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International Journal of Obesity (2005) Aug 2013Obesity has complex multifactorial aetiology. It has been suggested by many, but not all, reports that earlier pubertal maturation may increase adult obesity risk. We... (Meta-Analysis)
Meta-Analysis Review
Obesity has complex multifactorial aetiology. It has been suggested by many, but not all, reports that earlier pubertal maturation may increase adult obesity risk. We conducted a systemic review and meta-analysis in both women and men, and hypothesised that any association between pubertal timing and adult obesity is likely to be confounded by childhood adiposity. In addition, we investigated whether pubertal timing is related to other cardiometabolic risk and long-term cardiovascular morbidity/mortality. Literature search was undertaken using MEDLINE, EMBASE, Web of Knowledge and TRIP databases, with a hand search of references. Both authors independently reviewed and extracted pre-defined data from all selected papers. Meta-analyses were conducted using Review Manager (RevMan) 5.0.24. A total of 48 papers were identified. Out of 34 studies, 30 reported an inverse relationship between pubertal timing and adult body mass index (BMI), the main adiposity measure used. Meta-analysis of 10 cohorts showed association between early menarche (menarche <12 vs ≥12 years) and increased adult BMI, with a standardised mean difference of 0.34 kg m(-2) (95% confidence interval: 0.33-0.34). Heterogeneity was large (I(2)=92%) but reduced significantly when grouped by outcome age. Late menarche (menarche ≥15 vs <15 years) was associated with decreased adult BMI, with a standardised mean difference of -0.26 kg m(-2) (95% confidence interval: -0.36, -0.21) (seven cohorts). Only eight papers included data on childhood BMI; the majority reported that childhood BMI only partially attenuated association between early menarche and later obesity. Although not suitable for meta-analysis, data on cardiometabolic risk factors and puberty suggested negative association between earlier pubertal timing and cardiovascular mortality, hypertension, metabolic syndrome (MetS) and abnormal glycaemia. Earlier pubertal timing is predictive of higher adult BMI and greater risk of obesity. This effect appears to be partially independent of childhood BMI. Earlier pubertal development appears to also be inversely correlated with risk of other cardiometabolic risk factors and cardiovascular mortality. Further work is needed to examine potential mechanisms and the level at which interventions may be targeted.
Topics: Adiposity; Adolescent; Age of Onset; Body Mass Index; Cardiovascular Diseases; Child; Female; Humans; Male; Obesity; Puberty, Precocious; Risk Factors; Sexual Maturation; Time Factors
PubMed: 23164700
DOI: 10.1038/ijo.2012.177 -
Frontiers in Endocrinology 2024Central precocious puberty (CPP) is a common endocrine disorder in children, and its diagnosis primarily relies on the gonadotropin-releasing hormone (GnRH) stimulation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Central precocious puberty (CPP) is a common endocrine disorder in children, and its diagnosis primarily relies on the gonadotropin-releasing hormone (GnRH) stimulation test, which is expensive and time-consuming. With the widespread application of artificial intelligence in medicine, some studies have utilized clinical, hormonal (laboratory) and imaging data-based machine learning (ML) models to identify CPP. However, the results of these studies varied widely and were challenging to directly compare, mainly due to diverse ML methods. Therefore, the diagnostic value of clinical, hormonal (laboratory) and imaging data-based ML models for CPP remains elusive. The aim of this study was to investigate the diagnostic value of ML models based on clinical, hormonal (laboratory) and imaging data for CPP through a meta-analysis of existing studies.
METHODS
We conducted a comprehensive search for relevant English articles on clinical, hormonal (laboratory) and imaging data-based ML models for diagnosing CPP, covering the period from the database creation date to December 2023. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), summary receiver operating characteristic (SROC) curve, and area under the curve (AUC) were calculated to assess the diagnostic value of clinical, hormonal (laboratory) and imaging data-based ML models for diagnosing CPP. The I test was employed to evaluate heterogeneity, and the source of heterogeneity was investigated through meta-regression analysis. Publication bias was assessed using the Deeks funnel plot asymmetry test.
RESULTS
Six studies met the eligibility criteria. The pooled sensitivity and specificity were 0.82 (95% confidence interval (CI) 0.62-0.93) and 0.85 (95% CI 0.80-0.90), respectively. The LR+ was 6.00, and the LR- was 0.21, indicating that clinical, hormonal (laboratory) and imaging data-based ML models exhibited an excellent ability to confirm or exclude CPP. Additionally, the SROC curve showed that the AUC of the clinical, hormonal (laboratory) and imaging data-based ML models in the diagnosis of CPP was 0.90 (95% CI 0.87-0.92), demonstrating good diagnostic value for CPP.
