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Journal of Endocrinological... Oct 2023The clinical and hormonal overlap between neoplastic (CS) and non-neoplastic (NNH/pCS) hypercortisolism is a challenge. Various dynamic tests have been proposed to allow... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The clinical and hormonal overlap between neoplastic (CS) and non-neoplastic (NNH/pCS) hypercortisolism is a challenge. Various dynamic tests have been proposed to allow an early discrimination between these conditions, but to date there is no agreement on which of them should be used.
AIM
To provide an overview of the available tests and to obtain a quantitative synthesis of their diagnostic performance in discriminating NNH/pCS from CS.
METHODS
The included articles, published between 1990 and 2022, applied one or more second line tests to differentiate NNH/pCS from CS patients. For the NNH/pCS group, we admitted the inclusion of patients presenting clinical features and/or biochemical findings suggestive of hypercortisolism despite apparent lack of a pCS-related condition.
RESULTS
The electronic search identified 339 articles. After references analysis and study selection, we identified 9 studies on combined dexamethasone-corticotropin releasing hormone (Dex-CRH) test, 4 on Desmopressin test and 3 on CRH test; no study on Dex-Desmopressin met the inclusion criteria. Dex-CRH test provided the highest sensitivity (97%, 95 CI% [88%; 99%]). CRH tests showed excellent specificity (99%, 95% CI [0%; 100%]), with low sensitivity. Although metaregression analysis based on diagnostic odds ratio failed to provide a gold standard, CRH test (64.77, 95% CI [0.15; 27,174.73]) seemed to lack in performance compared to the others (Dex-CRH 138.83, 95% CI [49.38; 390.32] and Desmopressin 110.44, 95% CI [32.13; 379.63]).
DISCUSSION
Both Dex-CRH and Desmopressin tests can be valid tools in helping discrimination between NNH/pCS and CS. Further studies are needed on this topic, possibly focusing on mild Cushing's Disease and well-characterized NNH/pCS patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359774 , identifier CRD42022359774.
Topics: Humans; Diagnosis, Differential; Cushing Syndrome; Deamino Arginine Vasopressin; Hospitalization; Odds Ratio
PubMed: 37079177
DOI: 10.1007/s40618-023-02099-z -
Pituitary Oct 2023Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the... (Review)
Review
PURPOSE
Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the clinical, biochemical and radiological characteristics, management and therapeutic outcomes in men versus women is made.
METHODS
A structured search was conducted using the term 'giant prolactinoma'. Following inclusion criteria were used: diameter ≥ 40 mm, prolactin levels > 1000 ng/ml and no concomitant GH/ ACTH secretion.
RESULTS
196 cases were included [age: 38 (28-50) years, F/M ratio: 1/3.6]. Median tumor diameter was 53 (43-69) mm. Pituitary deficiency was present in 91% of cases, with hypogonadotropic hypogonadism being the most frequent. Most common presenting symptoms were visual impairment (73%) and headache (50%) in men and amenorrhea (58%) in women. 82% of cases were treated with a dopamine agonist (DA) as first-line treatment which led to normoprolactinemia, tumor shrinkage and visual improvement in 51%, 88% and 85% of cases, respectively. Surgery was performed in 29% of cases and all showed tumor remnant and persistent hyperprolactinemia. Women had a lower prolactin level and a smaller tumor diameter at diagnosis but pituitary deficiencies were more frequent and outcome was worse.
CONCLUSION
Giant prolactinomas are rare and have a male predominance. Visual impairment is the most frequent presenting symptom in men and amenorrhea in women. The gender-related difference in tumor size and level of prolactin was confirmed in this analysis where men had a larger diameter and a higher baseline prolactin level. DAs are the treatment of choice, irrespective of tumor size and presence of visual impairment. As only half of the cases achieved normoprolactinemia we do not, in contrast to previous literature, state giant prolactinomas to be exquisitely sensitive to DAs. Patient characteristics associated with persistent hyperprolactinemia after treatment with a DA were female gender, higher baseline prolactin and larger tumor size . This analysis did show TSH- and ACTH-deficiency to be more frequent after surgery which was not seen for LH/FSH deficiency.
