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Neuroendocrinology 2017The common exon 3 deletion polymorphism of the growth hormone receptor (d3-GHR) is associated with disease severity in acromegaly patients. The GHR antagonist... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The common exon 3 deletion polymorphism of the growth hormone receptor (d3-GHR) is associated with disease severity in acromegaly patients. The GHR antagonist pegvisomant (PEGV) is highly effective in treating severe acromegaly. Response to PEGV treatment seems to be influenced by d3-GHR and appears to be more responsive to PEGV, although available results remain conflicting.
OBJECTIVE
To assess the influence of d3-GHR on the responsiveness of acromegaly patients to PEGV by compiling the evidence derived from the largest available studies.
DESIGN
A systematic review of the literature identified three published studies and one conference abstract. Acromegaly patients (n = 324, 49.7% d3-GHR carriers) were treated with either PEGV monotherapy or PEGV combined with long-acting somatostatin analogues and/or cabergoline. A meta-analysis of raw data from these studies was performed.
RESULTS
No significant effect of the d3-GHR was observed while bringing insulin-like growth factor I (IGF-I) levels below the upper limit of normal with PEGV, which was defined as the lowest IGF-I level during PEGV treatment (mean difference: -2.3%; 95% CI: -6.5 to 1.8, p = 0.270). The PEGV dose required to achieve the lowest IGF-I levels was also not significantly influenced by individuals carrying d3-GHR (mean difference: 4.1 mg weekly; 95% CI: -5.1 to 13.2, p = 0.385). For both outcomes, separate analysis of PEGV monotherapy and combination treatment gave similar results.
CONCLUSION
Our findings suggest that the d3-GHR polymorphism has no effect on biochemical disease control in acromegaly, as it is not of added value for either the prediction of PEGV responsiveness or the determination of the required PEGV dose.
Topics: Acromegaly; Exons; Human Growth Hormone; Humans; Receptors, Somatotropin; Sequence Deletion
PubMed: 27513761
DOI: 10.1159/000448844 -
Acta Neurochirurgica Nov 2016In 2010, the Acromegaly Consensus Group revised the criteria for cure of acromegaly and thus rates of surgical remission need to be revised in light of these new... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In 2010, the Acromegaly Consensus Group revised the criteria for cure of acromegaly and thus rates of surgical remission need to be revised in light of these new thresholds. Two subgroups consisted of patients with discordant GH and IGF-1 levels and patients in remission according to the 2000 criteria, but not to the 2010 criteria, have been reported after adenomectomy and for these subgroups the precise incidence and management has not been established. The objective of the study was to update rates of surgical remission and complications and to evaluate the incidence, management, and long-term outcome of the two previously described subgroups of patients.
METHODS
Systematic review and meta-analysis of surgical series that defined remission according to the 2010 biochemical criteria.
RESULTS
We included 13 studies (1105 patients). The pooled rate of overall surgical remission was 54.8 % (95 % CI 44.4-65.2 %), and 72.2 % with previous criteria. Remission was achieved in 77.9 % (95 % CI 68.1-87.6 %) of microadenomas; 52.7 % (95 % CI 41-64.4 %) of macroadenomas; 29 % (95 % CI 20.1-37.8 %) of invasive and 68.8 % (95 % CI 60-77.6 %) of non-invasive adenomas. Complication rates were 1.2 % (95 % CI 0.6-1.9 %) for CSF leak, 1.3 % (95 % CI 0.6-2.1 %) for permanent diabetes insipidus, 8.7 % (95 % CI 4.8-12.5 %) for new anterior pituitary dysfunction and 0.6 % (95 % CI 0.1-1.1 %) for severe intraoperative hemorrhage. We identified an intermediate group of patients, defined as: (1) Remission according to one, but not the other biochemical criteria (GH or IGF-1) or 2010 criteria (14.3 % and 47.1 % cases), (2) Remission according to 2000, but not 2010 criteria (13.2-58.8 % cases). Two studies reported a remission rate of 56.5 % and 100 %, in the two subgroups respectively, in a long-term outcome without adjuvant therapy.
