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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 -
Frontiers in Endocrinology 2021The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs)... (Review)
Review
The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low and high expression of , low or mutated condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.
Topics: Acromegaly; Adenoma; Algorithms; Biomarkers; Endocrine Gland Neoplasms; Genetic Markers; Growth Hormone-Secreting Pituitary Adenoma; Humans; Image Processing, Computer-Assisted; Insulin-Like Growth Factor I; Ligands; Machine Learning; Magnetic Resonance Imaging; Models, Genetic; Octreotide; Phosphorylation; Precision Medicine; Receptors, Somatostatin; Somatostatin; Treatment Outcome
PubMed: 33796079
DOI: 10.3389/fendo.2021.648411 -
Journal of Clinical Neuroscience :... Feb 2018We investigated whether acromegaly has been diagnosed earlier at the Niigata Medical and Dental University Hospital.
PURPOSE
We investigated whether acromegaly has been diagnosed earlier at the Niigata Medical and Dental University Hospital.
METHODS
Patients with acromegaly (n = 81) who underwent their first transsphenoidal surgery from 2006 to 2015 were reviewed. Two groups were compared: those who underwent surgery between 2006 and 2010 (n = 35) and those who underwent surgery between 2011 and 2015 (n = 46). We compared clinical features and serum levels of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1), hypertension (HT) and diabetes mellitus (DM) prevalence between the two groups.
RESULTS
Compared with the early group, microadenomas (<10 mm) were more prevalent in the late group (0% vs. 15.2%, p < .05). Serum IGF-1 standard deviation score (SDS) was significantly lower in the late group (8.57 ± 2.50 vs. 6.44 ± 2.30, p < .001). In both groups, mean IGF-1 SDS was significantly lower in patients without DM than in those with DM (6.9 ± 2.6 vs. 8.3 ± 2.4, p = .02). Logistic regression analysis showed that serum GH and IGF-1 levels were significantly higher in patients with DM than in those without DM.
CONCLUSION
Regarding operated cases of GH-producing pituitary adenoma, acromegaly clinical manifestations tended to be milder at diagnosis in later years of the decade, and acromegaly was diagnosed at lower IGF-1 levels and in smaller lesions. Further study is mandatory for the generalization of this trend.
Topics: Acromegaly; Adenocarcinoma; Adult; Age of Onset; Aged; Diabetes Mellitus; Female; Human Growth Hormone; Humans; Hypertension; Insulin-Like Growth Factor I; Japan; Male; Middle Aged; Neurosurgical Procedures; Pituitary Neoplasms; Prevalence; Sphenoid Bone
PubMed: 29113856
DOI: 10.1016/j.jocn.2017.10.086 -
Frontiers in Endocrinology 2021The muscle is an endocrine organ controlling metabolic homeostasis. Irisin and myostatin are key myokines mediating this process. Acromegaly is a chronic disease with a...
INTRODUCTION
The muscle is an endocrine organ controlling metabolic homeostasis. Irisin and myostatin are key myokines mediating this process. Acromegaly is a chronic disease with a wide spectrum of complications, including metabolic disturbances.
PURPOSE
To examine the influence of acromegaly on irisin and myostatin secretion and their contribution to metabolic profile and body composition.
MATERIALS AND METHODS
In 43 patients with acromegaly and 60 controls, serum levels of irisin, myostatin, growth hormone (GH), insulin-like growth factor 1 (IGF-1), parameters of glucose, and lipid metabolism were determined. Body composition was assessed with dual-energy x-ray absorptiometry.
RESULTS
The irisin concentration was significantly lower in patients with acromegaly compared to controls (3.91 . 5.09 μg/ml, = 0.006). There were no correlations between irisin and GH/IGF-1 levels. In the study group, irisin was negatively correlated with fasting insulin ( = -0.367; = 0.042), HOMA-IR ( = -0.510; = 0.011), and atherogenic factors: Castelli I ( = -0.416; = 0.005), Castelli II ( = -0.400; = 0.001), and atherogenic coefficient (AC) ( = -0.417; = 0.05). Irisin and myostatin concentrations were also lower in acromegalics with insulin resistance than without (2.80 . 4.18 μg/ml, = 0.047; 81.46 . 429.58 ng/L, = 0.018, respectively). There were no differences between study group and controls in myostatin concentration. Myostatin levels negatively correlated with GH ( = -0.306; = 0.049), HOMA-IR ( = -0.046; = 0.411), and insulin levels ( = -0.429; = 0.016).
CONCLUSIONS
Decreased irisin concentrations in acromegaly may suggest impaired hormonal muscle function contributing to metabolic complications in this disorder. However, learning more about the association between myostatin and GH in acromegaly requires further studies. Nevertheless, it appears that myostatin is not critical for muscle mass regulation in acromegaly.
Topics: Acromegaly; Biomarkers; Body Composition; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Fibronectins; Follow-Up Studies; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Muscles; Myostatin; Prognosis
PubMed: 34795636
DOI: 10.3389/fendo.2021.728734 -
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 -
Hormone Research in Paediatrics 2022People 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... (Review)
Review
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.
Topics: Animals; Humans; Acromegaly; Dwarfism; Endocrine System Diseases; Growth Hormone; Human Growth Hormone; Pituitary Hormones, Anterior
PubMed: 36446319
DOI: 10.1159/000526440 -
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 -
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 -
The Journal of Clinical Endocrinology... May 2022Although most tumors in patients with acromegaly are benign and are cured or controlled by surgery and/or first-generation somatostatin receptor ligands therapy, some...
Although most tumors in patients with acromegaly are benign and are cured or controlled by surgery and/or first-generation somatostatin receptor ligands therapy, some can behave more aggressively and are resistant to these standard therapies. Acromegaly, if left untreated, is a rare and chronic disorder, commonly caused by a GH-producing pituitary adenoma and is associated with significant comorbidities and an increased mortality. Transsphenoidal surgery is considered the mainstay of acromegaly management, but medical therapy has an increasingly important role. However, disease activity is not fully controlled in a significant number of patients treated with surgery and/or high-dose first-generation somatostatin receptor ligand monotherapy. In these circumstances, therefore, repeated surgery, second-line medical therapy, and radiotherapy, alone or combined as multimodal therapeutic strategies should be considered, in a patient-centered perspective.
Topics: Acromegaly; Human Growth Hormone; Humans; Pituitary Neoplasms; Receptors, Somatostatin; Somatostatin
PubMed: 35090028
DOI: 10.1210/clinem/dgac037 -
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