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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).)

Introduction: Evidence on myocardial deformation, detected by speckle tracking echocardiography (STE), in patients with acromegaly is scanty., Aim: The aim of the present meta-analysis was to provide an updated information on left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) in patients with acromegaly and preserved LVEF., Methods: Following the PRISMA guidelines, systematic searches were conducted across bibliographic databases (Pub-Med, OVID, EMBASE and Cochrane library) to identify eligible studies from inception up to June 30-2024. Clinical studies published in English reporting data on LV mechanics in patients with acromegaly and controls were included. The statistical difference of the echocardiographic variables of interest between groups such as LVEF and global longitudinal strain (GLS) was calculated by standardized mean difference (SMD) with 95% confidence interval (CI) by using random-effects models., Results: Seven studies including 288 patients with acromegaly and 294 healthy individuals were considered for the analysis. Pooled average LVEF values were 64.6 ± 1.5% in the healthy control group and 64.0 ± 1.3% in the acromegaly group (SMD: - 0.21 ± 0.22, CI -0.62/0.22, p = 0.34); the corresponding values of GLS were - 19.1.1 ± 1.2% and - 17.5 ± 1.2% (SMD: -0.52 ± 0.27, CI - 1.05/0.01, p = 0.05). No difference was found between the two groups for both global circumferential strain (GCS) and global radial strain (GRS)., Conclusions: Our findings suggest that patients with acromegaly in which LVEF is completely comparable to healthy controls show an impairment in GLS of borderline statistical significance. Whether GLS assessment can actually unmask early alterations of systolic function in patients with acromegaly better than LVEF will need to be investigated by future studies., (© 2024. The Author(s).)

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.

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.)