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Endocrine Nov 2023To evaluate the incidence of malignancies in acromegaly and to identify risk factors for newly-diagnostic cancers, especially the excessive growth hormone (GH) and...
PURPOSE
To evaluate the incidence of malignancies in acromegaly and to identify risk factors for newly-diagnostic cancers, especially the excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1).
METHODS
A retrospective cohort including 1738 consecutive hospitalized patients with acromegaly in a single referral center between 2012 and 2020 (mean follow-up 4.3 years). A gender- and age-matched case-control study (280 patients from the cohort) was performed for risk factor analysis.
RESULTS
One hundred thirteen malignancies (67 diagnosed after acromegaly) were observed. The overall newly-diagnostic cancer risk of acromegaly was higher than the general population (standardized incidence ratio (SIR) 2.81; 95% CI 2.18-3.57). The risk of thyroid cancer (n = 33, SIR 21.42; 95% CI 13.74-30.08) and colorectal cancer (n = 8, SIR 3.17; 95% CI 1.37-6.25) was elevated. In the overall cohort, IGF-1 (ULN: 1.27 vs. 0.94, p = 0.057), GH (1.30 vs. 1.00 ng/ml, p = 0.12), and disease-controlled rate (34.9% vs. 45.9%, p = 0.203) at the last visit did not reach significance between patients with and without post-diagnostic cancer. In the case-control study, GH (1.80 vs. 0.90 ng/ml, p = 0.018) and IGF-1 (ULN: 1.27 vs. 0.91, p = 0.003) at the last visit were higher in patients with post-diagnostic cancers, with a lower disease-controlled rate. Elder age was a risk factor for cancer. Other metabolic comorbidities and the size of pituitary tumors were similar.
CONCLUSION
The risk of malignancies, especially thyroid cancer, was increased in patients with acromegaly in our center. More cancer screening should be considered when managing acromegaly, especially in patients with higher posttreatment GH and IGF-1.
Topics: Humans; Aged; Acromegaly; Retrospective Studies; Insulin-Like Growth Factor I; Case-Control Studies; Incidence; East Asian People; Pituitary Neoplasms; Thyroid Neoplasms; Risk Factors; Human Growth Hormone
PubMed: 37442901
DOI: 10.1007/s12020-023-03447-y -
Archives of Medical Research Sep 2023Despite the inherent heterogeneity of the information derived from national registries, they are a useful tool to investigate the epidemiological, clinical, biochemical... (Review)
Review
INTRODUCTION
Despite the inherent heterogeneity of the information derived from national registries, they are a useful tool to investigate the epidemiological, clinical, biochemical and treatment outcome characteristics of low prevalence conditions such as acromegaly. Although the information provided by single-center experiences is more homogeneous, these studies usually comprise a limited number of patients and thus, frequently lack statistical power.
AREAS COVERED
Registry-based Information regarding the epidemiology, clinical presentation, biochemical and imaging diagnosis, as well as therapeutic outcome and mortality in acromegaly is critically analyzed.
EXPERT OPINION
By gathering data from multiple centers in a specific Country, these registries generate important insights into the real-life behavior of this condition, that should be considered, both, in international consensus meetings and in the design of local, Country-specific diagnostic and therapeutic strategies.
Topics: Humans; Acromegaly; Human Growth Hormone; Adenoma; Somatostatin; Treatment Outcome; Registries; Insulin-Like Growth Factor I; Pituitary Neoplasms
PubMed: 37481822
DOI: 10.1016/j.arcmed.2023.102856 -
Endocrine Feb 2023Skeletal fragility with high risk of vertebral fractures (VFs) is an emerging complication of growth hormone (GH) hypersecretion. VFs often coexist with spine...
Skeletal fragility with high risk of vertebral fractures (VFs) is an emerging complication of growth hormone (GH) hypersecretion. VFs often coexist with spine arthropathy and both clinical conditions negatively impact on quality of life of acromegalic subjects. Management of spine osteopathy and arthropathy in acromegaly could be challenging since both complications can persist or even progress after biochemical control of disease. This article analyzes the latest evidence about possible pathophysiological links between VFs and spine arthropathy in active and controlled acromegaly, as well as the diagnostic and therapeutic aspects concerning the holistic management of acromegalic osteo-arthropathy.
