Search

Purpose: The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis (i.e., higher BSI indicates a lower bone's resistance to loads with consequent higher risk of fractures). We aimed to investigate the association between lumbar BSI and vertebral fractures (VFs) in acromegaly., Methods: Twenty-three patients with acromegaly (13 males, mean age 58 years; three with active disease) were evaluated for morphometric VFs, trabecular bone score (TBS), bone mineral density (BMD) and BSI at lumbar spine, the latter being corrected for the kyphosis as measured by low-dose X-ray imaging system (EOS®-2D/3D)., Results: Lumbar BSI was significantly higher in patients with VFs as compared to those without fractures (2.90 ± 1.46 vs. 1.78 ± 0.33, p = 0.041). BSI was inversely associated with TBS (rho -0.44; p = 0.034), without significant associations with BMD (p = 0.151), age (p = 0.500), BMI (p = 0.957), serum IGF-I (p = 0.889), duration of active disease (p = 0.434) and sex (p = 0.563)., Conclusions: Lumbar BSI corrected for kyphosis could be proposed as integrated parameter of spine arthropathy and osteopathy in acromegaly helping the clinicians in identifying patients with skeletal fragility possibly predisposed to VFs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications., (© 2024. Springer Nature Limited.)

Cardiovascular comorbidities owing to hormonal excess or deficiency are the main cause of mortality in patients with pituitary disorders. In patients with Cushing's Disease, there is an increased prevalence of cardiovascular diseases and/or risk factors including visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia, hypercoagulability as well as structural and functional changes in the heart, like cardiac hypertrophy and left ventricle (LV) dysfunction. Notably, these demonstrate limited reversibility even after remission. Furthermore, patients with acromegaly may manifest insulin resistance but also structural and functional heart changes, also known as "acromegalic cardiomyopathy". Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism as well as endothelial dysfunction. Hypopituitarism and conventional hormonal replacement therapy may also contribute to an unhealthy metabolic status, which promotes atherosclerosis and may lead to premature mortality. This review discusses the literature on cardiovascular risk in patients with pituitary disorders to increase physician awareness regarding this aspect of management in patients with pituitary disorders.

Purpose: In acromegaly, skeletal complications resulted to be associated with low quality of life (QoL) and high risk of falls. The aim of the present study was to perform a quantitative assessment of movement through gait analysis technique in patients with acromegaly., Study Population: Thirty-three acromegalic patients [9 with active disease (AD), 14 with controlled disease (CD) and 10 with disease remission (RD)] and 20 healthy subjects were enrolled for the study., Measurements: Kinetic and kinematic data were collected with 3D-gait analysis. Kinematic data were processed to compute the Gait Profile Score (GPS), a parameter that summarizes the overall deviation of kinematic gait data relative to unaffected population., Results: The acromegalic group showed longer stance phase duration (p < 0.0001) compared to controls. The GPS and several gait variable scores resulted to be statistically higher in the acromegalic group compared to healthy controls. GPS values were significantly higher in AD compared to CD (p < 0.05) and RD groups (p = 0.001). The AD group presented significantly higher values in terms of hip rotation and ankle dorsiflexion compared to CD and RD groups and with regard to the foot progression compared to RD. Interestingly, patients with RD exhibited a more physiological gait pattern., Conclusion: Acromegalic patients showed quantitative alterations of gait pattern, suggesting instability and increased risk of falls. Arthropathy, along with its associated abnormal joint loading, proprioceptive impairment and hyperkyphosis could be contributing factors. Disease control and remission appear to improve postural balance. A better knowledge on walking performance in acromegaly would help to develop specific rehabilitation programmes to reduce falls' risk and improve QoL., (© 2024. The Author(s).)

Objectives: This study aims to investigate whether the middle ear resonance frequency (RF) is affected in acromegaly, which causes growth in the skull bone., Methods: Thirty acromegaly patients and 38 volunteers were included in the study. Pure tone average scores and middle ear RF values of the groups that underwent pure tone audiometry, tympanometry, and multifrequency tympanometry tests were compared., Results: The pure tone mean was 14.95 ± 12.13 in acromegaly patients and 5.70 ± 8.52 in the control group (p:0.18). Sensorineural hearing loss(SNHL) was observed in 16.6% of the patients. The average middle ear RF was calculated as 815 ± 179.05 Hz in patients with acromegaly and 773 ± 127.15 in the control group. (p = 0.0001)., Conclusion: This study is the first to evaluate middle-ear RF in acromegaly patients. Acromegaly-induced changes in soft tissues and bone structures impact middle ear functions. In this patient group, we found an increase in middle ear RF without conductive-type hearing loss and a 16.6% rate of SNHL., Competing Interests: Declaration of competing interest No conflict of interest was declared by the authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species., Design: A comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed., Results: Acromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats. Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine., Conclusion: Acromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Arterial hypertension (AH) that accompanies acromegaly (AC) may lead to cardiovascular dysfunction. Such consequences may be detected with impedance cardiography (ICG), which is a noninvasive method of hemodynamic assessment. Early detection of subclinical hemodynamic alterations in AC patients may be crucial for optimizing treatment and preventing cardiovascular remodeling. The purpose of this study was to identify the hemodynamic parameters of the cardiovascular system that differentiate patients with AC from those in the control group (CG), with a particular emphasis on potential targets for medical therapy., Methods: This observational, prospective, clinical study involved a comparative analysis of 33 AC patients with no significant comorbidities and the controls selected via propensity score matching based on a set of baseline characteristics (age, sex, body mass index, mean blood pressure [MBP]), with comparable proportions of AH patients. The assessed hemodynamic parameters included the stroke volume index (SI), cardiac index, systemic vascular resistance index, velocity index (VI), acceleration index, Heather index (HI), and thoracic fluid content (TFC)., Results: Both the AC group and the CG had well-controlled AH (mean blood pressure of 121/77 mmHg and 119/76 mmHg, respectively). In terms of baseline characteristics, the AC group was characterized by a higher hear rate and lower creatinine levels than the CG (76.2 bpm vs. 66.8 bpm [p = 0.001] and 0.755 mg/dL vs. 0.850 mg/dL [p = 0.035], respectively). ICG assessment of AC patients and CG patients showed the former to have higher heart rates (73.5 bpm vs. 65.2 bpm; p = 0.003), lower SI (43.8 mL/m 2 vs. 53.4 mL/m 2 ; p = 0.0001), lower VI (42.1 1/1000/s vs. 49.3 1/1000/s; p = 0.037), lower HI (8.49 Ohm/s 2 vs. 13.4 Ohm/s 2 , p ≤ 0.0001), and higher thoracic fluid content (TFC) (38.4 1/kOhm vs. 28.1 1/kOhm; p ≤ 0.0001), respectively., Conclusions: Even with well-controlled hypertension, AC is associated with a high TFC, increased heart rate, and decreased indices of cardiac contractility. Hemodynamic changes in AC patients may be detected with the modern, noninvasive diagnostic tool, ICG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jurek, Krzesiński, Gielerak, Witek, Zieliński, Kazimierczak, Wierzbowski, Banak and Uziębło-Życzkowska.)

