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Frontiers in Endocrinology 2023Standard treatment for acromegaly focuses on the achievement of target absolute levels of growth hormone (GH) and insulin-like growth factor (IGF-I). The appropriateness... (Review)
Review
Standard treatment for acromegaly focuses on the achievement of target absolute levels of growth hormone (GH) and insulin-like growth factor (IGF-I). The appropriateness of these targets when measured using modern assay methods is not well defined. This paper reviews biochemical status assessed using methods available at the time and associated clinical outcomes. GH measurements were shown to provide an indication of changes in tumor size, and failure of GH suppression after glucose stimulation is associated with tumor recurrence. IGF-I levels were more closely associated with changes in symptoms and signs. Reduced GH and IGF-I concentrations were shown to be associated with increased longevity, although the degree of increase has only been analyzed for GH. Lowering of GH and IGF-I has consistently been associated with improved outcomes; however, absolute levels reported in previous studies were based on results from methods and reference ranges that are now obsolete. Applying previously described absolute thresholds as targets (e.g. "normal" IGF-I level) when using current methods is best applied to those with active acromegaly symptoms who could benefit from further lowering of biochemical markers. In asymptomatic individuals with mild IGF-I or GH elevations, targeting biochemical "normalization" would result in the need for combination pharmacotherapy in many patients without proven benefit. Measurement of both GH and IGF-I remains an essential component of diagnosis and monitoring the effectiveness of treatment in acromegaly; however, treatment goals based only on previously identified absolute thresholds are not appropriate without taking into account the assay and reference ranges being employed. Treatment goals should be individualized considering biochemical improvement from an untreated baseline, symptoms of disease, risks, burdens and costs of complex treatment regimens, comorbidities, and quality of life.
Topics: Humans; Acromegaly; Growth Hormone; Insulin-Like Growth Factor I; Reference Values; Quality of Life; Human Growth Hormone; Treatment Outcome
PubMed: 38027199
DOI: 10.3389/fendo.2023.1266339 -
Hormones (Athens, Greece) Mar 2021Acromegaly is a rare disease with a peak of incidence in early adulthood. However, enhanced awareness of this disease, combined with wide availability of magnetic...
BACKGROUND AND AIM
Acromegaly is a rare disease with a peak of incidence in early adulthood. However, enhanced awareness of this disease, combined with wide availability of magnetic resonance imaging (MRI), has increased the diagnosis of forms with mild presentation, especially in elderly patients. Moreover, due to increased life expectancy and proactive individualized treatment, patients with early-onset acromegaly are today aging. The aim of our study was to describe our cohort of elderly patients with acromegaly.
MATERIALS AND METHODS
This is a cross-sectional retrospective study of 96 outpatients. Clinical, endocrine, treatment, and follow-up data were collected using the electronic database of the University Hospital of Padova, Italy.
RESULTS
We diagnosed acromegaly in 13 patients, aged ≥65 years, presenting with relatively small adenomas and low IGF-1 secretion. Among them, 11 patients were initially treated with medical therapy and half normalized hormonal levels after 6 months without undergoing neurosurgery (TNS). Remission was achieved after TNS in three out of four patients (primary TNS in two); ten patients presented controlled acromegaly at the last visit. Acromegaly-related comorbidities (colon polyps, thyroid cancer, adrenal incidentaloma, hypertension, and bone disease) were more prevalent in patients who had an early diagnosis (31 patients, characterized by a longer follow-up of 24 years) than in those diagnosed aged ≥65 years (5 years of follow-up).
CONCLUSIONS
Elderly acromegalic patients are not uncommon. Primary medical therapy is a reasonable option and is effectively used, while the rate of surgical success is not reduced. A careful cost-benefit balance is suggested. Disease-specific comorbidities are more prevalent in acromegalic patients with a longer follow-up rather than in those diagnosed aged ≥65 years.
Topics: Acromegaly; Adenoma; Aged; Cross-Sectional Studies; Humans; Pituitary Neoplasms; Retrospective Studies
PubMed: 32840821
DOI: 10.1007/s42000-020-00235-5 -
Frontiers in Endocrinology 2021This study aimed to evaluate the bone turnover markers and bone microarchitecture parameters derived from high-resolution peripheral quantitative computed tomography...
PURPOSE
This study aimed to evaluate the bone turnover markers and bone microarchitecture parameters derived from high-resolution peripheral quantitative computed tomography (HR-pQCT) in active and controlled acromegaly patients.
