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The Journal of Clinical Endocrinology... Mar 2020The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of... (Meta-Analysis)
Meta-Analysis
CONTEXT
The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo-pituitary-end organ hormone axes, remains unclear.
OBJECTIVE
The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function.
METHODS
Eight electronic databases were searched for articles published up to May 8, 2018. Fixed or random effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals (CI). This study is reported following the PRISMA and MOOSE guidelines.
DATA SYNTHESIS
52 studies (22 low risk of bias) were included describing 18 428 subjects, consisting of patients with chronic pain (n = 21 studies) or on maintenance treatment for opioid addiction (n = 9) and healthy volunteers (n = 4). The most frequently used opioid was methadone (n = 13 studies), followed by morphine (n = 12). Prevalence of hypogonadism was 63% (95% CI: 55%-70%, 15 studies, 3250 patients, 99.5% males). Prevalence of hypocortisolism relying on dynamic and nondynamic testing was 15% (95% CI: 6%-28%, 5 studies, 205 patients, 57.5% males) and including only studies using the insulin tolerance tests 24% (95% CI 16%-33%, 2 studies, n = 97 patients). In 5 out of 7 studies, hyperprolactinemia was present. No clear effects on the somatotropic and hypothalamo-pituitary-thyroid axes were described.
CONCLUSIONS
Hypogonadism occurs in more than half of male opioid users, and hypocortisolism in approximately one-fifth of all patients. Periodical evaluation of at least the gonadal and adrenal axes is therefore advisable.
Topics: Analgesics, Opioid; Chronic Pain; Endocrine System Diseases; Humans; Hypogonadism; Pituitary Hormones; Prognosis
PubMed: 31511863
DOI: 10.1210/clinem/dgz022 -
Expert Review of Endocrinology &... Nov 2022Hyperprolactinemia has been proven to induce hypogonadism and metabolic derangements in both genders, while the consequences of prolactin (PRL) deficiency have been... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Hyperprolactinemia has been proven to induce hypogonadism and metabolic derangements in both genders, while the consequences of prolactin (PRL) deficiency have been poorly investigated.
AREAS COVERED
To systematically review and analyze data from clinical studies focusing on the metabolic consequences of abnormally high prolactin levels (HPRL) and low prolactin levels (LPRL). In addition, data from preclinical studies about underlying pathophysiological mechanisms were summarized and discussed.
EXPERT OPINION
PRL contributes to providing the correct amount of energy to support the mother and the fetus/offspring during pregnancy and lactation, but it also has a homeostatic role. Pathological PRL elevation beyond these physiological conditions, but also its reduction, impairs metabolism and body composition in both genders, increasing the risk of diabetes and cardiovascular events. Hence, hypoprolactinemia should be avoided as much as possible during treatment with dopamine agonists for prolactinomas. Patients with hypoprolactinemia, because of endogenous or iatrogenic conditions, deserve, as those with hyperprolactinemia, careful metabolic assessment.
Topics: Male; Pregnancy; Humans; Female; Prolactin; Hyperprolactinemia; Prolactinoma; Pituitary Neoplasms
PubMed: 36447418
DOI: 10.1080/17446651.2022.2144829 -
Frontiers in Endocrinology 2023Growth hormone (GH) affects metabolism and regulates growth in childhood. The most prominent feature of GH deficiency (GHD) in children is diminished height velocity...
BACKGROUND
Growth hormone (GH) affects metabolism and regulates growth in childhood. The most prominent feature of GH deficiency (GHD) in children is diminished height velocity that eventually leads to short stature. In adult-onset GHD, lean body mass (LBM) is reduced, and visceral fat mass (FM) increased. Beneficial effects of GH treatment on body composition in adults with GHD, including an increase in muscle mass and a decrease in FM, are well established. Relatively few studies have investigated the effects of GH treatment on the body composition of pediatric patients with idiopathic or hypothalamic-pituitary disease-associated GH deficiency. This systematic review aimed to summarize available evidence relating to the effects of GH treatment on body composition in children with GHD.
METHODS
The PubMed, Science Direct, Cochrane Trials, and Embase databases, were searched with keywords including "GH", "body composition", "children", and "growth hormone" for English-language articles, published between January 1999 and March 2021. Two reviewers independently evaluated the search results and identified studies for inclusion based on the following criteria: participants had a confirmed diagnosis of GHD (as defined in each study); participants were pediatric patients who were receiving GH or had stopped GH treatment, regardless of whether they were pre- or post-pubertal; the intervention was recombinant human GH (rhGH; somatropin); and outcomes included changes in body composition during or after stopping GH therapy. Data extracted from each study included study quality, study sample characteristics, study interventions, and body composition. Data on fat-free mass and LBM were combined into a single category of LBM.