CONCLUSION
Based on the outcomes of our meta-analysis, clinical and imaging data-based ML models are excellent diagnostic tools with high sensitivity, specificity, and AUC in the diagnosis of CPP. Despite the geographical limitations of the study findings, future research endeavors will strive to address these issues to enhance their applicability and reliability, providing more precise guidance for the differentiation and treatment of CPP.
Topics: Child; Humans; Artificial Intelligence; Machine Learning; Puberty, Precocious; Reproducibility of Results; Sensitivity and Specificity
PubMed: 38590824
DOI: 10.3389/fendo.2024.1353023 -
Developmental Medicine and Child... Dec 2019To evaluate neuropsychiatric comorbidities in children and adolescents with hypothalamic hamartoma.
AIM
To evaluate neuropsychiatric comorbidities in children and adolescents with hypothalamic hamartoma.
METHOD
We retrospectively analysed case notes for all individuals with hypothalamic hamartoma referred to Great Ormond Street Hospital, London, between 2000 and 2016. In addition, a systematic review aiming to identify all previous paediatric case series was performed. Psychiatric symptoms, demographics, physical comorbidities, and cognitive functioning were recorded for all cases where possible. Analyses were performed to determine which factors were associated with psychopathology and potential mechanisms investigated.
RESULTS
Forty-six cases were included in the case series (28 males, 18 females; mean age at assessment 11y 8mo [1y 11mo-16y 11mo, SD 4y 0mo]). Twenty-nine papers representing data from 264 cases met inclusion criteria for the systematic review. Overall, at least 50% of cases presented with psychopathology. Epilepsy, intellectual disability, and male sex were associated with externalizing disorders (attention-deficit/hyperactivity disorder, conduct and oppositional defiance disorders, and rage attacks). Intellectual disability mediated the effects of epilepsy on externalizing psychopathology. No factors were associated with internalizing disorders (anxiety and depressive disorders), although these were not well reported.
INTERPRETATION
Psychiatric comorbidities are highly prevalent in the presentation of paediatric hypothalamic hamartoma. The aetiology of psychopathology comprises a range of interacting biological and psychosocial factors with particular influence from epilepsy. Further research is required to achieve an evidence base for treatment.
WHAT THIS PAPER ADDS
Over half of children with hypothalamic hamartoma present with psychiatric comorbidity. Externalizing and internalizing disorders are present in approximately 60% and 30% of children with hypothalamic hamartomas respectively. Epilepsy and male sex are associated with externalizing psychopathology. Intellectual disability mediates the association between epilepsy and externalizing symptoms. No clear associations are evident for internalizing disorders or precocious puberty.
Topics: Adolescent; Child; Child, Preschool; Comorbidity; Epilepsy; Female; Hamartoma; Humans; Hypothalamic Diseases; Infant; Male; Mental Disorders; Sex Factors
PubMed: 30977116
DOI: 10.1111/dmcn.14241 -
Endocrine Jul 2023The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to...
PURPOSE
The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to elucidate challenges and intricacies in its diagnosis and management.
METHODS
It was a single centre study carried out in individuals with MAS and autonomous GH secretion (AGHS). In addition, a systematic search of literature across three databases (PubMed, Scopus and EMBASE) was performed from inception until May 31, 2021 to identify cases of MAS with AGHS in the pediatric age group (<18 years).
RESULTS
Three cases from authors centre and 42 cases identified from systematic literature review were analysed. Precocious puberty was the most common presenting endocrinopathy seen in 56.8% (25/44) cases, followed by hyperthyroidism (10/45), hypophosphatemia (4/45), and hypercortisolism (2/45). Cranio-facial fibrous dysplasia (CFFD) was seen in all while polyostotic fibrous dysplasia and Café au lait macule was seen in 40/45 (88.9%) and 35/45 (77.8%), respectively. Pituitary adenoma (58.3% microadenoma) was localized in 53.3% (24/45) cases on pituitary imaging. Biochemical and clinical remission of AGHS was achieved in 61.5% (24/45) cases with medical therapy.
