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Journal of Investigative Medicine : the... Aug 2023The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which... (Review)
Review
The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which focuses on each patient, is justified. Metabolomics would decipher the molecular mechanisms underlying the therapeutic response heterogeneity. Identification of altered metabolic pathways would open new horizons in the therapeutic management of acromegaly. This research aimed to evaluate the metabolomic profile in acromegaly and metabolomics' contributions to understanding disease pathogenesis. A systematic review was carried out by querying four electronic databases and evaluating patients with acromegaly through metabolomic techniques. In all, 21 studies containing 362 patients were eligible. Choline, the ubiquitous metabolite identified in growth hormone (GH)-secreting pituitary adenomas (Pas) by in vivo magnetic resonance spectroscopy (MRS), negatively correlated with somatostatin receptors type 2 expression and positively correlated with magnetic resonance imaging T2 signal and Ki-67 index. Moreover, elevated choline and choline/creatine ratio differentiated between sparsely and densely granulated GH-secreting PAs. MRS detected low hepatic lipid content in active acromegaly, which increased after disease control. The panel of metabolites of acromegaly deciphered by mass spectrometry (MS)-based techniques mainly included amino acids (especially branched-chain amino acids and taurine), glyceric acid, and lipids. The most altered pathways in acromegaly were the metabolism of glucose (particularly the downregulation of the pentose phosphate pathway), linoleic acid, sphingolipids, glycerophospholipids, arginine/proline, and taurine/hypotaurine. Matrix-assisted laser desorption/ionization coupled with MS imaging confirmed the functional nature of GH-secreting PAs and accurately discriminated PAs from healthy pituitary tissue.
Topics: Humans; Acromegaly; Growth Hormone-Secreting Pituitary Adenoma; Magnetic Resonance Imaging; Metabolomics; Adenoma
PubMed: 37139720
DOI: 10.1177/10815589231169452 -
Pituitary Jun 2022To evaluate the association between acromegaly and pregnancy in terms of disease activity, maternal and fetal outcomes. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the association between acromegaly and pregnancy in terms of disease activity, maternal and fetal outcomes.
METHODS
This systematic review was conducted according to the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. We focused on observational studies that included pregnant women with acromegaly. The outcomes were acromegaly activity, preterm birth, gestational diabetes, hypertension, eclampsia/preeclampsia, miscarriage, perinatal mortality, low birthweight, small for gestational age, and congenital malformations. Embase, Medline, LILACS, and CENTRAL were our source databases. To perform proportional meta-analyses, we used Stata Statistical Software 17.
RESULTS
Nineteen studies were included encompassing a total of 273 pregnancies in 211 women with acromegaly. The overall frequency of control of acromegaly during pregnancy was 62%, and of tumor growth was 9%. No fetal or maternal deaths were reported. The overall frequency of worsening of previous diabetes or development of gestational diabetes was 9%, and of previous hypertension or preeclampsia/eclampsia was 6%. The overall frequency of premature labor was 9% [from 17 studies of 263 pregnancies; 95% confidence interval (CI), 5-13%]; of spontaneous miscarriage was 4% (from 19 studies of 273 pregnancies; 95% CI, 2-11%); of small for gestational age was 5% (from 15 studies of 216 newborns; 95% CI, 3-9%); and of congenital malformations was 1% (from 18 studies of 240 newborns; 95% CI, 0-7%).
CONCLUSION
Pregnancy in women with acromegaly is frequently associated with disease control and is safe in relation to fetal and maternal outcomes, as in women without acromegaly.
Topics: Abortion, Spontaneous; Acromegaly; Diabetes, Gestational; Eclampsia; Female; Humans; Hypertension; Infant, Newborn; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth
PubMed: 35098440
DOI: 10.1007/s11102-022-01208-0 -
Journal of Clinical Medicine Dec 2022Acromegaly is characterized by a very particular alteration of bone microarchitecture, leading to increased vertebral fragility. However, due to inconsistent and... (Review)
Review
INTRODUCTION
Acromegaly is characterized by a very particular alteration of bone microarchitecture, leading to increased vertebral fragility. However, due to inconsistent and insufficient evidence, no guidelines are available for the evaluation of this osteopathy.
METHODS
We performed a literature review of studies published between 1968 and January 2022 on the PubMed and SCOPUS databases using the terms "acromegaly" and "vertebral fractures". Twenty-four studies were found eligible for inclusion, published between June 2005 and November 2021. Included studies evaluated acromegaly patients, who were assessed for the presence of vertebral fractures. We excluded case reports, reviews, meta-analyses, letters to the editor, articles not written in English, and research performed on the same set of patients without significant differences in study design. Risk of bias was avoided by following the ROBIS risk of bias recommendations. We executed rigorous data collection, and the results are depicted as a narrative overview, but also, as statistical synthesis. Limitations of the evidence presented in the study include study heterogeneity, small sample sizes, and a small number of prospective studies with short follow-up.
