Premature Pubarche: A Pragmatic Approach.

Premature pubarche (PP) is a common and usually benign variant of normal puberty most often seen in 5-year-old to 9-year-old children. Some providers routinely order laboratory testing and a bone age to try to rule out other diagnoses including nonclassic congenital adrenal hyperplasia and gonadal or adrenal tumors. I review the natural history of PP and studies which suggest that without clinical features such as rapid growth and progression or genital enlargement, it is unlikely that a treatable condition will be found. Therefore it is recommended that patients with PP not undergo testing unless there are red flags at the time of the initial visit.

Dose inhibin B or anti-Müllerian hormone relate to precocious puberty in girls? result of a systematic review and meta-analysis.

BACKGROUNDS: Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the results are inconsistent. OBJECTIVE: The aim of this meta-analysis was to assess whether the INHB and AMH levels changed in girls with precocious puberty relative to healthy controls. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched through June 2022. We included observational clinical studies reporting the serum levels INHB and AMH in girls with precocious puberty. Conference articles and observational study abstracts were included if they contained enough information regarding study design and outcome data. Case series and reports were excluded. An overall standard mean difference (SMD) between precocious puberty and healthy controls was estimated using a DerSimonian-Laird random-effects model. RESULTS: A total of 11 studies featuring 552 girls with precocious puberty and 405 healthy girls were selected for analysis. The meta-analysis showed that the INHB level of precocious puberty [including central precocious puberty (CPP) and premature the larche (PT)] were significantly increased. While there was no significant association between precocious puberty [including CPP, PT, premature pubarche (PP) and premature adrenarche (PA)] and the level of serum AMH. CONCLUSION: Scientific evidence suggested that the INHB level, but not the AMH level, altered in girls with precocious puberty compared with healthy controls. Through our results we think that INHB level might be a marker for the auxiliary diagnosis of precocious puberty (especially CPP and PT). Therefore, it is important to evaluate and thoroughly investigate the clinical indicators (e.g., INHB) in order to ensure early diagnosis and medical intervention, and the risk of physical, psychological and social disorders in immature girls with precocious puberty is minimized.

Premature pubarche during minipuberty - literature review and two case reports.

INTRODUCTION: Isolated premature pubarche (PP) in infancy may be the reason for many diagnostic difficulties. This is due to the low incidence and, therefore, the limited number of studies on this subject and the lack of strict laboratory standards because of the physiological variability of gonadotropic hormone and androgen concentrations during minipuberty. MATERIAL AND METHODS: We aimed to present current knowledge about PP in infancy based on the literature review and 2 cases of male infants with scrotal hair during minipuberty. RESULTS: Isolated hair in the pubic region in a boy during the period of minipuberty requires differential diagnosis. After excluding serious aetiology, it seems to be a mild, self-limiting variant of precocious puberty. The phenomenon is probably a result of increased sensitivity of the hair follicles to transiently increased androgen concentration. CONCLUSIONS: Isolated pubic hair in infancy as a mild, self-limiting variant of precocious puberty in infants should be a diagnosis of exclusion. The condition resolves spontaneously, but it absolutely requires further follow-up to exclude serious aetiology in the case of puberty progression.

A rare occurrence of non-classic congenital adrenal hyperplasia and type 1 diabetes mellitus in a girl with Prader-Willi Syndrome: Case report and review of the literature.

