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Clinical Endocrinology Jun 2024Pseudoacromegaly encompasses conditions with features of acromegaly/gigantism, but no growth hormone (GH) or insulin-like growth factor-1 (IGF-1) excess. We aimed to...
OBJECTIVE
Pseudoacromegaly encompasses conditions with features of acromegaly/gigantism, but no growth hormone (GH) or insulin-like growth factor-1 (IGF-1) excess. We aimed to review published pseudoacromegaly cases evaluated due to clinical suspicion of acromegaly.
DESIGN/PATIENTS
PubMed/Medline search was conducted to identify reported pseudoacromegaly cases, which were systematically reviewed to ensure they met eligibility criteria: (1) presentation suggestive of acromegaly; (2) acromegaly excluded based on normal GH, IGF-1 and/or GH suppression on oral glucose tolerance test (OGTT-GH); (3) diagnosis of the pseudoacromegaly condition was established. Data were retrieved from each case and analysed collectively.
RESULTS
Of 76 cases, 47 were males, mean ages at presentation and at first acromegaloid symptoms were 28 ± 16 and 17 ± 10 years, respectively. Most common conditions were pachydermoperiostosis (47%) and insulin-mediated pseudoacromegaly (IMP) (24%). Acromegaloid facies (75%) and acral enlargement (80%) were the most common features. Measurement of random GH was reported in 65%, IGF-1 in 79%, OGTT-GH in 51%. GH excess was more frequently excluded based on two tests (53%). Magnetic resonance imaging (MRI) was performed in 30 patients, with pituitary adenoma or hyperplasia being reported in eight and three patients, respectively. Investigations differed between cases managed by endocrine and non-endocrine specialists, the former requesting more often IGF-1, OGTT-GH and pituitary MRI.
CONCLUSIONS
Pseudoacromegaly is a challenging entity that may be encountered by endocrinologists. Pachydermoperiostosis and IMP are the conditions most often mimicking acromegaly. Adequate assessment of GH/IGF-1 is crucial to exclude acromegaly, which may be better performed by endocrinologists. Pituitary incidentalomas are common and require careful judgement to prevent unnecessary pituitary surgery.
Topics: Humans; Acromegaly; Male; Insulin-Like Growth Factor I; Female; Adult; Human Growth Hormone; Gigantism; Glucose Tolerance Test; Adolescent; Young Adult
PubMed: 38549284
DOI: 10.1111/cen.15053 -
Targeted Oncology May 2024Palbociclib in combination with endocrine therapy is approved for treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-)...
BACKGROUND
Palbociclib in combination with endocrine therapy is approved for treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. In addition to clinical trials, several real-world studies have evaluated the effectiveness of palbociclib. With increased life expectancy in the general population, breast cancer in older women is also expected to increase.
OBJECTIVE
The aim was to systematically review evidence from both clinical trials and real-world studies for palbociclib treatment outcomes in older patients with HR+/HER2- advanced/metastatic breast cancer (a/mBC). Older patients are often underrepresented in clinical trials, and real-world evidence (RWE) will enrich the analysis of palbociclib outcomes in this subgroup of patients.
DESIGN
A systematic literature search in PubMed, EMBASE, and Cochrane Library through May 4, 2023, yielded 2355 unique articles. A total of 52 articles (13 and 39 articles reporting results from seven randomized controlled trials [RCTs] and 37 RWE studies, respectively) were included based on study eligibility criteria.
RESULTS
All RCTs used age cutoffs of ≥ 65 years to define older population (n = 722; 437 received palbociclib); all RWE studies, except one with an age cutoff of > 60 years, had age cutoffs of ≥ 65 years or higher to define older population (n = 9840; 7408 received palbociclib). Overall, in studies that compared efficacy (progression-free survival [seven RCTs, 20 RWE studies], overall survival [four RCTs, 11 RWE studies], tumor response [three RWE studies], and clinical benefit rate [one RCT, two RWE studies]) and safety outcomes (three RCTs, three RWE studies) between older and younger patients, palbociclib showed similar benefits, regardless of age. Results from two RCTs and two RWE studies showed that global quality of life (QoL) was maintained in older patients receiving palbociclib. Overall, palbociclib dose modifications (two RWE studies), dose reductions (one RCT, seven RWE studies), and treatment discontinuation rates (three RCTs, three RWE studies) were higher in older patients compared with younger patients; however, these differences did not appear to adversely impact efficacy outcomes.