Topics: Female; Adult; Male; Humans; Prolactinoma; Pituitary Neoplasms; Hyperprolactinemia; Prolactin; Amenorrhea; Dopamine Agonists; Hypopituitarism; Vision Disorders; Adrenocorticotropic Hormone
PubMed: 37544978
DOI: 10.1007/s11102-023-01337-0 -
Journal of Assisted Reproduction and... Oct 2023To investigate the effectiveness and safety of 36 different therapies for recurrent implantation failure (RIF) patients. (Meta-Analysis)
Meta-Analysis Review
Comparative effectiveness and safety of 36 therapies or interventions for pregnancy outcomes with recurrent implantation failure: a systematic review and network meta-analysis.
PURPOSE
To investigate the effectiveness and safety of 36 different therapies for recurrent implantation failure (RIF) patients.
METHODS
We searched PubMed, Embase, the Cochrane Library (CENTRAL), Web of Science, and China National Knowledge Internet (CNKI) from inception to August 24, 2022, with language in both English and Chinese. Randomized controlled trials (RCTs) and observational studies that provided data with one of pregnancy outcomes on RIF patients were included in the network meta-analysis (NMA). The odds ratios (OR) and 95% credible interval (CrI) on pregnancy outcomes were summarized by NMA with a random-effects model. We also analyzed data from only RCTs and compared whether the optimal treatment is the same for different failed embryo transfer attempts.
RESULTS
The total of 29,906 RIF patients from 154 clinical studies (74 RCTs and 80 non-RCTs) were included in the NMA. In terms of implantation rate (IR), growth hormone (GH) (OR: 3.32, 95% CrI: 1.95-5.67) is the best treatment in all included studies; IVIG+PBMC (5.84, 2.44-14.1) is the best for clinical pregnancy rate (CPR); hyaluronic acid (HA) (12.9, 2.37-112.0) for live birth rate (LBR); and aspirin combined with glucocorticoids (0.208, 0.0494-0.777) for miscarriage rate (MR). The two-dimensional graphs showed that GH could maximize IR and CPR simultaneously; HA and GH could simultaneously increase IR and LBR to a large extent; HA could maximize IR and minimize MR.
CONCLUSION
IVIG+PBMC, GH, and embryo medium enriched with HA could significantly improve pregnancy outcomes in patients with RIF. It appears that combination therapy is a potential administration strategy.
TRIAL REGISTRATION
This study has been registered on PROSPERO (CRD42022353423).
Topics: Female; Pregnancy; Humans; Pregnancy Outcome; Network Meta-Analysis; Immunoglobulins, Intravenous; Abortion, Spontaneous; Human Growth Hormone; Growth Hormone; Hyaluronic Acid; Randomized Controlled Trials as Topic
PubMed: 37661207
DOI: 10.1007/s10815-023-02923-8 -
Journal of Neurosurgery Mar 2022A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and develop consensus recommendations.
METHODS
The authors performed a systematic review of the English-language literature up until June 2018 using the PRISMA guidelines. The PubMed (Medline), Embase, and Cochrane databases were searched. A total of 45 articles reporting single-institution outcomes of SRS for acromegaly, Cushing's disease, and prolactinomas were selected and included in the analysis.
RESULTS
For acromegaly, random effects meta-analysis estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rates were 97.0% (95% CI 96.0%-98.0%), 44.0% (95% CI 35.0%-53.0%), and 17.0% (95% CI 13.0%-23.0%), respectively. For Cushing's disease, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 92.0% (95% CI 87.0%-95.0%), 48.0% (95% CI 35.0%-61.0%), and 21.0% (95% CI 13.0%-31.0%), respectively. For prolactinomas, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 93.0% (95% CI 90.0%-95.0%), 28.0% (95% CI 19.0%-39.0%), and 12.0% (95% CI 6.0%-24.0%), respectively. Meta-regression analysis did not show a statistically significant association between mean margin dose with crude endocrine remission rate or mean margin dose with development of any new hypopituitarism rate for any of the secretory subtypes.