CONCLUSION
Diagnosing AGHS in MAS is challenging because of concomitant presence of CFFD, non-GH endocrinopathies associated height spurt and elevated serum IGF-1. GH-GTT should be performed in presence of elevated growth velocity and serum IGF-1 (>1 X ULN) despite adequate control of non-GH endocrinopathies. Medical management can lead to disease control in substantial number of cases and often entails use of multiple agents.
Topics: Child; Humans; Adenoma; Fibrous Dysplasia, Polyostotic; Growth Hormone; Insulin-Like Growth Factor I; Pituitary Neoplasms
PubMed: 36877453
DOI: 10.1007/s12020-023-03333-7 -
Journal of Child Neurology Jul 2013The main objective was to review the evidence for management of epilepsy associated with hypothalamic hamartomas. We performed a systemic review of the literature... (Review)
Review
The main objective was to review the evidence for management of epilepsy associated with hypothalamic hamartomas. We performed a systemic review of the literature through July 2012 that studied patients with hypothalamic hamartomas and related epilepsy. Articles meeting selection criteria were rated according to the American Academy of Neurology classification of evidence scheme. Recommendations were linked to the strength of the evidence and as follows: (a) precocious puberty is associated more with the pedunculated type and epilepsy typified by gelastic seizures with the sessile form of hypothalamic hamartomas (class III); (b) significant behavioral and cognitive deficits are associated with patients with hypothalamic hamartomas (class III); (c) video electroencephalography (EEG) findings are extremely variable particularly across the different ages and do not affect surgical outcome (class III); d) various surgical techniques (transcallosal and endoscopic resection) resulted in 49% to 54% seizure freedom, 15% with a pterional approach as well as about 40% with radiosurgery (class III).
Topics: Electroencephalography; Epilepsy; Evidence-Based Medicine; Hamartoma; Humans; Hypothalamic Diseases; Video Recording
PubMed: 23670254
DOI: 10.1177/0883073813488673 -
Acta Neurochirurgica. Supplement 2012Endoscopic third ventriculostomy (ETV) is an established treatment for hydrocephalus. Most studies focus on success rates, and complications are insufficiently charted.... (Review)
Review
INTRODUCTION
Endoscopic third ventriculostomy (ETV) is an established treatment for hydrocephalus. Most studies focus on success rates, and complications are insufficiently charted. The aim of this study was to perform a systematic review of ETV complications.
METHODS
A Medline search discovered 24 series of ETV (seven in children, five in adults, and 12 in a mixed-age group) with detailed complications reports.
RESULTS
The analysis included 2,672 ETVs performed on 2,617 patients. The cause of hydrocephalus was aqueductal stenosis in 25.9%, tumor 37.0%, meningomyelocele-Chiari II 6.1%, posthemorrhagic 5.8%, postinfectious 1.4%, cysts 3.3%, Chiari I 0.4%, Dandy-Walker malformation 0.3%, cerebellar infarct 0.9%, normal pressure hydrocephalus 1.3%, and not recorded 16.8%. Overall complication rate was 8.8%. Permanent morbidity was 2.1%, neurologic in 1.2% (hemiparesis, gaze palsy, memory disorders, and/or altered consciousness), hypothalamic in 0.9% (diabetes insipidus, weight gain, or precocious puberty). Intraoperative hemorrhage was present in 3.9%, severe in 0.6% (including four cases [0.14%] of basilar rupture). Other surgical complications were 1.13% (three thalamic infarcts, six subdural, six intracerebral, and two epidural hematomas). Cerebrospinal fluid (CSF) infections occurred in 1.8%, CSF leak in 1.7%, anesthetic complications (bradycardia and hypotension) in 0.19% of cases. Postoperative mortality was 0.22% (six patients; sepsis two, hemorrhage three, and thalamic injury one). Another two children suffered delayed "sudden death" (after 25 and 60 months), caused by acute hydrocephalus due to stoma occlusion. There were no differences between pediatric and adult patients or short and long series (cutoff 100 patients). All deaths were reported in long series. Complication rates were insignificantly higher in short series.
CONCLUSIONS
Permanent morbidity after ETV is 2.1%, mortality is 0.22%. The incidence of delayed "sudden death" is 0.07%.
Topics: Humans; Hydrocephalus; Postoperative Complications; Third Ventricle; Ventriculostomy
PubMed: 22116442
DOI: 10.1007/978-3-7091-0923-6_30 -
Frontiers in Endocrinology 2022The average age at thelarche has trended downwards worldwide since 1970s; however, the onset age of "precocious puberty", defined as the lower percentiles of thelarche...