Background: People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in "shows." Serious medical evaluation began in the late 19th century with the description of acromegaly and its association with pituitary tumors. In the early 20th century, multiple investigators attempted to extract a growth-promoting factor from the anterior pituitary and then, over the decades, to purify it and distinguish it from other anterior pituitary hormones. With relatively pure growth hormone (GH), its biological activity in growth promotion and as a metabolic hormone were studied, and species specificity became apparent: primate GH was the only GH active in man. Human GH was prepared from cadaveric pituitaries and distributed by the NIH to treat children with GH deficiency, but there was never enough pituitary hGH for all of the children who required it. When Creutzfeldt-Jakob disease was found in some patients who received pituitary GH, the production and FDA approval of biosynthetic hGH dramatically accelerated. With a large supply, one could treat those who were GH deficient and test its efficacy in other causes of short stature; longer acting versions of hGH have now been developed, tested, and in a few instances received FDA approval., Summary: It has been a long journey from the description of over- and underproduction of GH in animals to the production and clinical use of the biosynthetic hormones., Key Messages: The efforts of basic scientists led to the extraction and purification of GH. Clinical scientists have expanded the appropriate use of hGH for short children with conditions in addition to GH deficiency., (© 2022 S. Karger AG, Basel.)

Purpose: Acromegaly is a rare disease and is associated with increased cardiovascular (CV) morbidity and mortality, especially in patients with uncontrolled disease. We aimed to analyze the prevalence and severity of cardiomyopathy and valvular heart disease in a large cohort of patients with a confirmed acromegaly diagnosis, at baseline and after treatment., Methods: We retrospectively reviewed an institutional approved database; 190 patients with confirmed acromegaly and follow-up data available (years 2006-2018). Patients with at least one baseline echocardiogram, were included. Demographic, disease control and echocardiogram variables were collected for analysis., Results: Of the 190 patients 110 (58%) had a baseline echocardiogram and 43 (39.1%) had at least one follow-up echocardiogram after surgical, medical or multimodal treatment. Baseline left ventricular hypertrophy (LVH) prevalence was 17.8% (64.7% concentric; 35.3% eccentric), diastolic and systolic dysfunction, and overt cardiomyopathy with heart failure were 15.8, 7.9, and 3.0%, respectively. Concentric remodeling of the left ventricle (LV) was noted in 31.4% of patients without LVH. Valve defects were found in 87.3% of patients (14.6% with significant valvular heart disease)., Conclusion: Early diagnosis of acromegaly and disease control should be attempted to prevent LVH/LV dysfunction and development of valvular heart disease. Concentric LV remodeling develops prior to obvious LV hypertrophy in almost a third of patients with acromegaly, which is a novel finding. Similar to other epidemiological studies, we found a high prevalence of LVH/LV dysfunction. Although possible, reversal of systolic and diastolic dysfunction is sporadic after treatment of acromegaly., (© 2021. Italian Society of Endocrinology (SIE).)

Objective: To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC)., Methods: Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included., Results: Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations., Conclusion: Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease., (© 2021. Italian Society of Endocrinology (SIE).)

Context: Whether cancer risk in acromegaly is increased remains controversial, and the risk of benign tumors has been little studied., Objective: To investigate the incidence of benign and malignant tumors in acromegaly in a nationwide population-based study., Methods: Adult patients diagnosed with acromegaly between 1987 and 2017 were identified in the Swedish National Patient Registry. The diagnoses of benign and malignant tumors were recorded. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) for neoplasms with 95% CIs were calculated using the Swedish general population as reference., Results: The study included 1296 patients (52% women). Mean (SD) age at diagnosis was 51.6 (14.7) years. Median (range) follow-up time was 11.7 (0-31) years. Overall, 186 malignancies were identified in acromegalic patients compared with 144 expected in the general population (SIR 1.3; 95% CI 1.1-1.5). The incidence of colorectal and anal cancer (SIR 1.5; 95% CI 1.0-2.2), and renal and ureteral cancer (SIR 4.0; 95% CI 2.3-6.5) was increased, whereas the incidence of malignancies of the respiratory system, brain, prostate, and breast was not. Only 3 cases of thyroid cancer were recorded. Mortality due to malignancies was not increased (SMR 1.1; 95% CI 0.9-1.4). Incidence of benign tumors was increased more than 2-fold (SIR 2.4; 95% CI 2.1-2.7)., Conclusion: Patients with acromegaly had an increased risk of both benign and malignant tumors, including colorectal and anal cancer, and renal and ureteral cancer. Whether this is associated with acromegaly itself or due to more intensive medical surveillance remains to be shown., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Recent studies suggest that cortical bone could also play a role in vertebral fracture (VF) development in acromegaly., Objective: Evaluate the occurrence of VFs and their relationship to dual energy x-ray absorptiometry-derived bone parameters., Methods: A single-center 2-year prospective study of acromegaly patients was conducted. Each subject had L1-4 spine, femoral neck and total hip (TH) areal BMD measured using DXA, and trabecular bone score (TBS) measurement performed. 3D Shaper™ was used to assess proximal femur trabecular and cortical volumetric (v)BMD, cortical surface (s)BMD, and cortical thickness (Cth). VF assessment was performed using the lateral spine imaging IVA™ mode with a Hologic Horizon® densitometer using a semiquantitative approach. Study outcomes were assessed at 2 time points: baseline and month 24., Results: 70 acromegaly patients (34 M/36F; average 55.1 years) were studied, including 26 with active disease. In 13 patients, 9 with controlled disease, VF was observed. A decrease in TBS, sBMD, neck trabecular vBMD, TH, and neck cortical vBMD in VF compared with non-VF subjects was observed (P < .05). Multivariate analysis of fracture prediction showed TH cortical vBMD as the best fracture prediction parameter with area under the curve of 0.774. TBS was negatively associated with fasting plasma glucose and glycated hemoglobin (HBA1c) at each time point during the follow-up., Conclusion: From the total number of 13 VF subjects, 9 were in the controlled disease group. The most sensitive and specific predictor of incident VF was TH cortical vBMD, suggesting that cortical bone is involved in fracture development., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Regarding the inconclusive results of previous investigations, this study aimed to determine the association between pathology, as a possible predictor, with remission outcomes, to know the role of pathology in the personalized decision making in acromegaly patients., Methods: A retrospective cohort study was performed on the consecutive surgeries for growth hormone (GH) producing pituitary adenomas from February 2015 to January 2021. Seventy-one patients were assessed for granulation patterns and prolactin co-expression as dual staining adenomas. The role of pathology and some other predictors on surgical remission was evaluated using logistic regression models., Results: Among 71 included patients, 34 (47.9%) patients had densely granulated (DG), 14 (19.7%) had sparsely granulated (SG), 23 (32.4%) had dual staining pituitary adenomas. The remission rate was about 62.5% in the patients with SG and DG adenomas named single staining and 52.2% in dual staining groups. Postoperative remission was 1.53-folds higher in the single staining adenomas than dual staining-one (non-significant). The remission rate was doubled in DG group compared to two other groups (non-significant). By adjusting different predictors, cavernous sinus invasion and one-day postoperative GH levels decreased remission rate by 91% (95% CI: 0.01-0.67; p = 0.015) and 64% (95% CI: 0.19-0.69; p < 0.001), respectively. Responses to the medications were not significantly different among three groups., Conclusion: Various pathological subtypes of pituitary adenomas do not appear to have a predictive role in estimating remission outcomes. Cavernous sinus invasion followed by one-day postoperative GH is the strongest parameter to predict biochemical remission., (© 2021. The Author(s).)

