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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 -
The Journal of Clinical Endocrinology... Aug 2022Diabetes is a major risk factor for cardiovascular disease and death but its effect on outcomes in acromegaly is unknown. (Observational Study)
Observational Study
CONTEXT
Diabetes is a major risk factor for cardiovascular disease and death but its effect on outcomes in acromegaly is unknown.
OBJECTIVE
This work aimed to study whether diabetes affects morbidity and mortality in patients with acromegaly.
METHODS
A nationwide (Sweden), observational, matched-cohort study was conducted. Patients diagnosed with acromegaly between 1987 and 2020 were identified in the Swedish National Patient Registry and those with concomitant type 2 diabetes in the National Diabetes Registry and Drug Registry. The risk of overall mortality, and cardiovascular mortality and morbidity were estimated using Cox regression.
RESULTS
The study included 254 patients with acromegaly and concomitant type 2 diabetes (ACRO-DM group) and 532 without diabetes (ACRO group). Mean (SD) age at baseline was 62.6 (11.4) and 60.0 (12.1) years (P = .004) and the mean (SD) duration of acromegaly was 6.8 (8.1) and 6.0 (6.2) years (P = .098) in the ACRO-DM and ACRO groups, respectively. Overall mean follow-up was 9.2 years. The unadjusted overall mortality rate per 1000 person-years was 35.1 (95% CI, 27.2-44.7) and 20.1 (95% CI, 16.5-24.3) in the respective groups. The hazard ratio (HR) for overall mortality adjusted for multiple confounders was 1.58 (95% CI, 1.12-2.23) in the ACRO-DM group compared with the ACRO group. Cardiovascular mortality (HR 2.11; 95% CI, 1.09-4.10) and morbidity (HR 1.49; 95% CI, 1.21-1.82) were also increased in the ACRO-DM group.
CONCLUSION
The presence of diabetes in patients with acromegaly was associated with increased overall mortality as well as increased cardiovascular mortality and morbidity.
Topics: Acromegaly; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Humans; Morbidity
PubMed: 35779017
DOI: 10.1210/clinem/dgac400 -
Medicina (Kaunas, Lithuania) Jun 2022Somatostatin receptor ligands (SRLs) represent a true milestone in the medical therapy for acromegaly. The first-generation SRLs (FG-SRLs), octreotide and lanreotide,... (Review)
Review
Somatostatin receptor ligands (SRLs) represent a true milestone in the medical therapy for acromegaly. The first-generation SRLs (FG-SRLs), octreotide and lanreotide, have demonstrated good efficacy in disease control and tumor shrinkage, and are still considered first-line medical therapies. The development of long-acting release (LAR) formulations has certainly improved the therapeutic tolerability of these drugs, although many patients still experience therapy-related burden. As such, new formulations have recently been developed to improve adherence and therapeutic efficacy and more solutions are on the way. In the case of FG-SRL-resistant disease, pasireotide, the only second generation SRL currently available, demonstrated superiority in disease control and tumor shrinkage compared to FG-SRLs. However, its use in clinical practice is still limited due to concern for impairment in glucose homeostasis. In this review, we discuss the news about the present and future role of SRLs in acromegaly, exploring the therapeutical frontiers of this drug class. Moreover, we provide practical guidance on the use of pasireotide, based on the data in the literature and our clinical experience.
Topics: Acromegaly; Humans; Ligands; Receptors, Somatostatin
PubMed: 35744057
DOI: 10.3390/medicina58060794 -
Pituitary 2009In 1886 Pierre Marie used the term "acromegaly" for the first time and gave a full description of the characteristic clinical picture. However several others had already... (Review)
Review
In 1886 Pierre Marie used the term "acromegaly" for the first time and gave a full description of the characteristic clinical picture. However several others had already given clear clinical descriptions before him and sometimes had given the disease other names. After 1886, it gradually became clear that pituitary enlargement (caused by a pituitary adenoma) was the cause and not the consequence of acromegaly, as initially thought. Pituitary adenomas could be found in the great majority of cases. It also became clear that acromegaly and gigantism were the same disease but occurring at different stages of life and not different diseases as initially thought. At the end of the 19th and beginning of the 20th century most information was derived from case descriptions and post-mortem examinations of patients with acromegaly or (famous) patients with gigantism. The stage was set for further research into the pathogenesis, diagnosis and therapy of acromegaly and gigantism.
Topics: Acromegaly; Gigantism; History, 19th Century; History, 20th Century; Humans; Pituitary Neoplasms
PubMed: 18683056
DOI: 10.1007/s11102-008-0138-y -
Journal of Patient-reported Outcomes Feb 2023Patient-reported outcome (PRO) measures are important to consider when evaluating treatments, yet there are no PRO measures for patients with acromegaly that have been...
