Brain MRI in girls with central precocious puberty: a time for new approaches

2021 ◽  
Author(s):  
Ana Pinheiro Machado Canton ◽  
Ana Claudia Latronico
Keyword(s):  
Precocious Puberty ◽  
Brain Mri ◽  
Central Precocious Puberty ◽  
New Approaches

scholarly journals SUN-725 Clinical and Genetic Features of Families with Maternally Inherited Central Precocious Puberty

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Flávia Rezende Tinano ◽  
Ana Pinheiro Machado Canton ◽  
Luciana Ribeiro Montenegro ◽  
Andrea de Castro Leal ◽  
Carolina Ramos ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Association Studies ◽  
Brain Mri ◽  
Family Members ◽  
Central Precocious Puberty ◽  
Breast Development ◽  
Female Group ◽  
Genome Wide Association Studies ◽  
Abnormal Gait ◽  
Genetic Features

Abstract Context: The clinical recognition of familial central precocious puberty (CPP) has significantly increased in the last years. This fact can be related to the recent descriptions of genetic causes associated with this pediatric condition, such as loss-of-function mutations of two imprinted genes (MKRN3 and DLK1). Inherited defects in both genes cause paternally inherited CPP. However, no genetic abnormality has been described in families with maternally inherited CPP so far. Objectives: To characterize the clinical and genetic features of several families with maternally inherited CPP. Setting and Participants: We analyzed clinical and genetic features of children with familial CPP. No brain MRI alterations were detected in the selected patients with CPP. MKRN3 and DLK1 pathogenic mutations were excluded. Whole-exome sequencing was performed in selected cases. Results: We studied 177 children from 141 families with familial CPP. Paternal inheritance was evidenced in 44 families (31%), whereas 58 (41%) had maternally inheritance. Indeterminate inheritance was detected in the remaining families. Maternally inherited CPP affected mainly female patients (69 girls and two boys). Thelarche occurred at mean age of 6.1 ± 1.9 years in this female group. Most of girls had Tanner 3 (41%) and Tanner 4 (35%) breast development at first evaluation. One boy had additional syndromic features (macrosomia, autism, bilateral eyelid ptosis, high arcade palate, irregular teeth and abnormal gait). The pedigree analysis of patients with maternally inherited CPP revealed the following affected family members: 42 mothers, 10 grandmothers, 11 sisters, 12 aunts, and 11 female cousins. Most of the families (41) had two affected consecutive generations, while eight families had three affected generations. No consanguinity was referred. Ongoing molecular analysis revealed two rare heterozygous variants in the boy with syndromic CPP and three affected family members with precocious menarche (mother, maternally half-sister, and maternally aunt): a frameshift deletion (p.F144fs) in MKKS; and a missense variant (p.P267L) in UGT2B4, which encodes a protein involved in estrogen hydroxylation and it was related to menarche timing in genome-wide association studies. Conclusions: Maternally inherited CPP was diagnosed mainly in girls, who had thelarche at mean age of 6 years old. Dominant pattern of inheritance was more prevalent, with direct maternal transmission in 72% of the studied families. New candidate genes might be implicated with maternally inherited CPP.

scholarly journals Coexistence of central precocious puberty and intraventricular arachnoid cyst: a brief literature update

2020 ◽  
Vol 3 (1) ◽  
pp. 65-70
Author(s):  
Gonzalo Oliván-Gonzalvo ◽  
◽  
Vicente Calatayud-Maldonado ◽  
Keyword(s):  
Arachnoid Cyst ◽  
Precocious Puberty ◽  
Pubertal Development ◽  
Brain Mri ◽  
Central Precocious Puberty ◽  
Mass Effect ◽  
Ventricular Volume ◽  
Gnrh Analog ◽  
Hypothalamic Pituitary Axis ◽  
Velum Interpositum