Prader-Willi syndrome (PWS) is a rare genetic disorder resulting from lack of expression of the paternally derived chromosome 15q11-13, associated with several complications, including pubertal disorders, short stature, hyperphagia, obesity, glucose metabolism abnormalities, scoliosis, obstructive sleep apnea syndrome (OSAS) and behavioral problems. We report the case of a girl affected by PWS who presented at the age of 5.9 with premature pubarche, accelerated linear growth and advanced bone age (BA). She was subsequently diagnosed with non-classic congenital adrenal hyperplasia (CAH) confirmed by genetic analysis. Considering the clinical, biochemical, and genetic findings, hydrocortisone therapy was started to prevent rapid BA acceleration and severe compromission of final height. During infancy, short stature and low levels of insulin-like growth factor-1 (IGF-1) for age and gender led to suspicion of growth hormone deficiency (GHD), confirmed by stimulation testing (arginine and clonidine). rhGH therapy was administered and continued until final height was reached. During endocrinological follow up she developed impaired glucose tolerance with positive markers of ß-cell autoimmunity (anti-glutamic acid decarboxylase antibodies, GAD Ab), which evolved over time into type 1 diabetes mellitus and insulin therapy with a basal-bolus scheme and an appropriate diet were needed.

Evaluation of Glucose Metabolism and Cardiovascular Risk Factors in Prepubertal Girls with Premature Pubarche

Objective: Premature pubarche (PP) is a risk factor for metabolic syndrome (MS). The aim was to evaluate if glucose-insulin metabolism, cardiovascular risk factors, familial cardiovascular risk factors (FCVRF) created a risk for insulin resistance (IR) and if PP was a risk factor alone for MS in normal weight prepubertal girls with PP. Methods: Thirty-five prepubertal, non-obese girls with PP with normal birth weight and 35 age-matched control girls were evaluated for FCVRF, anthropometric measurements, blood pressure, lipid profile, fasting blood glucose-insulin, hemoglobin A1c (HbA1c), sex hormone binding globulin (SHBG), leptin, adiponectin, tumor necrosis factor-alpha (TNF-α), androgen levels, and bone age. Oral glucose tolerance test was performed in PP participants. Homeostasis model of assessment of IR (HOMA-IR), fasting glucose/insulin ratio, atherogenic index (AI), and free androgen index (FAI) were calculated. PP participants were further stratified by FCVRF. Results: HbA1c, lipid profile, testosterone, leptin, adiponectin, TNF-α, HOMA-IR, glucose/insulin ratio, AI, and fasting glucose-insulin levels were similar. In the PP group FAI was significantly higher (p=0.001), whereas SHBG was significantly lower (p=0.010) than the control group. Leptin levels of FCVRF+ and FCVRF- subgroups were 15.2±9.1 and 9.7±7.2 ng/mL, respectively and the difference was significant (p=0.016). Conclusion: As PP does not appear to be a risk factor alone for impaired glucose metabolism and IR in prepubertal non-obese girls with normal birth weight, it is our opinion that it is unnecessary to examine in detail such cases before puberty. Low SHBG levels in the PP group and high leptin levels in FCVRF+ subgroup might suggest that these may be predictive for MS in the future.

A proof of concept of a machine learning algorithm to predict late-onset 21-hydroxylase deficiency in children with premature pubic hair.

In children with premature pubarche (PP), late onset 21-hydroxylase deficiency (21-OHD), also known as non-classical congenital adrenal hyperplasia (NCCAH), can be routinely ruled out by an adrenocorticotropic hormone (ACTH) test. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a quantitative assay of the circulating steroidome can be obtained from a single blood sample. We hypothesized that, by applying multivariate machine learning (ML) models to basal steroid profiles and clinical parameters of 97 patients, we could distinguish children with PP from those with NCCAH, without the need for ACTH testing. Every child presenting with PP at the Trousseau Pediatric Endocrinology Unit between 2016 and 2018 had a basal and stimulated steroidome. Patients with central precocious puberty were excluded. The first set of patients (year 1, training set, n = 58), including 8 children with NCCAH verified by ACTH test and genetic analysis, was used to train the model. Subsequently, a validation set of an additional set of patients (year 2, n = 39 with 5 NCCAH) was obtained to validate our model. We designed a score based on an ML approach (orthogonal partial least squares discriminant analysis). A metabolic footprint was assigned for each patient using clinical data, bone age, and adrenal steroid levels recorded by LC-MS/MS. Supervised multivariate analysis of the training set (year 1) and validation set (year 2) was used to validate our score. Based on selected variables, the prediction score was accurate (100%) at differentiating premature pubarche from late onset 21-OHD patients. The most significant variables were 21-deoxycorticosterone, 17-hydroxyprogesterone, and 21-deoxycortisol steroids. We proposed a new test that has excellent sensitivity and specificity for the diagnosis of NCCAH, due to an ML approach.

