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The decline in age at puberty in the general population has been paralleled by an increase in the number of girls referred for evaluation of precocious puberty (PP). In 1999, The Lawson Wilkins Pediatric Endocrine Society recommended a lowering of the age limit for evaluation of PP in girls. However, the limited evidence on which these recommendations were based led many experts to question these new suggestions. The emergence of new European pubertal timing data evaluated by robust clinical as well as biochemical markers has broadened our insight on how to interpret the recent pubertal changes. The recent pubertal trends have resulted in a concomitant lowering of the lower limit of normality of the pubertal onset. However, evidence suggests that age at the gonadotropin and sex steroid surges have not changed. Thus, it looks as if an increasing proportion of contemporary early pubertal girls may experience isolated gonadotropin-independent thelarche rather than central PP, which may not be discernible on pubertal examination alone. Thus, the population-based limits of normality should not be directly translated into revision of age limits for evaluation of PP due to the risk of misdiagnosing rapid progressive PP as well as intracranial and other underlying pathology., (Copyright © 2012 S. Karger AG, Basel.)

Unlabelled: Central precocious puberty may result from organic brain lesions, but is most frequently of idiopathic origin. Clinical or biochemical factors which could predict a pathological brain MRI in girls with CPP have been searched for. With the recent decline in age at pubertal onset among US and European girls, it has been suggested that only girls with CPP below 6 years of age should have brain MRI performed., Objective: To evaluate the outcome of brain MRI in girls referred with early signs of puberty in relation to age at presentation as well as clinical and biochemical parameters., Method: A single-center study of 229 consecutive girls with early or precocious puberty who had brain imaging performed. We evaluated medical history, clinical and biochemical factors, and four groups were defined based on the outcome of their MRI., Results: Thirteen out of 208 (6.3%) girls with precocious puberty, but no other sign of CNS symptoms, had a pathological brain MRI. Importantly, all 13 girls were above 6 years of age, and 6 girls were even 8-9 years old. Twenty girls (9.6%) had incidental findings on brain MRI. Furthermore, 21 girls had known CNS pathology at time of evaluation. Basal LH was significantly higher in girls with newly diagnosed CNS pathology compared to girls with a non-pathological MRI (p = 0.025); no cut of value was found as values overlapped., Conclusion: A high frequency of 6-8 year old girls with precocious puberty in our study had a pathological brain MRI, which could not be predicted from any clinical nor biochemical parameters. Thus, we believe that girls with precocious pubertal development of central origin before 8 years of age should continue to be examined by a brain MRI.

Objective: A decrease in age at pubertal onset has been observed internationally. The aim of this study was to describe a large cohort of Caucasian girls referred with signs of early puberty according to etiology and compare biochemical characteristics., Methods: In this single-center study, we included 449 consecutive Caucasian girls who were referred with signs of early puberty during the years 1993-2009. We evaluated pubertal stage, height, weight, and bone age. FSH, LH, estradiol, and inhibin B were determined, and a standard GnRH test was performed. Brain magnetic resonance imaging was performed to rule out pathologies., Results: During the period from 1993-2008, we found an increase in the number of girls in most diagnostic groups. Of 449 girls, 88 had central precocious puberty (CPP), and 12 of these had an organic origin. A total of 129 had early-normal variant (8-9 yr), 69 had premature thelarche, and 49 premature adrenarche. Receiver operating characteristic analyses revealed that basal LH was superior in predicting the maximal LH level during GnRH testing in comparison with FSH, estradiol, and inhibin B levels. Basal LH levels were above the age-related 2 sd in 26.2, 19.6, 65.1, and 75.0% of girls with, respectively, early-normal variant, premature thelarche, idiopathic CPP, and organic CPP, but LH levels below the detection limit were also seen among girls with a pubertal GnRH test., Conclusion: We observed an increasing number of girls referred because of early pubertal signs. An elevated basal LH was highly predictive of a pubertal GnRH test result, whereas a low LH did not exclude central pubertal activation.

Context: Early menarche is associated with increased risk of cardiovascular disease in adulthood. It is unknown whether metabolic risk factors are adversely affected in girls with central precocious puberty (CPP) already at time of diagnosis., Objective: The objective of the study was to evaluate metabolic profiles in girls with early normal puberty (EP) and CPP., Design and Setting: This was a combined cross-sectional and longitudinal study at a tertiary center of pediatric endocrinology., Patients and Intervention: Twenty-three girls with EP or CPP and 115 controls with normal pubertal timing were evaluated by oral glucose tolerance test, dual-energy x-ray absorptiometry scan, and fasting blood samples. Fifteen girls (13 CPP) were treated with GnRH agonists (GnRHa) and reevaluated after 12 and 52 wk of treatment., Main Outcome Measures: Insulin and glucose levels during oral glucose tolerance test and fasting lipid levels were measured., Results: At the time of diagnosis, girls with CPP had higher fasting insulin, triglyceride, and low-density lipoprotein-cholesterol levels as well as lower insulin sensitivity and high-density lipoprotein/total cholesterol ratios (all P<0.05) compared with controls after adjustment for pubertal stage and body fat percentage. Age at pubertal onset positively predicted insulin sensitivity for a given pubertal stage (P=0.04) in girls with EP and CPP. Insulin sensitivity decreased significantly during 1 yr of GnRHa treatment (P=0.04)., Conclusions: Girls with CPP had adverse metabolic profiles at the time of diagnosis compared with puberty-matched controls. In addition, those with the earliest onset of puberty had the most adverse metabolic profiles. Surprisingly, metabolic profiles deteriorated even further after withdrawal of sex steroids by GnRHa treatment.