Central precocious puberty (CPP) is a rare disease. The mean annual incidence in girls is 0.8-1.1/100,000 and in boys 0-0.1/100,000. Intracranial arachnoid cysts (ICACs) are usually congenital and represent 1% of intracranial masses in newborns. Intraventricular location is rare. The objective of this work is to carry out a literature updated review of the coexistence of CPP and intraventricular arachnoid cyst (IVAC). ICACs are usually asymptomatic but can present with CPP in 10-40% of patients. IVACs represents only 0.3-1.4% of ICACs, and most seemed originate from the velum interpositum cistern. CPP in girls is usually idiopathic, while in 30-70% of boys are due to an intracranial lesion. Therefore, the coexistence of PPC and IVAC is very rare in boys and exceptional in girls. The exact mechanism of a cyst´s influence on the hypothalamic-pituitary axis is not completely understood. Theories include increased ventricular volume, associated mass effect on the hypothalamus, and direct compression of portions of the hypothalamic-pituitary axis. Analysis of LH peaks after GnRH testing is the gold standard for the diagnosis of CPP. Brain MRI should be part of the assessment in boys and also in girls since clinical features, including age and sex, are not helpful in predicting those with underlying brain pathology. In cases of CPP with IVAC, surgery does not have any effect on the course of pubertal development. The indication for surgery is the onset of neurological symptoms. The medical treatment selected, safe and effective, is GnRH analog depot preparations. In conclusion, there seems to be a consensus for the diagnosis and management of the coexistence of CPP and IVAC, but the etiopathogenesis is not yet well recognized.

scholarly journals SUN-081 High Throughput Genetic Analysis Revealed Novel Genomic Loci and Candidate Genes Involved in Central Precocious Puberty Associated with Complex Phenotypes

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ana Pinheiro-Machado Canton ◽  
Ana Krepischi ◽  
Luciana Ribeiro Montenegro ◽  
Silvia Costa ◽  
Carla Rosenberg ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Clinical Features ◽  
High Throughput ◽  
Precocious Puberty ◽  
Brain Mri ◽  
Central Precocious Puberty ◽  
University Hospital ◽  
Genetic Defects ◽  
Normal Brain ◽  
Complex Phenotypes

Abstract Background: Central precocious puberty (CPP) is mostly described as an isolated entity. Few studies have shown an association of CPP with complex cases or genetic syndromes, but without making inferences on molecular causalities. Objective: To genetically investigate a cohort of patients with CPP associated with complex phenotypes using high throughput methodologies. Patients and methods: From a large cohort of patients with idiopathic CPP followed at a university hospital outpatient clinic, thirty-eight patients were selected for high throughput genetic investigation for presenting at least 3 additional clinical features and conditions, characterizing complex phenotypes. All had normal brain MRI. Pathogenic allelic variants in CPP known genes were initially excluded. All patients were submitted to genomic microarray (SNP or CGH arrays). A subset of patients was also submitted to whole-exome sequencing (11 cases) or target panel sequencing (18 cases). Results: Among the group of 38 patients (35 girls, 4 boys; 21 sporadic, 17 familial), mean age at puberty onset was 5.8 ±2.1 and 8.3 ±3.0 yr in girls and boys, respectively. The more prevalent clinical features described included metabolic, growth and neurocognitive phenotypes; less prevalent features included dysmorphic features and congenital anomalies. Pathogenic or probably pathogenic genetic defects were identified in 9 cases: 5 sporadic (all identified as de novo) and 4 familial. Defects in sporadic cases were as follows: three cases with 7q11.23 deletion (Williams syndrome); one girl with ventricular arrhythmia presenting a rare 1p31.3 duplication, involving NFIA gene coding a transcription factor of NFI family with hypothalamic expression; and one girl with imperforate anus and learning difficulties with rare frameshift variants in AREL1 gene (p.Ser229Aspfs*3) coding an ubiquitin ligase, and TNRC6B gene (p.Gly665Leufs*35) coding a regulator of translational inhibition. In the four familial cases, the genetic defects segregated with CPP in a dominant inheritance mode. Three cases from unrelated families presented growth phenotypes and Xp22.33 deletions, including SHOX gene and other elements. One boy with maternal familial CPP and autism had two rare potentially pathogenic variants: a frameshift deletion in MKKS gene (p.Phe144Leufs*14); and a missense variant (p.Pro267Leu) in UGT2B4 gene. Interestingly, the later gene encodes a protein involved in estrogen hydroxylation and is associated to menarche timing in GWAS. Conclusion: Novel genetic defects were identified in 23% cases of CPP associated with complex phenotypes. Three chromosomal regions represented loci potentially implicated in CPP: Xp22.33, 7q11.23 and 1p31.3. Five genes were identified as candidate genes associated with CPP: NFIA, AREL1, TNRC6B, MKKS and UGT2B4.