Investigation of early puberty prevalence and time of addition thelarche to pubarche in girls with premature pubarche: two-year follow-up results.

We aimed to determine the prevalence of early puberty in girls with premature pubarche and analyze the time interval between their pubarche and succeeding thelarche. This study included 60 female children with premature pubarche. We retrospectively collected clinical, laboratory, and radiological findings from all participants. We investigated the time interval between pubarche and thelarche in cases wherein premature pubarche was followed by thelarche. The mean age at onset of pubarche was 6.93 ± 0.79 yr old. Among the participants, 16.7% were preterm, 20% were small for gestational age (SGA), and 55% were overweight or obese. The mean time interval between pubarche and thelarche was 11.20 ± 7.41 mo. The mean serum DHEA-S level was higher in the preterm group (p = 0.016), and DHEA-S levels were generally higher in the SGA group (p = 0.004). This study documented the presence of being overweight or obese and having more advanced growth than their genetic potential in half of the patients who had premature pubarche. In addition to these identified risk factors, obesity-independent DHEA-S levels were observed to be higher in patients who had early puberty with the first six months of their follow-up considered to be the most critical time in predicting early puberty.

Polycystic Ovary Syndrome: Ontogeny in Adolescence.

The pathophysiology of symptomatic polycystic ovary syndrome (PCOS) often unfolds across puberty, but the ontogeny of PCOS is difficult to study because, in general, its pathophysiology is well entrenched before the diagnosis can be confirmed. However, the study of high-risk groups (daughters of women with PCOS, girls with premature pubarche, and girls with obesity) can offer insight in this regard. Available data support the hypothesis that the pubertal development of PCOS involves various combinations of genetic predisposition, intrauterine programming, hyperinsulinism, and numerous other abnormalities that provoke reproductive symptoms (eg, hyperandrogenism, ovulatory dysfunction) in response to the pubertal increase in gonadotropin secretion.

Role of Body Weight in the Onset and the Progression of Idiopathic Premature Pubarche.

BACKGROUND: The term premature pubarche (PP) refers to the appearance of pubic hair before age 8 in girls and before age 9 in boys. Although idiopathic PP (often associated with premature adrenarche) is considered an extreme variation from the norm, it may be an initial sign of persistent hyperandrogenism. Factors contributing to PP onset and progression have not been identified to date. AIMS: The objectives of this study are to describe a group of Italian children with PP, to identify potential factors for its onset, and to define its clinical and biochemical progression. METHODS: We retrospectively enrolled all infants born between 2001 and 2014 with PP. Children with advanced bone age (BA) underwent functional tests to determine the cause of PP. Hormonal analysis and BA determination were performed annually during a 4-year follow-up period. RESULTS: A total of 334 children with PP were identified: idiopathic PP (92.5%, associated with premature adrenarche in some cases); related to precocious puberty (6.6%); late-onset 21-hydroxylase deficiency (0.9%). Low birth weight was associated with premature adrenal activation. Body mass index (BMI) was the only factor that influenced the progression of BA during follow-up. CONCLUSIONS: Low birth weight is a predisposing factor for premature adrenal activation. The increase in BMI in patients with idiopathic PP during the 4-years of follow-up was responsible for BA acceleration. We recommend prevention of excessive weight gain in children with PP and strict adherence to follow-up in order to prevent serious metabolic consequences.

