ABSTRACT
Aim
Aetiological factors affecting the phenotype of adrenarche are largely unknown. This study investigated the phenotypic variability of premature adrenarche.
Methods
In this cross‐sectional retrospective registry study, data on 91 mainly Caucasian children diagnosed with premature adrenarche were retrieved from patient records. Hormonal and growth‐related variables were analysed, and the data were further divided into subgroups to explore variations in different phenotypes of premature adrenarche.
Results
We studied 91 children with premature adrenarche (23% boys) with median ages of 7.5 years (range 4.5–8.9) for boys and 6.8 years (4.3–8.0) for girls. They displayed increased height and weight, elevated androgen levels, and clinical signs of androgen action. Bone age was advanced by approximately 1 year, with overweight children showing more advanced bone age and linear growth. Adult heights predicted with bone age were comparable to mean parental heights. Girls with more advanced bone age had higher dehydroepiandrosterone sulfate (DHEAS) levels. Interestingly, early (< 6 years) diagnosed children exhibited higher height standard deviation scores but lower DHEAS levels compared to those diagnosed later (≥ 6 years).
Conclusions
Despite advanced bone age, predicted adult heights remained normal in premature adrenarche. Subgroup differences suggested the heterogeneity of aetiological factors in premature adrenarche.
Keywords: adrenal cortex, adrenarche, adult height, bone age, dehydroepiandrosterone sulfate
Summary.
Premature adrenarche presents with variable clinical features, and this study examined clinical, hormonal and growth characteristics in Finnish children diagnosed between 2014 and 2023.
Most children exhibited typical features of premature adrenarche, including advanced bone age, elevated androgen levels, and increased height and weight, with subgroup differences suggesting phenotypic variability.
Despite growth acceleration, predicted adult height remained normal, questioning the routine need for bone age assessment in all cases.
Abbreviations
- DHEAS
Dehydroepiandrosterone sulfate
- SD
Standard deviation
1. Introduction
Adrenarche refers to the maturation of the zona reticularis of the adrenal cortex. It leads to increased production of androgen precursors, such as dehydroepiandrosterone sulfate (DHEAS), androstenedione and 11‐hydroxyandrostenedione [1]. Androgen levels begin to rise in early childhood [2], eventually causing clinical signs of androgen action. These signs include pubic and axillary hair, adult‐like body odour, oily skin and hair, and acne or comedones [1]. Low birth weight, rapid growth, and weight gain in early childhood are associated with increased serum DHEAS levels and earlier timing of adrenarche [3, 4, 5]. However, factors regulating the timing and strength of adrenarche remain largely unknown.
According to current criteria, adrenarche is considered premature if clinical androgenic signs and elevated circulating DHEAS levels are observed before the age of eight in girls and nine in boys [1, 6, 7]. DHEAS levels over 1 μmol/L are traditionally considered a threshold for diagnosing premature adrenarche, although clinical signs can also appear with lower levels [6, 8]. The physical manifestations of adrenarche typically develop gradually, often beginning with adult‐type body odour and oily skin, and followed later by the appearance of pubic hair (i.e., pubarche) [6, 7]. This sequence reflects the progressive increase in androgen secretion from the maturing zona reticularis and the variable sensitivity of peripheral target tissues in modifying and expressing androgen effects. In this context, very early pubarche may be viewed as a more pronounced or ‘severe’ presentation of premature adrenarche. The diagnosis of premature adrenarche requires the exclusion of other causes of excess androgen production and effects, such as virilising tumours, central puberty, or congenital adrenal hyperplasia. With criteria that included at least one clinical sign and DHEAS concentration above one μmol/L, the prevalence of premature adrenarche was 8.6% in girls and 1.8% in boys in a Finnish cohort study [8].
Children with premature adrenarche are typically taller and heavier than their peers, and their bone age is often advanced compared to their chronological age [1, 9]. These physical characteristics are associated with elevated adrenal androgen production [10, 11], which may persist into late puberty [12]. However, the factors determining the degree of bone age and growth advancement remain largely unclear. Interestingly, children with markedly different growth trajectories, hormonal profiles, and clinical manifestations of androgen activity may show similar degrees of skeletal maturation.
The accelerated growth seen in these children reflects an earlier use of their growth potential [13]. This observation has raised concerns about a possible reduction in final adult height, particularly among those with more drastic phenotypes of premature adrenarche. While most children with premature adrenarche seem to achieve an adult height within their genetically determined target range [13, 14, 15, 16], the contribution of childhood bone age advancement to adult height outcomes has not been extensively studied.
Weight status also plays a role in skeletal development. Being overweight in childhood is associated with advanced bone age [10, 11, 15, 17], although sex steroids contribute to bone maturation independently of body weight [10]. Notably, overweight associated with premature adrenarche appears to attenuate by adulthood [1, 14, 16, 18, 19].
