Neuroimaging in 205 consecutive Children Diagnosed with Central Precocious Puberty in Denmark.

INTRODUCTION: A brain magnetic resonance image (MRI) is considered part of routine evaluation in children diagnosed with central precocious puberty (CPP) to rule out intracranial pathology. We evaluated the occurrence of pathological findings on neuroimaging among children diagnosed with CPP. METHODS: A retrospective study based on an evaluation of 1544 children referred with early signs of puberty from 2009-2019. Of these, 205 children (29 boys) with confirmed CPP had a brain MRI performed, and we report MRI results, pubertal stage, bone age, and hormonal analyses. All abnormal MRI results were re-evaluated by a trained neuroradiologist. RESULTS: A new intracranial pathology was found by brain MRI in 6 out of 205 patients aged 1.5 to 6.1 years. The occurrence of intracranial pathology was 3/162 (1.8%) and 3/24 (12.5 %) in girls and boys respectively. CONCLUSION: Organic causes of precocious puberty are more frequent in boys with CPP than in girls. No cases of organic CPP were seen above age 6.1 years of age. The age cut off value for routine brain MRI could be lowered to seven or perhaps even six years of age for girls, except in rapidly progressing puberty or presence of neurological symptoms. IMPACT: In our study of children with central precocious puberty (CPP), intracranial pathology is a rare cause and occurs only in younger children. It supports the general trend, that younger children are at higher risk of having organic causes to CPP and supports the clinical practice, that only high-risk patients with CPP should undergo routine brain MRI.

Minipuberty of human infancy - A window of opportunity to evaluate hypogonadism and differences of sex development?

Activation of the hypothalamic-pituitary-gonadal (HPG) axis happens in 3 phases during life. The first phase is during fetal life and is only separated from the second phase, called minipuberty, by the high concentration of placental hormones at birth. The third period of activation of the HPG axis is puberty and is well-described. Minipuberty consists of the neonatal activation of the HPG axis, mainly in the first 1-6 months, where the resulting high levels of gonadotropins and sex steroids induce the maturation of sexual organs in both sexes. With gonadal activation, testosterone levels rise in boys with peak levels after 1-3 months, which results in penile and testicular growth. In girls, gonadal activation leads to follicular maturation and a fluctuating increase in estrogen levels, with more controversy regarding the actual influence on the target tissue. The regulation of the HPG axis is complex, involving many biological and environmental factors. Only a few of these have known effects. Many details of this complex interaction of factors remain to be elucidated in order to understand the mechanisms underlying the first postnatal activation of the HPG axis as well as mechanisms shutting down the HPG axis, resulting in the hormonal quiescence observed between minipuberty and puberty. Minipuberty allows for the maturation of sexual organs and forms a platform for future fertility, but the long-term significance is still not absolutely clear. However, it provides a window of opportunity in the early detection of differences of sexual development, offering the possibility of initiating early medical treatment in some cases.