Genotype-phenotype correlations in children and adolescents with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

BACKGROUND: Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by mutations in the active 21-hydroxylase gene (CYP21A2). The clinical symptoms can vary greatly. To date, no systematic studies have been undertaken in Germany. AIMS: Description of the phenotype, evaluation of the diagnostics and genotype-phenotype correlation PATIENTS AND METHODOLOGY: Retrospective analysis of the data of 134 patients (age range 0.1-18.6 years) in a multicentre study covering 10 paediatric endocrinology centres in Bavaria and Baden-Württemberg. The data was gathered on site from the medical records. Two hundred and thirty-three alleles with a mutation of the CYP21A2 gene were identified in 126 patients. A genotype-phenotype correlation of the mutation findings was undertaken (C1, severe/mild; C2, mild/mild). Individuals with a heterozygous mutation of the CYP21A2 were also included (C3). The data was collected with the approval of the ethics committee of the University Hospital of Erlangen during the period of 2014 and 2015. RESULTS (MW ± SD): One hundred and seventeen out of 134 patients (115 f, 29 m) were symptomatic. The chronological age (CA) at diagnosis was 7.1 ± 4.4 years. The most frequent symptom (73.5%) was premature pubarche. The height-SDS on diagnosis was 0.8 ± 1.3 and the BMI-SDS was 0.8 ± 1.2. Bone age (BA) was ascertained in 82.9% of the symptomatic patients. The difference between BA and CA was 1.9 ± 1.4 years. Basal 17OHP concentrations were 14.5 ± 19.1 ng/ml (18 patients < 2 ng/ml). In total, 58.1% mild and 34.7% severe mutations were found. The most common mutation was p.Val281Leu (39.1%); 65.8% of the patients could be allocated to group C1. No phenotypical differences were found between the 3 mutation groups. The 17OHP levels (basal and after ACTH) in the standard ACTH stimulation test were highest in group C1 and also significantly higher in group C2 as in C3, the ACTH-stimulated cortisol levels (ng/ml) were significantly lower in groups C1 (192.1 ± 62.5) and C2 (218 ± 50) than in C3 (297.3 ± 98.7). CONCLUSION: Most of the patients have symptoms of mild androgenisation. Male patients are underdiagnosed. Diagnostics are not standardised. Differences between the types of mutations are found in the hormone concentrations but not in phenotype. We speculate that further, as yet not clearly defined, factors are responsible for the development of the respective phenotypes.

Clinical, biochemical and gender characteristics of 97 prepubertal children with premature adrenarche.

Background Premature adrenarche (PA) is defined as the appearance of clinical signs of androgen action associated with levels of dehydroepiandrosterone sulfate (DHEAS) ≥40 µg/dL, before age 8 years in girls and 9 years in boys, without breast or testicular enlargement. The aim of this study was to characterize a population of prepubertal Caucasian children with PA and to compare them with regard to gender and body mass index (BMI) (normal BMI vs. overweight/obesity). Methods We performed a cross-sectional study of Portuguese Caucasian prepubertal children followed, due to PA, in pediatric endocrinology clinics of a university hospital. Results Eighty-two girls and 15 boys were included (mean age at evaluation: 7.4 ± 1.3 years). The mean birth weight was 2990 ± 689 g; only two children were small for gestational age. Girls presented premature pubarche at a younger age (median [interquartile range (IQR)] 6 (5-6) years vs. 7 (7-8) years in boys; p < 0.001). No gender differences were found for gestational age, birth weight, maternal age at menarche, anthropometry, bone age advancement or androgen levels. The majority of the subjects were overweight or obese (59%). Overweight/obese PA children were taller and had a more advanced bone age than normal-BMI PA children. Overweight/obese children presented higher levels of DHEAS and androstenedione. Bone age advancement and DHEAS were correlated (r = 0.449; p = 0.05). Conclusions We found no evidence of reduced fetal growth. Girls presented premature pubarche at a younger age. No major gender differences in androgen levels were found in prepuberty. Obese and overweight PA children tend to be taller, have a more advanced bone age and higher levels of androgens than normal-BMI PA children.

Low DHEAS Concentration in a Girl Presenting with Short Stature and Premature Pubarche: A Novel PAPSS2 Gene Mutation.