Topics: Humans; Acromegaly; Quality of Life; Bone Density; Spinal Fractures; Human Growth Hormone
PubMed: 36574147
DOI: 10.1007/s12020-022-03258-7 -
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 -
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 -
Endocrine Practice : Official Journal... Mar 2022Acromegaly is associated with significant morbidity and mortality if it is not appropriately treated. In addition to insulin-like growth factor 1 and growth hormone... (Review)
Review
Acromegaly is associated with significant morbidity and mortality if it is not appropriately treated. In addition to insulin-like growth factor 1 and growth hormone normalization as well as tumor shrinkage, the treatment goals include relieving symptoms, managing complications, and improving patients' quality of life. Surgical resection is a first-line treatment option for most patients, with few being pretreated preoperatively with medications. Somatostatin receptor ligands (SRLs), injectable and, more recently, oral capsules, have been the cornerstone of first-line medical therapy for persistent disease. However, several factors, including sparsely granulated adenomas, absent or low somatostatin receptor status, T2-hyperintensity imaging, young age, and aryl hydrocarbon receptor-interacting protein mutations, can predict first-generation SRL resistance. Patients with these characteristics may be better candidates for the growth hormone receptor antagonist pegvisomant, or in cases of large tumors, the second-generation SRL pasireotide. Combination therapy should be further pursued in patients who remain biochemically uncontrolled or have a high remnant tumor after monotherapy. An efficacious and cost-effective pegvisomant dose-sparing effect of SRLs when used in combination has been demonstrated. With such a wide array of medical treatment options, it is becoming increasingly important to tailor treatment to patients' unique characteristics and preferences, with a goal of personalizing management to achieve high-quality outcomes.
Topics: Acromegaly; Adenoma; Combined Modality Therapy; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Quality of Life; Receptors, Somatostatin
PubMed: 35032649
DOI: 10.1016/j.eprac.2021.12.017 -
Polish Archives of Internal Medicine Jun 2022Acromegaly is a chronic, slowly progressive disorder caused mostly by growth hormone (GH)-producing pituitary neuroendocrine tumors (PitNETs). Recently, the associations...
INTRODUCTION
Acromegaly is a chronic, slowly progressive disorder caused mostly by growth hormone (GH)-producing pituitary neuroendocrine tumors (PitNETs). Recently, the associations between sex and age at the time of diagnosis and the course of acromegaly have been a focus of debate.
OBJECTIVES
The aim of our study was to evaluate the association between sex and age at the time of diagnosis of acromegaly and the clinical features, biochemical status, severity of the disease, and comorbidities.
PATIENTS AND METHODS
This was a single‑center study conducted in a group of consecutive patients with acromegaly and no family history of PitNETs. The participants were divded into 2 subgroups according to sex (male, female) and 3 subgroups according to age at the time of diagnosis: i) younger (≤40 years), ii) middle‑aged (41-59 years), and iii) elderly patients (≥60 years).
RESULTS
Our study included 101 patients (41 men, 60 women) who met the eligibility criteria. The mean (SD) age at the time of diagnosis was 47.3 (14.1) years and the median diagnostic delay was 5 years (interquartile range, 3-10). Age at the time of diagnosis and diagnostic delay were not statistically different in men and women. Levels of insulin‑like growth factor 1 (IGF‑1) above the upper limit of age‑adjusted normal range (%ULN IGF‑1) were greater in men than in women (mean [SD], 174.8% [98.9%] vs 109.4% [66.6%]; P = 0.002), while there was no significant difference in terms of %ULN IGF‑1 between the age groups. Median basal and nadir GH levels did not differ between the sexes. Men presented with hypogonadism more frequently than women (54% vs 26%; P = 0.005). Hyperprolactinemia, hypogonadism, and macroadenoma were more frequently observed in the younger patients than in the middle‑aged and elderly individuals (all P <0.05).
CONCLUSIONS
According to our results, hypogonadism and greater IGF‑1 values were more frequently observed in men with acromegaly. Hyperprolactinemia, hypogonadism, and macroadenoma were more frequent in patients with acromegaly aged 40 years or younger.
Topics: Acromegaly; Adult; Age Distribution; Delayed Diagnosis; Female; Humans; Hyperprolactinemia; Hypogonadism; Insulin-Like Growth Factor I; Male; Middle Aged; Pituitary Neoplasms; Retrospective Studies; Sex Distribution
PubMed: 35289160
DOI: 10.20452/pamw.16232 -
Journal of Psychosomatic Research Aug 2022The main aim of the study was to investigate the factors related to the biopsychosocial complexity in the group of patients with acromegaly with different disease... (Observational Study)
Observational Study
OBJECTIVES
The main aim of the study was to investigate the factors related to the biopsychosocial complexity in the group of patients with acromegaly with different disease activity.
METHODS
A cross-sectional observational study was performed. First, a linguistic adaptation of the INTERMED - self-assessment questionnaire (IMSA) and after that the assessment of the biopsychosocial complexity among patients with acromegaly and the factors which relate to the complexity was made. The following tools were used to assess: biopsychosocial complexity: The INTERMED -self-assessment (IMSA); quality of life: The World Health Organization Quality of Life - BREF (WHOQoL) and Acromegaly Quality of Life questionnaire (AcroQol); mental state: The General Health Questionnaire - 28 (GHQ-28).