Purpose: This study aimed to evaluate the retinal blood vessel parameters and the foveal avascular zone (FAZ) area using optical coherence tomography angiography (OCTA) in patients with acromegaly in comparison with healthy controls., Methods: A total of 45 patients with acromegaly and 45 healthy controls were included in this study. In all patients, the vessel density (VD) of the deep and superficial macular vascular networks and the foveal avascular zone (FAZ) were measured using OCTA. The correlation of insulin-like growth factor 1 (IGF-1) level and disease duration with deep macular VD and FAZ values was analyzed. All parameters were registered. Results were assessed and compared between the two groups., Results: Deep macular plexus VD values were lower in patients with acromegaly compared to the control group. No significant differences in VD values in the superficial segment, except for that in the inferior parafovea ( P = .01) were found between the two groups. Furthermore, patients with acromegaly showed enlargement in the superficial ( P = .30) and deep FAZ areas ( P < .001). IGF-1 level and disease duration showed a significant negative correlation with the deep whole image ( R = -0.216, P = .041, R = -0.339, P = .001, respectively), deep parafovea ( R = -0.271, P = .01; R = -0.372, P < .001, respectively), deep parafovea superior hemi ( R = -0.342, P = .001; R = -0.350, P = .001, respectively), deep parafovea temporal ( R = -0.224, P = .034; R = -0.234, P = .026, respectively), deep parafovea nasal ( R = -0.320, P = .002; R = -0.361, P < .001, respectively), and deep parafovea superior VD values ( R = -0.293, P = .005; R = -0.307, P = .003, respectively) and a significant positive correlation with the deep FAZ area values ( R = 0.244, P = .02; R = 0.329, P = .002, respectively)., Conclusion: VD values in the deep macular capillary plexus were lower in patients with acromegaly, and the superficial and deep FAZ area enlarged. Patients with acromegaly may have an increased risk of developing ocular vascular complications. OCTA can be used to evaluate retinal blood VD in patients with acromegaly.

Purpose: Evaluation of the lacrimal gland volume (LGV) and its correlation with tear film functions, serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in acromegaly patients compared to a control group was aimed., Methods: This prospective case-control study included the eyes of 38 patients with uncontrolled (UA) and 48 patients with controlled acromegaly (CA) and 44 patients with nonfunctioning pituitary adenoma. LGV of the patients was evaluated at the baseline, 3rd, and 6th-month visits with magnetic resonance imaging. Schirmer's test, tear breakup time (TBUT), and ocular surface disease index (OSDI) scores were evaluated at the same visits. Their correlation with serum IGF-1 and GH was investigated. Main outcome measure was the difference in mean LGV., Results: The mean LGV of the acromegaly patients at the baseline visit (116.0 ± 33.2 mm 3 ) and the 3rd-month visit (119.5 ± 36.4 mm 3 ) was higher than the control group (65.2 ± 22.3 mm 3 and 63.2 ± 22.3 mm 3 , respectively; p < 0.001) without any significant difference between the UA and CA patients in the LGV in three consecutive visits (p > 0.05). Among all patients, IGF-1 and GH levels showed a positive correlation with the LGV (p < 0.001; r = 0.52; r = 0.6, respectively). However, Schirmer, TBUT, and OSDI scores did not show any difference among the three groups at each visit (p > 0.05)., Conclusion: Acromegaly patients may have larger lacrimal glands compared to the controls and this increase correlated with the increased IGF-1 and GH levels. Lacrimal gland volume may have no effect on its tear film related functions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Patients with acromegaly show musculoskeletal symptoms which may persist despite disease control. Increased i.m. fat fraction is a known cause of muscle dysfunction in several disorders., Objective: To assess the degree of fat fraction in thigh muscles of controlled acromegaly patients and its relationship with muscle dysfunction., Methods: In a cross-sectional study, we included 36 patients with controlled acromegaly and 36 matched controls. We assessed the percentage of fat fraction in each thigh muscle, using MRI 2-point Dixon sequence, and muscle performance and strength using the gait speed, timed up and go, 30-s chair stand, and hand grip strength tests. We evaluated joint symptoms using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC)., Results: Intramuscular fat fraction was greater in patients than controls (P < 0.05 for muscle compartments, rectus femoris (RF), vastus intermedius (VI), adductor magnus (AM) and semimembranosus). Patients had slower gait speed and poorer performance on the 30-s chair stand and timed up and go tests than controls (P < 0.05). The greater fat fraction in the combined anterior-posterior compartment and in each muscle was associated with worse performance on timed up and go (P < 0.05). The fat fraction in the anterior-posterior compartment predicted performance on timed up and go after adjusting for muscle area, IGF-I and WOMAC functional and pain scores (β = 0.737 P < 0.001)., Conclusions: Patients with controlled acromegaly have greater thigh i.m. fatty infiltration, which is associated with muscle dysfunction. Futures studies are needed to elucidate the mechanisms underlying this relationship.

Acromegaly is a chronic disease due to growth hormone (GH) and insulin-like growth factor 1 (IGF-1) excess. It is associated with various systemic complications including cardiovascular disease. Arterial hypertension occurs in about 20% to 30% of patients. Its pathogenesis is mainly related to the increase in plasma volume secondary to a sodium retaining actions of GH and IGF-1 in the kidney, but abnormalities in vessel architecture and reactivity participate. Left ventricular hypertrophy and diastolic dysfunctions were frequently reported in echo-based studies and are mostly mild and without clinical consequences. Recent cardiac MRI studies described a much lower frequency of myocardial hypertrophy than echo-based assessments. Progression to systolic dysfunction with congestive heart failure is nowadays very rare. Risk of coronary heart disease and of clinically significant arrythmias does not seem to be increased. Acromegaly-related cardiac valve abnormalities may be related to fibrotic changes and seem to persist after effective treatment of acromegaly. Advances in acromegaly treatment over the last decades significantly diminished the cardiovascular burden of the disease, with the cardiovascular disease anymore being the leading cause of death., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function., Design: Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment., Results: Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment., Conclusions: Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Acromegaly patients were reported to have an increased arterial stiffness that could contribute to the frequent cardiovascular complications in this population. The chronic excess of GH and IGF-1 may lead to arterial stiffening via different mechanisms, including hypertension, impaired glucose tolerance and dyslipidemia, however, it is not known whether the activation of GH/IGF-1 axis might influence arterial stiffening independently of cardiovascular risk factors. The objective of this prospective case-control study was to compare arterial stiffness assessed with pulse-wave velocity (PWV) in acromegaly versus non-acromegaly group with similar cardiovascular risk profile., Design: This prospective case-control study included 27 patients with active acromegaly, who underwent the assessment of clinical, physiological, biochemical parameters and the evaluation of PWV with applanation tonometry. We used "The epidemiology of cardiovascular disease in different regions of the Russian Federation" study database (n = 522) to establish a non-acromegaly control group with similar cardiovascular risk profile (n = 54). Non-acromegaly control participants underwent the same assessment as acromegaly patients except for the measurement of serum GH and IGF-1 levels. We compared PWV in acromegaly patients to the general non-acromegaly cohort and its subset, matched with acromegaly patients for cardiovascular risk factors. We also investigated the associations of PWV with clinical, physiological and biochemical parameters in acromegaly and non-acromegaly group using correlation and regression analysis with adjustment for age and sex., Results: Acromegaly patients had lower PWV (6.70 (5.75-7.65) m/s) compared to unmatched non-acromegaly control cohort (7.50 (6.70-8.57) m/s, p = 0.01) and to the non-acromegaly control group matched for cardiovascular risk factors (7.45 (6.73-8.60), p < 0.01). In non-acromegaly control group PWV was associated with BMI (ρ = 0.40, p < 0.01; β = 0.09, p < 0.01), obesity (r = 0.46, p < 0.01; β = 1.36, p < 0.01), systolic blood pressure (ρ = 0.60, p < 0.01; β = 0.05, p < 0.01), diastolic blood pressure (ρ = 0.62, p < 0.01; β = 0.07, p < 0.01), triglycerides (ρ = 0.55, p < 0.01; β = 0.58, p = 0.04), glucose (ρ = 0.54, p < 0.01; β = 0.70, p < 0.01) and diabetes (r = 0.40, p < 0.01; β = 1.10, p = 0.03), while in acromegaly group PWV was associated with IGF-1 expressed in mcg/ml (ρ = -0.49, p ≤0.01; β = -0.002, p ≤0.01) and in percentage of the upper limit of the normal (ρ = -0.47, p = 0.01; β = -0.005, p ≤0.01) as well as with diuretics treatment (β = -1.17, p = 0.03)., Conclusions: PWV is decreased in acromegaly patients compared to non-acromegaly control participants with similar cardiovascular risk profile. Future studies need to explore the role of GH/IGF-1 axis in the regulation of arterial wall properties and the reliability of PWV as a prognostic marker of cardiovascular complications in acromegaly., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: In acromegaly, chronic exposure to impaired GH and IGF-I levels leads to the development of typical acromegaly symptoms, and multiple systemic complications as cardiovascular, metabolic, respiratory, endocrine, and bone disorders. Acromegaly comorbidities contribute to decreased life quality and premature mortality. The aim of our study was to assess the frequency of acromegaly complications and to evaluate diagnostic methods performed toward recognition of them., Materials and Methods: It was a retrospective study and we analyzed data of 179 patients hospitalized in the Department of Endocrinology, Diabetes and Isotope Therapy in Wroclaw Medical University (Poland) in 1976 to 2018 to create a database for statistical analysis., Results: The study group comprised of 119 women (66%) and 60 men (34%). The median age of acromegaly diagnosis was 50.5 years old for women (age range 20-78) and 46 for men (range 24-76). Metabolic disorders (hyperlipidemia, diabetes, and prediabetes) were the most frequently diagnosed complications in our study, followed by cardiovascular diseases and endocrine disorders (goiter, pituitary insufficiency, osteoporosis). BP measurement, ECG, lipid profile, fasting glucose or OGTT were performed the most often, while colonoscopy and echocardiogram were the least frequent., Conclusions: In our population we observed female predominance. We revealed a decrease in the number of patients with active acromegaly and an increase in the number of well-controlled patients. More than 50% of patients demonstrated a coexistence of cardiac, metabolic and endocrine disturbances and only 5% of patients did not suffer from any disease from those main groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rolla, Jawiarczyk-Przybyłowska, Halupczok-Żyła, Kałużny, Konopka, Błoniecka, Zieliński and Bolanowski.)