CONCLUSIONS
SRS offers effective tumor control of hormone-producing pituitary adenomas in the majority of patients but a lower rate of endocrine improvement or remission.
Topics: Acromegaly; Humans; Hypopituitarism; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prolactinoma; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 34479203
DOI: 10.3171/2021.2.JNS204440 -
Frontiers in Endocrinology 2023To appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with diminished ovarian reserve (DOR) undergoing fertilization (IVF).
METHODS
Relevant RCTs published in Chinese or English were identified through a comprehensive search of nine databases from the period of database inception to April 20, 2023. We included trials investigating adjuvant GH during ovarian stimulation and reported the subsequent outcomes. The group with adjuvant GH treatment and the group without adjuvant GH treatment were set up as the trial and control groups, respectively. The quality of RCTs was measured according to the Cochrane Collaboration Handbook.
RESULTS
Of the 579 studies initially identified, 10 RCTs comprising 852 infertile women with DOR were included. The GH dose of individual trials ranged between 3 and 5 IU/day. Overall, we judged the trials to be at high risk of bias in the blinding domain. Pooled results showed that GH was associated with an increased clinical pregnancy rate (RR = 1.63, 95%CI [1.31, 2.03], < 0.0001) and a greater number of oocytes retrieved (MD = 0.91, 95%CI [0.47, 1.35], < 0.0001). Favorable associations were also observed when ovarian stimulation was combined with GH therapy for improving the optimal embryos rate (RR = 1.84, 95%CI [1.30, 2.59], = 0.0005) and the number of optimal embryos (MD = 0.28, 95%CI [0.08, 0.48], = 0.005) along with reducing the cycle cancellation rate (RR = 0.46, 95%CI [0.24, 0.89], = 0.02). Moreover, GH resulted in an increase in the fertilization rate (RR = 1.33, 95%CI [1.18, 1.50], < 0.00001) and the embryo implantation rate (RR = 1.56, 95%CI [1.21, 2.01], = 0.0006). In addition, there was a significant enhancement in estradiol levels (SMD = 1.18, 95%CI [0.46, 1.91], = 0.001) and endometrial thickness (MD = 0.75, 95%CI [0.41, 1.09], < 0.0001) on the day of hCG. With regard to the total number of days and total dose of gonadotrophins used, GH treatment was correlated with shorter days (MD = -0.26, 95%CI [-0.46, -0.06], = 0.01) and lower dose (MD = -460.97, 95%CI [-617.20, -304.73], < 0.00001) of gonadotrophins applied during ovarian stimulation. Furthermore, GH in conjunction with the GnRH antagonist protocol was more conducive to improving the number of oocytes retrieved when compared with the GnRH agonist protocol ( < 0.0001). Moreover, a notable association was also seen in IVF combined with GH more than or equal to 4.5 IU/day to increase the number of optimal embryos and estradiol levels on the day of hCG ( < 0.05).
CONCLUSION
For infertile women with DOR undergoing IVF, adjuvant treatment with GH during ovarian stimulation protocols showed better clinical outcomes, shorter days and lower dosages of gonadotrophin required. Furthermore, well-designed RCTs are needed to verify our results in the future.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk PROSPERO (CRD42023421739).
Topics: Pregnancy; Female; Humans; Growth Hormone; Gonadotropin-Releasing Hormone; Ovarian Reserve; Gonadotropins; Fertilization in Vitro; Infertility, Female; Human Growth Hormone; Ovarian Diseases; Estradiol
PubMed: 38027219
DOI: 10.3389/fendo.2023.1215755 -
Hormone Research in Paediatrics 2024Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing.
METHODS
Embase, MEDLINE, and Cochrane Library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children.
