Girls with Premature Adrenarche Have Accelerated Early Childhood Growth

doi:10.1016/j.jpeds.2008.12.038

The Journal of Pediatrics

Volume 154, Issue 6, June 2009, Pages 882-887

https://doi.org/10.1016/j.jpeds.2008.12.038 Get rights and content

Objective

To evaluate the effect of premature adrenarche (PA) on prepubertal growth.

Study design

The prepubertal growth of 54 girls with PA and 52 control girls was analyzed retrospectively. Birth measures were noted, and childhood length/height and weight were measured annually until age 5 years and at the current visit (at a median age of 7.6 years). The growth variables were correlated with serum insulin-like growth factor (IGF)-1, dehydroepiandrosterone sulfate, and insulin concentrations.

Results

There were no significant differences in birth length or weight standard deviation scores (SDSs) between the 2 study groups. The girls with PA demonstrated a significant length SDS increment during the first 2 years of life (median +1.0 SDS; P < .001). Compared with controls, they were taller (median current height 1.2 vs 0 SDS; P < .001) and gained more weight throughout childhood. The difference in weight-for-height became significant at a later age compared with the difference in height. Median serum IGF-1 concentration adjusted for both age and body mass index SDS was higher in the PA group (24 vs 19 nmol/L; P < .031).

Conclusions

PA was not associated with small birth size in our population. Girls with PA had enhanced growth already in early childhood, which was not explained by weight gain. Enhanced IGF-1 production may contribute to the prepubertal growth acceleration in PA.

Section snippets

Methods

A total of 54 prepubertal girls with PA and 52 healthy control children were examined. The inclusion criteria were any clinical sign of adrenarche (including pubic/axillary hair, acne, comedones, adult-type body odor, and oily hair) before age 8 years. The age at examination had to be less than 9 years. All girls in Northern Savo (a region in eastern Finland with a population of 250 000) who met these criteria between October 2004 and January 2006 were invited to participate in the study. Study

Birth Size, Parental Height, and Maternal Menarche

Median BW, BW SDS, and ponderal index did not differ significantly between the PA and control children (Table I). The same was true for BL SDS (Table I; Figure), although median BL was lower in the girls with PA (Table I). Among the girls with PA, there was no difference in the birth measures between those with and without pubarche (detailed data not shown). Six girls (4/54 with PA and 2/52 controls; P = .36) were born preterm (<37 weeks' gestation). The frequency of SGA (BW or BL <−2.0 SDS)

Discussion

The girls with PA exhibited accelerated prepubertal growth compared with the normal control girls, and the most pronounced gain in length/height SDS in the children with PA occurred during the first 2 years of life. Girls with PA also gained more weight than the control girls during the prepubertal period, but the enhanced early growth in height seemed to be independent of weight gain.

The girls with PA showed a significant upward bend in length SD curves during the first 2 years of life; the