Background: Acromegaly is a rare, chronic disorder that mostly results from growth hormone (GH)-secreting pituitary adenoma. Transsphenoidal surgery is the first-line treatment of this adenoma. This study aimed to identify factors associated with remission outcome in patients with GH-secreting pituitary adenomas following transsphenoidal surgery., Methods: Patients with GH-secreting pituitary adenomas who underwent transsphenoidal surgery for tumor removal at Songklanagarind Hospital between January 2003 and December 2019 were retrospectively reviewed. The primary outcome was the remission of disease at the last follow-up using 2000 and 2010 consensus criteria. Using logistic regression analysis, various factors were analyzed for association with disease remission outcome., Results: This study included 51 patients. The remission rate of GH-secreting pituitary microadenomas and macroadenomas following transsphenoidal surgery were 100% and 43.75%, respectively. Multivariate analysis showed that preoperative insulin-like growth factor 1 index ≥2.5 and Knosp classification grade 3-4 were significantly associated with nonremission outcome (P < 0.001 and P = 0.012, respectively). Patients with both of these factors had poor outcomes and never achieved remission after treatment, while patients with neither of these factors had high remission rates (87.5%) following surgery. Four of 6 (66.7%) patients who underwent repeat surgery gained remission., Conclusions: Preoperative insulin-like growth factor 1 index ≥2.5 and Knosp classification grade 3-4 were important prognostic factors that determined remission outcome after treatment. Patients who have both of these poor prognostic factors should be aggressively treated with surgery, medication, and probably radiation to optimally control the disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The impairment of skeletal muscle function is one of the most debilitating least understood co-morbidity that accompanies acromegaly (ACRO). Despite being one of the major determinants of these patients' poor quality of life, there is limited evidence related to the underlying mechanisms and treatment options. Although growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels are associated, albeit not indisputable, with the presence and severity of ACRO myopathies the precise effects attributed to increased GH or IGF-1 levels are still unclear. Yet, cell lines and animal models can help us bridge these gaps. This review aims to describe the evidence regarding the role of GH and IGF-1 in muscle anabolism, from the basic to the clinical setting with special emphasis on ACRO. We also pinpoint future perspectives and research lines that should be considered for improving our knowledge in the field.

Background: Musculoskeletal disorders in acromegaly compromise upper and lower limb activity. Corresponding changes can be better assessed by a functional capacity test incorporating multitasking, such as the Glittre Activities of Daily Living Test (GA-T)., Objectives: To evaluate functional capacity in adults with acromegaly using the GA-T and to correlate functional capacity with hand function and health-related quality of life., Methods: The GA-T was applied to 36 patients with acromegaly and an equal number of healthy individuals. Additionally, participants completed the Acromegaly Quality of Life (AcroQoL) questionnaire and underwent a chronic pain assessment using a map of the human body, a hand function evaluation using the Cochin Hand Functional Scale (CHFS), and a handgrip strength test., Results: Relative to the comparison group, patients with acromegaly required more time to perform the GA-T, showed worse hand function, and reported that squatting to accomplish shelving tasks was the major difficulty. GA-T time was correlated with the AcroQoL global score, handgrip strength, and the CHFS (rs=-0.487, p= 0.002; rs=-0.369, p= 0.026; rs= 0.538, p= 0.0007, respectively)., Conclusions: Patients with acromegaly exhibited a reduced functional capacity as assessed by the GA-T. Additionally, an association was identified between the total GA-T time and both hand function and quality of life.

Introduction: Acromegaly is a disease characterized by elevated growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels. Surgery is the only curative treatment, while medical therapies are administered life-long. To date, almost 30% of patients treated with the currently available medical therapies do not achieve biochemical control., Areas Covered: This review focuses on new drugs in development for acromegaly. In detail, we provide an overview of the new molecules designed to improve disease control rate (such as novel somotostatin receptor ligands and antisense oligonucleotides), as well as the new formulations of existing medications aiming to improve patients' compliance (e.g. oral or long-acting subcutaneous octreotide)., Expert Opinion: The constant progresses in the medical treatment of acromegaly could lead to an individualized therapy based on tumor, as well as patient's characteristics. Besides disease control, patient's need represents a major target of medical treatment in chronic diseases such as acromegaly, in order to improve compliance to therapy and patients' quality of life.