RESULTS
Twenty-five articles (n = 1,433 children) were identified, describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n = 6 studies), chronic renal failure (n = 3), Noonan syndrome (n = 1), and growth hormone deficiency (n = 1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference = -0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total = 397) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total = 284).
CONCLUSIONS
Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.
Topics: Child; Humans; Human Growth Hormone; Growth Hormone; Body Height; Growth Disorders; Dwarfism, Pituitary; Recombinant Proteins
PubMed: 37075730
DOI: 10.1159/000530578 -
Gynecological Endocrinology : the... Dec 2023This systematic review and meta-analysis aimed at summarizing the evidence concerning circulating asprosin, and related endocrine and metabolites in women with and... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis aimed at summarizing the evidence concerning circulating asprosin, and related endocrine and metabolites in women with and without the polycystic ovary syndrome (PCOS). We performed a comprehensive literature search in Pubmed, Web of Science, Scielo, and Chinese National Knowledge Infrastructure for studies published until May 20, 2022, that evaluated circulating asprosin levels in women with and without PCOS, regardless of language. The quality of studies was assessed with the Newcastle-Ottawa Scale. Random-effects models were used to estimate mean differences (MD) or standardized MD (SMD) and their 95% confidence interval (CI). We evaluated eight studies reporting 1,050 PCOS cases and 796 controls of reproductive age. Participants with PCOS were younger (MD = -2.40 years, 95% CI -2.46 to -2.33), with higher values of asprosin (SMD = 2.57, 95% CI 1.64-3.50), insulin (SMD = 2.73, 95% CI 1.18-4.28), homeostatic model assessment of insulin resistance (SMD = 2.70, 95% CI 0.85-4.55), luteinizing hormone (SMD = 2.33, 95% CI 0.60-4.06), total testosterone (SMD = 4.06, 95% CI 1.89-6.22), dehydroepiandrosterone sulfate (SMD = 2.38, 95% CI 0.37-4.40), and triglycerides (SMD = 1.20, 95% CI 0.13 to 2.27). Moreover, PCOS women had lower circulating levels of sex hormone-binding globulin (SMD = -3.36, 95% CI -4.92 to -1.80), and high-density lipoprotein-cholesterol (SMD = -0.85, 95% CI -1.69 to -0.01); with no significant differences observed for glucose, total cholesterol, and low-density lipoprotein-cholesterol levels. Circulating asprosin levels were significantly higher in women with PCOS as compared to those without the syndrome.
Topics: Female; Humans; Cholesterol, HDL; Insulin; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome
PubMed: 36480935
DOI: 10.1080/09513590.2022.2152790 -
Headache May 2023To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology. (Review)
Review
OBJECTIVE
To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology.
BACKGROUND
The features of migraine attacks, including characteristics, duration, frequency, and prevalence, are sex-dependent with variability across a lifetime, indicating the involvement of the hypothalamus-pituitary-gonadal axis. Prolactin is a key regulator of this axis, and a new line of evidence implicates prolactin signaling in sex-related differences in pain perception.
METHODS
In this systematic review, we searched PubMed and EMBASE for the terms prolactin, hyperprolactinemia, macroprolactinemia, hypoprolactinemia, migraine, headache, head pain, and trigeminal pain pathway to find preclinical studies investigating prolactin signaling in headache and migraine. Two reviewers independently screened 841 articles for population, intervention, comparison, outcome, and study design. Studies were restricted to the English language and were excluded if they had a nonexperimental methodology.
RESULTS
Of a total of 15 preclinical articles selected, 11 were both ex vivo and in vivo, 3 were ex vivo, and 1 was an in vivo study. The main findings were that prolactin receptors are distributed in the trigeminal pain pathway, and prolactin induced migraine-like behavior in rodents. Moreover, prolactin signaling has a crucial role in calcitonin gene-related peptide (CGRP) release, a key molecule in migraine pathogenesis, and prolactin gene deletion attenuated CGRP-induced migraine-like behavior.