BACKGROUND
The average age at thelarche has trended downwards worldwide since 1970s; however, the onset age of "precocious puberty", defined as the lower percentiles of thelarche age, has been rarely reported. This systematic review aims to evaluate secular trends in age at thelarche among Chinese girls.
METHODS
This systematic review on the age at thelarche during puberty among Chinese girls was conducted systematic search of both Chinese (Chinese National Knowledge Infrastructure, WanFang Database, and the Chinese Scientific Journals Database) and English (PubMed, Cochrane Library, and Embase) databases. Data were analyzed using the GraphPad Prism v9.0.
RESULTS
A total of 16 studies involving 177,886 Chinese girls were synthesized. The QualSyst scores of these studies were high at an average of 21.25. The timing of Tanner breast stage 2 (B2) occurred earlier over time at the P, P, and median ages. Weighted analyses revealed that the overall onset age of B2 tended to be younger at P, P, and P. The age of B2 varied across regions and areas. For example, P, P, and median age of B2 in years were younger in southern regions than that in northern regions of China (P: 5.94 . 7.3; P: 6.6 . 7.9; median age: 8.26 . 9.5), and median age of B2 in urban areas (8.26 years) was earlier than that in rural areas (10.29 years). In addition, median age of B2 from 12 single-center studies was earlier than that from 4 multicenter studies (8.26 . 9.18 years).
CONCLUSIONS
The current findings indicated that pubertal breast development age among Chinese girls presented an advanced trend over the past 20 years, which urges the necessity to revisit and redefine "precocious puberty" and provides useful recommendations for clinical practice.
Topics: Female; Humans; Child, Preschool; Child; Young Adult; Adult; East Asian People; Puberty; Puberty, Precocious; Breast; China
PubMed: 36506059
DOI: 10.3389/fendo.2022.1042122 -
Systematic review of ghrelin response to food intake in pediatric age, from neonates to adolescents.The Journal of Clinical Endocrinology... May 2014Food intake and energy balance are regulated during the lifespan with critical changes in each specific period (infancy, adulthood, aging). Some of ghrelin's changes may... (Review)
Review
OBJECTIVE
Food intake and energy balance are regulated during the lifespan with critical changes in each specific period (infancy, adulthood, aging). Some of ghrelin's changes may contribute to the regulation of food intake and weight in children. We aimed to analyze the ghrelin response to feeding in lean or obese subjects from birth to adolescence.
METHODS
We searched PubMed, Scopus, Google Scholar, Cochrane, and EMBASE (December 1999 to February 2013) and identified 62 relevant articles, of which 29 were suitable to be included.
RESULTS AND CONCLUSIONS
Total ghrelin response to meals is particular, with refractoriness in neonates and lean children and an inhibition that starts from puberty. Total ghrelin levels are decreased after meals, irrespective of pubertal stages in obese children and adolescents. Conversely, total ghrelin is decreased after an oral glucose tolerance test in all ages, with the exception of neonates. Data on unacylated ghrelin response are scant but resemble those of total ghrelin. The acylated ghrelin response to meals or oral glucose tolerance test is discordant, although a precocious inhibition followed by a rise back is present in both lean and obese children. The post-feeding profile in children with Prader-Willi syndrome is also peculiar, with a conserved and deeper inhibition of all ghrelin forms.
Topics: Adolescent; Body Weight; Child; Child, Preschool; Eating; Ghrelin; Humans; Obesity; Postprandial Period
PubMed: 24601727
DOI: 10.1210/jc.2013-4010 -
The Lancet. Oncology Aug 2007Suspicion of a CNS tumour is classically raised by symptoms of raised intracranial pressure, focal deficits (including seizures), or papilloedema. Development of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Suspicion of a CNS tumour is classically raised by symptoms of raised intracranial pressure, focal deficits (including seizures), or papilloedema. Development of guidelines is needed for the identification and referral of children who might have a CNS tumour. We did a systematic literature review and meta-analysis to identify the clinical presentation of childhood CNS tumours to provide evidence to support the development of guidelines to assist with the identification and referral for imaging of children who might have a central nervous system tumour.
METHODS
Medline, Embase, and PubMed were searched for cohort studies and case series in children, published between January, 1991, and August, 2005, detailing the symptoms and signs at diagnosis of a CNS tumour.