In girls, premature adrenarche is associated with earlier onset of thelarche and menarche [9, 13, 14, 20], reflecting an overall acceleration of pubertal development. This early maturation, coupled with prolonged exposure to higher levels of androgens, may have unfavourable effects on metabolic regulation. Indeed, premature adrenarche may serve as an early indicator of later adverse metabolic and reproductive outcomes in some cases [21].
Finnish children with premature adrenarche have previously been studied (e.g., [2, 3, 5, 8, 9, 13, 16, 18, 19]), but no retrospective real‐life studies on patient registries have been conducted in Finland. The objective of this study was to investigate factors governing premature adrenarche and its clinical manifestations, such as growth advancement and clinical signs, in Finnish children diagnosed with premature adrenarche. We hypothesised that the children would express typical characteristics of premature adrenarche, such as elevated DHEAS and other adrenal androgens, advanced bone age, and variable clinical signs of androgen action.
2. Patients and Methods
Patients with the E27.0 diagnosis code according to the International Classification of Diseases, 10th Edition (ICD‐10) [22] were retrieved from the Kuopio University Hospital patient register between 1 January 2014 and 31 December 2023. Subsequently, all visits other than the initial visits were excluded, and the dataset retained only the first visit of each patient, during which premature adrenarche was recorded as a diagnosis. Premature adrenarche diagnoses were confirmed by at least one clinical sign of androgen action and DHEAS levels above one μmol/L before the age of 8 years in girls or 9 years in boys through review of patient records. It was ensured that other potential causes of hyperandrogenism (virilizing tumours, precocious central puberty, and congenital adrenal hyperplasia) had been appropriately excluded.
Initially, 119 patients with premature adrenarche (19.3% boys) were identified. Of these, 25 girls over 8 years of age and two boys over 9 years of age were excluded. In addition, one girl with central precocious puberty, confirmed by the gonadotropin‐releasing hormone stimulation test, was removed from the dataset. The final dataset comprised 91 premature adrenarche patients (23.1% boys) and their background characteristics, auxological measurements, clinical findings, and hormone concentrations (Figure 1).
FIGURE 1.
Flowchart illustrating the subject selection process for this study.
Additional variables were derived from retrieved data. Bone age standard deviation (SD) scores and predicted adult height values were calculated using the BoneXpert method and the Adult Height Predictor software, Version 3. This software is based on the BoneXpert artificial intelligence system for bone age analysis (Visiana, Hørsholm, Denmark) [23, 24]. BoneXpert predicts the child's adult height based on ethnicity, gender, age, height, bone age, and parental heights. The difference between bone age and chronological age was also calculated. Birth weight and length SD score values and all age and sex‐standardised childhood length/height SD scores, body mass index (BMI) SD score, and ISO‐BMI values were calculated using the Finnish national references [25]. ISO‐BMI was converted from prepubertal BMI, and it represents a BMI that is used for adults. Mid‐parental height was calculated as the mean of parental heights, corrected for sex: −6.8 cm for girls and +6.8 cm for boys.
To gain insights into possible differences in the aetiology of premature adrenarche among these children, the data were also divided into different subgroups based on predefined variables of interest. These variables included the difference between bone age and chronological age (< +1 vs. ≥ +1 years), age at diagnosis (< 6 vs. ≥ 6 years), and weight status (normal or underweight vs. overweight or obese).
Biochemical concentrations were also extracted from the patient records. They had been determined by an accredited laboratory either in Kuopio (Islab, Kuopio, Finland) or in Helsinki (HUSLAB, Helsinki, Finland). DHEAS, luteinising hormone (LH), and follicle‐stimulating hormone (FSH) concentrations were assessed using the electrochemiluminescence method, and androstenedione, testosterone, estradiol, and 17‐hydroxyprogesterone concentrations using liquid chromatography–tandem mass spectrometry. The sensitivities of the assays were 0.01 nmol/L for estradiol, 0.1 μmol/L for DHEAS, 0.1 U/L for LH and FSH, 0.5 nmol/L for 17‐hydroxyprogesterone, 0.1 nmol/L for androstenedione, and 0.3 nmol/L for testosterone.
Statistical analyses were performed using SPSS Version 29 (IBM Corp, New York, USA). The distributions of the variables were analysed by observing histograms. Correlations between variables were determined using two‐tailed Pearson's correlation coefficients. A linear regression model was used to identify factors affecting the outcome variables. Differences between the groups were analysed using the Mann–Whitney U‐test with continuous variables and the Chi‐square test with categorical variables. A p‐value of less than 0.05 was considered statistically significant.
2.1. Ethics
This retrospective register study was carried out in accordance with the ethical principles stated in the Declaration of Helsinki and the Finnish Act on the Secondary Use of Health and Social Data (552/2019). This study protocol was reviewed and approved by the Wellbeing Services County of Northern Savo (Kuopio, Finland). Registry data were acquired under a data permit issued by Wellbeing Services County of Northern Savo (Kuopio, Finland) pursuant to section 38 of the Finnish Act on the Secondary Use of Health and Social Data (552/2019). Pursuant to sections 6 and 35 of the same Act, the use of data covered by such data permit does not require consent of the participants.