Objective: In this study, we considered to assess the presence of estrogen receptors (ER) and the expression of estrogen receptor genes (ESR) in the surgical tissue samples of acromegaly patients and the control group patients with nonfunctioning adenoma and their association with disease activity. We also aimed to determine the significance of ER positivity in acromegaly patients and to find out whether it carries a potential to be used as a predictor of prognosis and therapy regimen in the future., Design: This study was conducted on a total of 67 patients over 18 years of age. The study group consisted of 34 patients with acromegaly and 33 patients with nonfunctioning pituitary adenoma. The pre- and post-operative basal pituitary hormone levels and magnetic resonance images (MRI) of all patients, as well as their remission status of all acromegaly patients were evaluated. Immunohistochemical (IHC) staining procedures for ER-α were performed on surgical tissue samples. Real-time quantitative polymerase chain reaction (RT-qPCR) method was used to determine the levels of ESR1 and ESR2 gene expressions., Results: We found that IHC staining for ER-α was positive in 31.3% and 45.5% of the patients with acromegaly and nonfunctioning adenoma respectively. There was no statistically significant difference of ER-α positivity, ER-α immunoreactivity score and ESR1/ESR2 gene expression levels among the study groups (p > .05). Nevertheless, the expression of ESR1 gene was found to be 0.26 times more, and the ESR2 gene to be 0.11 times less in the acromegaly group compared to those of the nonfunctioning adenoma group. Additionally, we detected the positivity of ER-α only in acromegaly patients who were in remission. An inverse association was found between the pre-operative insulin-like growth factor-1 (IGF-1) levels and the expressions of ESR1/ESR2 gene in acromegaly patients. So these results indicated that the high ESR1 and ESR2 gene expressions in acromegaly patients are associated to the decrease of pre-operative IGF-1 values. Also an inverse association was found between the pre-operative adenoma volume and ESR1 Ct values, means that increase in ESR1 gene expression is associated to the decrease of adenoma volume., Conclusions: The current results may suggest the use of these parameters as useful prognostic markers because all ER-positive acromegaly patients were in remission and the high ESR1 and ESR2 gene expressions in acromegaly patients is associated to the decrease of pre-operative IGF-1 values. Our results need to be supported by further studies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Cardiac comorbidity is one of the leading causes of death among acromegaly patients. We aimed to investigate the reversibility of acromegalic cardiac involvement after surgical treatment using the gold standard method, cardiovascular magnetic resonance, and to explore the effects of endocrine remission and gender on reversibility., Methods: In this single-center, prospective cohort study, fifty untreated acromegaly patients were enrolled. Comprehensive cardiac assessments were performed using a 3.0 T magnetic resonance scanner before and 3 and 12 months after transsphenoidal adenomectomy., Results: Preoperatively, left ventricular (LV) enlargement (13.0%), LV systolic dysfunction (6.5%), right ventricular (RV) enlargement (4.3%), RV systolic dysfunction (2.2%) and myocardial fibrosis (12.0%) were identified. On average, the LV and RV ejection fractions of acromegaly patients were higher than the healthy reference values. Male patients had thicker LV myocardia, wider ventricular diameters and more dilated pulmonary artery roots than female patients. After surgery, LV myocardial hypertrophy was reversed, the left atrium was remodeled, and ventricular systolic dysfunction recovered to normal. Cardiac alterations were detected early in the 3 rd postoperative month and persisted until the 12 th month. The interventricular septum was initially thickened in the 3 rd postoperative month and then recovered at the 12th month. Notable postoperative cardiac reversibility was observed in male patients but did not occur in all female patients. Patients achieving endocrine remission with normalized hormone levels had thinner LV myocardia than patients without normalized hormone levels., Conclusion: Our findings demonstrated that some of the cardiac involvement in acromegaly patients is reversible after surgical treatment which lowers hormone levels. Endocrine remission and gender significantly impacted postoperative cardiac reversibility., (Copyright © 2020 Guo, Cao, Cao, Li, Liu, Wang, Gao, Bao, Xing and Wang.)

Background: Acromegaly is a rare disease resulting in clinical sequelae with significant morbidity and mortality due to the central tumor mass effect and prolonged growth hormone (GH) hypersecretion., Objectives: The goal is to describe the epidemiology, clinical features, presence of comorbidities, and treatment outcomes of acromegaly in Saudi Arabia., Methods: Data was collected through a retrospective review of the charts of all patients diagnosed with acromegaly from nine major hospitals in Saudi Arabia over a period of more than 25 years., Results: A total of 195 patients (116 males and 79 females), with a mean age at diagnosis of 43 ± 12 (males) and 46 ± 14 years (females), from nine major hospitals were identified and included in the analysis. All cases were caused by pituitary adenomas, of which 92.4% were macroadenomas. Headache, coarse facial features, acral growth, and sweating/oily skin were by far the most frequent presenting complaints. The most common comorbidities were diabetes mellitus (51.7%), followed by hypertension (50%) and visual field defect (30.5%). The vast majority (95%) of patients were treated surgically (98%). Twenty-four percent also received radiotherapy, and 74.4% received medical therapy. When stringent criteria were applied for assessment of outcomes of therapy, 28.7% of the patients were cured and 30.1% had their disease under control, while 28.7% were found to have active disease despite receiving multimodal therapy., Conclusions: Our findings highlight the need for a national acromegaly registry to enable early identification, evaluation, and selection of the best therapeutic approaches to improve the outcome and remission rate of the disease.

Background: In acromegaly patients; it has been observed that heart failure may develop even in the absence of predisposing factors such as hypertension, diabetes mellitus, so a specific acromegalic cardiomyopathy has been suggested. We aimed to evaluate the fQRS frequency in acromegaly patients and the left ventricular (LV) functions of acromegaly patients with fQRS. Methods: Our study included 60 acromegalic patients. Each patient underwent conventional echocardiography and tissue Doppler imaging. The patients included were separated into two groups: those with (n:23) and without (n:37) fQRS. Results: Significant differences were identified between fQRS(+) and fQRS (-) groups with respect to disease duration ( p  < .001), Left ventricular end diastolic volume (EDV) ( p  < .001), E velocity ( p  < .001), E \ A ratio ( p  < .001), E ' velocity ( p  < .001), E / E ' ratio ( p  < .001), isovolumic relaxation time (IVRT) ( p  < .001), MPI ( p  < .001). Disease duration (odds ratio [OR]: 2.120 (1.023-1.703 95% confidence interval [CI]), p  = .002), E ' (OR:3.029 (1.013-1.703 95% CI) p  = .004) and fQRS (OR:4.59 (1.94-10.87 95% CI), p  = .001) were identified as the independent predictors of myocardial performance index (MPI). However, disease duration (OR:1.078 (1.030-1.128 95% CI), p  = .001), E / E ' (OR: 1.43 (1.22-1.97 95% CI), p  = .001), IVRT (OR:1.65 (1.32-2.06 95% CI), p  = .001) and MPI (OR:1.014 (1.004-1.024 95% CI), p  = .002) were the independent predictors of fQRS. Conclusions: fQRS was frequent and an independent predictor of MPI that was independelty associated with LV dysfunction in patients with acromegaly. In light of these findings the presence of fQRS is thought to be an indicator of acromegalic CMP development.

Objective: Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism., Subjects and Methods: In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter., Results: Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism., Conclusions: Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75.

This is a narrative review of literature introducing somatostatin receptors (SSTRs) as part of understanding the somatotroph cells since they are positive in normal cells but also in tumoral cells as seen in somatotropinoma, a growth hormone (GH)-producing neoplasia, which causes acromegaly. They are five subtypes of SSTRs (1 to 5), which are immunohistochemically positive in different proportions in somatotropinomas. SSTR types 2 and 5 are most frequent in GH-secreting adenomas and they are both targeted by medical therapy with somatostatin analogues (SSTAs) like first generation Octreotide and Lanreotide (mainly targeting SSTR2) and second generation Pasireotide (with highest affinity for SSTR5), thus heterogeneous SSTRs configuration into the tumor explains different pattern of response to treatment and it might predict it once the SSTRs immunostaining is performed. Monoclonal antibodies are used for immunohistochemical detection of SSTRs; currently, a lack of standardization is presented, and scoring systems, such as Volante, H-score or human epidermal growth factor receptor 2 (HER2)-score, are applied. Immunoreactive markers like SSTRs are the U-turn in clinical practice regarding somatotropinomas since the configuration of subtypes 2 and 5 explains the responsiveness to medical therapy like SSTA. Further achievement of disease control is imperiously necessary because acromegaly has an increased rate of morbidity and mortality.