RESULTS
Sixteen studies reporting changes in body composition (i.e., FM and LBM) associated with GH treatment in children with GHD were identified and included in the review. Collectively, these studies demonstrated that FM decreased, and LBM increased in response to GH replacement therapy.
CONCLUSION
Despite study limitations (i.e., potential effects of diet and physical activity were not considered), we concluded that a periodic body composition assessment is required to ensure that a satisfactory body composition is achieved during GH replacement therapy in children with GHD.
Topics: Child; Humans; Body Composition; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism
PubMed: 36843617
DOI: 10.3389/fendo.2023.1093691 -
Cephalalgia : An International Journal... Feb 2023To systemically review clinical studies investigating the role of prolactin and its receptors in headache and migraine. (Review)
Review
OBJECTIVE
To systemically review clinical studies investigating the role of prolactin and its receptors in headache and migraine.
BACKGROUND
Migraine prevalence is more common in women compared to men. As prolactin is a crucial regulator of the hypothalamus-pituitary-gonadal axis, prolactin and its receptors might contribute to signaling mechanisms underlying migraine.
METHODS
In this systematic review, we searched PubMed and EMBASE with the terms: prolactin, hyperprolactinemia, macroprolactinemia, hypoprolactinemia, migraine, headache, head pain and trigeminal pain pathway for clinical 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
Nineteen clinical studies met the inclusion criteria and were included in the qualitative and quantitative analysis. The main findings were that serum prolactin levels were found to be higher in individuals with migraine compared to healthy controls, and prolactinomas (prolactin-secreting pituitary adenomas) were correlated with higher incidence of headache in otherwise healthy individuals and migraine attacks in individuals with migraine.
CONCLUSION
Considerable evidence suggests a key role of prolactin and its receptors in migraine pathophysiology. Further randomized and placebo-controlled clinical studies targeting prolactin signaling are needed to further clarify influences of prolactin in migraine attack initiation.
Topics: Male; Humans; Female; Prolactin; Headache; Prolactinoma; Migraine Disorders; Hyperprolactinemia; Pituitary Neoplasms
PubMed: 36718026
DOI: 10.1177/03331024221136286 -
Journal of Pediatric Endocrinology &... Jun 2022Registries are considered valuable data sources for identification of pediatric conditions treated with growth hormone (GH), and their follow-up. Currently, there is no... (Review)
Review
BACKGROUND
Registries are considered valuable data sources for identification of pediatric conditions treated with growth hormone (GH), and their follow-up. Currently, there is no systematic literature review on the scope and characteristics of pediatric GH registries. Therefore, the purpose of this systematic review is to identify worldwide registries reported on pediatric GH treatment and to provide a summary of their main characteristics.
CONTENT
Pediatric GH registries were identified through a systematic literature review. The search was performed on all related literature published up to January 30th, 2021. Basic information on pediatric GH registries, their type and scope, purpose, sources of data, target conditions, reported outcomes, and important variables were analyzed and presented.
SUMMARY
Twenty two articles, reporting on 20 pediatric GH registries, were included in this review. Industrial funding was the most common funding source. The main target conditions included in the pediatric GH registries were: growth hormone deficiency, Turner syndrome, Prader Willi syndrome, small for gestational age, idiopathic short stature, and chronic renal insufficiency. The main objectives in establishing and running pediatric GH registries were assessing the safety and effectiveness of the treatment, describing the epidemiological aspects of target growth conditions and populations, serving public health surveillance, predicting and measuring treatment outcomes, exploring new and useful aspects of GH treatment, and improving the quality of patient care.
OUTLOOK
This systematic review provides a global perspective on pediatric GH registries which can be used as a basis for the design and development of new GH registry systems at both national and international levels.
Topics: Child; Dwarfism, Pituitary; Growth Disorders; Growth Hormone; Human Growth Hormone; Humans; Registries
PubMed: 35567286
DOI: 10.1515/jpem-2022-0045 -
Journal of Assisted Reproduction and... Feb 2022This systematic review aimed to identify baseline patient demographic and controlled ovarian stimulation characteristics associated with a suboptimal response to GnRHa... (Review)
Review
PURPOSE
This systematic review aimed to identify baseline patient demographic and controlled ovarian stimulation characteristics associated with a suboptimal response to GnRHa triggering, and available options for prevention and management of suboptimal response.