CONCLUSIONS
Overall remission with transsphenoidal surgery is achieved in ∼55 % of patients. For the intermediate group of patients, future prospective studies with long-term follow-up are required to determine the long-term biochemical remission rates and clinical implications.
Topics: Acromegaly; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Pituitary Neoplasms; Postoperative Complications
PubMed: 27586125
DOI: 10.1007/s00701-016-2903-4 -
Neuroendocrinology 2023Acromegaly is characterized by impaired bone quality and increased fracture risk. However, due to the pathophysiology of acromegalic osteopathy, bone mineral density... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acromegaly is characterized by impaired bone quality and increased fracture risk. However, due to the pathophysiology of acromegalic osteopathy, bone mineral density (BMD) does not represent a reliable predictor for fragility fractures in this setting. Trabecular bone score (TBS) has been recently evaluated as an alternative index of skeletal fragility in acromegalic patients. However, no conclusive data are still available in this regard.
METHODS
PubMed/Medline, EMBASE, Cochrane Library, Ovid, and CINAHL databases were systematically searched until June 2022 for studies reporting data either about the comparison of TBS values between acromegalic patients and non-acromegalic controls or about the relationship - within acromegalic patients - between TBS values and fracture risk. Effect sizes were pooled through a random-effect model.
RESULTS
Eight studies were eligible for inclusion in the meta-analysis, encompassing 336 acromegalic patients and 490 non-acromegalic controls. Overall, TBS was significantly lower in acromegalic patients compared to controls (-0.089, 95% CI: [-0.111, -0.067], p < 0.01), irrespective of acromegaly disease activity and gonadal status. With respect to fracture risk, TBS was significantly lower in acromegalic patients with vertebral fractures than in those without (-0.099, 95% CI: [-0.166, -0.032], p < 0.01).
CONCLUSION
In this meta-analysis, we specifically assessed the role of TBS as an index of bone quality and fracture risk in patients with acromegaly. Our results support the notion that TBS could be of value in the assessment and management of skeletal fragility in acromegalic patients, especially in light of the poor information provided in this setting by BMD.
Topics: Humans; Cancellous Bone; Acromegaly; Absorptiometry, Photon; Lumbar Vertebrae; Bone Density
PubMed: 36617407
DOI: 10.1159/000528199 -
Endocrine Jan 2019Acromegaly is a rare disease that often requires drug treatment to achieve control, with pegvisomant being one of the most widely used therapies. In the present paper,... (Meta-Analysis)
Meta-Analysis
PURPOSE
Acromegaly is a rare disease that often requires drug treatment to achieve control, with pegvisomant being one of the most widely used therapies. In the present paper, we aimed to obtain evidence regarding the effectiveness and safety of pegvisomant by reviewing real-world observational longitudinal studies.
METHODS
A systematic review was performed with a meta-analysis of event rates (95% confidence interval (CI)) using a random effects model. Sensitivity and subgroup analyses were performed (comprehensive meta-analysis 2.0). The systematic review was performed in accordance to preferred reporting items for systematic reviews and meta-analyses, meta-analysis of observational studies in epidemiology, and Cochrane recommendations (PROSPERO register CRD 42017059880). PubMed, Scopus, Web of Science, and SciELO were used to search for literature. Observational studies in patients using pegvisomant for the treatment of acromegaly were included.
RESULTS
Initially, 552 papers were retrieved from the databases; and 31 articles were included in the qualitative analysis and 14 in the quantitative analysis. Eight primary meta-analyses were performed. The overall rate of patients with disease control was of 60.9% (51.8-69.3%; 95% CI). When considering patients under monotherapy, the control rate was 71.7% (64.0-78.4%; 95% CI). Tumor growth was estimated in 7.3% (4.7-11.1%; 95% CI) and elevation of transaminases in 3.0% (1.7-5.2%; 95% CI).
CONCLUSIONS
The real-world data showed that the effectiveness of pegvisomant is not as high as reported in interventional studies. Acromegaly appears to be better controlled when pegvisomant is used as a monotherapy. No serious adverse events were associated with the use of pegvisomant; however, given the high cost of this drug, further studies are required.