Context: Reports on the incidence, characteristics, and comorbidity in Asian patients with acromegaly are scarce., Objective: To evaluate the incidence of acromegaly and the risk of comorbidities in East Asia, especially South Korea., Design: This nationwide population-based cohort study using the Korean Health Insurance Review and Assessment claims database evaluated the incidence of acromegaly, initially diagnosed from 2010 to 2013. We identified comorbidities during, before, and 2 years after diagnosis. Acromegaly and control cases (718 and 7180, respectively) were included in the analysis., Setting: A longitudinal case-control study using a nationwide population cohort., Results: The mean annual incidence rate of acromegaly was 3.57 cases per 1 000 000. Malignancies occurred in 61 patients with acromegaly (8.5%) during the study period and thyroid cancer was the most common malignancy (n = 38). In the acromegaly group, the overall risk of malignancy was higher: hazard ratio (HR), 2.82 (95% confidence interval [CI]: 2.12-3.74). Malignancy risk was more pronounced in females, with increased risk from the prediagnosis period that is sustained until the postdiagnosis period. Prevalence of diabetes mellitus (DM) and heart failure increased significantly in acromegalic patients. Over the entire period, DM developed in 51.1% and 57.0% of male and female acromegalic patients, respectively. Mortality risk was higher (HR 1.65, 95%; CI: 1.13-2.41) and statistically significant in females (HR 1.75, 95%; CI: 1.07-2.84)., Conclusion: Comorbidities associated with acromegaly differed by sex in Korean subjects. High malignancy and mortality risk should be considered in female patients when managing acromegaly in Korea., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Acromegaly is a relatively rare chronic hormonal disease resulting in disfigurement. In 90% of cases, acromegaly is caused by a benign pituitary monoclonal human growth hormone-secreting tumor. The aim of the present study was to determine the presence of left ventricular (LV) deformation abnormalities using three-dimensional speckle-tracking echocardiography in a group of acromegalic patients., Methods: Thirty-eight acromegalic patients were involved in the study. Thirteen patients were excluded due to inadequate image quality. The mean age of the remaining patients was 57.2±13.6 years and seven were male. Their data were compared to an age- and gender-matched control population, which consisted of 34 healthy volunteers (mean age: 52.7±4.9 years, 15 male)., Results: Global and mean segmental LV radial strain (RS) (33.2±13.4% vs. 25.2±10.8%, p=0.01 and 36.0±12.1% vs. 28.2±10.0%, p=0.009, respectively) proved to be significantly higher in acromegaly compared to controls. Active acromegalic patients had significantly higher global and mean segmental LV-RS (35.5±14.4% vs. 25.2±10.8%, p=0.03 and 37.9±13.3% vs. 28.2±10.0%, p=0.03, respectively) compared to controls. Between the active and inactive acromegaly groups, only basal LV circumferential strain (-30.2±4.8% vs. -26.7±4.1%, p=0.02) was found to be significantly different., Conclusion: The presented clinical, demographic, therapeutic and echocardiographic features demonstrate that active acromegaly is associated with enhanced LV RS as compared to healthy controls and those with inactive acromegaly., (Copyright © 2020 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: Growth hormone (GH) activity might be implicated in male reproductive function. One previous study has suggested significantly reduced semen quality in untreated acromegalic patients due to both reduced sperm counts and sperm motility., Design and Methods: A retrospective study comprising ten uncontrolled hypogonadal acromegalic patients (median age 29 years) who delivered semen for cryopreservation before initiation of testosterone therapy. Semen variables and hormone concentrations were compared to those of ten non-acromegalic hypogonadal men with pituitary disease (age 31 years) and those of young healthy men., Results: Acromegalic patients vs. non-acromegalic patients had a higher percentage of progressive motile spermatozoa (62 vs. 47%, p = 0.04). Eight of ten acromegalic patients and 82% of controls had total sperm counts above 39 million and progressive motile spermatozoa above 32% (p = 0.55), corresponding to the WHO 2010 reference levels for expected normal fertility for these variables. Non-acromegalic patients vs. healthy controls had reduced percentage of progressive motile spermatozoa (47 vs. 57%, p = 0.02) and only five of ten patients had semen quality above the WHO reference level, which was significantly lower than observed in healthy controls (p = 0.022). Total sperm counts were similar between both patient groups and controls. There were no differences in reproductive hormone levels between acromegalic patients vs. non-acromegalic patients (p-values between 0.10 and 0.61). Compared to healthy controls both patient groups had severely reduced serum testosterone, calculated free testosterone., Conclusions: Despite severe hypoandrogenism acromegalic patients had semen quality similar to healthy controls based on determination of the number of progressively motile spermatozoa. By contrast non-acromegalic pituitary patients had reduced sperm motility. Our data do not support reduced semen quality in acromegaly.

Objective: Respiratory disorders are common complications of acromegaly patients. We conducted a large-scale survey in the patients with acromegaly and demonstrated the characteristics of their lung function and blood gas., Methods: A prospective cohort study was conducted with 115 patients with active acromegaly and 56 patients with nonfunctioning pituitary adenomas. All patients underwent clinical, biological, radiological, lung functional and blood gas assessments., Results: Acromegaly patients had a higher lung volume than those with nonfunctioning adenomas (forced vital capacity value (FVC) and FVC% predicted: p < 0.001). The small airway was less obstructive in acromegaly patients (higher FEV1% predicted, PEF% predicted, MEF75% predicted, MEF50% predicted, MEF25% predicted: p ≤ 0.001 for all analyses, FEV1/FVC: p = 0.151). The average partial pressure of carbon dioxide in acromegaly patients was higher (p < 0.001), but there was no significant difference in the average partial pressure of oxygen or oxygen saturation between the two groups (p > 0.05). In acromegaly patients, the average age of patients with small airway obstruction was higher than that of patients with normal lung function (p < 0.05), but no significant difference in GH or IGF-1 levels between the two groups were found (p > 0.05)., Conclusion: The acromegaly patients in this cohort had increased lung volume. However, there was no evidence demonstrating hypoxemia in acromegaly patients. The small airway was less obstructive in acromegaly patents. Small airway obstruction was observed in elderly patients with acromegaly., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Radiofrequency echographic multi-spectrometry (REMS) is a recently introduced non-ionising technology employed in the evaluation of osteoporosis. The aim of our study was to compare bone mineral density (BMD) in acromegaly patients and healthy controls by performing novel REMS densitometry. The second objective was to analyse the correlation between results of REMS and classical dual-energy X-ray absorptiometry (DXA) in acromegaly patients., Material and Methods: We enrolled 33 patients with acromegaly (AG) and 24 controls (CG). The acromegaly patients were divided into two subgroups: well-controlled acromegaly (WCA) and surgery-cured acromegaly (SCA). REMS was performed in all participants, while DXA was performed only in the acromegaly group. IGF-I and GH levels were measured in acromegaly patients., Results: Bone mineral density of the lumbar spine (LS) and the femoral neck (FN) obtained from REMS did not reveal significant differences between AG, CG, WCA, and SCA. Similarly, there were no significant differences in BMD measured by DXA at the LS and at the FN between WCA and SCA. Significant positive correlations between IGF-I concentrations and BMD obtained from both REMS and DXA were detected in the AG and WCA. In the AG and WCA, there were positive correlations between T-scores and LS BMD obtained from both methods., Conclusions: Radiofrequency echographic multi-spectrometry is a potential method in assessment of bone status in acromegaly. Further studies with participation of active disease patients are needed.

