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Pituitary Dec 2018Acromegaly is a rare disease that results in the enlargement of body extremities and in organomegaly. Treatments include surgery, drugs, and radiotherapy, which are all... (Review)
Review
PURPOSE
Acromegaly is a rare disease that results in the enlargement of body extremities and in organomegaly. Treatments include surgery, drugs, and radiotherapy, which are all onerous. Therefore, well-conducted cost-analyses are crucial in the decision-making process.
METHODS
A systematic review of cost-effectiveness studies on acromegaly therapies was performed following PRISMA and Cochrane recommendations. The search for records was conducted in PubMed, Scopus, and Web of Science (May 2018). The quality of the included studies was assessed using the Joana Briggs Institute Tool.
RESULTS
From initial 547 records, 16 studies were included in the review. The studies could present more than one economic evaluation, and encompassed cost-effectiveness (n = 13), cost-utility (n = 5), and cost-consequence (n = 1) analyses. All studies were model-based and evaluated only direct medical costs. Eleven records did not mention discounting and only 10 performed sensitivity analyses. The characteristic of the studies, the cost-effectiveness results and the studies' conclusions are described and commented upon. The main limitation of the studies was discussed and aspects to improve in future studies were pointed out.
CONCLUSIONS
Cost-effectiveness studies on acromegaly have been performed in several scenarios, evaluating different phases of treatment. However, the studies present limitations and, overall, were considered of moderate quality. Further economic models should be developed following health economics guidelines recommendations, and must improve transparency.
Topics: Acromegaly; Cost-Benefit Analysis; Human Growth Hormone; Humans; Octreotide; Peptides, Cyclic; Somatostatin
PubMed: 30159696
DOI: 10.1007/s11102-018-0908-0 -
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 -
Pituitary Dec 2018Multiple studies investigated preclinical markers of peripheral vascular damage in acromegaly (ACRO) reporting discordant results. The aim of this study was to run a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Multiple studies investigated preclinical markers of peripheral vascular damage in acromegaly (ACRO) reporting discordant results. The aim of this study was to run a meta-analysis to examine whether intima media thickness (IMT), flow mediated dilation (FMD) and arterial pulse wave velocity (PWV) are affected in acromegalic patients and to assess the impact of effective treatment of growth hormone excess on these outcomes.
STUDY SELECTION
Twenty-seven studies comparing ACRO vs control (CON) populations and active (ACT) vs inactive (INACT) ACRO were included in the meta-analysis.
DATA SYNTHESIS
ACRO compared to CON have higher IMT (ES = 0.83, 95% C.I. 0.35-1.30), p = 0.001, impaired FMD (ES = - 1.59, 95% C.I. - 2.33 to - 0.85, p < 0.0001) and higher PWV (ES = 0.76 95% C.I. 0.37-1.16, p = 0.0001). When patients with ACT vs INACT disease were considered IMT was higher (ES = 0.43, 95% C.I. 0.02-0.84, p = 0.041) and FMD was impaired (ES = - 0.66, 95% C.I. - 1.28 to 0.04, p = 0.038) in ACT patients. Meta-regression analysis of studies comparing IMT in ACT vs INACT acromegalic patients showed a significant and inverse association between the effect size and the percent of hypertensive (p = 0.025) and diabetic (p = 0.041) patients.
CONCLUSIONS
IMT, FMD and arterial stiffness are impaired in acromegaly showing that these patients may be at increased risk of atherosclerosis. In patients with active disease these preclinical markers of atherosclerosis are worse compared to patients with inactive disease but the role of diabetes and hypertension is prevailing on growth hormone excess.
Topics: Acromegaly; Atherosclerosis; Biomarkers; Humans
PubMed: 30225826
DOI: 10.1007/s11102-018-0911-5 -
Pituitary Apr 2021This review is aimed at examining whether the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is higher in Caucasian, adult, treatment-naïve patients with... (Meta-Analysis)
Meta-Analysis
PURPOSE
This review is aimed at examining whether the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is higher in Caucasian, adult, treatment-naïve patients with acromegaly (ACRO) than in the reference population independently of diabetes presence and to evaluate the impact of treatment [surgery and somatostatin analogues (SSAs)] on its assessment.
METHODS
We systematically reviewed in PubMed and Web of Science from July 1985 to December 2019, registered with the code number CRD42020148737. The inclusion criteria comprised studies conducted in Caucasian adult treatment-naïve patients with active ACRO in whom HOMA-IR or basal insulin and glucose were reported. Three reviewers screened eligible publications, extracted the outcomes, and assessed the risk of biases.
