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The Journal of Clinical Endocrinology... Jul 2020
Topics: Breast; Endocrine Disruptors; Gynecomastia; Humans; Lavandula; Male; Puberty, Precocious
PubMed: 32379886
DOI: 10.1210/clinem/dgaa227 -
The Journal of Clinical Endocrinology... Jul 2020
Topics: Breast; Endocrine Disruptors; Gynecomastia; Humans; Lavandula; Male; Puberty, Precocious
PubMed: 32379885
DOI: 10.1210/clinem/dgaa226 -
Journal of Clinical Research in... Nov 2020Premature thelarche (PT) is defined as isolated breast development in girls before eight years of age. Gonadotropin-releasing hormone (GnRH) stimulation test is...
OBJECTIVE
Premature thelarche (PT) is defined as isolated breast development in girls before eight years of age. Gonadotropin-releasing hormone (GnRH) stimulation test is sometimes used to distinguish between PT and central precocious puberty (CPP), although the interpretation of the test at early ages is challenging. The objective of this study was to determine the follicle stimulating hormone (FSH) and luteinizing hormone (LH) responses to GnRH stimulation in girls with PT below 3 years of age.
METHODS
A standardized GnRH stimulation test, bone age and pelvic ultrasound were evaluated and those without pubertal progression after a minimum of one-year follow up were included in the study.
RESULTS
On GnRH stimulation test, the median (range) baseline LH was 0.29 (0.10-0.74) IU/L, baseline FSH was 4.96 (3.18-7.05) mIU/mL, and the peak median LH was 5.75 (3.31-8.58) IU/L with the peak mean±standard deviation FSH was 40.38±20.37 mIU/mL. Among the patients, 33.3% (n=10) had baseline LH >0.3 IU/L, 67% (n=20) had peak LH >5 IU/l and 16.6% (n=5) >10 IU/L. The mean peak LH/FSH ratio was 0.17±0.09 and was ≤0.43 in all participants.
CONCLUSION
Although consensus statements usually define baseline LH >0.3-0.5 IU/L, peak LH >5 IU/L, and LH/FSH ratios >0.66-1.0 as diagnostic cut-offs for CPP, in children below 3 years of age, the baseline and peak LH values may be similar to pubertal values, possibly due to mini-puberty. A dominant FSH response on GnRH stimulation test is more valuable than the peak LH response in the diagnosis of PT.
Topics: Breast; Child, Preschool; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Infant; Luteinizing Hormone; Male; Prognosis; Puberty, Precocious
PubMed: 32349465
DOI: 10.4274/jcrpe.galenos.2020.2019.0202 -
Frontiers in Neurology 2020The pubertal growth suppressive effects of gonadotropin hormone releasing hormone agonists (GnRHa) are well-known, although it remains unclear if long-term GnRHa...
The pubertal growth suppressive effects of gonadotropin hormone releasing hormone agonists (GnRHa) are well-known, although it remains unclear if long-term GnRHa treatment influences the brain function of treated children. The present study investigated the differences in the homotopic resting-state functional connectivity patterns in girls with idiopathic central precocious puberty (ICPP) with and without GnRHa treatment using voxel-mirrored homotopic connectivity (VMHC). Eighteen girls with ICPP who underwent 12 months of GnRHa treatment, 40 treatment-naïve girls with ICPP, and 19 age-matched girls with premature thelarche underwent resting-state functional magnetic resonance imaging using a 3T MRI. VMHC method was performed to explore the differences in the resting-state interhemispheric functional connectivity. The levels of serum pubertal hormones, including luteinizing hormone (LH), follicular-stimulating hormone, and estradiol, were assessed. Correlation analyses among the results of clinical laboratory examinations, neuropsychological scales, and VMHC values of different brain regions were performed with the data of the GnRHa treated group. Significant decreases in VMHC of the lingual, calcarine, superior temporal, and middle frontal gyri were identified in the untreated group, compared with the control group. Medicated patients showed decreased VMHC in the superior temporal gyrus, when compared with the controls. Compared to the unmedicated group, the medicated group showed a significant increase in VMHC in the calcarine and middle occipital gyrus. Moreover, a positive correlation was observed between basal LH levels and VMHC of the middle occipital gyrus in medicated patients. These findings indicate that long-term treatment with GnRHa was associated with increased interhemispheric functional connectivity within several areas responsible for memory and visual process in patients with ICPP. Higher interhemispheric functional connectivity in the middle occipital gyrus was related to higher basal LH production in the girls who underwent treatment. The present study adds to the growing body of research associated with the effects of GnRHa on brain function.
PubMed: 32082242
DOI: 10.3389/fneur.2020.00017 -
Italian Journal of Pediatrics Dec 2019Premature thelarche (PT) is a benevolent ailment affecting young girls. Multiple factors are reported to correlate with this condition, but the mechanisms responsible... (Comparative Study)
Comparative Study
BACKGROUND
Premature thelarche (PT) is a benevolent ailment affecting young girls. Multiple factors are reported to correlate with this condition, but the mechanisms responsible for the onset of PT have not yet been fully investigated. This study aimed to evaluate the relationship of nutrient intake, insulin resistance and lipid profile with PT.