Topics: Acromegaly; Human Growth Hormone; Humans; Longitudinal Studies; Observational Studies as Topic
PubMed: 30145746
DOI: 10.1007/s12020-018-1729-7 -
BMC Endocrine Disorders Jan 2024Management of recurrent acromegaly is challenging for both neurosurgeons and endocrinologists. Several treatment options including repeat surgery, medical therapy, and...
BACKGROUND AND OBJECTIVE
Management of recurrent acromegaly is challenging for both neurosurgeons and endocrinologists. Several treatment options including repeat surgery, medical therapy, and radiation are offered for such patients. The efficacy of these modalities for the treatment of recurrence has not been studied previously in the literature. In this study, we aim to systematically review the existing cases of recurrence and come to a conclusion regarding the appropriate treatment in such cases.
METHOD
A systematic review was performed through PubMed, Scopus, Web of Science, and Cochrane database to identify studies reporting the treatment outcome of recurrent acromegaly patients. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the included studies were reviewed for primary and secondary treatment, complications, and outcomes of the secondary treatment.
RESULTS
The systematic review retrieved 23 records with 95 cases of recurrent acromegaly. The mean time of recurrence was 4.16 years after the initial treatment. The most common primary treatment was surgery followed by radiotherapy. The remission rate was significantly higher in medical and radiotherapy compared to surgical treatment.
CONCLUSION
In cases of recurrent acromegaly, the patient may benefit more from radiotherapy and medical therapy compared to surgery. As the quality of evidence is low on this matter feature studies specifically designed for recurrent patients are needed.
Topics: Humans; Acromegaly; Treatment Outcome; Reoperation
PubMed: 38279102
DOI: 10.1186/s12902-023-01533-w -
Journal of Neuro-oncology May 2024In patients with acromegaly, secondary treatment options in cases of hormonal non-remission or tumor progression include repeat transsphenoidal surgery (TSS),... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
In patients with acromegaly, secondary treatment options in cases of hormonal non-remission or tumor progression include repeat transsphenoidal surgery (TSS), radiation-based treatment (RT), or medical therapy (MT). In this study, we aim to evaluate the clinical effectiveness of various second-line treatment options for acromegaly.
METHODS
Using the PRISMA guideline, a systematic review was performed by searching MEDLINE (PubMed), Web of Science, Scopus, and Cochrane electronic bibliographic databases from conception to the end of 2022. Outcomes of interest included hormonal remission rate, complications, and mortality associated with each treatment modality for refractory acromegaly.
RESULTS
A total of 79 studies including 3,208 refractory acromegaly patients (44.90% males) were analyzed, with a mean patient age of 43.89 years. There was a statistically significant difference between various therapeutic modalities in terms of remission rate, with MT offering the highest remission rate (62.55%), followed by RT (50.15%) and TSS (37.39%). Subgroup analysis of radiotherapeutic and medical modalities did not show a significant difference in remission rate between different kinds of sub-modalities in each treatment approach. Recurrence following secondary treatment was not different in patients treated with reoperation TSS compared to other modalities.
CONCLUSIONS
The management of persistent and recurrent acromegaly optimally requires a multimodal approach. In different scenarios of refractory acromegaly based on previous treatment, secondary treatments may vary in terms of remission rate and complications. Medical agents provide considerable effectiveness as a second-line therapy for recurrent or persistent disease. In selected cases, however, reoperation still provides an opportunity for cure or freedom from medications. The findings of this study may help clinicians to prioritize varying options involved in this multifaceted decision-making process.