scholarly journals SAT-520 Unusual Case of Hypothyroidism Possibly Due to Dialysis Leading to Van Wyk Grumbach Syndrome (VWGS)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jenice Chummar ◽  
Parissa Salemi
Keyword(s):  
Renal Transplantation ◽  
Thyroid Hormone ◽  
Precocious Puberty ◽  
Chronic Renal Disease ◽  
Early Recognition ◽  
Hormone Replacement ◽  
Brain Mri ◽  
Central Precocious Puberty ◽  
Primary Hypothyroidism ◽  
Poor Growth

Abstract BACKGROUND: Van Wyk Grumbach Syndrome (VWGS) is characterized by precocious central puberty in the setting of juvenile chronic primary hypothyroidism with symptom regression following thyroxine replacement. Clinical Case: A 2 year old girl with dysplastic kidneys and chronic renal disease had been treated by her nephrologist with growth hormone for poor growth. She was referred to Endocrinology for evaluation of bloody dialysate thought to be retrograde menstrual flow. Pelvic US showed bilateral large cystic adnexae possibly ovarian cysts versus septated collections of dialysate fluid. Hormone measurements showed pubertal levels of LH 0.4mIU/mL and FSH 5.4mIU/mL, with a relatively low Estradiol 5.3pg/mL. Brain MRI showed impressive pituitary enlargement measuring 1.3cm craniocaudally. Additional laboratory testing was notable for a low normal free T4 fT4 0.9ng/dL and markedly elevated TSH>1000uIU/mL and Prolactin 835ng/mL. Thyroid US showed thyroid enlargement, and echogenic and hyper vascular gland. Anti-thyroid antibodies titers were normal, AM cortisol and IGF1 were also normal for age. We speculate that this case of profound hypothyroidism was due to dialysis, as thyroid function improved after the child underwent renal transplantation. Levothyroxine was discontinued 5 months after renal transplantation. Elevated TSH may induce a form of pseudopuberty as the TSH alpha subunit is similar to that of LH and binds to the LH receptor to stimulate the ovaries with cyst formation. Conclusion: In VWGS, primary hypothyroidism with elevated TSH induces central precocious puberty. This child’s bloody diasylate was likely the result of transient central precocious puberty associated with uncontrolled primary hypothyroidism with elevated TSH and prolactin. Although the literature on dialysis suggests minimal thyroid hormone losses, this case shows the importance of monitoring thyroid hormones in dialysis patients. Early recognition of VWGS and initiation of thyroid hormone replacement can lead to resolution of symptoms.

scholarly journals Findings of Brain Magnetic Resonance Imaging in Girls with Central Precocious Puberty Compared with Girls with Chronic or Recurrent Headache

2021 ◽  
Vol 10 (10) ◽  
pp. 2206
Author(s):  
Shin-Hee Kim ◽  
Moon Bae Ahn ◽  
Won Kyoung Cho ◽  
Kyoung Soon Cho ◽  
Min Ho Jung ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Precocious Puberty ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Central Precocious Puberty ◽  
Resonance Imaging ◽  
Mri Findings ◽  
Magnetic Resonance Imaging Mri ◽  
Few Data