METHODS
This cross-sectional study involved 55 acromegaly patients from a tertiary hospital (23 males and 32 females, aged 45.0 ± 11.6 years). Firstly, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and markers for bone turnover were assessed. Next, we derived peripheral bone microstructure parameters and volumetric bone mineral density (vBMD) through HR-pQCT. These parameters were compared between acromegaly patients and 110 healthy controls, as well as between 27 active and 28 controlled acromegaly patients. Moreover, the relationship between GH/IGF-1 and bone microstructure parameters was analyzed through multiple linear regression.
RESULTS
As compared with healthy controls, acromegaly patients exhibited elevated cortical vBMD, reduced trabecular vBMD, and increased trabecular inhomogeneity in the distal radius and tibia. While controlled acromegaly patients had slower bone turnover, they did not necessarily have better bone microstructure relative to active patients in intergroup comparison. Nevertheless, multiple regression indicated that higher IGF-1 was associated with lower tibial stiffness and failure load. Additionally, males with higher IGF-1 typically had larger trabecular separation, lower trabecular number, and larger cortical pores in the radius. Moreover, patients with elevated GH typically had more porous cortical bone in the radius and fewer trabeculae in the tibia. However, the compromised bone strength in active patients was partially compensated by increased bone thickness. Furthermore, no significant linkage was observed between elevated GH/IGF-1 and the most important HR-pQCT parameters such as trabecular volumetric bone density.
CONCLUSION
Acromegaly adversely affected bone quality, even in controlled patients. As the deterioration in bone microstructure due to prolonged GH/IGF-1 exposure was not fully reversible, clinicians should be aware of the bone fragility of acromegaly patients even after they had achieved biochemical remission.
Topics: Acromegaly; Adult; Bone Density; Bone Remodeling; Bone and Bones; Cross-Sectional Studies; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Tomography, X-Ray Computed
PubMed: 34603213
DOI: 10.3389/fendo.2021.738895 -
Archives of Endocrinology and Metabolism 2020Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and...
OBJECTIVE
Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism.
SUBJECTS AND METHODS
In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter.
RESULTS
Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism.
CONCLUSIONS
Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75.
Topics: Acromegaly; Adult; Cross-Sectional Studies; Female; Goiter, Nodular; Humans; Hypothyroidism; Male; Middle Aged; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Ultrasonography
PubMed: 32555993
DOI: 10.20945/2359-3997000000247 -
The Pan African Medical Journal 2023Acromegaly is defined as an acquired dysmorphytic syndrome due to excessive secretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1)....
Acromegaly is defined as an acquired dysmorphytic syndrome due to excessive secretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1). This is a retrospective study of patients who were hospitalized in the Endocrinology Department of the Mohammed V Military Academic Hospital in Rabat over a period of 14 years (2008 to 2022), reporting on their clinical, paraclinical and evolutionary profiles and comparing the results with the data in the literature. Nineteen patients were included in our study. The mean age was 42.7 ± 11.6 years, with a male predominance. The clinical manifestations were dominated by a dysmorphic syndrome present in 97.4% of cases, followed by complications related to acromegaly in 88.9% of cases. The diagnosis was made when GH and IGF-1 values were elevated in 88.9% and 93.8% of cases, respectively; with a mean GH value of 25.1 μg/L. Magnetic resonance imaging (MRI) was used to diagnose the location of pituitary adenoma in all cases, 78.9% of which were macroadenomas and 21.1% microadenomas. The majority of patients (78.9%) had recourse to transsphenoidal surgery. Medical treatment was carried out in 89.5% of cases. Postoperative radiotherapy was performed in 33% of cases. Disease control was achieved in 30.1% of cases. This study shows the complex management of acromegaly. Disease control is a necessary condition in order to avoid complications, but is often difficult to obtain.
Topics: Humans; Male; Adult; Middle Aged; Female; Acromegaly; Insulin-Like Growth Factor I; Retrospective Studies; Treatment Outcome; Human Growth Hormone; Pituitary Neoplasms
PubMed: 38465009
DOI: 10.11604/pamj.2023.46.116.41952 -
Value in Health : the Journal of the... Jul 2018Acromegaly results from the hypersecretion of growth hormone. Because of the low incidence rates of this disease worldwide, few clinical trials evaluating drug... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acromegaly results from the hypersecretion of growth hormone. Because of the low incidence rates of this disease worldwide, few clinical trials evaluating drug treatments have been conducted.
OBJECTIVES
To conduct the first network meta-analysis simultaneously comparing all available drugs used in acromegaly treatment so as to provide more robust evidence in this field.