RESULTS
Of 118 originally selected studies, 15 met the inclusion criteria. HOMA-IR was higher in ACRO than the reference population, with mean difference and (95% confidence intervals) of 2.04 (0.65-3.44), even in ACRO patients without diabetes, 1.89 (1.06-2.73). HOMA-IR significantly decreased after treatment with either surgery or SSAs - 2.53 (- 3.24- - 1.81) and - 2.30 (- 3.05- - 1.56); respectively. However, the reduction of HOMA-IR due to SSAs did not improve basal glucose.
CONCLUSION
HOMA-IR in treatment-naïve ACRO patients is higher than in the reference population, even in patients without diabetes. This finding, confirms that insulin resistance is an early event in ACRO. Our results also suggest that HOMA-IR is not an adequate tool for assessing insulin resistance in those patients treated with SSAs.
Topics: Acromegaly; Diabetes Mellitus; Humans; Insulin Resistance
PubMed: 33085039
DOI: 10.1007/s11102-020-01092-6 -
Pituitary Feb 2023In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of serum biomarkers of colonic polyps in patients with acromegaly.
METHODS
We reviewed studies on serum biomarkers of colonic polyps in patients with acromegaly, published on PubMed, Embase, Cochrane Library, Medline, and Chinese databases from January 1, 1966, to May 8, 2022. Meta-analysis and systematic review were conducted using Stata MP 14.0.
RESULTS
Eight articles were included in this study. The mean (standard deviation) concentrations of serum biomarkers for acromegaly with and without colorectal polyps were extracted from these studies. Meta-analysis results showed that, compared to patients without colonic polyps, the levels of insulin-like growth factor-1 × upper limit of normal range (IGF-1 × ULN) and fasting insulin were significantly increased; while the levels of growth hormone (GH) were significantly decreased in patients with acromegaly and colonic polyps (IGF-1 × ULN: SMD 0.23; 95% CI 0.03-0.42, p < 0.05) (fasting insulin: SMD 0.95; 9 5% CI 0.11-1.8, p < 0.05) (GH: SMD - 0.25; 95% CI - 0.41 to - 0.08, p < 0.05). IGF-1 and FPG levels did not differ significantly (IGF-1: SMD -0.03; 95% CI - 0.22 to 0.17, p > 0.05) (FPG: SMD 0.14; 95% CI - 0.23 to 0.52, p > 0.05). The systematic review results suggest no significant differences in hemoglobin A1C, TSH, free thyroxine, FT4, T3, PRL, total cholesterol, HDL, LDL, fibrinogen, clathrate antigen, serum antigen 19-9, and α-fetoprotein levels, but serum Klotho levels.
CONCLUSION
We present the first meta-analysis and systematic review of serum biomarkers in patients with acromegaly or colonic polyps. The prevalence of colonic lesion polyps, is associated with higher IGF-1 × ULN levels, higher insulin levels in acromegaly. Further research is required to confirm GH and serum soluble Klotho levels as biomarkers of colonic polyps. When IGF-1 × ULN, fasting insulin levels change in patients with acromegaly, the occurrence of colonic polyps should be monitored. Early detection may reduce the possibility of developing malignant colon neoplasms.
Topics: Humans; Acromegaly; Colonic Polyps; Insulin-Like Growth Factor I; Growth Hormone; Human Growth Hormone; Insulin; Biomarkers
PubMed: 36542278
DOI: 10.1007/s11102-022-01287-z -
Endocrine Practice : Official Journal... Aug 2015When patients with acromegaly have residual disease following surgery, adjuvant radiation therapy is considered. Both stereotactic radiosurgery (SRS) and conventional... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
When patients with acromegaly have residual disease following surgery, adjuvant radiation therapy is considered. Both stereotactic radiosurgery (SRS) and conventional fractionated radiotherapy (RT) are utilized. We conducted a systematic review and meta-analysis to synthesize the existing evidence and compare outcomes for SRS and RT in patients with acromegaly.
METHODS
We searched Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through April 2014 for studies in which SRS or RT were used in patients with acromegaly. Outcomes evaluated were serum insulin-like growth factor-I (IGF-I) and growth hormone (GH) levels, biochemical remission, all-cause mortality, hypopituitarism, headaches, and secondary malignancies. We pooled outcomes using a random-effects model.
RESULTS
The final search yielded 30 eligible studies assessing 2,464 patients. Compared to RT, SRS was associated with a nonsignificant increase in remission rate at the latest follow-up period (52% vs. 36%; P = .14) and a significantly lower follow-up IGF-I level (-409.72 μg/L vs. -102 μg/L, P = .002). SRS had a lower incidence of hypopituitarism than RT; however, the difference was not statistically significant (32% vs. 51%, respectively; P = .05).
CONCLUSION
SRS may be associated with better biochemical remission, and it had a lower risk of hypopituitarism with at least 1 deficient axis when compared with RT; however, the confidence in such evidence is very low due to the noncomparative nature of the studies, high heterogeneity, and imprecision.