CONCLUSION
Preclinical data indicate a key role of prolactin and its receptors in mechanisms causing migraine. Further randomized and placebo-controlled clinical studies targeting prolactin signaling are needed to further clarify the influences of prolactin in migraine-attack initiation.
Topics: Humans; Calcitonin Gene-Related Peptide; Headache; Migraine Disorders; Pain; Prolactin; Animals; Mice; Rats
PubMed: 36752584
DOI: 10.1111/head.14412 -
Neuroscience and Biobehavioral Reviews Nov 2022The last couple of decades have witnessed a rapid accumulation of studies implicating oxytocin (OT) in several neurobiological underpinnings of human behaviour and their... (Review)
Review
The last couple of decades have witnessed a rapid accumulation of studies implicating oxytocin (OT) in several neurobiological underpinnings of human behaviour and their impairment in psychiatric illness. Specifically, a neuroimaging genetics approach is helping elucidate the impact of variations in OT pathway genes on the human brain. In this review, we provide the first systematic account and discussion of all previous findings arising from human neuroimaging (epi)genetic studies of OT-related genes. To improve our mechanistic interpretation of such findings, we used data from the Genotype-Tissue Expression project to explore the functional impact the genetic variations may have on the human transcriptome. As a result, we provide an up-to-date summary of brain circuits found to be impacted by OT-relevant (epi)genetic variability, map brain pathways linking OT genes to disease, and highlight several (epi)genetic factors that modulate brain responses to intranasal OT. Finally, we provide some suggestions we believe might improve future research in the field.
Topics: Humans; Administration, Intranasal; Brain; Neuroimaging; Oxytocin; Transcriptome
PubMed: 36228928
DOI: 10.1016/j.neubiorev.2022.104912 -
Journal of Ovarian Research Feb 2023Hysterectomy is one of the most frequently gynecologic surgeries performed in premenopausal women. Many premenopausal patients are unwilling to undergo hysterectomy due... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hysterectomy is one of the most frequently gynecologic surgeries performed in premenopausal women. Many premenopausal patients are unwilling to undergo hysterectomy due to the probable decreased ovarian function. The aim of this study is to determine the effect of hysterectomy on ovarian function.
METHODS
A meta-analysis has been reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and the A Measurement Tool to Assess Systematic Reviews (AMSTAR) guidelines. We mainly searched the Embase, PubMed and Web of Science databases for eligible studies. The outcomes were the levels of common indicators of ovarian function, such as anti-müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, estradiol (E2) and luteinizing hormone (LH). The evidence was synthesized using meta-analysis via fixed or random effect model according to heterogeneity. Subgroup analyses were performed to examine the potential sources of heterogeneity.
RESULTS
The 14 included studies were conducted between 1989 and 2021, involving a total of 1,457 premenopausal women with 760 and 697 in the hysterectomy and control group, respectively. We found that hysterectomy damage ovarian function compared to the control group, with lower AMH level [Weighted mean difference (WMD) = -0.56, 95% confidence interval (95% CI): -0.72 to -0.39, P = 0.000], higher FSH levels (WMD = 2.96, 95% CI: 1.47 to 4.44, P = 0.000), lower inhibin B levels (WMD = -14.34, 95% CI: -24.69 to -3.99, P = 0.000) and higher LH levels (WMD = 4.07, 95% CI: 1.78 to 6.37, P = 0.000). In addition, E2 levels have a decreasing trend (WMD = -17.13, 95% CI: -35.10 to 0.85, P = 0.631) in the hysterectomy group but were not statistically significant.
CONCLUSION
Hysterectomy has a negative impact on ovarian function, especially in female patients over 40 years old. So, the older patients should closely monitor their ovarian function for early diagnosis and treatment of menopausal symptoms.
Topics: Female; Humans; Adult; Luteinizing Hormone; Follicle Stimulating Hormone; Hysterectomy; Ovary; Estradiol; Anti-Mullerian Hormone
PubMed: 36759829
DOI: 10.1186/s13048-023-01117-1