CONCLUSIONS
In this systematic review, data from RCTs showed that palbociclib was effective, well tolerated, and maintained QoL in older patients with HR+/HER2- a/mBC. Palbociclib treatment in older patients in real-world settings was associated with similar clinical benefit as in RCTs.
PROSPERO REGISTRATION
CRD42023444195.
Topics: Humans; Breast Neoplasms; Pyridines; Piperazines; Female; Aged; Neoplasm Metastasis
PubMed: 38546943
DOI: 10.1007/s11523-024-01046-z -
International Journal of Endocrinology 2024Metformin is commonly prescribed to treat polycystic ovary syndrome (PCOS) patients, but in some cases, it may not be effective even at high doses or may cause... (Review)
Review
Comparative Effectiveness of Antidiabetic Drugs as an Additional Therapy to Metformin in Women with Polycystic Ovary Syndrome: A Systematic Review of Metabolic Approaches.
BACKGROUND
Metformin is commonly prescribed to treat polycystic ovary syndrome (PCOS) patients, but in some cases, it may not be effective even at high doses or may cause intolerable side effects. Therefore, recent studies have examined the impact of combining metformin with other antidiabetic medications.
METHODS
A systematic search was performed in Scopus, PubMed, Web of Science, and Embase up to 30 June 2023. All interventional studies that assessed the efficacy of different antidiabetic agents were included.
RESULTS
Among the 3488 records found in the primary search, 16 papers were included. Our study showed that dipeptidyl peptidase-4 inhibitors (DPP4i) had the most significant impact on glycemic profile, while thiazolidinediones (TZDs) had the most influence on lipid levels. However, it was observed that patients taking only metformin experienced a greater increase in high-density lipoprotein cholesterol (HDL-C) levels. Glucagon-like peptide-1 receptor agonists (GLP1RAs) effectively modified various anthropometric measurements, such as weight, body mass index, waist circumference, and waist-to-hip ratio. The effects of different antidiabetic drugs on hormone levels were inconclusive, although testosterone levels were more affected by GLP1RA, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and TZDs. None of the combined therapies showed a significant change in blood pressure.
CONCLUSION
Since PCOS is a metabolic disorder, choosing the best combination of antidiabetic drugs in the clinical course of PCOS patients will be very important. Today, it seems that we need a new metabolic approach for better treatment of the metabolic aspects of these patients.
PubMed: 38500709
DOI: 10.1155/2024/9900213 -
Endocrine Mar 2024Growth hormone deficiency (GHD) is the most common pituitary hormone deficiency and is one of the main causes of short stature in children and adolescents. The aim of... (Review)
Review
OBJECTIVE
Growth hormone deficiency (GHD) is the most common pituitary hormone deficiency and is one of the main causes of short stature in children and adolescents. The aim of this study is to evaluate the epidemiology of pediatric GHD worldwide, since no other systematic review has been published so far.
METHODS
We searched PubMed, Embase, and Web of Science up to July 2023 to find epidemiological studies involving children with GHD. Two review authors independently screened articles, extracted data and performed the quality assessment.
RESULTS
We selected 9 epidemiological studies published from 1974 to 2022. The range of prevalence was 1/1107-1/8,646. A study based on a registry of GH users in the Piedmont region (Italy) reported the highest mean prevalence. In the included studies, the mean incidence ranged from 1/28,800 to 1/46,700 cases per year. One study reported a 20-year cumulative incidence of 127/100,000 for boys and 93/100,000 for girls. Studies were heterogeneous in terms of population (age and GHD etiology) and diagnostic criteria. As for the methodological quality of included studies, all but one study satisfied the majority of the checklist items.