OBJECTIVE: Dehydroepiandrosterone (DHEA) sulfotransferase (SULT2A1) converts DHEA to DHEA sulfate (DHEAS) which prevents bioactive androgen excess. This enzymatic reaction requires PAPS (3'-phospho-adenosine-5'-phosphosulfate) biosynthesis mediated by PAPS synthase 2 (PAPSS2). Here, we report a patient presenting with short stature and premature pubarche due to a novel homozygous mutation in the PAPPS2 gene. CASE REPORT: A 7.5-year-old girl was referred for short stature. She was born at term with a birth weight of 2,850 g and her parents were first cousins. At presentation, her height was 113.0 cm (-2.1 SDS) and weight was 28.3 kg (+0.9 SDS), her arm span was 115.0 cm, and upper to lower segment ratio was 1.2. Her pubic hair and breast development were at Tanner stage III and I, respectively. Radiographs revealed mild lumbar scoliosis and platyspondyly and irregular vertebral endplates in the thoracolumbar region. Her serum DHEAS was low (39 ng/mL). The plasma DHEAS/DHEA ratio was significantly decreased on 2 separate measurements (4.4 and 19.8; normal range 31-345). PAPSS2 gene analysis identified a homozygous p.L440Wfs*12 (c.1318_1330 delCTACTACACCCTC) variant. This is the first report of a large deletion leading to a frameshift effect in the PAPSS2 gene and a truncated PAPSS2 protein. CONCLUSION: We describe the third case with PAPSS2 deficiency presenting with premature pubarche, and the first large deletion in the PAPSS2 gene. Although PAPSS2 deficiency is a rare cause of premature pubarche and adrenal androgen excess, it should be considered, especially in cases with disproportionate short stature and clinical hyperandrogenism associated with low plasma DHEAS concentration.

Management of the Female With Non-classical Congenital Adrenal Hyperplasia (NCCAH): A Patient-Oriented Approach.

Non-classical congenital adrenal hyperplasia (NCCAH) is considered to be a common monogenic inherited disease, with an incidence range from 1:500 to 1:100 births worldwide. However, despite the high incidence, there is a low genotype-phenotype correlation, which explains why NCCAH diagnosis is usually delayed or even never carried out, since many patients remain asymptomatic or are misdiagnosed as suffering from other hyperandrogenic disorders. For affected adolescent and adult women, it is crucial to investigate any suspicion of NCCAH and determine a firm and accurate diagnosis. The Synacthen test is a prerequisite in the event of clinical suspicion, and molecular testing will establish the diagnosis. In most cases occurring under 8 years of age, the first symptom is premature pubarche. In some cases, due to advanced bone age and/or severe signs of hyperandrogenism, initiation of hydrocortisone treatment prepubertally may be considered. Our unifying theory of the hyperandrogenic signs system and its regulation by internal (hormones, enzymes, tissue sensitivity) and external (stress, insulin resistance, epigenetic, endocrine disruptors) factors is presented in an attempt to elucidate both the prominent genotype-phenotype heterogeneity of this disease and the resultant wide variation of clinical findings. Treatment should be initiated not only to address the main cause of the patient's visit but additionally to decrease abnormally elevated hormone concentrations. Goals of treatment include restoration of regular menstrual cyclicity, slowing the progression of hirsutism and acne, and improvement of fertility. Hydrocortisone supplementation, though not dexamethasone administration, could, as a general rule, be helpful, however, at minimum doses, and also for a short period of time and, most likely, not lifelong. On the other hand, in cases where severe hirsutism and/or acne are present, prescription of oral contraceptives and/or antiandrogens may be advisable. Furthermore, women with NCCAH commonly experience subfertility, therefore, there will be analysis of the appropriate approach for these patients, including during pregnancy, based mainly on genotype. Besides, we should keep in mind that since the same patient will have changing requirements through the years, the attending physician should undertake a tailor-made approach in order to cover her specific needs at different stages of life.