FINDINGS
Data regarding vertebral fractures (VFs) in acromegaly and their influencing factors are variable. Twenty-four studies were included, nine out of which had a prospective design. The smallest group of acromegaly patients had 18 subjects and the largest included 248 patients. Prevalence ranges between 6.5% and 87.1%, although most studies agree that it is significantly higher than in controls. VFs also have a higher incidence (between 5.6% and 42%) and are more frequently multiple (between 46.15% and 71%). Evidence shows that disease activity and active disease duration are influencing factors for the prevalence and incidence of VFs. Nonetheless, hypogonadism does not seem to influence the frequency of VFs. While reports are conflicting regarding the use of bone mineral density in acromegaly, evidence seems to be slightly in favor of it not being associated with VFs. However, trabecular bone score is significantly lower in fractured patients, although no prospective studies are available.
INTERPRETATION
Vertebral fractures evaluation should be performed with regularity in all acromegalic patients, especially in the presence of active disease. Disease activity is an important determinant of vertebral fracture incidence and prevalence, although hypogonadism is less so. To clarify the predictive value of both BMD and TBS for vertebral fractures, additional, larger, prospective studies are necessary.
PubMed: 36614962
DOI: 10.3390/jcm12010164 -
Journal of Endocrinological... Oct 2022Acromegaly is a rare chronic disease characterized by systemic comorbidity and reduced quality of life. Although achieving biochemical control has always been the... (Review)
Review
PURPOSE
Acromegaly is a rare chronic disease characterized by systemic comorbidity and reduced quality of life. Although achieving biochemical control has always been the primary goal of acromegaly therapy, recent evidence has shown that the traditional assessment does not adequately capture the complexity of symptoms and patients' perception. These findings result in the need to improve a fast decision-making process of the clinician, who should not only take into account biochemical-instrumental criteria, but also patients' symptoms. With the aim of supporting the clinician in the diagnostic and therapeutic decision-making process several disease-specific tools have been developed. The aim of this review is to provide a description of the acromegaly-specific tools, presenting their main features, their application in daily practice, and their efficacy and utility.
METHODS
A systematic search of Medline/PubMed, ISI-Web of Knowledge, and Google Scholar databases was done.
RESULTS
Specific instruments and questionnaires have recently been developed to assist clinicians in the assessment of acromegaly. These are either Patient-Reported Outcome tools, such as Acromegaly Quality of Life Questionnaire (AcroQoL) and Pain Assessment Acromegaly Symptom Questionnaire (PASQ), or Clinician-Reported Outcome tools, such as ACROSCORE, SAGIT and Acromegaly Disease Activity Tool (ACRODAT). Such tools are extremely flexible and, therefore, have been widely adopted by endocrinologists and other professionals, so much so that they have also been included as recommendations in the 2018 international guidelines.
CONCLUSION
Questionnaires and tools are useful in the management of acromegaly patients. They help clinicians evaluate patients' symptoms and could assist in the evaluation of disease activity.
Topics: Acromegaly; Comorbidity; Databases, Factual; Humans; Quality of Life; Surveys and Questionnaires
PubMed: 35322391
DOI: 10.1007/s40618-022-01782-x -
PloS One 2023The incidence of cancer in acromegaly patients may be higher than that in the general population, although this has not been fully elucidated yet. This study analyzed... (Meta-Analysis)
Meta-Analysis
The incidence of cancer in acromegaly patients may be higher than that in the general population, although this has not been fully elucidated yet. This study analyzed the risk of various important types of cancer in acromegaly patients. The study was registered in INPLASY (registration number: INPLASY202340037). The PubMed, Web of Science, and EMBASE databases were searched for studies based on strict inclusion and exclusion criteria, from the time of database inception up to June 30, 2022. All observational studies of acromegaly patients with cancer were included, without language restrictions. We used the Newcastle-Ottawa scale (NOS) checklist to assess the quality of evidence. A meta-analysis revealed the relationship between acromegaly and cancer using the standardized incidence rates (SIRs) and 95% confidence intervals (CIs) retrieved from the included studies. Nineteen studies were included and analyzed. The overall incidence of cancer (SIR = 1.45, 95%CI = 1.20-1.75), as well as that of thyroid (SIR = 6.96, 95%CI = 2.51-19.33), colorectal and anal (SIR = 1.95, 95%CI = 1.32-2.87), brain and central nervous system (SIR = 6.14, 95%CI = 2.73-13.84), gastric (SIR = 3.09, 95%CI = 1.47-6.50), urinary (SIR = 2.66, 95%CI = 1.88-3.76), hematological (SIR = 1.89, 95%CI = 1.17-3.06), pancreatic and small intestine (SIR = 2.59, 95%CI = 1.58-4.24), and connective tissue (SIR = 3.15, 95%CI = 1.18-8.36) cancers, was higher among patients with acromegaly than among the general population. No association between acromegaly and hepatobiliary, respiratory, reproductive, skin, breast, or prostate cancer was observed. This study demonstrated that acromegaly patients have a modestly increased chance of cancer as compared to the general population. Risk factors for cancer need to be further explored to monitor patients with acromegaly at a high risk for cancer more carefully.