CONCLUSIONS
The included studies are mostly European, so the provided estimates cannot be considered global. International multicentre studies are needed to compare epidemiological estimates of GHD among different ethnical groups. Considering the considerable cost of human recombinant GH, the only available therapy to treat GHD, understanding accurate epidemiological estimates of GHD in each country is fundamental for resource allocation.
PubMed: 38498128
DOI: 10.1007/s12020-024-03778-4 -
Growth Hormone & IGF Research :... Apr 2024Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate... (Review)
Review
OBJECTIVE
Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate from concerns about adverse effects and the uncritical use as an anti-aging agent. Nevertheless, beneficial effects for selected patients suffering from certain acute and chronic illnesses could justify its use at an advanced age. This systematic review analyzes randomized controlled studies of GH interventions in older patients with different comorbidities to assess both, beneficial and harmful effects.
DESIGN
A systematic search strategy was implemented to identify relevant studies from PubMed, MEDLINE, and The Cochrane Library.
INCLUSION CRITERIA
participants aged over 65 years, randomized controlled trials involving human growth hormone (GH) and presence of at least one additional comorbidity independent of a flawed somatotropic axis.
RESULTS
The eight eligible studies encompassed various comorbidities including osteoporosis, frailty, chronic heart failure, hip fracture, amyotrophic lateral sclerosis and hemodialysis. Outcomes varied, including changes in body composition, physical performance, strength, bone mineral density, cardiovascular parameters, quality of life and housing situation. Study protocols differed greatly in GH application frequency (daily, 2nd day or 3×/week), doses (0.41 mg-2.6 mg; mean 1.3 mg per 60 kg patient) and duration (1-12 months; mean 7 months). Mild dose-related side effects were reported, alongside noticeable positive impacts particularly on body composition, functionality, and quality of life.
CONCLUSION
Despite limited evidence, GH treatment might offer diverse benefits with few adverse effects. Further research with IGF-I dependent indication and clear outcomes, incorporating IGF-I dependent GH titration in older adults is warranted.
Topics: Aged; Humans; Comorbidity; Growth Hormone; Human Growth Hormone; Insulin-Like Growth Factor I; Quality of Life; Randomized Controlled Trials as Topic; Aging
PubMed: 38489867
DOI: 10.1016/j.ghir.2024.101584 -
Cancer Imaging : the Official... Mar 2024This review aimed to assess the predictive value of background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) as an imaging biomarker for... (Review)
Review
Predictive value of background parenchymal enhancement on breast magnetic resonance imaging for pathological tumor response to neoadjuvant chemotherapy in breast cancers: a systematic review.
OBJECTIVES
This review aimed to assess the predictive value of background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) as an imaging biomarker for pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT).
METHODS
Two reviewers independently performed a systemic literature search using the PubMed, MEDLINE, and Embase databases for studies published up to 11 June 2022. Data from relevant articles were extracted to assess the relationship between BPE and pCR.
RESULTS
This systematic review included 13 studies with extensive heterogeneity in population characteristics, MRI follow-up points, MRI protocol, NACT protocol, pCR definition, and BPE assessment. Baseline BPE levels were not associated with pCR, except in 1 study that reported higher baseline BPE of the younger participants (< 55 years) in the pCR group than the non-pCR group. A total of 5 studies qualitatively assessed BPE levels and indicated a correlation between reduced BPE after NACT and pCR; however, among the studies that quantitatively measured BPE, the same association was observed only in the subgroup analysis of 2 articles that assessed the status of hormone receptor and human epidermal growth factor receptor 2. In addition, the predictive ability of early BPE changes for pCR was reported in several articles and remains controversial.
CONCLUSIONS
Changes in BPE may be a promising imaging biomarker for predicting pCR in breast cancer. Because current studies remain insufficient, particularly those that quantitatively measure BPE, prospective and multicenter large-sample studies are needed to confirm this relationship.