METHODS
A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Collaboration recommendations (PROSPERO database under the registration number CRD42017059880). The electronic searches were conducted in PubMed (MEDLINE), Scopus, and Web of Science databases. Randomized controlled trials comparing any drug for the treatment of acromegaly head-to-head or versus placebo were included. Outcomes concerning the efficacy and safety of treatments were evaluated. The statistical analyses were performed using Aggregate Data Drug Information System version 1.16.8 (drugis.org, Groningen, The Netherlands).
RESULTS
The initial search retrieved 2059 articles. Of these, 10 randomized controlled trials were included in a qualitative analysis and 7 in a quantitative analysis. The network meta-analysis for the efficacy outcome (number of patients achieving insulinlike growth factor 1 control) showed that pegvisomant and lanreotide autogel were statistically superior to placebo (odds ratio [95% credible interval] 0.06 [0.00-0.55] and 0.09 [0.01-0.88]). No further differences were found. The probability rank indicated that pegvisomant and pasireotide have the highest probabilities (33% and 34%, respectively) of being the best therapeutic options. No major side effects were noted.
CONCLUSIONS
Pegvisomant is still a good option for acromegaly treatment, but pasireotide seems to be a promising alternative. Nevertheless, other important key factors such as drug costs and effectiveness (real-world results) should be taken into account when selecting acromegaly treatment.
Topics: Acromegaly; Adolescent; Adult; Aged; Aged, 80 and over; Female; Hormone Antagonists; Human Growth Hormone; Humans; Male; Middle Aged; Peptides, Cyclic; Receptors, Somatotropin; Somatostatin; Treatment Outcome; Young Adult
PubMed: 30005760
DOI: 10.1016/j.jval.2017.12.014 -
Journal of Korean Medical Science Jun 2021Acromegaly is a rare, slowly progressive disease. Its mechanism is not fully understood, and epidemiological research on Korean patients with acromegaly is scarce. The...
BACKGROUND
Acromegaly is a rare, slowly progressive disease. Its mechanism is not fully understood, and epidemiological research on Korean patients with acromegaly is scarce. The purpose of this study was to determine the incidence and prevalence of acromegaly and assess the comorbidities and survival benefits based on treatment options.
METHODS
This nationwide population-based cohort study was conducted using data of the Korean Health Insurance Review and Assessment claims database to evaluate the incidence of newly diagnosed acromegaly cases during 2013-2017.
RESULTS
During the 5-year period, 1,093 patients were newly diagnosed with acromegaly. The average annual incidence was 4.2 cases per million per year, and the prevalence was 32.1 cases per million during this period. The incidence of hypertension was low after medical treatment (hazard ratio, 0.257; 95% confidence interval, 0.082-0.808; = 0.020), but the incidence of diabetes showed no significant difference across treatment modalities. Over a period of 6 years since diagnosis, we found that patients treated for acromegaly had a significantly higher survival rate than those untreated ( < 0.001).
CONCLUSION
The annual incidence rate of Korean patients with acromegaly was similar to that reported in previous studies. Using nationwide population data, our study emphasized the importance of treatment in acromegaly patients.
Topics: Acromegaly; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Comorbidity; Diabetes Mellitus; Female; Humans; Hypertension; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Prevalence; Republic of Korea; Retrospective Studies; Survival Analysis; Survival Rate; Young Adult
PubMed: 34128596
DOI: 10.3346/jkms.2021.36.e159 -
Experimental and Clinical Endocrinology... Nov 2022To investigate the clinical characteristics and associated factors of colonic polyps in patients with acromegaly.
PURPOSE
To investigate the clinical characteristics and associated factors of colonic polyps in patients with acromegaly.
METHODS
Clinical characteristics and colonoscopy findings of 86 acromegaly patients who received treatment were retrospectively reviewed, and colonoscopy findings and the correlation with growth hormone (GH)-secreting pituitary adenoma (GHPA) volume and hormonal/metabolic levels were analyzed.