RESULTS
The final analysis included 71 patients. According to the principal component analysis the mental state (GHQ-28) and the quality of life (AcroQol) are the most important factors related to the clinical complexity among patients with acromegaly. In the model created by a stepwise regression analysis for the total IMSA score higher growth hormone (GH) concentration, longer illness duration, and better general quality of life were included as the protective factors of the clinical complexity. By contrast, a high score in the severe depression subscale of GHQ-28 was a factor of higher clinical complexity.
CONCLUSION
The mental state and quality of life are the most important determinants of the clinical complexity in the group of patients with acromegaly whereas the biochemical normalization is of lesser importance.
Topics: Acromegaly; Cross-Sectional Studies; Human Growth Hormone; Humans; Quality of Life; Surveys and Questionnaires
PubMed: 35644085
DOI: 10.1016/j.jpsychores.2022.110946 -
The Journal of Clinical Endocrinology... Dec 2023Nonalcoholic fatty liver disease (NAFLD) is a metabolical disorder and can lead to liver fibrosis. Because it is commonly seen, several noninvasive scores (NS) have been...
CONTEXT
Nonalcoholic fatty liver disease (NAFLD) is a metabolical disorder and can lead to liver fibrosis. Because it is commonly seen, several noninvasive scores (NS) have been validated to identify high-risk patients. Patients with NAFLD have been shown to have higher serum angiopoietin-like protein-8 (ANGPTL-8) levels.
OBJECTIVE
The risk of NAFLD is known insufficiently in acromegaly. Moreover, the utility of the NS and the link between NAFLD and ANGPTL-8 in acromegaly is unknown.
METHODS
Thirty-two patients with acromegaly (n = 15, active [AA] and n = 17, controlled acromegaly [CA]) and 19 healthy controls were included. Magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) was used to evaluate hepatic steatosis, and magnetic resonance elastography to evaluate liver stiffness measurement. ANGPTL-8 levels were measured with ELISA.
RESULTS
Median liver MRI-PDFF and NAFLD prevalence in AA were lower than in CA (P = .026 and P < .001, respectively). Median magnetic resonance elastography-liver stiffness measurement were similar across groups. Of the NS, visceral adiposity index, fatty liver index, hepatic steatosis index, and triglyceride-glucose index (TyG) all showed positive correlation with the liver MRI-PDFF in the control group. However, only TyG significantly correlated with liver fat in the AA and CA groups. There was no correlation between traditional NAFLD risk factors (body mass index, waist circumference, C-reactive protein, homeostasis model assessment for insulin resistance, visceral adipose tissue) and liver MRI-PDFF in the AA and CA. Patients with acromegaly with NAFLD had lower GH, IGF-1, and ANGPTL-8 levels than in those without NAFLD (P = .025, P = .011, and P = .036, respectively).
CONCLUSION
Active acromegaly may protect from NAFLD because of high GH. In patients with acromegaly, NAFLD risk cannot be explained with classical risk factors; hence, additional risk factors must be identified. TyG is the best score to evaluate NAFLD risk. Lower ANGPTL-8 in patients with acromegaly and NAFLD implies this hormone may be raised because of insulin resistance rather than being a cause for NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Insulin Resistance; Acromegaly; Liver; Liver Cirrhosis; Magnetic Resonance Imaging; Triglycerides
PubMed: 37590020
DOI: 10.1210/clinem/dgad490 -
Expert Review of Endocrinology &... May 2020: Acromegaly and gigantism entail increased morbidity and mortality if left untreated, due to the systemic effects of chronic GH and IGF-1 excess. Guidelines for the... (Review)
Review
: Acromegaly and gigantism entail increased morbidity and mortality if left untreated, due to the systemic effects of chronic GH and IGF-1 excess. Guidelines for the diagnosis and treatment of patients with GH excess are well established; however, the presentation, clinical behavior and response to treatment greatly vary among patients. Numerous markers of disease behavior are routinely used in medical practice, but additional biomarkers have been recently identified as a result of basic and clinical research studies.: This review focuses on genetic, molecular and genomic features of patients with GH excess that have recently been linked to disease progression and response to treatment. A PubMed search was conducted to identify markers of disease behavior in acromegaly and gigantism. Markers already considered as part of routine studies in clinical care guidelines were excluded. Literature search was expanded for each marker identified. Novel markers not included or only partially covered in previously published reviews on the subject were prioritized.: Recognizing the most relevant markers of disease behavior may help the medical team tailoring the strategies for approaching each case of acromegaly and gigantism. This customized plan should make the evaluation, treatment and follow up process more efficient, greatly improving the patients' outcomes.
Topics: Acromegaly; Biomarkers; Gigantism; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Insulin-Like Growth Factor I
PubMed: 32372673
DOI: 10.1080/17446651.2020.1749048