Topics: Male; Humans; Acromegaly; Neoplasms; Risk Factors; Incidence; Prostatic Neoplasms; Skin
PubMed: 38032888
DOI: 10.1371/journal.pone.0285335 -
European Journal of Endocrinology Jul 2021To date, no systematic reviews and meta-analysis on the global epidemiology of acromegaly are available in the literature. The aims of this study are to provide a... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To date, no systematic reviews and meta-analysis on the global epidemiology of acromegaly are available in the literature. The aims of this study are to provide a systematic review and a meta-analysis of the global epidemiology of acromegaly and to evaluate the quality of study reporting for the identified studies.
METHODS
MEDLINE, EMBASE and The Cochrane Library databases were searched for studies assessing the epidemiology of acromegaly from inception until 31 January 2020. We included original observational studies written in English, reporting acromegaly prevalence and/or incidence for a well-defined geographic area. Two reviewers independently extracted data and performed quality assessments. Prevalence and incidence pooled estimates were derived by performing a random-effects meta-analysis.
RESULTS
A total of 32 studies were included in the systematic review, and 22 of them were included in the meta-analysis. The pooled prevalence of acromegaly was 5.9 (95% CI: 4.4-7.9) per 100 000 persons, while the incidence rate (IR) was 0.38 (95% CI: 0.32-0.44) cases per 100 000 person-years. For both prevalence and IR, considerable between-study heterogeneity was found (I2 = 99.3 and 86.0%, respectively). The quality of study reporting was rated as the medium for 20 studies and low for 12 studies.
CONCLUSIONS
Although the largest amount of heterogeneity was due to the high precision of the studies' estimates, data source and geographic area could represent relevant study-level factors which could explain about 50% of the total between-study variability. Large-scale high-quality studies on the epidemiology of acromegaly are warranted to help the public health system in making decisions.
Topics: Acromegaly; Data Accuracy; Epidemiologic Research Design; Geography; Global Health; Humans; Observational Studies as Topic
PubMed: 34061771
DOI: 10.1530/EJE-21-0216 -
Pituitary Aug 2023Diagnostic delay is high in acromegaly and leads to increased morbidity and mortality. The aim of this study is to systematically assess the most prevalent clinical... (Review)
Review
OBJECTIVE
Diagnostic delay is high in acromegaly and leads to increased morbidity and mortality. The aim of this study is to systematically assess the most prevalent clinical signs, symptoms and comorbidities of acromegaly at time of diagnosis.
DESIGN
A literature search (in PubMed, Embase and Web of Science) was performed on November 18, 2021, in collaboration with a medical information specialist.
METHODS
Prevalence data on (presenting) clinical signs, symptoms and comorbidities at time of diagnosis were extracted and synthesized as weighted mean prevalence. The risk of bias was assessed for each included study using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data.
RESULTS
Risk of bias and heterogeneity was high in the 124 included articles. Clinical signs and symptoms with the highest weighted mean prevalence were: acral enlargement (90%), facial features (65%), oral changes (62%), headache (59%), fatigue/tiredness (53%; including daytime sleepiness: 48%), hyperhidrosis (47%), snoring (46%), skin changes (including oily skin: 37% and thicker skin: 35%), weight gain (36%) and arthralgia (34%). Concerning comorbidities, acromegaly patients more frequently had hypertension, left ventricle hypertrophy, dia/systolic dysfunction, cardiac arrhythmias, (pre)diabetes, dyslipidemia and intestinal polyps- and malignancy than age- and sex matched controls. Noteworthy, cardiovascular comorbidity was lower in more recent studies. Features that most often led to diagnosis of acromegaly were typical physical changes (acral enlargement, facial changes and prognatism), local tumor effects (headache and visual defect), diabetes, thyroid cancer and menstrual disorders.
CONCLUSION
Acromegaly manifests itself with typical physical changes but also leads to a wide variety of common comorbidities, emphasizing that recognition of a combination of these features is key to establishing the diagnosis.
Topics: Humans; Acromegaly; Prevalence; Delayed Diagnosis; Comorbidity; Headache; Hypertension; Diabetes Mellitus
PubMed: 37210433
DOI: 10.1007/s11102-023-01322-7 -
Clinical Endocrinology Jan 2023Acromegaly is a condition characterized by an overproduction of growth hormone which infers high morbidity and mortality if left untreated. The objective of this review... (Review)
Review
OBJECTIVE
Acromegaly is a condition characterized by an overproduction of growth hormone which infers high morbidity and mortality if left untreated. The objective of this review is to analyse and appraise the current evidence for the generalized use of preoperative medications and the various surgical approaches as described in the literature.