Topics: Acromegaly; Humans; Radiosurgery
PubMed: 26247235
DOI: 10.4158/EP14574.OR -
Acta Neurochirurgica Nov 2017The aim of this systematic review is to evaluate the long-term endocrine outcomes and postoperative complications following endoscopic vs. microscopic transsphenoidal... (Comparative Study)
Comparative Study Review
PURPOSE
The aim of this systematic review is to evaluate the long-term endocrine outcomes and postoperative complications following endoscopic vs. microscopic transsphenoidal resection (TSR) for the treatment of acromegaly.
METHODS
A literature review was performed, and studies with at least five patients who underwent TSR for acromegaly, reporting biochemical remission criteria and long-term remission outcomes were included. Data extracted from each study included surgical technique, perioperative complications, biochemical remission criteria, and long-term remission outcomes.
RESULTS
Fifty-two case series from 1976 to 2016 met the inclusion criteria, comprising 4375 patients. Thirty-six reports were microsurgical (n = 3144) and 13 were endoscopic (n = 940). Three studies compared microsurgical (n = 111) to endoscopic TSR outcomes (n = 180). The overall initial and long-term remission rates were 58.2 vs. 57.4% and 69.2 vs. 70.2% for the microsurgical and endoscopic groups, respectively. For microadenomas, the initial and long-term remission rates were 77.6 vs. 82.2% and 76.9 vs. 73.5% for microsurgical and endoscopic approaches, respectively. For macroadenomas, the initial and long-term remission rates were 46.9 vs. 60.0% and 40.2 vs. 61.5% for microsurgical and endoscopic approaches, respectively. The rates of postoperative CSF leak were 3.0 vs. 2.3% for the microscopic and endoscopic groups, respectively. The rates of hypopituitarism and transient diabetes insipidus were 6.7 vs. 6.4% and 9.0 vs. 7.8% for the microscopic and endoscopic groups, respectively.
CONCLUSIONS
Both endoscopic and microsurgical approaches for TSR of growth hormone-secreting adenomas are viable treatment options for patients with acromegaly, and yield similarly high rates of remission under the most current consensus criteria.
Topics: Acromegaly; Cerebrospinal Fluid Leak; Endoscopy; Growth Hormone-Secreting Pituitary Adenoma; Humans; Hypopituitarism; Microsurgery; Pituitary Neoplasms; Postoperative Complications; Sphenoid Bone; Treatment Outcome
PubMed: 28913667
DOI: 10.1007/s00701-017-3318-6 -
Frontiers in Endocrinology 2022Pasireotide (PAS) is a novel somatostatin receptor ligands (SRL), used in controlling hormonal hypersecretion in both acromegaly and Cushing's Disease (CD). In previous... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Pasireotide (PAS) is a novel somatostatin receptor ligands (SRL), used in controlling hormonal hypersecretion in both acromegaly and Cushing's Disease (CD). In previous studies and meta-analysis, first-generation SRLs were reported to be able to induce significant tumor shrinkage only in somatotroph adenomas. This systematic review and meta-analysis aim to summarize the effect of PAS on the shrinkage of the pituitary adenomas in patients with acromegaly or CD.
MATERIALS AND METHODS
We searched the Medline database for original studies in patients with acromegaly or CD receiving PAS as monotherapy, that assessed the proportion of significant tumor shrinkage in their series. After data extraction and analysis, a random-effect model was used to estimate pooled effects. Quality assessment was performed with a modified Joanna Briggs's Institute tool and the risk of publication bias was addressed through Egger's regression and the three-parameter selection model.
RESULTS
The electronic search identified 179 and 122 articles respectively for acromegaly and CD. After study selection, six studies considering patients with acromegaly and three with CD fulfilled the eligibility criteria. Overall, 37.7% (95%CI: [18.7%; 61.5%]) of acromegalic patients and 41.2% (95%CI: [22.9%; 62.3%]) of CD patients achieved significant tumor shrinkage. We identified high heterogeneity, especially in acromegaly (I of 90% for acromegaly and 47% for CD), according to the low number of studies included.
DISCUSSION
PAS treatment is effective in reducing tumor size, especially in acromegalic patients. This result strengthens the role of PAS treatment in pituitary adenomas, particularly in those with an invasive behavior, with progressive growth and/or extrasellar extension, with a low likelihood of surgical gross-total removal, or with large postoperative residual tissue.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022328152, identifier CRD42022328152.
Topics: ACTH-Secreting Pituitary Adenoma; Acromegaly; Adenoma; Humans; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Somatostatin
PubMed: 35846311
DOI: 10.3389/fendo.2022.935759