Topics: Humans; Acromegaly; Combined Modality Therapy; Neoplasm Recurrence, Local
PubMed: 38587609
DOI: 10.1007/s11060-024-04658-7 -
Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review.Pituitary 2010Long-acting somatostatin analogs (SSA) are widely used for the treatment of acromegaly achieving biochemical control of the disease in 50-75% of the patients. One of the... (Comparative Study)
Comparative Study Review
Long-acting somatostatin analogs (SSA) are widely used for the treatment of acromegaly achieving biochemical control of the disease in 50-75% of the patients. One of the goals of the treatment of acromegaly is the control of tumor growth, especially in patients in whom SSAs are used as first-line therapy. Over the recent years, there has been growing evidence that SSAs are able to induce tumor shrinkage in patients with acromegaly. However, most of the data are from patients under treatment with octreotide, either subcutaneously or intramuscularly with long-acting formulation, whereas the data on lanreotide SR or Autogel are very few. Indeed, octreotide and lanreotide, i.e. the two commercially available SSAs, show slight differences in pharmacokinetics and patterns of receptor affinities with potentially different therapeutic effects. We aimed to perform a systematic review of literature data concerning the shrinkage effects of long-acting lanreotide in patients with acromegaly. The analysis was focused on the following issues: differences in shrinkage effects between primary and secondary medical treatment, predictive value of baseline tumor volume and correlation between biochemical control and shrinkage effects. The peer-reviewed medical literature was searched to identify clinical trials studying the effects of lanreotide SR or Autogel on adenoma size in acromegaly. To be included in this analysis, studies had one of the following designs: randomized controlled trial; prospective, nonrandomized trial; retrospective study. Twenty-two studies were found to be eligible for the final analysis, in which tumor size was measured as an end-point for lanreotide treatment. Overall a total of 32.8% of patients experienced a variable degree (from 10 to 77%) of tumor shrinkage during lanreotide SR or Autogel treatment. The analysis showed that tumor shrinkage was more frequent in naïve patients as compared with those previously treated by radiotherapy, surgery or drugs other than lanreotide. The data on the correlation between tumor shrinkage and baseline tumor size were discordant, but when baseline tumor size was specified, more than 80% of patients undergoing shrinkage under lanreotide Autogel had macroadenomas. Finally, with lanreotide Autogel there was no evident correlation between biochemical response and tumor shrinkage. Our systematic review of the literature shows that lanreotide particularly when used as first-line therapy is able to quite frequently induce tumor shrinkage in patients with acromegaly. This finding suggests that this drug may have a role in the primary treatment of acromegaly.
Topics: Acromegaly; Antineoplastic Agents; Humans; Octreotide; Peptides, Cyclic; Somatostatin; Tumor Burden
PubMed: 19189218
DOI: 10.1007/s11102-009-0169-z -
Reviews in Endocrine & Metabolic... Apr 2024The review discusses the relationship between acromegaly and uterine fibroids. It highlights variations in research methodologies and inconsistent findings, emphasizing... (Review)
Review
The review discusses the relationship between acromegaly and uterine fibroids. It highlights variations in research methodologies and inconsistent findings, emphasizing the complex nature of fibroid development and the role of the somatotropic axis. Additionally, it addresses demographic factors and examines the potential impact of therapies on the risk and prevalence of uterine fibroids in individuals with acromegaly. We conducted an analysis of previously published literature that examined the repercussions of acromegaly on gynecological health in female cohorts, with specific attention directed towards elucidating the prevalence of uterine fibroids. We suggest that larger, more focused studies are needed to understand the specific impact of different treatments on the occurrence of gynecological issues in acromegaly patients. Additionally, our study emphasizes the importance of factors such as disease duration and treatment effectiveness. We hypothesize that a relationship between acromegaly and uterine fibroids may occur. However, it remains an area of ongoing research, with the need for larger, multi-center studies to draw more definitive conclusions.
PubMed: 38668933
DOI: 10.1007/s11154-024-09883-z -
Clinical Endocrinology Nov 2016Growth hormone (GH) and insulin-like growth factor I (IGF-I) are the principal biomarkers used to assess disease activity in acromegaly, and any discrepancy between them... (Meta-Analysis)
Meta-Analysis Review
The ongoing challenge of discrepant growth hormone and insulin-like growth factor I results in the evaluation of treated acromegalic patients: a systematic review and meta-analysis.