In the present study, the results of brain magnetic resonance imaging (MRI) in girls with central precocious puberty (CPP) were compared those in with girls evaluated for headaches. A total of 295 girls with CPP who underwent sellar MRI were enrolled. A total of 205 age-matched girls with chronic or recurrent headaches without neurological abnormality who had brain MRI were included as controls. The positive MRI findings were categorized as incidental non-hypothalamic–pituitary (H–P), incidental H–P, or pathological. Positive MRI findings were observed in 39 girls (13.2%) with CPP; 8 (2.7%) were classified as incidental non-H–P lesions, 30 (10.2%) as incidental H–P lesions, and 1 (0.3%) as a pathological lesion (tuber cinereum hamartoma). The prevalence of positive MRI findings in girls with CPP did not differ from girls with headaches (13.2% vs. 12.2%, p = 0.74). The prevalence of incidental H–P lesions in girls with CPP <6 years of age, 6–6.9 years of age, and 7–7.9 years of age was 21.2%, 13.5%, and 9.6%, respectively (p = 0.21). Known pathological lesions were detected in only one (3.0%) girl with CPP aged <6 years and in no girls with CPP aged 6–7.9 years. Microadenomas were detected in no girls with CPP aged <6 years and in 5 (1.9%) girls with CPP aged of 6–7.9 years. Our findings call into question the routine use of brain MRI in girls with CPP, especially in girls 6 years or older. Current guidelines recommend a follow-up MRI in cases of microadenoma, but few data exist to support this recommendation for children.

Utility of basal LH in comparison to the GnRH test for identifying central precocious puberty in girls

2014 ◽  
Author(s):  
Elizabeth Shepherd ◽  
Leena Patel ◽  
Indi Banerjee ◽  
Peter Clayton ◽  
Sarah Ehtisham ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Central Precocious Puberty

High prevalence of syndromic disorders in patients with non-isolated central precocious puberty

2019 ◽  
Author(s):  
Wannes S ◽  
Elmaleh-Berges M ◽  
Simon D ◽  
Zenaty D ◽  
Martinerie L ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Central Precocious Puberty ◽  
High Prevalence

Development of Prediction Models Using Machine Learning Algorithms for Girls with Suspected Central Precocious Puberty: Retrospective Study (Preprint)

2018 ◽  
Author(s):  
Liyan Pan ◽  
Guangjian Liu ◽  
Xiaojian Mao ◽  
Huixian Li ◽  
Jiexin Zhang ◽  
...  
Keyword(s):  
Machine Learning ◽  
Retrospective Study ◽  
Random Forest ◽  
Precocious Puberty ◽  
Prediction Models ◽  
Central Precocious Puberty ◽  
Machine Learning Algorithms ◽  
Stimulation Test ◽  
Gnrh Analogue ◽  
Prediction Probability

BACKGROUND Central precocious puberty (CPP) in girls seriously affects their physical and mental development in childhood. The method of diagnosis—gonadotropin-releasing hormone (GnRH)–stimulation test or GnRH analogue (GnRHa)–stimulation test—is expensive and makes patients uncomfortable due to the need for repeated blood sampling. OBJECTIVE We aimed to combine multiple CPP–related features and construct machine learning models to predict response to the GnRHa-stimulation test. METHODS In this retrospective study, we analyzed clinical and laboratory data of 1757 girls who underwent a GnRHa test in order to develop XGBoost and random forest classifiers for prediction of response to the GnRHa test. The local interpretable model-agnostic explanations (LIME) algorithm was used with the black-box classifiers to increase their interpretability. We measured sensitivity, specificity, and area under receiver operating characteristic (AUC) of the models. RESULTS Both the XGBoost and random forest models achieved good performance in distinguishing between positive and negative responses, with the AUC ranging from 0.88 to 0.90, sensitivity ranging from 77.91% to 77.94%, and specificity ranging from 84.32% to 87.66%. Basal serum luteinizing hormone, follicle-stimulating hormone, and insulin-like growth factor-I levels were found to be the three most important factors. In the interpretable models of LIME, the abovementioned variables made high contributions to the prediction probability. CONCLUSIONS The prediction models we developed can help diagnose CPP and may be used as a prescreening tool before the GnRHa-stimulation test.

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