METHODS
Two hundred sixty-three girls with PT, and 222 healthy girls of similar age were enrolled into this study. Their demographics, Tanner stage of breast development, nutrient intake, insulin resistance and lipid profiles were compared.
RESULTS
Daily protein and fat intakes, insulin resistance parameters including serum insulin-like growth factor 1, fasting glucose to insulin ratio, quantitative insulin check index and homeostasis model of assessment of insulin resistance, as well as serum levels of triacylglycerol, total cholesterol and low-density lipoprotein, were all significantly altered in PT patients. Daily intake of energy and carbohydrate, and serum level of high-density lipoprotein protein were statistically indistinguishable between PT patients and healthy controls.
CONCLUSION
Chinese girls with PT are potentially insulin resistant, which warrants more clinical attention and further investigation to address the underlying etiology.
Topics: Age Factors; Blood Glucose; Case-Control Studies; Child; China; Energy Intake; Female; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Nutrients; Puberty, Precocious; Reference Values; Risk Assessment; Statistics, Nonparametric
PubMed: 31856872
DOI: 10.1186/s13052-019-0758-z -
Physiological Research Feb 2020This study aims to investigate serum makorin ring finger protein 3 (MKRN3) levels in girls with idiopathic central precocious puberty (ICPP) and premature thelarche...
This study aims to investigate serum makorin ring finger protein 3 (MKRN3) levels in girls with idiopathic central precocious puberty (ICPP) and premature thelarche (PT), in order to determine whether circulating MKRN3 level is associated with ICPP and PT. A total of 90 girls were enrolled in the stud. 30 age-matched girls were allocated for each group (ICPP, PT and healthy controls [HC], respectively). The base LH (B-LH) and E2 levels were higher in ICPP girls than those in HC and PT girls. The peak LH (P-LH) levels and P-LH/P-FSH values were obviously higher in ICPP girls than those in PT girls, while higher peak FSH (P-FSH) levels were detected in PT girls when compared to those in ICPP girls. Kisspeptin levels were lower in HC girls than those in ICPP and PT girls. MKRN3 levels were the highest in HC girls among the three groups. There were relatively strong negative correlations among MKRN3, kisspeptin and P-LH/P-FSH. Circulating MKRN3 can have an important role in the onset of ICPP and PT. However, this should not be used as an independent diagnostic criterion for diagnosing ICPP or differentiating ICPP from PT, but should be used only as an adjunctive diagnostic biomarker.
Topics: Asian People; Breast; Case-Control Studies; Child; Female; Humans; Puberty, Precocious; Ubiquitin-Protein Ligases
PubMed: 31852205
DOI: 10.33549/physiolres.934222 -
Annals of Pediatric Endocrinology &... Sep 2019Precocious puberty refers to the development of secondary sex characteristics before ages 8 and 9 years in girls and boys, respectively. Central precocious puberty (CPP)...
PURPOSE
Precocious puberty refers to the development of secondary sex characteristics before ages 8 and 9 years in girls and boys, respectively. Central precocious puberty (CPP) is caused by premature activation of the hypothalamus-pituitary-gonadal (HPG) axis and causes thelarche in girls before the age of 8. A gonadotropin-releasing hormone (GnRH) stimulation test is the standard diagnostic modality for diagnosing CPP. However, the test cannot always be used for screening because it is expensive and time-consuming. This study aimed to find alternative reliable screening parameters to identify HPG axis activation in girls <8 years old (CPP) and for girls 8-9 years old (early puberty, EP).
METHODS
From January 2013 to June 2015, medical records from 196 girls younger than 9 years old with onset of breast development were reviewed, including 126 girls who had a bone age (BA) 1 year above their chronological age. All patients underwent a GnRH stimulation test, and 117 underwent pelvic sonography. The girls were divided into 4 groups based on age and whether the GnRH stimulation test showed evidence of central puberty. Subanalyses were also conducted within each group based on peak luteinizing hormone (LH) level quartiles.
RESULTS
Basal serum LH level was the most sensitive marker for screening CPP and EP. The cutoff values were 0.245 IU/L for CPP under 8 years old (P=0.049, area under the curve [AUC]=0.764, 88% sensitivity, 48% specificity) and 0.275 IU/L for EP between 8-9 years old (P=0.005, AUC=0.813, 79% sensitivity, 77% specificity). Peak LH level decreased as BMI z-score among subgroups increased when there was no difference in BA; however, higher BA eliminated this effect.
CONCLUSION
Basal serum LH level is a useful screening parameter for diagnosing CPP and EP in girls. Peak LH levels were lower with increasing BMI z-score, although older BA eliminated this effect.
PubMed: 31607109
DOI: 10.6065/apem.2019.24.3.164 -
The Journal of Clinical Endocrinology... Nov 2019Previous case reports associated prepubertal gynecomastia with lavender-containing fragrances, but there appear to be no reports of premature thelarche.
CONTEXT
Previous case reports associated prepubertal gynecomastia with lavender-containing fragrances, but there appear to be no reports of premature thelarche.