BACKGROUND
Patient-reported outcome (PRO) measures are important to consider when evaluating treatments, yet there are no PRO measures for patients with acromegaly that have been developed in accordance with US Food and Drug Administration guidance. Acromegaly is a rare, chronic condition caused by hypersecretion of growth hormone. Disease activity is monitored by measurement in serum of growth hormone and insulin-like growth factor-I. The objectives of this research were to develop the Acromegaly Symptom Diary (ASD), establish a scoring algorithm, and evaluate the psychometric measurement properties of the ASD.
METHODS
Semistructured interviews consisting of concept elicitation and cognitive debriefing components were conducted with 16 adult participants with acromegaly. The concept elicitation component identified symptoms important to individuals with acromegaly. The cognitive debriefing component gathered information about the participants' experience with each proposed item of the ASD, their thought process for answering each question, and their interpretation of the items. The psychometric properties of the draft ASD were then evaluated using data from the ACROBAT Evolve (NCT03792555; n = 13) and ACROBAT Edge (NCT03789656; n = 47) clinical trials.
RESULTS
The 16 participants from the interviews described ongoing symptoms, with the most frequently reported being joint pain (n = 13) and fatigue (n = 12), followed by swelling (n = 8), headache (n = 7), and mood swings (n = 6), and were able to interpret and understand the ASD items and had no issues with the 24-hour recall period. From data collected in the clinical studies, the psychometric properties of internal consistency (0.91 - 0.80), test-retest reliability with item-level and total ASD scores (> 0.70), baseline construct validity (r ≥ |0.38|) across scales, and responsiveness to change (r = 0.52-0.56) were supported for the ASD. The proposed preliminary threshold range to characterize a meaningful change from the patients' perspective for the ASD total is a 4- to 6-point change for improvement or worsening out of a total score of 70.
CONCLUSION
These findings provide qualitative and quantitative evidence to support the ASD as fit for the purpose of evaluating the symptom experience of patients with acromegaly in clinical trials.
Topics: Adult; Humans; Acromegaly; Reproducibility of Results; Surveys and Questionnaires; Mental Recall; Growth Hormone
PubMed: 36792844
DOI: 10.1186/s41687-023-00541-7 -
The Journal of Clinical Endocrinology... Nov 2023Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I...
CONTEXT
Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I (IGF-I). Medical therapies, including the somatostatin receptor ligand (SRL) pasireotide, are frequently used to restore biochemical control.
OBJECTIVE
As patients often receive therapy over prolonged periods, long-term data from real-life settings are needed.
METHODS
A retrospective analysis was performed using a prospectively maintained database of all patients with acromegaly from our primary care center who were enrolled in clinical studies with pasireotide (first visit November 2008). The main outcome measures were safety and biochemical control (age-adjusted IGF-I ≤ upper limit of normal).
RESULTS
Patients (n = 50) entered 4 parental studies and 30 continued in the rollover; at data cutoff (June 2022), 27 were still receiving pasireotide. Overall, median (range) exposure was 58 (3-137) months. Normal IGF-I was achieved in 54%, and acromegaly symptoms and quality of life were improved with treatment. No predictors of pasireotide response were identified; however, controlled patients had smaller tumors and lower GH at baseline. Tumor volume reduction occurred in 63% of evaluable patients (n = 10/16). Most patients presented hyperglycemic events, including 63.2% of patients with normal glucose before treatment. Older patients and those with higher IGF-I, glucose, and HbA1c at baseline had higher glucose and HbA1c during pasireotide treatment.
CONCLUSION
Pasireotide provided clinical benefit and was well tolerated for more than 11 years of treatment in acromegaly patients, most of whom were resistant to first-generation SRLs.
Topics: Humans; Acromegaly; Insulin-Like Growth Factor I; Glycated Hemoglobin; Retrospective Studies; Quality of Life; Treatment Outcome; Human Growth Hormone; Growth Hormone; Glucose; Adenoma
PubMed: 37357993
DOI: 10.1210/clinem/dgad378 -
Italian Journal of Pediatrics Aug 2017Referral for an assessment of tall stature is less common than for short stature. Tall stature is defined as a height more than two standard deviations above the mean... (Review)
Review
Referral for an assessment of tall stature is less common than for short stature. Tall stature is defined as a height more than two standard deviations above the mean for age. The majority of subjects with tall stature show a familial tall stature or a constitutional advance of growth (CAG), which is a diagnosis of exclusion. After a careful physical evaluation, tall subjects may be divided into two groups: tall subjects with normal appearance and tall subjects with abnormal appearance. In the case of normal appearance, the paediatric endocrinologist will have to evaluate the growth rate. If it is normal for age and sex, the subject may be classified as having familial tall stature, CAG or obese subject, while if the growth rate is increased it is essential to evaluate pubertal status and thyroid status. Tall subjects with abnormal appearance and dysmorphisms can be classified into those with proportionate and disproportionate syndromes.A careful physical examination and an evaluation of growth pattern are required before starting further investigations. Physicians should always search for a pathological cause of tall stature, although the majority of children are healthy and they generally do not need treatment to cease growth progression.The most accepted and effective treatment for an excessive height prediction is inducing puberty early and leading to a complete fusion of the epiphyses and achievement of final height, using testosterone in males and oestrogens in females. Alternatively, the most common surgical procedure for reducing growth is bilateral percutaneous epiphysiodesis of the distal femur and proximal tibia and fibula.This review aims to provide up-to-date information and suggestions about the diagnosis and management of children with tall stature.
