% in patients with controlled acromegaly, despite normal mean bone mineral density (BMD) values. Whether these fractures occur during the active acromegaly phase or after remission is achieved is not known., Objective: Our objective was to study the natural progression of VFs and contributing risk factors in patients with controlled acromegaly over a 2.5-year follow-up period., Methods: Forty-nine patients (mean age 61.3 ± 11.1 years, 37% female) with controlled acromegaly for ≥ 2 years after surgery, irradiation, and/or medical therapy and not using bisphosphonates were included in the study. Conventional spine radiographs including vertebrae Th4-L4 were assessed for VFs according to the Genant method. VF progression was defined as development of new/incident fractures and/or a minimum 1-point increase in the Genant scoring of preexisting VFs. BMD was assessed by dual-energy x-ray absorptiometry (Hologic 4500)., Results: Prevalence of baseline VFs was 63%, being highest in men, and fractures were unrelated to baseline BMD. VF progression was documented in 20% of patients, especially in men and in case of ≥ 2 VFs at baseline. VF progression was not related to BMD values or BMD changes over time., Conclusion: Findings from this longitudinal study show that VFs progress in the long term in 20% of patients with biochemically controlled acromegaly in the absence of osteoporosis or osteopenia. These data suggest that an abnormal bone quality persists in these patients after remission, possibly related to pretreatment long-term exposure to high circulating levels of GH.

Acromegaly is characterized by excessively high GH and IGF1 levels. Recent data suggest that soluble Klotho (sKlotho) is also elevated in patients with active acromegaly. sKlotho decreases towards normal following removal of the GH-producing pituitary adenoma. The Klotho gene was identified in mice following its accidental disruption by ectopic DNA. It is an ageing suppressor gene of restricted expression (mainly in kidneys, brain, and parathyroid and pituitary glands) encoding a transmembrane protein, mKlotho. mKlotho serves as a co-receptor in fibroblast growth factor 23 (FGF23) signalling. FGF23 promotes urinary phosphate excretion and inhibits the synthesis of calcitriol. The ectodomain of mKlotho is enzymatically released to result in a humoral factor, sKlotho, which exerts systemic effects (on ion channels and signalling pathways), possibly by working as an enzyme that modifies glycans of cell surface glycoproteins. GH enhances renal phosphate reabsorption and calcitriol production, i.e. exerts effects in the proximal tubule opposing those attributed to mKlotho, and attenuates calciuria in the distal tubule similar to sKlotho. sKlotho can be measured in extracellular fluids (serum, urine and cerebrospinal fluid (CSF)) by an ELISA. In line with predominant expression of Klotho in kidneys and choroid plexus, concentrations of sKlotho are particularly high in urine and CSF. Determination of sKlotho in serum and urine (both presumably reflecting GH action on the kidneys) could be used as a supplementary tool in the diagnosis and follow-up of patients with acromegaly. The question arises whether GH exerts selected actions via modifying activities of Klotho.

Pituitary tumors are the third most common primary intracranial neoplasm. Pathologic proliferation of the somatotrophs results as overproduction of growth hormone presenting as acromegaly. In pituitary adenomas typical visual field (VF) defect is bitemporal hemianopsia but tumor size and optic chiasmal position may cause variable VF defects and VF examination may remain normal. We retrospectively reviewed the medical records of 23 acromegalic patients with pituitary adenomas who received VF tests in the Department of Ophthalmology and Endocrinology, Ondokuz Mayis University Hospital, between 2000 and 2012. Pituitary tumor volume was calculated after performing measurements of tumor diameter in three orthogonal planes using Cavalieri's principle. VF test was performed with a Humphrey field analyzer 750 using a 4-mm² Goldmann size III stimulus. The mean age of the 23 patients (11 male/12 female) was 50.4 ± 11.9 years. 15 patients (65.2 %) had normal VF, two patients (9 %) had quadrantanopsia, three patients (13 %) had hemianopsia and three patients (13 %) had three quadrantanopsia. Among the patients with normal VF, four patients had a suprasellar mass that was elevating the chiasm and spreading along the optic tracts. We also observed VF defects typical of a chiasmal compression even though no suprasellar extension was detected in a few cases. Tumor volume of the patients with VF defects was significantly larger than tumor volume of patients with normal VF (p = 0.02). Tumor volume is an important parameter in VF defects. Advanced neuroimaging assesments should always be complemented in patients even with normal VF.