OBJECTIVE
Growth hormone (GH) and insulin-like growth factor I (IGF-I) are the principal biomarkers used to assess disease activity in acromegaly, and any discrepancy between them renders interpretation of results inconclusive. Purpose of this study was to assess the frequency of this discrepancy and identify parameters that might affect its occurrence.
DESIGN
A systematic review of MEDLINE and Scopus was performed (1987-2013) followed by a meta-analysis to address the frequency of discrepant results between GH and IGF-I levels. Meta-regression and subgroup analyses were performed assessing the effects of the year of publication, the different types of GH testing and GH assays used, as well as the impact of treatment with somatostatin analogues (SSAs) on the occurrence of this discrepancy.
RESULTS
The analysis retrieved 39 eligible studies totalling 7071 patients. The pooled discordance rate between GH and IGF-I was 25·7% (95% CI: 22·3-29·4), and the predominant format was that of elevated IGF-I with normal GH levels (15·3%, 95% CI: 12·5-18·7). No significant correlation between the discordance rate and the year of publication was shown; whereas, the use of ultrasensitive GH assays resulted in higher discordance rates (30·7%, 95% CI: 25·9-35·9 vs 19·8%, 95% CI: 14·1-27·2, P = 0·04) as did treatment with SSAs (32·5%, 95% CI: 27·8-37·4) vs (21·6%, 95% CI: 17·8-25·6, P = 0·001).
CONCLUSIONS
Discrepancy between GH and IGF-I results is encountered in a quarter of treated patients with acromegaly, especially when using ultrasensitive GH assays or in patients receiving SSAs, a fact that the clinician should take into consideration when making clinical decisions.
Topics: Acromegaly; Biomarkers; Growth Hormone; Humans; Insulin-Like Growth Factor I
PubMed: 27292418
DOI: 10.1111/cen.13129 -
Pituitary Aug 2015Whether the preoperative use of somatostatin analogues (SA) improves surgical outcomes in acromegaly is still a matter of debate. (Comparative Study)
Comparative Study Meta-Analysis Review
Preoperative somatostatin analogues versus direct transsphenoidal surgery for newly-diagnosed acromegaly patients: a systematic review and meta-analysis using the GRADE system.
UNLABELLED
Whether the preoperative use of somatostatin analogues (SA) improves surgical outcomes in acromegaly is still a matter of debate.
OBJECTIVE
We conducted a systematic review of randomized, controlled trials that compared the short-term outcomes of preoperative use of SA (Pre-SA) with direct TSS (No-SA) for the treatment of newly diagnosed acromegaly.
METHODS
Embase, Pubmed, Lilacs, and Central Cochrane were used as our data sources. The primary outcomes were no need for any adjuvant treatment 3 months after surgery, based on biochemical results (GH nadir after OGTT <1 μg/L and normal IGF-1 for age and gender), quality of life and mortality. The included trials were analyzed using the Grading of Recommendations Assessment, Development, and Evaluation approach.
RESULTS
A total of 2.099 references were identified and two reviewers independently screened the titles and abstracts. From the 14 potentially eligible studies, four were included and ten were excluded due to lack of randomization or different outcomes. A pool of 261 patients was randomly assigned to Pre-SA or No-SA. Meta-analysis of IGF1 normalization showed a significant difference in favor of Pre-SA (RR 2.47; 95% CI 1.66, 3.77). Adding a GH nadir on OGTT ≤1 μg/L, we found a RR of 2.15 (95% CI 1.39, 3.33). Quality of evidence for no need of adjuvant postoperative treatment was moderate, but for improving quality of life was very low and for mortality was absent.
CONCLUSION
Pre-SA increases the chance of biochemical control of acromegaly 3 months after TSS in patients harboring GH-secreting pituitary macroadenomas.
Topics: Adenoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Glucose Tolerance Test; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Neoadjuvant Therapy; Neurosurgical Procedures; Octreotide; Peptides, Cyclic; Preoperative Care; Quality of Life; Somatostatin
PubMed: 25261979
DOI: 10.1007/s11102-014-0602-9