Topics: Acromegaly; Adolescent; Anthropometry; Body Height; Child; Diagnosis, Differential; Dimensional Measurement Accuracy; Female; Gigantism; Growth Hormone; Humans; Male; Physical Examination
PubMed: 28774346
DOI: 10.1186/s13052-017-0385-5 -
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 -
BMC Endocrine Disorders May 2023Pregnancy in acromegaly is uncommon and still in debate for fear of tumor progression or potential threat to both mother and fetus's health. Besides, the data for... (Review)
Review
BACKGROUND
Pregnancy in acromegaly is uncommon and still in debate for fear of tumor progression or potential threat to both mother and fetus's health. Besides, the data for pregnancy complications in uncontrolled acromegaly is limited. Thus, the objective of this study was to summarize pregnancy safety and disease courses after pregnancy in acromegalic patients and review their clinical characteristics based on disease activity in the literature.
METHODS
An evaluation of eight acromegalic women from Peking Union Medical College Hospital (PUMCH) with 11 pregnancies was conducted. We also summarized a literature review of 82 disease-active pregnancies and 63 disease-controlled pregnancies with acromegaly. A second analysis was conducted to compare pregnancy courses and outcomes in different disease activities.
RESULTS
Before pregnancy, all patients had macroadenomas and underwent pituitary surgery. Pregnancy occurred at a median of 6 years (4-10) after the diagnosis of acromegaly. Assisted reproductive therapy was needed in 42.9% of participants. No cases had a premature birth or congenital malformations. Biochemical control was achieved in 50% of females before pregnancy and 75% at the last follow-up after delivery. Data analysis showed no differences in the prevalence of gestational diabetes mellitus (GDM) or pregnancy-induced hypertension (PIH) between acromegaly-active or acromegaly-controlled groups. The GDM prevalence in patients diagnosed during pregnancy (33.3%) was higher than that in patients diagnosed before pregnancy (4.8%) (p = 0.001).
CONCLUSION
Pregnancy without biochemical control in acromegaly and receiving medical treatment during pregnancy are not rare and generally safe for the fetus. There could be a higher prevalence of PIH in acromegalic pregnancies. The treatment of acromegaly and related complications can be managed with regular follow-up after pregnancy.
Topics: Pregnancy; Humans; Female; Infant; Acromegaly; China; Family; Data Analysis; Diabetes, Gestational
PubMed: 37161564
DOI: 10.1186/s12902-023-01341-2 -
Frontiers in Endocrinology 2023Cushing's syndrome, acromegaly and neuroendocrine disorders are characterized by an excess of counterregulatory hormones, able to induce insulin resistance and glucose... (Review)
Review
Cushing's syndrome, acromegaly and neuroendocrine disorders are characterized by an excess of counterregulatory hormones, able to induce insulin resistance and glucose metabolism disorders at variable degrees and requiring immediate treatment, until patients are ready to undergo surgery. This review focuses on the management of diabetes mellitus in endocrine disorders related to an excess of counterregulatory hormones. Currently, the landscape of approved agents for treatment of diabetes is dynamic and is mainly patient-centred and not glycaemia-centred. In addition, personalized medicine is more and more required to provide a precise approach to the patient's disease. For this reason, we aimed to define a practical therapeutic algorithm for management of diabetes mellitus in patients with glucagonoma, pheochromocytoma, Cushing's syndrome and acromegaly, based on our practical experience and on the physiopathology of the specific endocrine disease taken into account. This document is addressed to all specialists who approach patients with diabetes mellitus secondary to endocrine disorders characterized by an excess of counterregulatory hormones, in order to take better care of these patients. Care and control of diabetes mellitus should be one of the primary goals in patients with an excess of counterregulatory hormones requiring immediate and aggressive treatment.
Topics: Humans; Cushing Syndrome; Acromegaly; Neuroendocrine Tumors; Diabetes Mellitus; Hormones
PubMed: 37842314
DOI: 10.3389/fendo.2023.1248985