FINDINGS
74 papers (n=4171) met the inclusion criteria. 56 symptoms and signs at diagnosis were identified, ranked by frequency, and clustered according to age, anatomical criteria, and genetic criteria. The most frequent symptoms and signs at diagnosis were: headache (33%), nausea and vomiting (32%), abnormalities of gait and coordination (27%), and papilloedema (13%) for intracranial tumours; macrocephaly (41%), nausea and vomiting (30%), irritability (24%), and lethargy (21%) for children aged under 4 years with intracranial tumours; reduced visual acuity (41%), exophthalmia (16%), and optic atrophy (15%) for children with an intracranial tumour and neurofibromatosis; nausea and vomiting (75%), headache (67%), abnormal gait and coordination (60%), and papilloedema (34%) for posterior fossa tumours; unspecified symptoms and signs of raised intracranial pressure (47%), seizures (38%), and papilloedema (21%) for supratentorial tumours; headache (49%), abnormal eye movements (21%), squint (21%), and nausea and vomiting (19%) for central brain tumours; abnormal gait and coordination (78%), cranial nerve palsies (52%), pyramidal signs (33%), headache (23%), and squint (19%) for brainstem tumours; and back pain (67%), abnormalities of gait and coordination (42%), spinal deformity (39%), focal weakness (21%), and sphincter disturbance (20%) for spinal-cord tumours. Other features noted were weight loss, growth failure, and precocious puberty. Symptoms of raised intracranial pressure were absent in more than half of children with brain tumours. Other neurological features were heterogeneous and related to tumour location.
INTERPRETATION
Apart from raised intracranial pressure, motor and visual system abnormalities, weight loss, macrocephaly, growth failure, and precocious puberty also suggest presence of an intracranial tumour. Children with signs and symptoms that could result from a CNS tumour need a thorough visual and motor system examination and an assessment of growth and pubertal status. Occurrence of multiple symptoms and signs should alert clinicians to possible CNS tumours.
Topics: Central Nervous System Neoplasms; Child; Child Behavior Disorders; Headache; Humans; Neuropsychological Tests; Unconsciousness; Vision Disorders; Vomiting
PubMed: 17644483
DOI: 10.1016/S1470-2045(07)70207-3 -
Pituitary Oct 2021POU1F1 mutations are prevalent in Indian CPHD cohorts. Genotype-phenotype correlation is not well-studied.
CONTEXT
POU1F1 mutations are prevalent in Indian CPHD cohorts. Genotype-phenotype correlation is not well-studied.
AIM
To describe phenotypic and genotypic spectrum of POU1F1 mutations in our CPHD cohort and present systematic review as well as genotype-phenotype analysis of all mutation-positive cases reported in world literature.
METHODS
Retrospective study of POU1F1 mutation-positive patients from a western-Indian center. PRISMA guidelines based pubmed search of published literature of all mutation-positive patients.
RESULTS
Our cohort had 15 POU1F1 mutation-positive patients (9 index, 6 relatives). All had severe GH, TSH and prolactin deficiencies (GHD, TSHD and PD). TSHD was diagnosed earliest followed by GHD (median ages: TSHD-6 months, GHD-3 years), while PD was more variable. Two sisters had central precocious puberty at 7 years of age. Pubic hair was deficient in all post-pubertal patients (females: P1-P2, males: P3-P4). Splice-site/intronic/frameshift mutations were most common, while missense/nonsense mutations were less frequent (33%). Review of world literature yielded 114 patients (82 index patients) from 58 studies. GHD was present in all patients. TSHD was spared in 12.5% and PD in 4.4% patients. Missense/nonsense mutations accounted for 75% of spectrum. Phenotype-genotype analysis revealed higher mean peak-GH levels (1.1 vs 0.2 ng/ml, p = 0.008) and lower prevalence of anterior-pituitary hypoplasia (63.6% vs 86.3%, p = 0.03) in patients with heterozygous than homozygous and compound heterozygous mutations.
CONCLUSIONS
We present largest series of POU1F1 mutation-positive patients. Precocious puberty and defective pubarche are lesser-appreciated phenotypic features. Our mutation spectrum is different from that of world literature. Patients with heterozygous mutations have milder phenotype.
Topics: Female; Humans; Hypopituitarism; Male; Mutation; Retrospective Studies; Transcription Factor Pit-1; Transcription Factors
PubMed: 33742319
DOI: 10.1007/s11102-021-01140-9