DESIGN
A thorough search from MEDLINE via PubMed, EMBASE, and Cochrane Library has been performed which identified a total of 37 papers.
CONCLUSION
The preoperative use of somatostatin receptor agonists (SAs) in acromegaly is a controversial topic with current guidelines suggesting against their generalized routine use. Most authors noticed an insignificant long-term remission of acromegaly when given SAs compared with nil preoperative therapy, except for invasive macroadenomas as SAs have been found to reduce the tumour volume and aid towards the total resection of the adenoma. Furthermore, according to the evidence available, endoscopic transsphenoidal surgery is the optimum method for hypophysectomy in terms of its remission and safety profile.
PubMed: 35726150
DOI: 10.1111/cen.14790 -
Pituitary Dec 2022Vertebral fractures (VFs) are a potential complication in acromegaly. However, the etiology of this skeletal fragility is unknown. This review aimed to evaluate the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Vertebral fractures (VFs) are a potential complication in acromegaly. However, the etiology of this skeletal fragility is unknown. This review aimed to evaluate the effect of acromegaly on VFs, bone turnover, areal bone mineral density (aBMD), and bone quality/microarchitecture. The effect of disease activity and gonadal status in these determinants of skeletal fragility was also evaluated.
METHODS
Articles published in English until September 6, 2020 on PubMed and Embase that reported at least one determinant of skeletal fragility in acromegalic patients, were included. Odds ratio (OR) to evaluate the risk of VFs and the standardized mean difference (SMD) to evaluate bone turnover, aBMD and bone quality/microarchitecture were calculated.
RESULTS
Fifty-eight studies met eligibility criteria, assembling a total of 2412 acromegalic patients. Of these, 49 studies were included in the meta-analysis. Acromegalic patients, when compared to non-acromegalic patients, had higher risk of VFs [OR 7.00; 95% confidence interval (CI) 2.80-17.52; p < 0.0001], higher bone formation (SMD 1.14; 95% CI 0.69-1.59; p < 0.00001), higher bone resorption (SMD 0.60; 95% CI 0.09-1.10; p = 0.02) and higher aBMD at the femoral neck (SMD 0.36; 95% CI 0.15-0.57; p = 0.0009). No significant differences were found regarding aBMD at lumbar spine. Considering the results of the different techniques evaluating bone quality/microarchitecture, the main reported alterations were a decrease in trabecular bone thickness and density, and an increase in trabecular separation. The presence of active disease and/or hypogonadism were associated with worst results.
CONCLUSION
Patients with acromegaly are at increased risk of VFs, mainly because of deterioration in bone microarchitecture.
Topics: Humans; Acromegaly; Bone Density; Spinal Fractures; Lumbar Vertebrae; Hypogonadism; Absorptiometry, Photon
PubMed: 35867180
DOI: 10.1007/s11102-022-01256-6 -
The prevalence of acromegaly is higher than previously reported: Changes over a three-decade period.Clinical Endocrinology Dec 2022To study time-related changes in the prevalence and patient characteristics of acromegaly, as well as to assess the impact of changes in treatment on disease control.
OBJECTIVE
To study time-related changes in the prevalence and patient characteristics of acromegaly, as well as to assess the impact of changes in treatment on disease control.
METHODS
A total of 107 patients with acromegaly were identified by healthcare registries and subsequently validated by patient chart review over a three-decade period (1992-2021). A systematic literature review focusing on the incidence and prevalence of acromegaly was performed identifying 31 studies.
RESULTS
The prevalence of acromegaly significantly increased throughout the study period (R = 0.94, p < .001) and was 122 cases/10 persons in 2021 whereas the annual incidence remained constant at 4.6 cases/10 persons. The age at the first sign of acromegaly and the age at diagnosis significantly increased during the study period, whereas growth hormone and insulin-like growth factor I decreased. Incidentalomas constituted 32% of all cases diagnosed with acromegaly in the last decade. Primary surgery was used in 93% of all cases, and repeated surgery decreased from 24% to 10% during the three decades. The use of first-generation somatostatin analogues (21%-48%) and second-line medical treatment (4%-20%) increased with a concomitant improvement of biochemical disease control (58%-91%).
CONCLUSION
The prevalence of acromegaly is higher than previously reported and the clinical presentation has shifted towards a milder phenotype. Modern treatment of acromegaly enables individualized treatment and disease control in the majority of patients.
Topics: Humans; Acromegaly; Prevalence; Adenoma; Somatostatin; Human Growth Hormone; Insulin-Like Growth Factor I
PubMed: 36163677
DOI: 10.1111/cen.14828