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Normal growth pattern variations [i.e., constitutional advancement and constitutional delay of growth and puberty (CAGP and CDGP)] are the mirror image of each other and are associated with early puberty (EP) and delayed puberty (DP), respectively. Differences between CAGP and CDGP relate not only to auxological characteristics (height, weight) but also to insulin-like growth factor-1 (IGF-1). IGF-1 levels in CAGP are above average whereas in CDGP they are below average, suggesting a role for IGF-1 in the induction of these growth patterns. Herein, we provide data suggesting that early activation of the growth hormone (GH)/IGF-1 axis induces the growth pattern of CAGP. Moreover, we suggest that IGF-1 is a decisive factor for the release of the gonadotropin-releasing hormone (GnRH) inhibition brake that occurs in prepuberty. It is therefore crucial for puberty onset.
Natural progression of premature pubarche and underlying diseases
2018, Anales de Pediatria
La pubarquia precoz (PP) es generalmente considerada como una enfermedad benigna, pero puede ser el primer signo de una enfermedad subyacente.
Analizar la etiología y la evolución de parámetros antropométricos, analíticos y de riesgo metabólico, en pacientes con PP.
Estudio retrospectivo, descriptivo y analítico, de 92 pacientes afectos de PP. Se evaluaron medidas antropométricas y analíticas, la edad ósea y marcadores de metabolismo lipídico.
Muestra de 92 pacientes (67 mujeres y 25 varones) con PP, con una edad media de 7,1 ± 0,6 años las mujeres y 8,3 ± 0,7 los varones. El 7,7% fueron pequeños para la edad gestacional. La edad ósea estaba adelantada (1,2 ± 0,1 años). Veintiún pacientes fueron clasificados como PP idiopática (23%), 60 como adrenarquia precoz idiopática (65%) y 11 como hiperplasia suprarrenal congénita no clásica (12%). La pubertad se mostró adelantada respecto a la media (11 ± 0,9 años en varones versus 9,9 ± 0,8 años en mujeres), así como la edad de la menarquia (11,8 ± 1,1 años), p < 0,001. La talla final alcanzada es próxima a la talla genética. Existe una correlación positiva entre el Z-score del índice de masa corporal, la glucemia y el colesterol LDL, así como una tendencia a la hiperinsulinemia.
El presente estudio demuestra como la PP en la mayoría de los casos supone una patología benigna, no siendo infrecuente la hiperplasia suprarrenal congénita no clásica (12%). Estos pacientes presentaron un adelanto puberal, de la edad ósea y de la menarquia. El crecimiento fue adecuado, alcanzando prácticamente su talla genética. La PP asociada a obesidad presenta alteraciones analíticas de riesgo metabólico.
Premature pubarche (PP) is generally thought to be a benign condition, but it can also be the first sign of underlying disease.
To analyse the aetiology and the evolution of the anthropometric, analytical and metabolic risk parameters of a group of patients with PP.
A descriptive and analytical retrospective study of 92 patients affected by PP. Anthropometry, analyses, bone age and indicators of lipid metabolism were all evaluated.
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.
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.
Advanced bone age as an indicator facilitates the diagnosis of precocious puberty
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Diagnosis of central precocious puberty has always been challenging in clinical practice. As an important method in the diagnosis of central precocious puberty, luteinizing hormone-releasing hormone stimulation test is complex and time-consuming. In many cases, clinical traits are inconsistent with luteinizing hormone-releasing hormone stimulation test results, therefore not reliable for diagnosis. In this study, the authors intended to find an indicator that predicts the results of the luteinizing hormone-releasing hormone stimulation test among subjects with early pubertal signs.
Cases of 382 girls with early breast development before 8 years old and luteinizing hormone-releasing hormone stimulation test before 9 years old were included and underwent follow-up tests. Patients with peak luteinizing hormone level ≥5 IU/L were considered positive in the luteinizing hormone-releasing hormone stimulation test. Anthropometric data, body mass index, bone age evaluation, blood hormones levels of luteinizing hormone, estradiol, follicle-stimulating hormone, and uterine and ovarian volumes were analyzed.
Subjects with positive results in the initial test demonstrated early bone maturation, accelerated growth, and elevated basal blood luteinizing hormone, estradiol, and follicle-stimulating hormone levels, when compared with subjects with negative results in the initial test. Subjects with positive results in the follow-up test presented a more advanced bone age and more accelerated linear growth, when compared with subjects with negative results in the follow-up test.
According to the statistical analysis, advanced bone age is the most effective predictor of the result of luteinizing hormone-releasing hormone stimulation test.
O diagnóstico da puberdade precoce central sempre foi complicado na prática clínica. Como um importante método no diagnóstico de puberdade precoce central, o teste de estimulação do hormônio liberador do hormônio luteinizante é complexo e demorado. Em muitos casos, as características clínicas são incompatíveis com os resultados do teste de estimulação do hormônio liberador do hormônio luteinizante e, assim, não são confiáveis para o diagnóstico. Neste estudo, visamos constatar um indicador que previsse os resultados do teste de estimulação do hormônio liberador do hormônio luteinizante entre indivíduos com sinais puberais precoces.
Foram incluídos casos de 382 meninas com desenvolvimento precoce das mamas antes dos 8 anos de idade e teste de estimulação do hormônio liberador do hormônio luteinizante antes dos 9 anos e elas foram submetidas a testes de acompanhamento. Os resultados das pacientes com nível máximo de hormônio luteinizante ≥ 5 IU/L foram consideradas positivos no teste de estimulação do hormônio liberador do hormônio luteinizante. Foi feita uma análise dos dados antropométricos, do índice de massa corporal, da avaliação da idade óssea, dos níveis sanguíneos de hormônio luteinizante, volumes uterinos e ovarianos de estradiol (E2) e do hormônio folículo-estimulante.
Os indivíduos com resultado positive no teste inicial demonstraram maturação precoce do osso, crescimento acelerado e níveis sanguíneos elevados de hormônio luteinizante, estradiol e hormônio folículo-estimulante, em comparação aos indivíduos com resultados negativos no teste inicial. Os indivíduos com resultados positivos no teste de acompanhamento apresentaram um maior avanço na idade óssea e crescimento linear mais acelerado, em comparação aos indivíduos com resultados negativos no teste de acompanhamento.
De acordo com a análise estatística, a idade óssea avançada é o indicador mais efetivo do resultado do teste de estimulação do hormônio liberador do hormônio luteinizante.
Early Adiposity Rebound and Premature Adrenarche
2017, Journal of Pediatrics
Citation Excerpt :
TH was average, thus excluding familial tall stature while just 1 of the 82 children with PA was small for gestational age. Our findings of early growth acceleration and obesity in children with PA are in line with those of a recent Finnish study.11 Moreover, we show that early age at AR occurs in all subcategories of children with PA (boys, girls, obese, nonobese, CAG, non-CAG) suggesting a relation between AR and adrenarche onset, with the former happening approximately 2 years before the latter.
To examine differences in the growth pattern and the age at adiposity rebound (AR) between children with premature adrenarche (PA) and their healthy peers (controls).
In this cross-sectional study of 82 prepubertal children with PA and 63 controls, the main outcome measures were height and body mass index SDS progression, from birth to presentation at the clinic, baseline biochemical and hormonal evaluation, bone age determination, and age at AR.
Children with PA were significantly taller and more adipose than controls from the first years of life. 33% of children with PA presented the growth pattern of constitutional advancement of growth (ie, early growth acceleration) vs 19% of controls (P = .045). Children with PA had an earlier AR compared with controls; mean age at AR in girls with PA was 3.73 (1.03) years vs 4.93 (1.36) years for control girls (P = .001) and in boys with PA was 3.45 (0.73) vs 5.10 (1.50) years in control boys (P = .048). Both obese and nonobese girls with PA were taller and had earlier age at AR compared with nonobese controls.
Early AR and constitutional advancement of growth may be triggering factors for adrenal androgen production and PA.
Physiology and Disorders of Puberty
2015, Williams Textbook of Endocrinology
Adrenarche and Adrenopause
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View all citing articles on Scopus