Introduction: The aim of the study was to evaluate global longitudinal strain (GLS) in patients with naive acromegaly with normal left ventricular (LV) ejection fraction (EF)., Material and Methods: Forty-three consecutive patients with naive acromegaly with normal LV systolic function as measured by EF, examined from 2008 to 2016, and 52 patients of a control group matched for age and sex underwent two-dimensional speckle-tracking echocardiography to assess GLS., Results: The median GLS was significantly lower in the acromegaly group than in the control group (in %, -16.6 vs. -20.7; p < 0.01). The majority of acromegalic patients (n = 26; 60.5%) had abnormal GLS. Patients with impairment in GLS had a longer median duration of acromegaly symptoms (in years, 10.0 vs. 5.0; p < 0.05) and greater LV thickness (posterior wall in mm, 12.5 vs. 12.0; p < 0.05) compared to those with normal GLS. Patients with abnormal GLS had higher IGF-1 concentration, but without statistical significance. Diabetes mellitus and arterial hypertension, which are more common in acromegaly, were not significant determinants of abnormal GLS. The mean left ventricular mass index (LVMI) was increased in the acromegaly group compared to controls (in g/m², 136 vs. 97; p < 0.01). There was a significant negative correlation between LVMI and GLS (R = -0.47; p < 0.01)., Conclusions: Naive acromegalic patients presented abnormal GLS, which indicates subclinical systolic dysfunction in these patients. It has not been proven that arterial hypertension and diabetes mellitus are significant determinants of abnormal GLS.

Objective: Although the focus of acromegaly treatment is the hormonal control of the disease, a new perspective must be given to the functional rehabilitation of these patients, especially when considering the recent increase in survival. The aim of this study was to evaluate the effects of therapist-oriented home rehabilitation (TOHR) on patients with acromegaly., Patients and Methods: Seventeen adults with acromegaly followed an exercise programme from a booklet with instructions for each exercise prescribed, for 2 months, and were reassessed after 1 month of washout. At each of the 3 timepoints (before and after the intervention and at the 1-month follow-up), the participants were subjected to the following assessments: body composition through bioimpedance, health-related quality of life (HRQoL) using the Acromegaly Quality of Life (AcroQoL) questionnaire, general fatigue through the Functional Assessment of Chronic Illness Therapy-Fatigue scale, handgrip strength, lower extremity functionality using isometric dynamometry and the Lower Extremity Functional Scale (LEFS), body balance through stabilometry, and functional capacity through 6-minute walking distance (6MWD)., Results: After performing TOHR, improvements in general fatigue, quadriceps muscle strength, LEFS, 6MWD, balance control and all AcroQoL dimensions were observed (all P < 0.05). After 1 month of washout, however, these gains were lost for all parameters, except the LEFS and balance control., Conclusions: In acromegaly, TOHR results in improvements in muscle function, functional capacity, general fatigue, body balance, and HRQoL. Large randomized controlled trials are needed to replicate these benefits and to recommend rehabilitation, especially for those with long-term illness.

Acromegaly is a systemic disease associated with increased morbidity, presenting cardiovascular, metabolic, respiratory, neoplastic, endocrine, articular and bone complications. Most of these comorbidities can be prevented or delayed with adequate disease treatment and, more recent studies with the use of modern treatments of acromegaly, have shown a change in the severity and prevalence of these complications. In addition, acromegaly is associated with increased mortality, but recent studies (especially those published in the last decade) have shown a different scenario than older studies, with mortality no longer being increased in adequately controlled patients and a change in the main cause of death from cardiovascular disease to malignancy. In this review, we discuss this changing face of acromegaly summarizing current knowledge and evidence on morbimortality of the disease. Arch Endocrinol Metab. 2019;63(6):630-7.

Acromegaly is an insidious disease, usually resulting from growth hormone hypersecretion by a pituitary adenoma. It is most often diagnosed during the 3rd to 4th decade of life. However, recent studies have shown an increase in the incidence and prevalence of acromegaly in the elderly, probably due to increasing life expectancy. As in the younger population with acromegaly, there is a delay in diagnosis, aggravated by the similarities of the aging process with some of the characteristics of the disease. As can be expected elderly patients with acromegaly have a higher prevalence of comorbidities than younger ones. The diagnostic criteria are the same as for younger patients. Surgical treatment of the pituitary adenoma is the primary therapy of choice unless contraindicated. Somatostatin receptor ligands are generally effective as both primary and postoperative treatment. The prognosis correlates inversely with the patient's age, disease duration and last GH level. Arch Endocrinol Metab. 2019;63(6):638-45.

Purpose: Arthropathy is a common and disabling complication of acromegaly. Since in this condition radiological findings rarely correspond to functional impairment, we elected to quantify in a large cohort of acromegalic patients: the degree of motor disability compared with data from general population, the impact of joint involvement on quality of life and work productivity, and to look for associated factors., Methods: In 211 acromegalic patients, 131 with controlled disease and 80 with active disease, eight validated scales were used to evaluate the (i) prevalence and distribution of arthropathy, (ii) degree of motor disability and joint symptoms (VAS, AIMS symptoms and WOMAC), (iii) quality of life (AcroQoL and PASQ) and work capability (WPAI:GH) as consequences of joint complications., Results: Using the WOMAC questionnaire, for which population based normative values are available, a significantly higher prevalence and severity of motor disability was detected in acromegalics compared to the general population from literature. The results provided by the different questionnaires turned out to be highly concordant. All measures of motor disability correlated both with impaired quality of life and motor disability and were worse in females and in patients with higher BMI., Conclusions: The questionnaires VAS, AIMS symptoms, and WOMAC (this latter both as a whole and with its functionality subscale), with their scores, proved to be the most adequate tools to evaluate motor disability and its consequences on both quality of life and work productivity in acromegaly. Female gender and higher BMI are associated with worse articular symptoms.

Purpose: Patients with acromegaly may have balance abnormalities due to changes in body composition. We aim to compare static and dynamic balances in patients with acromegaly and healthy volunteers, and to evaluate the effects of exercise on balance in patients with acromegaly., Methods: This prospective study included 25 patients with acromegaly followed at endocrinology clinic of Cerrahpasa Medical Faculty and 13 healthy volunteers. The acromegalic patients were divided into 2 groups. Group A (n = 11) attended an exercise program 3 days/week for 3 months, whereas group B (n = 14) and healthy volunteers (Group C) were exercise-free. Bipedal and unipedal stance static and dynamic balance tests were performed using a Prokin 252N device., Results: The ages, demographic characteristics, and body compositions were similar. In acromegalic patients, the static balance parameters of displacement of center-of-pressure in anterior-posterior direction (C.o.P.Y) while eyes open (p = 0.002) and on left leg (p = 0.001), in left-right direction (C.o.P.X) on right leg (p = 0.03), eyes-closed average medio-lateral velocity (AMLV) (p = 0.001) and the dynamic parameter of forward/backward front/right standard deviation (FBFRSD) (p = 0.02) were significantly different from healthy controls. When the exercise effect on balance was evaluated between group A and B, there were significant improvements in most parameters of dynamic balance measurements of both forward-backward and medial-lateral sway (FBFRSD, FBDME, and RLBLSD) (p = 0.02, p = 0.02, and p = 0.004, respectively) after exercise in group A., Conclusions: Patients with acromegaly had impairments at various static and dynamic balance parameters, especially in posterior direction. After a 3-month exercise program, the dynamic balance profoundly improved, but static balance was relatively preserved in patients with acromegaly.