Premature Pubarche due to Exogenous Testosterone Gel or Intense Diaper Rash Prevention Cream Use: A Case Series.

BACKGROUND/AIMS: Premature pubarche is associated with conditions such as virilizing congenital adrenal hyperplasia, androgen-secreting tumors, and exogenous exposure to androgen products. We describe the clinical and hormonal features of a series of children who were referred to endocrine evaluation due to premature pubarche. METHODS: This is a retrospective case series study of 14 children with premature pubarche and/or virilization. Five were unintentionally exposed to testosterone gel (parental use). Nine patients were intensely exposed to diaper rash prevention creams. Clinical and laboratory data were revised. RESULTS: Moderate to severe virilization was detected in the 5 patients (2 boys and 3 girls) who were exposed to testosterone gel. These patients had pubic hair development associated with clitoromegaly (3/3), penile enlargement (2/2), and accelerated growth (5/5). Testosterone levels were elevated in 4/5 patients associated with normal prepubertal gonadotropin levels and adrenal androgen precursors. The 9 children who were intensely exposed to diaper rash prevention creams had mild pubarche (intermediate hair) without any other clinical manifestation of pubertal development. Three of them exhibited pubic hair thinning after cream withdrawal. CONCLUSION: Unintentional topical androgen exposure or the intense use of diaper rash prevention cream should be ruled out in children with precocious pubarche and/or virilization signs to avoid misdiagnosis and expendable investigation.

Clinical characteristics and etiological analysis of premature pubarche:A report of 55 cases / 中国实用儿科杂志

OBJECTIVE: To analyse the clinical characteristics,aetiology distribution,and metabolic risk parameters of patients with with premature pubarche(PP). METHODS: A retrospective study was performed in 55 patients affected by PP,who received ACTH stimulation test,and the data were evaluated. Among them 17 cases were detected CYP21 A2 gene,and indicators of lipid metabolism of idiopathic premature adrenarche(IPA,15 cases)and idiopathic premature pubarche(IPP,14 cases)were analyzed. RESULTS: The sample included 55 patients with PP(53 female and 2 male),with a mean pubarche age of(7.2±0.9)years for girls and(7±0.8)years for boys. There was an accelerated bone age(BA/CA ratio>1)(1.20 ± 1.5)in girls. A total of 9 patients were classified as non-classic congenital adrenal hyperplasia(NCCAH,16.4%),15 as IPA(27.3%),14 as IPP(25.4%),16 as HPGA function launch(29.1%)and 1 with exaggerated adrenarche(EA,1.8%). There was no significant difference in the diagnostic rate of NCCAH between ACTH stimulation test and CYP21 A2 gene detection(P=0.596). The sex hormone binding protein(SHBP)of IPA was reduced(P=0.007). CONCLUSION: The etiology of premature pubarche-non-classic congenital adrenal hyperplasia(16.4%)is not uncommon. The ACTH stimulation test is useful for the diagnosis of NCCAH,but the sensitivity is not 100%.

Hipertricosis cubital en una paciente con pubarquia precoz: Caso clmico / Hypertrichosis cubiti in a girl with precocious puberty: Case report

La hipertricosis cubital es un aumento localizado de la densidad, longitud y espesor del vello. Es una entidad benigna con muy escasos pacientes descritos en la literatura médica (alrededor de medio centenar). La mitad de los casos descritos asocian otros defectos o malformaciones, y la otra mitad son problemas puramente estéticos. La pubarquia precoz en niñas se define como el inicio del vello púbico antes de los 8 años de edad. Se presenta a una paciente de 6 años con la asociación no descrita previamente de hipertricosis cubital y pubarquia precoz.

Hypertrichosis cubiti is a localized increase in hair density, length and thickness. It is an uncommon and benign entity with very few patients described in the medical literature (more or less than half a hundred). Half of the described patients associate other defects or malformations and the other half are purely aesthetic cases. Early pubarche in girls is defined as the onset of pubic hair before 8 years of age. We present a six-year-old patient with the association not previously described of hypertrichosis cubiti and precocious pubarche.