Background: Acromegaly may lead to balance disturbances and fear of falling due to changes in body composition and co-morbidities., Aim: The aim of this study was to evaluate balance and fear of falling in acromegalic patients and their relation with disease characteristics., Materials and Methods: Forty-eight acromegalic patients and 41 age- and gender-matched controls were enrolled in the study. The median ages of the patients and controls were 48 (25-75) and 50 (25-67) yr, respectively. Berg Balance Scale (BBS) and one-leg stance test (OLST) were used to compare dynamic and static balance respectively, 50 meters walking test was used to compare functional capacity and falls efficacy scale-international (FES-I) was used to compare fear of falling between the groups., Results: Balance tests (BBS and 50 meter walking test) and fear of falling (FES-I) were significantly disturbed in patients compared with controls. There was no significant difference in OLST. BBS and OLST were negatively and FES-I was positively correlated with age. FES-I was negatively correlated with BBS and OLST was positively correlated with 50 meters walking test. Only OLST was negatively correlated with disease duration. Logistic regression analysis revealed that balance was not affected by the presence of co-morbidities, postoperative vision loss and disease control., Conclusions: This is the first study showing that balance is disturbed in acromegalic patients. This disturbance is not related to disease control and co-morbidities but somewhat to disease duration.

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., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Acromegaly is associated with a variety of cardiovascular disturbances such as left ventricular hypertrophy, diastolic cardiac dysfunction, and hypertension. Left ventricular (LV) dyssynchrony means the impairment of synchronicity and is defined as the loss of the simultaneous peak contraction of corresponding cardiac segments. The objective of this study was to investigate whether acromegalic patients have left ventricular dyssynchrony. Dyssynchrony was evaluated in 30 patients with active acromegaly and 30 controls. All the patients and controls were subjected to a tissue synchronization imaging. The time to regional peak systolic tissue velocity (Ts) in LV by the six-basal-six-mid-segmental model was measured on ejection phase TSI images and four TSI parameters of systolic dyssynchrony were computed. All TSI parameters of LV dyssynchrony increased in patients with acromegaly compared to the controls: the standard deviation (SD) of the 12 LV segments Ts (43.5 ± 13.5 vs 26.2 ± 12.5, p < 0.001); the maximal difference in Ts between any 2 of the 12 LV segments (133.3 ± 38 vs 84.6 ± 37.6, p < 0.001); the SD of the 6 basal LV segments (41.1 ± 15.9 vs 25.4 ± 14.8, p = 0.001); and the maximal difference in Ts between any 2 of the 6 basal LV segments (102.6 ± 37.5 vs 65.2 ± 36.9, p = 0.001). In addition, there were significant relationships between the levels of growth hormone/insulin-like growth factor-1 and Ts-SD-12. LV synchronicity has been impaired in patients with acromegaly. Left ventricular dyssynchrony is associated with disease activity and it may contribute to the harmful cardiovascular effects of acromegaly.