Acromegaly is a rare chronic, systemic disorder caused by excessive growth hormone (GH) secretion from a somatotroph pituitary adenoma. GH hypersecretion leads to overproduction of insulin-like growth factor-1 (IGF-1), which contributes to the somatic overgrowth, physical disfigurement, onset of multiple systemic comorbidities, reduced quality of life (QoL) and premature mortality of uncontrolled patients. Somatostatin receptor ligands, dopamine agonists and a GH receptor antagonist are currently available for medical therapy of acromegaly. The main aim of treatment is biochemical normalisation, defined as age-normalised serum IGF-1 values and random GH levels <1.0 μg/L. However, there is an increasing evidence suggesting that achieving biochemical control does not always decrease the burden of disease-related comorbidities and/or improve patients' QoL. This lack of correlation between biochemical and clinical control can be due to both disease duration (late diagnosis) or to the peculiarity of a given comorbidity. Herein we conducted ad hoc literature searches in order to find the most recent and relevant reports on biochemical and clinical disease control during medical treatment of acromegaly. Particularly, we analyse and describe the relationship between biochemical, as well as clinical disease control in patients with acromegaly receiving medical therapy, with a focus on comorbidities and QoL. In conclusion, we found that current literature data seem to indicate that clinical disease control (besides biochemical control), encompassing clinical signs and symptoms, comorbidities and QoL, emerge as a primary focus of acromegaly patient management.

Purpose: To determine both static and dynamic plantar data of acromegalic subjects while barefoot., Methods: Seventy acromegalic patients and 48 age-, sex-, weight- and height-matched healthy controls were included. Plantar variables were measured using the footscan gait system. The data included the width and length of each foot, relative force distribution in each quadrant, mean force applied to each foot and maximum pressure while walking. Maximum pressure data were obtained from ten parts of the foot. Injury risk assessments of five different regions were performed. To analyze balance, center of pressure (CoP) measurements were performed. The patients with acromegaly were compared with the controls. Furthermore, a comparison of patients with active and controlled acromegaly was performed., Results: The foot was wider in acromegalic patients. The mean force on each foot was higher in cases of acromegaly (acromegaly: 1027 ± 180 N, control: 908 ± 180 N, p = 0.001). In the acromegalic individuals, the maximum pressure in the midfoot was higher, while the medial heel maximum pressure was lower (midfoot maximum pressure acromegaly: 11.3 ± 3.5 N/cm 2 , control: 8.9 ± 3.7 N/cm 2 , p = < 0.001). Injury risk was similar. CoP measurements elicited intact balance. In terms of static and dynamic plantar data, there was no difference between patients with active and controlled acromegaly., Conclusions: This is the first study to demonstrate that compared with healthy controls, patients with acromegaly experience great force on their feet while standing and high pressure in the midfoot during walking. Podiatric evaluation, custom molded orthotics and individualized rehabilitation programs for acromegalic patients may provide better force and pressure distribution throughout the foot and improve gait and skeletal symptoms.

Growth hormone (GH) exerts a diverse set of effects across many tissues including fat, muscle, bone, kidney, heart, and liver. GH is also a diabetogenic hormone in that it inhibits the actions of insulin. Acromegaly, a condition traditionally characterized by increased levels of growth hormone secretion as a result of pituitary adenoma, results in increased tissue growth, lipolysis, and can result in patients with hyperglycemia and hyperinsulinemia. While current treatment modalities have greatly improved prognoses for most patients, a significant number present clinical symptoms of acromegaly with elevated levels of IGF-1 in the absence of increased GH levels, a phenomenon known as micromegaly. This condition presents a challenge to most currently used treatments since the high circulating IGF-1 levels are independent of elevated levels of GH. It has been previously shown that advanced glycation end products (AGE) can stimulate IGF-1 secretion by human monocytes in vitro, demonstrating a possible mechanism for increased IGF-1 levels. To further investigate AGE/GH/IGF-1 interaction, we have reanalyzed a publicly available RNAseq dataset from subcutaneous adipose tissue of patients with acromegaly. S100A1, a member of the calgranulin family of proteins and ligand of the AGE receptor, was shown to be significantly upregulated in patients with acromegaly. These findings identify an important consideration that may help explain the counterintuitive nature of micromegaly, while simultaneously providing new insight into the role of GH in diabetic, inflammatory, and immune pathologies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.

Acromegaly is characterized by increased release of growth hormone and, consequently, insulin-like growth factor I (IGF1), most often by a pituitary adenoma. Prolonged exposure to excess hormone leads to progressive somatic disfigurement and a wide range of systemic manifestations that are associated with increased mortality. Although considered a rare disease, recent studies have reported an increased incidence of acromegaly owing to better disease awareness, improved diagnostic tools and perhaps a real increase in prevalence. Acromegaly treatment approaches, which include surgery, radiotherapy and medical therapy, have changed considerably over time owing to improved surgical procedures, development of new radiotherapy techniques and availability of new medical therapies. The optimal use of these treatments will reduce mortality in patients with acromegaly to levels in the general population. Medical therapy is currently an important treatment option and can even be the first-line treatment in patients with acromegaly who will not benefit from or are not suitable for first-line neurosurgical treatment. Pharmacological treatments include somatostatin receptor ligands (such as octreotide, lanreotide and pasireotide), dopamine agonists and the growth hormone receptor antagonist pegvisomant. In this Primer, we review the main aspects of acromegaly, including scientific advances that underlie expanding knowledge of disease pathogenesis, improvements in disease management and new medical therapies that are available and in development to improve disease control.

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Endocrine Society.)

Introduction: There are conflicting results regarding the frequency of hypertension (HT) and values of related parameters in patients with acromegaly., Aim: We aimed to determine the frequency of HT and values of its associated parameters in patients with acromegaly., Methods: 57 patients with newly diagnosed acromegaly were included in this study. Renal ultrasonography (US) was performed in addition to routine evaluation of acromegaly. Renal resistive index (RRI), renal pulsatility index (RPI), and accelerated time were measured using Doppler US., Results: Hypertension was detected in 16 patients (28.1%) with newly diagnosed acromegaly. Serum triglyceride, TSH, growth hormone, and insulin growth factor 1 levels were higher and HDL levels were lower in acromegaly patients with HT. RRI and RPI values were found to be higher in acromegaly patients with HT. In logistic regression analysis, only the RRI value was found to be independently related to the presence of HT. Based on this analysis, it was determined that the frequency of HT increases 2.99 times for each increase in RRI of 0.05 units. When ROC analysis was performed, it was found that the area under the ROC curve was 0.781. In the same analysis, when the cutoff value for RRI was taken to be 0.70, the development of HT in acromegaly patients was determined with 75% sensitivity and 78% specificity., Conclusions: In patients with newly diagnosed acromegaly, HT frequency was significantly increased and it was independently associated with the RRI value. Therefore, these patients should be closely monitored for HT-the most frequent and important cardiovascular risk factor-and treated before they develop target organ damage.

Simpson-Golabi-Behmel syndrome (SGBS) is a rare genetic condition and is inherited in an X-linked recessive manner. The disease is caused by a change in the nucleotide sequence of an X-linked gene encoding glypican 3, a protein belonging to the heparan-sulfate membrane proteoglycan family. SGBS case studies are almost entirely restricted to the pediatric population. Scarce literature describing SGBS course in adults may be due to both the high mortality of SGBS patients in childhood and low rate of SGBS diagnosis in adults. We present a case of a 39-year-old man with an initial diagnosis of acromegaly. Genetic tests revealed a hitherto unreported deletion in the GPC3 gene. SGBS manifestations in our patient included tall stature, dysmorphic features, and central nervous system (CNS) anatomical pathology. MRI of the head visualized abnormalities of median line structures, a feature consistent with SGBS: an unclosed craniopharyngeal canal, a sellar-suprasellar cyst, dysmorphic pituitary gland, and a cyst of the septum pellucidum. Moreover, cardiomyopathy complicated by life-threatening paroxysmal ventricular tachycardia was diagnosed. Although various cardiac anomalies are often found in SGBS, their pathogenesis is unclear and may be multifactorial. We believe that the presented case contributes to a better understanding of SGBS and may help clinicians in introducing prophylaxis and treatment for its comorbidities., (© 2018 Wiley Periodicals, Inc.)