OBJECTIVE
To add to a case series about lavender-fragranced product use and breast growth in children and to measure endocrine-disrupting chemical activity of essential oil components.
DESIGN, SETTING, AND PATIENTS
Patients experiencing premature thelarche or prepubertal gynecomastia with continuous exposure to lavender-fragranced products were evaluated in the pediatric endocrinology departments of two institutions. Mechanistic in vitro experiments using eight components of lavender and other essential oils were performed at National Institute of Environmental Health Sciences.
MAIN OUTCOME MEASURES
Case reports and in vitro estrogen and androgen receptor gene expression activities in human cell lines with essential oils.
RESULTS
Three prepubertal girls and one boy with clinical evidence of estrogenic action and a history of continuous exposure to lavender-containing fragrances were studied. Breast growth dissipated in all patients with discontinuation of the fragranced products. Some of the components tested elicited estrogenic and antiandrogenic properties of varying degrees.
CONCLUSION
We report cases of premature thelarche that resolved upon cessation of lavender-containing fragrance exposure commonly used in Hispanic communities. The precise developmental basis for such conditions could be multifactorial. In vitro demonstration of estrogenic and antiandrogenic properties of essential oil components suggests essential oils in these cases could be considered a possible source and supports a possible link with idiopathic prepubertal breast development. Whether the level of lavender oil estrogenic potency is sufficient to cause these effects is unknown.
Topics: Breast; Cell Line, Tumor; Child; Child, Preschool; Endocrine Disruptors; Estrogen Receptor alpha; Female; Gynecomastia; Humans; Lavandula; Male; Nuclear Receptor Coactivator 2; Oils, Volatile; Plant Oils; Puberty, Precocious; Receptors, Androgen
PubMed: 31393563
DOI: 10.1210/jc.2018-01880 -
Journal of Pediatric Endocrinology &... Jun 2019Background Delayed puberty and hypogonadism are common in children with chronic kidney disease and in renal transplant recipients, but precocious puberty has rarely been...
Background Delayed puberty and hypogonadism are common in children with chronic kidney disease and in renal transplant recipients, but precocious puberty has rarely been reported in these populations. We describe six girls with precocious and/or early-onset, rapidly progressive puberty before and following renal transplantation. Methods Of 112 children under the age of 18 years (67 boys, 45 girls) who received renal transplants between 2010 and 2018, six girls presented with precocious or rapidly progressive early puberty at ages 6-7/12, 7-2/12, 7-4/12, 8, 8-8/12 and 8-11/12 years. Clinical evaluation included measurements of height, weight, body mass index (BMI), Tanner staging and bone age assessment. Gonadotropin responses to intravenous gonadotropin releasing hormone (GnRH) or intramuscular triptorelin acetate were determined. Results Tanner breast stage 3 was noted at 2-6 years following renal transplantation in five girls, four with preserved kidney function. One girl began puberty before renal transplantation. Peak luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels were 6.5, 20.2, 7.83, 19.1, 9 and 2.2 mIU/mL and 13, 8.3, 8.01, 7.5, 8.1 and 7.7 mIU/mL, respectively. Treatment with an intramuscular slow-release formulation of triptorelin acetate every 4 weeks slowed progression of breast development. Conclusions Although delayed puberty is more common in children with renal disease, precocious puberty can also be seen. Evaluation of growth and puberty by a pediatric endocrinologist should be part of the routine care for all children following kidney transplantation.
Topics: Biomarkers; Body Height; Body Weight; Child; Estradiol; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Luteinizing Hormone; Postoperative Complications; Prognosis; Puberty, Precocious; Sexual Maturation
PubMed: 31141486
DOI: 10.1515/jpem-2019-0050 -
Frontiers in Pediatrics 2019Puberty is a sensitive period of life characterized by the appearance of secondary sex characteristics which leads to a complete sexual maturation. It physiologically... (Review)
Review
Puberty is a sensitive period of life characterized by the appearance of secondary sex characteristics which leads to a complete sexual maturation. It physiologically starts between the age of 8 and 13 years in girls and 9 and 14 years in boys. In the last two decades, several studies have showed that start of puberty has moved up to younger ages by 12-18 months, and some of the hypotheses trying to explain this change include the role of nutritional status and obesity and the influence of extrinsic factors such as exposure to endocrine-disrupting chemicals (EDCs), as well. The hypothalamic-hypophysis-gonadal axis develops during embryogenesis, and except for a period of activation immediately after birth, remains suppressed until the onset of pubertal development. At the beginning of puberty, the pulse generator is reactivated, probably due to progressive stimulatory influences on GnRH neurons from glial signals and neurotrasmitters. Kisspeptin and its receptor play a fundamental role in this phase. Premature Pubarche/Adrenarche, Premature Thelarche, and Premature Menarche are incomplete forms of precocious pubertal development that have their origin in endocrine mechanisms that only recently have started to be understood. It is important to distinguish these forms from the complete ones in order to reassure patients and parents about the non-evolution of pubertal progression and avoid non-useful treatments with analogous LHRH.
PubMed: 31139600
DOI: 10.3389/fped.2019.00147