Topics: Humans; Female; Prospective Studies; Neoadjuvant Therapy; Breast; Breast Neoplasms; Magnetic Resonance Imaging; Retrospective Studies; Multicenter Studies as Topic
PubMed: 38462607
DOI: 10.1186/s40644-024-00672-0 -
European Journal of Cancer (Oxford,... May 2024Overall survival (OS) is a universally accepted measure of clinical benefit; however, prolonged follow-up is needed to observe sufficient events. Disease-free survival...
BACKGROUND
Overall survival (OS) is a universally accepted measure of clinical benefit; however, prolonged follow-up is needed to observe sufficient events. Disease-free survival (DFS) has been widely adopted as a primary endpoint for early breast cancer (EBC) trials, as follow-up is comparatively shorter. Here, we present an analysis evaluating DFS as a surrogate for OS for adjuvant treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) EBC.
METHODS
A systematic literature review which included randomized controlled trials (RCTs) with ≥80% of adult patients with HR+/HER2- EBC was conducted. The RCTs evaluated various systemic therapeutic categories; key inclusion criteria included reporting of DFS and OS hazard ratios (HRs) and mature OS data. Spearman rank correlation and weighted linear regression analyses evaluated DFS and OS HR correlation. A scenario analysis tested base-case analysis robustness, and a parallel analysis using patient-level data was conducted.
RESULTS
The base case (N = 14 RCTs) showed an unweighted Spearman coefficient of 0.81 between OS and DFS (weighted: 0.81), with 84% of the variability in OS explained by DFS differences (R from weighted regression). The surrogate threshold effect (Burzykowski T, Buyse M. Pharm Stat. 2006;5:173-186) was 0.82 for DFS/OS HR. Scenario analysis (n = 9 RCTs), which excluded chemotherapy trials, and patient-level analysis using FACE trial data were consistent with the base-case analysis.
CONCLUSIONS
These analyses support DFS as a reliable surrogate endpoint for OS in adjuvant HR+/HER2- EBC trials. Using DFS as a surrogate measure will permit timelier access to novel treatments for patients with HR+/HER2- EBC.
Topics: Adult; Humans; Female; Disease-Free Survival; Breast Neoplasms; Progression-Free Survival; Proportional Hazards Models; Chemotherapy, Adjuvant; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38460476
DOI: 10.1016/j.ejca.2024.113977 -
Cureus Feb 2024This systematic review aims to determine the role of the growth hormone receptor (GHR) gene in skeletal malocclusion and its significant influence on the growth of the... (Review)
Review
Role of the Growth Hormone Receptor (GHR) Gene in Skeletal Class II Malocclusion and Its Significant Influence on the Skeletal Facial Profile in Both the Sagittal and Vertical Dimensions: A Systematic Review.
This systematic review aims to determine the role of the growth hormone receptor (GHR) gene in skeletal malocclusion and its significant influence on the growth of the maxilla and the mandible in both sagittal and vertical dimensions. A search of the electronic databases of PubMed, Google Scholar, and Cochrane up to and including the year 2023 was made. In addition to this, a hand search of orthodontic and dentofacial orthopaedic journals was carried out. This search included randomized control trials. The Mesh terms used were "skeletal class II malocclusion", "mandibular retrognathism", "sagittal malocclusion", "genetic expression", "genetic factors", "genetic study", "genetic polymorphism", and "single nucleotide polymorphism". The inclusion criteria included studies such as clinical trials and orthopaedic appliances in the presurgical phase. The exclusion criteria for the study were studies not in the English language, case reports, case series, and studies with irrelevant data. It has been cited in various literature that polymorphic variations of the GHR gene could cause variations in mandibular morphogenesis affecting both the mandibular body length and ramal height. However, its effects are quite variable and are based on different population groups. Polymorphism of the GHR gene can be considered a reliable indicator predicting variations in affecting the growth of the mandible with greater significance in affecting the vertical ramal height compared to the body length of the mandible. Its effects on the maxillary skeletal base are rather limited comparatively.