RESULTS
The prevalence of colonic polyps in acromegaly patients was 40.7% and increased significantly with advanced age, especially in those ≥50 years. Multiple polyps (62.8%) and colonic polyps in the left colon (54.2%) were detected more frequently. Compared to acromegaly patients without polyps, those with polyps displayed higher insulin-like growth factor-1 × upper limit of normal (IGF-1×ULN) levels (=0.03). IGF-1 levels and GHPA volumes in patients with polyps showed increasing trends, although the differences were not significant. GH levels were higher in patients with polyps of diameter ≤5 mm than those with polyps of diameter >5 mm (=0.031). The univariate and multivariate logistic regression analysis revealed that GHPA volumes (OR: 1.09, 95% CI: 1.01-1.20; =0.039) and IGF-1×ULN Q2 levels (OR: 6.51, 95% CI: 1.20-44.60; =0.038) were independent factors for predicting the risk of colonic polyp occurrence in acromegaly patients. A nomogram was prepared to evaluate the risk of colonic polyps in acromegaly patients.
CONCLUSION
The acromegalic patients are a population with a high prevalence of colonic polyps. GHPA volumes and IGF-1×ULN levels may be predictors of colonic polyp occurrence.
Topics: Humans; Middle Aged; Colonic Polyps; Acromegaly; Insulin-Like Growth Factor I; Retrospective Studies; Growth Hormone-Secreting Pituitary Adenoma; Adenoma
PubMed: 36075228
DOI: 10.1055/a-1913-7900 -
Growth Hormone & IGF Research :... Jun 2020Acromegaly is a disease characterized by overproduction of growth hormone (GH). As a consequence of excessive GH secretion, circulating insulin-like growth factor-I... (Review)
Review
Acromegaly is a disease characterized by overproduction of growth hormone (GH). As a consequence of excessive GH secretion, circulating insulin-like growth factor-I (IGF-I) is elevated in active (untreated) acromegaly. IGF-I is often used as a marker of disease activity and growth hormone status in acromegaly. Although IGF-I can directly improve insulin sensitivity and glucose uptake in muscles, the excessive GH secretion in active acromegaly frequently leads to insulin resistance, glucose intolerance and even diabetes. In this review evidence will be discussed that in active acromegaly chronically elevated IGF-I, insulin and soluble Klotho (S-Klotho) levels play a pathophysiological role in the development of IGF-I receptor (IGF-IR) resistance. It is postulated that as soon as circulating IGF-I, insulin and S-Klotho rise above a certain level the IGF-IR becomes relatively resistant to actions of IGF-I. The development of a degree of IGF-IR resistance for metabolic actions may help to explain why in active acromegaly diabetogenic effects of GH predominate and are not completely counteracted and neutralized by elevated circulating levels of IGF-I. Further studies are necessary in order to support this hypothesis.
Topics: Acromegaly; Animals; Diabetes Mellitus; Glucose Intolerance; Humans; Insulin Resistance; Receptor, IGF Type 1
PubMed: 32339897
DOI: 10.1016/j.ghir.2020.101319 -
Kidney International Oct 2023Acromegaly is a chronic systemic disease caused by excess levels of growth hormone and insulin-like growth factor-1 and is associated with numerous complications....
Acromegaly is a chronic systemic disease caused by excess levels of growth hormone and insulin-like growth factor-1 and is associated with numerous complications. Significantly, there is a lack of longitudinal data on kidney complications in patients with acromegaly. As such, we investigated the risk of end-stage kidney disease (ESKD) (stage 5D, 5T) in these patients with nationwide data obtained from the National Health Information Database of the National Health Insurance Service in Republic of Korea. A retrospective cohort study was conducted of 2.187 patients with acromegaly and 10,935 age- and sex-matched (1:5) control subjects without acromegaly over a mean follow-up period of 6.51 years. The study outcomes were analyzed using Cox proportional hazards regression analysis controlling for age, sex, household income, residential area, type 2 diabetes, hypertension, dyslipidemia, urolithiasis, congestive heart failure, myocardial infarction, stroke, and atrial fibrillation. The incidence (per 1,000 person-years) ESKD was 2.00 among patients with acromegaly but only 0.46 among controls, (hazard ratio 4.35 (95% confidence interval 2.63-7.20)) implicating a significantly higher risk. After adjustment for covariates, the risk of ESKD (2.36 (1.36-4.12)) was still significantly higher in patients with acromegaly than that in controls. Among the covariates, diabetes and hypertension were significant facilitators between acromegaly and ESKD in mediation analysis. Pituitary surgery and somatostatin analogues did not significantly change these associations. Thus, acromegaly may be linked with a higher risk for ESKD both independently and through mediators such as diabetes and hypertension.
Topics: Humans; Acromegaly; Cohort Studies; Diabetes Mellitus, Type 2; Hypertension; Kidney Failure, Chronic; Retrospective Studies; Risk Factors; Male; Female
PubMed: 37490954
DOI: 10.1016/j.kint.2023.06.037