[Hypertrichosis cubiti in a girl with precocious puberty: Case report]. / Hipertricosis cubital en una paciente con pubarquia precoz: Caso clmico.

Hypertrichosis cubiti is a localized increase in hair density, length and thickness. It is an uncommon and benign entity with very few patients described in the medical literature (more or less than half a hundred). Half of the described patients associate other defects or malformations and the other half are purely aesthetic cases. Early pubarche in girls is defined as the onset of pubic hair before 8 years of age. We present a six-year-old patient with the association not previously described of hypertrichosis cubiti and precocious pubarche.

La hipertricosis cubital es un aumento localizado de la densidad, longitud y espesor del vello. Es una entidad benigna con muy escasos pacientes descritos en la literatura médica (alrededor de medio centenar). La mitad de los casos descritos asocian otros defectos o malformaciones, y la otra mitad son problemas puramente estéticos. La pubarquia precoz en niñas se define como el inicio del vello púbico antes de los 8 años de edad. Se presenta a una paciente de 6 años con la asociación no descrita previamente de hipertricosis cubital y pubarquia precoz.

[Natural progression of premature pubarche and underlying diseases]. / Evolución natural de la pubarquia precoz y posibles patologías asociadas.

INTRODUCTION: Premature pubarche (PP) is generally thought to be a benign condition, but it can also be the first sign of underlying disease. OBJECTIVE: To analyse the aetiology and the evolution of the anthropometric, analytical and metabolic risk parameters of a group of patients with PP. MATERIAL AND METHODS: A descriptive and analytical retrospective study of 92 patients affected by PP. Anthropometry, analyses, bone age and indicators of lipid metabolism were all evaluated. RESULTS: The sample included 92 patients with PP (67 female and 25 male), with a mean age of 7.1±0.6 for girls and 8.3±0.7 for boys. Small for gestational age was recorded in 7.7%. There was an accelerated bone age (1.20±0.1 years). A total of 21 patients were classified as idiopathic (23%), 60 as idiopathic premature adrenarche (65%), and 11 with non-classic congenital adrenal hyperplasia (12%). Puberty was reached early (11+0.9 years old in boys and 9.9±0.8 in girls), as was menstruation age (11.8+1.1 years old), P<.001. The stature finally reached was close to their genetic stature. There is a positive correlation between body mass index, blood glucose and LDL cholesterol, as well as a tendency towards hyperinsulinaemia. CONCLUSIONS: The present study shows that PP is a benign condition in the majority of cases, but non-classic congenital adrenal hyperplasia (12%) is not uncommon. Menstruation and puberty started early and bone age was accelerated. Growth was normal, and more or less in line with genetic size. PP associated with obesity is linked with analytical variations of metabolic risks.

Children with premature pubarche: is an alterated neonatal 17-Ohp screening test a predictive factor?

BACKGROUND: Neonatal screening for 21 hydroxylase deficiency is designed to detect classical form of congenital adrenal hyperplasia (CAH). It is still unclear whether newborns who result false positives at neonatal screening might later develop signs of androgen excess. The aim of this study is to verify whether a slightly elevated 17-OHP at newborn screening is a predictive factor for premature pubarche. METHODS: We evaluated all infants born between 2001 and 2014 with premature pubarche. In case of increased bone age, they were submitted to functional tests to find out the cause of their symptoms. Their 17-OHP values at newborn screening for CAH were reconsidered. RESULTS: We identified 330 patients (269 females, 61 males) with premature pubarche. All these children had a normal 17-OHP at newborn screening with the exception of a child, born preterm and not affected by CAH. CONCLUSIONS: An elevated 17-OHP at newborn screening is not a predictive factor for premature pubarche. A likely cause of increased 17-OHP level at screening is an immaturity of adrenal gland or a neonatal stress. Therefore a strict follow up of these neonates during childhood is not necessary.