PubMed: 38449954
DOI: 10.7759/cureus.53596 -
Children (Basel, Switzerland) Feb 2024Growth hormone treatment has effectively restored normal growth in children with growth hormone deficiency (GHD); however, it poses challenges in compliance with a daily... (Review)
Review
Once-Weekly Somapacitan as an Alternative Management of Growth Hormone Deficiency in Prepubertal Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.
Growth hormone treatment has effectively restored normal growth in children with growth hormone deficiency (GHD); however, it poses challenges in compliance with a daily growth hormone injection regimen, leading to low adherence and persistence rates. Once-weekly Somapacitan is a potential alternative for treating children with GHD. This study aimed to evaluate the efficacy, safety, and adherence of once-weekly subcutaneous Somapacitan compared to daily growth hormone injection in prepubertal children with GHD. A search for the published records was carried out on 17 October 2023 utilizing the searching feature available on PubMed, Embase, and Scopus. Primary study outcomes included (1) efficacy, measured by height velocity (HV), standard deviation score (SDs), height SDs, insulin-like growth factor-SDs (IGF-I SDs), and bone age vs. chronological age ratio (BA vs. CA); (2) safety, assessed through adverse events and injection site reactions; and (3) adherence, determined by the percentage of the sample completing treatments. Secondary outcomes evaluated disease burden scores, divided into three subgroup domains: emotional well-being, physical functional, and social well-being scores. We retrieved 6 studies that were eligible for the systematic review (417 versus 186 for intervention and control, respectively). Only 2 of the total included studies were eligible for pooled analysis (175 versus 82 for intervention and control, respectively). The efficacy profile of Somapacitan was similar to daily growth hormones, indicated by HV (mean difference (MD = 0.04; = 0.96), HV SDs (MD = -0.71; = 0.09), height SDs (MD = 0.11; = 0.69), IGF-I SDs (MD = 0.06; = 0.70), and CA vs. BA (MD = 0.67; = 0.70)), demonstrated similar and non-inferior outcomes. Treatment adherence is 3 times higher in the Somapacitan group as compared to control (OR = 3.02; = 0.03) with adherence rates reaching 95% and 88% for Somapacitan and Norditropin, respectively. The disease burden measurement is similar in Somapacitan and daily growth hormones (MD = -0.62; = 0.83), as indicated by the Growth Hormone Deficiency-Child Impact Measure. In almost all outcomes, the level of confidence is strong. The confidence level in the data is generally strong, but for CA vs. BA and the subgroup of severe adverse events with heterogeneity >50%, the confidence level is moderate. Although the efficacy and safety profiles of Somapacitan were found to be similar to those of daily growth hormones, a reduced frequency of once-weekly Somapacitan injections led to increased adherence. PROSPERO registration: CRD42023473209.
PubMed: 38397339
DOI: 10.3390/children11020227 -
Fish Physiology and Biochemistry Apr 2024Catfish are a highly diverse group of fish that are found in various regions across the globe. The significance of catfish culture extends to various aspects, including... (Review)
Review
Catfish are a highly diverse group of fish that are found in various regions across the globe. The significance of catfish culture extends to various aspects, including food security, economic advancement, preservation of cultural legacy, and ecological stewardship. The catfish industry is presently encountering unprecedented challenges as a consequence of the variability in water temperature caused by climate change. Temperature is a significant abiotic component that regulates and restricts fish physiology throughout their life cycle. The impact of severe temperatures on various species of catfish is dependent upon the magnitude of the stressor and additional influencing factors. This paper presents an analysis of the effects of temperature fluctuations on various aspects of catfish species, including growth and survival, blood parameters, enzymatic and hormone response, oxygen consumption rates, sound generation and hearing skills, nutritional requirements, and other phenotypic attributes. While this review is certainly not exhaustive, it offers a broad synopsis of the ideal temperature ranges that are most favorable for several catfish species. In-depth research to investigate the interacting impacts of severe temperature occurrences in conjunction with other associated environmental stresses on a wider variety of catfish species is crucial in order to further our understanding of how catfish species will respond to the anticipated climate change in the future.
Topics: Animals; Catfishes; Temperature; Sound
PubMed: 38367084
DOI: 10.1007/s10695-024-01323-8