Continuum of phenotypes and sympathoadrenal function in premature adrenarche

Utriainen, Pauliina; Voutilainen, Raimo; Jääskeläinen, Jarmo

doi:10.1530/eje-08-0367

Cited by 45 publications

(53 citation statements)

References 47 publications

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“…Indeed, there is some inconsistency in the literature where PP is often used synonymously for PA. First, some of these studies only scored the onset of pubic hair growth but lack biochemical confirmation of increased adrenal androgen production. Second, equating the two terms would limit the attention to the development of pubic hair only, but ignore other signs of increased androgen action including adult-type body odour and oily hair and skin (23, 46,47,50,51). Conversely, some investigators have defined PA very strictly as the biochemical detection of a premature increase in circulating adrenal androgens irrespective of the clinical presentation (52).…”

Section: Pa: Definitions and Differential Diagnosismentioning

confidence: 99%

“…Distinct conditions manifesting PA include milder and nonclassic variants of congenital adrenal hyperplasia (CAH) that have been diagnosed in 0-40% of children with PP (51,(61)(62)(63)(64)(65), depending on the pre-selection bias applied to the studied cohorts. Baseline blood sampling for measurement of DHEAS, androstenedione, 17a-hydroxyprogesterone (17OHP), testosterone, and sex hormone binding globulin (SHBG) will be generally sufficient to confirm increased adrenal androgens and to differentiate between IPA, CAH, and virilising tumours (55,61).…”

Section: Pa: Definitions and Differential Diagnosismentioning

confidence: 99%

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Premature adrenarche: novel lessons from early onset androgen excess

Idkowiak

Lavery

Dhir

et al. 2011

European Journal of Endocrinology

110

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Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

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Section: Pa: Definitions and Differential Diagnosismentioning

confidence: 99%

Section: Pa: Definitions and Differential Diagnosismentioning

confidence: 99%

Premature adrenarche: novel lessons from early onset androgen excess

Idkowiak

Lavery

Dhir

et al. 2011

European Journal of Endocrinology

110

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“…However, serum androgen bioactivity was not correlated with serum DHEAS or A4 concentrations in any subgroup of children. PA is characterized by clinical signs of androgenic activity that do not correlate well with circulating adrenal androgen concentrations: children may have these signs alongside relatively low circulating DHEAS levels, or they may have increased DHEAS concentrations without any phenotypic signs (3,23,24). The peripheral intracrine metabolism of weak adrenal androgen metabolites is known to be essential for the relevant androgenic effects.…”

Section: Androgen Bioactivity In Pamentioning

confidence: 99%

“…Children participating in our PA study have been presented previously (3). From this group, we studied serum samples of 73 prepubertal children with PA (mean age: 7.45 y, SD: 0.92 y, 10 boys) and 97 healthy control children (mean age: 7.49 y, SD: 0.89 y, 18 boys).…”

Section: Subjects and Serum Assaysmentioning

confidence: 99%

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Serum androgen bioactivity is low in children with premature adrenarche

et al. 2014

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Background: Clinical findings in children with premature adrenarche (PA) correlate only partly with circulating levels of adrenal androgens. It is not known whether the prepubertal low circulating concentrations of testosterone (T) and dihydrotestosterone, together with those of adrenal androgens, are capable of activating the androgen receptor. Methods: This cross-sectional study was performed at a university hospital. Circulating androgen bioactivity was measured in 67 prepubertal children with clinical signs of PA and 94 control children using a novel androgen bioassay. results: Circulating androgen bioactivity was low in the PA and control children. In the subgroup of children (n = 28) with serum T concentration over the assay sensitivity (0.35 nmol/l) and a signal in the androgen bioassay, we found a positive correlation between androgen bioactivity and serum T (r = 0.50; P < 0.01) and the free androgen index (r = 0.61; P < 0.01) and a negative correlation with serum sex hormone-binding globulin concentration (r = −0.41; P < 0.05). conclusion: Peripheral metabolism of adrenal androgen precursors may be required for any androgenic effects in PA. However, the limitations in the sensitivity of the bioassay developed herein may hide some differences between the PA and control children. t he reticular zone (zona reticularis (ZR)) of the adrenal cortex starts to develop from small focal islets in early childhood (1). Later on, continuous ZR begins to produce weak androgen precursors, mostly dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), and this phenomenon is referred to as adrenarche. During adrenarche, increasing androgenic activity leads to greasiness of the skin and hair, comedones/acne, adult-type body odor, and finally to the development of axillary and pubic hair. Though not uniformly used, adrenarche may be defined as premature (premature adrenarche (PA)) if these clinical signs are evident together with elevated serum levels of adrenal androgens before the age of 8 y in girls or 9 y in boys (2).In both normal-timed and PA, the clinical signs of androgen activity do not correlate well with the circulating levels of DHEA, DHEAS, or androstenedione (A4) (2,3). In peripheral tissues such as the skin, DHEA and DHEAS interconvert via hydroxysteroid sulfotransferase and steroid sulfatase (4), but DHEAS desulfonation in the liver is controversial (5). DHEAS is biologically inactive, and DHEA is only a weak androgen receptor (AR) agonist (6), but they are present in the serum of PA subjects in excess concentrations.The effects of androgens are mediated via the AR, resulting in the activation of target gene transcription (7). Whereas testosterone (T) and dihydrotestosterone (DHT) are potent AR agonists, the affinity of adrenal androgen precursors to AR is weak (6,8), and prereceptor level conversion to more potent androgens is needed for the full activation of AR. In peripheral tissues, DHEA is converted to the most potent androgen, DHT, through A4 and T. The main enzymes responsible for this intracrine co...

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