METHODS
PubMed, Google Scholar, Medline, and the Cochrane Library were searched for keywords related to GnRHa triggering, and peer-reviewed articles from January 2000 to September 2021 included.
RESULTS
Thirty-seven studies were included in the review. A suboptimal response to GnRHa triggering was more likely following long-term or recent oral contraceptive use and with a low or high body mass index. Low basal serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol serum levels were correlated with suboptimal oocyte yield, as was a low serum LH level on the day of triggering. A prolonged stimulation period and increased gonadotropin requirements were correlated with suboptimal response to triggering. Post-trigger LH < 15 IU/L best correlated with an increased risk for empty follicle syndrome and a lower oocyte retrieval rate. Retriggering with hCG may be considered in patients with suboptimal response according to post-trigger LH, as in cases of failed aspiration.
CONCLUSION
Pre-treatment assessment of patient characteristics, with pre- and post-triggering assessment of clinical and endocrine cycle characteristics, may identify cases at risk for suboptimal response to GnRHa triggering and optimize its utilization.
Topics: Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Oocyte Retrieval; Ovulation Induction
PubMed: 35306603
DOI: 10.1007/s10815-021-02359-y -
Pituitary Feb 2024Isolated adrenocorticotropic hormone deficiency (IAD) is considered to be a rare disease. Due to the nonspecific clinical presentation, precise data on the prevalence... (Review)
Review
Isolated adrenocorticotropic hormone deficiency (IAD) is considered to be a rare disease. Due to the nonspecific clinical presentation, precise data on the prevalence and incidence are lacking. In this systematic review, we aimed to analyse the clinical characteristics, association with autoimmune diseases, and management of acquired idiopathic IAD cases. A structured search was conducted after developing a search strategy combining terms for acquired (idiopathic) IAD. Articles describing an adult case with a diagnosis of ACTH deficiency using dynamic testing, no deficiency of other pituitary axes, and MRI of the brain/pituitary protocolled as normal, were included. Exclusion criteria were cases describing congenital IAD, cases with another aetiology for IAD, and articles where full text was not available. In total 42 articles were included, consisting of 85 cases of acquired idiopathic IAD. Distribution by sex was approximately equal (F:M; 47:38). Lethargy was the most common presenting symptom (38%), followed by weight loss (25%), anorexia (22%), and myalgia/arthralgia (12%). Eight cases (9.5%) presented with an Addison crisis. 31% of cases had an autoimmune disease at diagnosis of which Hashimoto hypothyroidism was the most frequent. Data about follow-up was scarce; dynamic testing was repeated in 4 cases of which 2 showed recovery of the adrenal axis. We report the largest case series of acquired idiopathic IAD to date. Our systematic review highlights the lack of a clear definition and diagnostic work-up. Based on the findings in this review a proposition is made for a flowchart to diagnose acquired idiopathic IAD.
Topics: Adult; Humans; Endocrine System Diseases; Adrenal Insufficiency; Adrenocorticotropic Hormone; Hypoglycemia; Genetic Diseases, Inborn
PubMed: 38151529
DOI: 10.1007/s11102-023-01366-9 -
Clinical Endocrinology Jan 2004The effect of GH replacement on bone mineral density (BMD) in adults with GH deficiency (GHD) is uncertain. We carried out a systematic review of randomized trials that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effect of GH replacement on bone mineral density (BMD) in adults with GH deficiency (GHD) is uncertain. We carried out a systematic review of randomized trials that compared GH to no active treatment, with BMD as an outcome.
METHODS
We searched electronic databases to identify articles, abstracts and conference proceedings to March 2002. We also checked reference lists in included studies and expert reviews. Two reviewers independently extracted the data on study design and change in BMD. The results of individual trials were combined by fixed effects model meta-analysis using weighted mean difference (WMD) of change in BMD at the lumbar spine (our primary outcome) and other sites.
FINDINGS
Eighteen trials that included 700 patients met the inclusion criteria. Maximum follow-up was for 12 weeks (1 trial), 6 months (14 trials), 12 months (1 trial), 18 months (1 trial) and 24 months (1 trial). Reporting quality of both study design and results was poor. Ten trials (458 subjects) were included in the meta-analysis. We excluded those eight trials from which sufficient data could not be extracted. We found a mean change in BMD, at the lumbar spine with GH treatment, of 0.01 g/cm2 after 6 and 12 months, 0.02 g/cm2 after 18 months and 0.03 g/cm2 after 24 months. Statistical significance at the 0.05 level was just achieved at 6 and 12 months but was significant at 18 and 24 months. These changes are small and may be influenced by bias.