: Supported by the Kuopio University Hospital, Pediatric Research Foundation, National Graduate School of Clinical Investigation, Academy of Finland, Finnish Medical Foundation, and Sigrid Jusélius Foundation. The authors declare no conflicts of interest.

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Original articleGirls with Premature Adrenarche Have Accelerated Early Childhood Growth

Objective

Study design

Results

Conclusions

Section snippets

Methods

Birth Size, Parental Height, and Maternal Menarche

Discussion

Beitr Pathol

J Pediatr

Premature adrenarche: normal variant or forerunner of adult disease?

Endocr Rev

Adrenarche: physiology, biochemistry and human disease

Clin Endocrinol (Oxf)

Precocious growth of sexual hair without other secondary sexual development; premature pubarche, a constitutional variation of adolescence

Pediatrics

Benign premature adrenarche: clinical features and serum steroid levels

Acta Paediatr Scand

Growth of patients with 21-hydroxylase deficiency: an analysis of the factors influencing adult height

Pediatr Res

The midgrowth spurt in healthy children is not caused by adrenarche

J Clin Endocrinol Metab

Estrogen: consequences and implications of human mutations in synthesis and action

J Clin Endocrinol Metab

Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche

J Clin Endocrinol Metab

Childhood metabolic syndrome and its components in premature adrenarche

J Clin Endocrinol Metab

Elevated free IGF-1 levels in prepubertal Hispanic girls with premature adrenarche: relationship with hyperandrogenism and insulin sensitivity

J Clin Endocrinol Metab

Natural history of premature pubarche: an auxological study

J Clin Endocrinol Metab

Follow up of growth and steroids in premature adrenarche

Eur J Pediatr

The natural history of premature adrenarche

J Pediatr Endocrinol Metab

Original article
Girls with Premature Adrenarche Have Accelerated Early Childhood Growth