Context: Traditionally, acromegaly is viewed as a disease resulting from GH hypersecretion from an autonomous pituitary somatotropinoma., Objective: To test the hypothesis that GH secretion in acromegaly is still subjected to normal hypothalamic control, we studied the daily rhythmicity of GH secretion in normal controls and patients with newly diagnosed, untreated acromegaly., Design and Setting: This was an observational inpatient study in the General Clinical Research Center at the University of Michigan., Patients or Other Participants: One hundred four normal controls and 67 acromegalic patients were included in the study., Intervention: The intervention consisted of frequent blood sampling over 24 hours., Main Outcome Measure(s): We hypothesized that acromegalic patients would show rhythmicity, sexual dimorphism, and age-related decline of GH secretion similar to normal controls., Results: Both normal controls and the patients exhibited 3 major GH waves with the highest values at 12:00 pm, 5:00 pm, and 1:00 am (P < .001 for all). Both controls and patients exhibited a clear appearance of the nocturnal GH waves, irrespective of the gender (P < .001 for all). The amplitude of the maximal (nocturnal) GH secretory wave (1:00 am) as compared with the nadir GH secretion (9:00 am) was clearly different between the 2 groups, with a significantly smaller magnitude in acromegaly (P < .001). A subsequent subanalysis of both groups was performed separately for both genders. Similar to the entire groups, both controls and patients exhibited a clear appearance of the nocturnal GH waves, irrespective of the gender (P < .001 for all). Patients with clearly elevated GH values have shown an age-related decline of GH secretion (r = -0.35, P < .001), similar to controls., Conclusions: The analysis of GH profiles in multiple patients with untreated acromegaly discloses the persistence of the hallmarks of the central control of GH regulation, ie, nictohemeral rhythmicity, sexual dimorphism, and an age-related decline of GH output.

This study aims to evaluate the presence of arthropathy in the large peripheral joints most commonly affected in acromegaly and to classify the severity according to the functional assessment of each joint to identify any factor that could predict the development of arthropathy and its level of severity. Seventy-one acromegalic patients were interviewed and underwent a physical examination of the knees, hips, and shoulders to identify the presence of arthropathy. The disease was functionally classified as more severe or less severe, according to a specific functional scale. We studied 21 males (29.5%) and 50 females (70.5%) with a mean age of 49.5 ± 14.5 years. Arthropathy in the studied joints was observed in 40 patients (prevalence of 56%), and a statistically significant association with the presence of arthropathy was observed for three of the evaluated factors: increased body mass index (BMI), older age at diagnosis of acromegaly, and female gender. There was no association with disease control or other factors related to acromegaly. We classified 19 patients as having more functionally severe arthropathy and identified two factors associated with its development: increased BMI and lower levels of insulin-like growth factor type I. The relationship of factors such as female sex and BMI, which are also related to osteoarthritis, with arthropathy in acromegalic patients suggested a high prevalence of irreversible joint disease present at diagnosis of acromegaly. We highlight the BMI, which was associated with either the presence of arthropathy or more severe arthropathy, which demonstrates the importance of body weight control in the management of acromegalic patients.

Introduction: Published data suggest that patients with acromegaly have an increased prevalence of prostate disorders., Objective: To evaluate prostatic disorders in acromegalic patients comparing these results after one year of treatment of acromegaly and with a group of healthy men., Materials and Methods: This study was composed of two parts: sectional study comparing patients with healthy controls (baseline) and prospective, longitudinal study (at baseline and after one year of treatment). Forty acromegalic patients were enrolled and evaluated at baseline and after one year with the application of international prostatic symptoms score (IPSS), digital rectal examination, measurements of growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein-3 (IGFBP-3), sex hormone-binding globulin (SHBG), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, total and free prostate-specific antigen (PSA) levels and prostate ultrasonography (US). Thirty healthy men were selected as control group., Results: We stratified patients and controls according to age, considering 40 years-old as cut off. Healthy controls under 40 had IPSS values lower than acromegalic patients. When considering only older patients and controls prostate hyperplasia and structural abnormalities were more frequent in acromegalics. After one year of treatment there was significant decrease in GH, IGF-I and prostate volume in acromegalics over 40 years-old., Conclusions: Acromegalics under 40 have more urinary symptoms according to IPSS and above 40 years-old higher frequency of structural changes and increased prostate volume than healthy men. Significant reduction of GH and IGF-I levels during treatment of acromegaly leads to decrease in the prostate volume.