CONCLUSION
There is evidence of a small effect of GH replacement on bone mineral density in adults with GH deficiency. The clinical importance of this is uncertain.
Topics: Adult; Bone Density; Databases, Bibliographic; Female; Follow-Up Studies; Fractures, Bone; Growth Hormone; Humans; Lumbar Vertebrae; Male; Randomized Controlled Trials as Topic; Time Factors
PubMed: 14678294
DOI: 10.1111/j.1365-2265.2004.01935.x -
Clinical Endocrinology Sep 2021Many studies have reported that the thyroid-stimulating hormone (TSH) reference interval is susceptible to external factors, such as age, sex, race, region and iodine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many studies have reported that the thyroid-stimulating hormone (TSH) reference interval is susceptible to external factors, such as age, sex, race, region and iodine intake. However, no meta-analysis has comprehensively explored the effect of these factors on the TSH reference interval.
METHODS
Articles published from January 1960 to January 2020 were searched in PubMed, Embase, Cochrane, Scopus, Medline English databases and CNKI, WanFang and CQVIP Chinese databases. In total, 19 studies were ultimately included. All data were analysed using Review Manager 5.3, STATA 16.0 software, GraphPad Prism 8.0 and Microsoft Excel 2010 to draw the TSH concentration curve.
RESULTS
The TSH reference interval was significantly influenced by sex and age. The mean of TSH concentration in females was 0.27 mIU/L higher than that in males. Reference interval of TSH is divided into 20-59 years old and >60 years old age groups in males, and 20-39 years old and >40 years old age groups in females. Regardless of sex, TSH concentrations all increase with age. In iodine-deficient areas, TSH reference intervals were generally lower than those in iodine-sufficient or iodine-excessive areas. The TSH reference interval in Asia and North American countries was generally higher than that in most European countries. In the subgroup analyses of sample size, region and assay methods and manufacturers, the between-group differences were significant.
CONCLUSION
The TSH reference interval was significantly influenced by sex, age, iodine intake, sample size, region, and assay methods and manufacturers, but other factors should not be ignored. Therefore, it is necessary for each laboratory to validate an appropriate TSH reference interval based on local conditions.
Topics: Adult; Databases, Factual; Female; Humans; Iodine; Male; Middle Aged; Nutritional Status; Reference Values; Thyrotropin; Young Adult
PubMed: 33662155
DOI: 10.1111/cen.14454 -
Frontiers in Endocrinology 2023Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer,... (Meta-Analysis)
Meta-Analysis
AIMS
Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer, combined with spironolactone, an antiandrogen medication, may exert complementary effects on PCOS. We therefore performed a meta-analysis of trials in which metformin combined with spironolactone was applied to treat PCOS to evaluate the efficacy and safety of the combination therapy.
METHODS
We retrieved the PubMed, Embase, Scopus, Cochrane Library, CNKI, CBM, Wangfang, and VIP databases for literatures published from their inception to December 16, 2022 on the effects of metformin combined with spironolactone in the treatment of PCOS. Inclusion criteria according to P.I.C.O.S criteria were: PCOS patients, metformin combined with spironolactone interventions, metformin alone control group, and randomized controlled trials with the following outcome data: body mass index (BMI), hirsutism score, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and side effects including nausea, vomiting, diarrhea and drug withdrawal.
RESULTS
Our results revealed that metformin combined with spironolactone significantly reduced BMI and TT, but that it exerted no significant effects on hirsutism score, or on FSH or LH concentrations. Combined treatment also resulted in a significant diminution in FBG and insulin resistance using the HOMA-IR when the interventional time was greater than 6 months. In addition, the combination did not have a higher occurrence of adverse reactions than metformin alone.
CONCLUSION
Compared with metformin alone, metformin combined with spironolactone therapy may be more effective in reducing BMI and serum androgen levels, but the combination showed no significant effect on the hirsutism score or gonadotropin hormone levels, and was not associated with an elevation in side-effects. Moreover, when the treatment course was greater than 6 months, combination therapy reduced FBG and improved insulin resistance more effectively than metformin alone. However, more research is needed to determine the most effective course of treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022355515.
Topics: Female; Humans; Hirsutism; Insulin Resistance; Polycystic Ovary Syndrome; Spironolactone; Drug-Related Side Effects and Adverse Reactions; Follicle Stimulating Hormone, Human; Luteinizing Hormone
PubMed: 37635987
DOI: 10.3389/fendo.2023.1223768