3. Results
3.1. Background Characteristics and Clinical Findings
The background characteristics of the 70 girls and 21 boys with premature adrenarche are shown in Table 1. The majority (96%) were Caucasian. Most of the girls with premature adrenarche had been born slightly smaller than average Finnish children (Table 1). Three of the 21 boys (21%) and three of the 70 girls (7%) were born small for gestational age (SGA), while two boys (14%) and eight girls (18%) were born preterm. Both sexes had an increased mean height and BMI at diagnosis (Table 1). Girls were diagnosed earlier than boys. The appearance of adult‐type body odour was the most common and usually the first sign of premature adrenarche (Table 1). At the same time, four (6%) of the girls and two (10%) of the boys only expressed accelerated growth or bone age development despite having DHEAS levels of over one μmol/L. Children with premature pubarche showed higher DHEAS levels, with a mean of 2.6 μmol/L with premature pubarche compared to 2.1 μmol/L without premature pubarche, with a p‐value of 0.20.
TABLE 1.
Background characteristics of 70 girls and 21 boys with premature adrenarche.
| Boys (n = 21) | Girls (n = 70) | p | |
|---|---|---|---|
| At birth | |||
| Gestational age, weeks | 39.0 (38.4 to 39.7) a | 38.2 (37.2 to 39.3) b | 0.70 |
| Birth weight, kg | 3.6 (3.3 to 3.9) c | 3.1 (3.0 to 3.3) d | 0.01 |
| Birth weight, SD score | −0.2 (−1.3 to 1.0) a | −0.7 (−1.1 to −0.4) e | 0.47 |
| Birth length, cm | 50.9 (49.7 to 52.1) c | 48.8 (48.0 to 49.6) d | 0.02 |
| Birth length, SD score | 0.2 (−0.9 to 1.2) a | −0.6 (−0.9 to −0.2) e | 0.10 |
| Born preterm, n (%) | 2 (14) | 8 (18) | 0.73 |
| Born small for gestational age, n (%) | 3 (21) | 3 (7) | 0.12 |
| At diagnosis | |||
| Age, years | 7.5 (6.9 to 8.1) | 6.8 (6.5 to 7.0) | 0.004 |
| Height, cm | 131.8 (127.5 to 136.1) | 126.2 (124.4 to 128.0) | 0.02 |
| Height, SD score | 1.0 (0.4 to 1.6) | 0.9 (0.6 to 1.1) | 0.79 |
| Weight, kg | 31.5 (28.1 to 34.9) | 28.8 (27.3 to 30.3) | 0.17 |
| ISO‐BMI | 25.4 (23.0 to 27.8) | 24.5 (23.4 to 25.5) | 0.72 |
| BMI, SD score | 0.7 (0.2 to 1.1) | 0.8 (0.4 to 1.1) | 0.45 |
| Clinical signs present (%) | |||
| Accelerated growth | 10 | 6 | 0.54 |
| Adult‐type body odour | 86 | 79 | 0.47 |
| Oily hair | 14 | 37 | 0.05 |
| Acne/comedones | 29 | 33 | 0.71 |
| Axillary hair | 0 | 16 | 0.05 |
| Pubic hair (Tanner ≥ P2) | 19 | 23 | 0.71 |
| Weight classification according to ISO‐BMI (%) | |||
| Underweight (< 17) | 0 | 4 | 0.69 |
| Normal weight (17.0–24.9) | 57 | 53 | |
| Overweight (25.0–29.9) | 24 | 31 | |
| Obese (> 30) | 19 | 11 | |
Note: Continuous variables are expressed as mean (95% CI). and categorical variables as %. Differences between the boys and the girls were analysed using the Mann–Whitney U‐test with continuous variables and the Chi‐square test with categorical variables. p‐values less than 0.05 are highlighted in bold. ISO‐BMI was translated from prepubertal BMI SDS, corresponding to BMI used for adults. Weight classification was done according to Finnish growth references.
Abbreviations: BMI, body mass index; SD, standard deviation.
n = 13.
n = 44.
n = 19.
n = 64.
n = 41.
3.2. Hormone Levels and Bone Age
Table 2 presents hormone levels separately in girls and boys. All children with premature adrenarche had elevated DHEAS and androstenedione concentrations [26]. All subjects had LH values at prepubertal levels (< 0.3 mU/L). 17‐hydroxyprogesterone values were low, providing evidence for excluding congenital adrenal hyperplasia. Estradiol values were quantifiable for 23 girls (≥ 0.01 nmol/L), while 22 girls had estradiol concentrations below the sensitivity limit of 0.01 nmol/L.
TABLE 2.
Differences in hormone levels between the girls and the boys.
| All children | Boys (n = 21) | Girls (n = 70) | p | |
|---|---|---|---|---|
| DHEAS, μmol/L | 2.3 (2.0–2.5) l | 2.7 (2.0–3.3) a | 2.1 (1.9–2.4) g | 0.20 |
| Androstenedione, nmol/L | 1.0 (0.9–1.2) m | 0.9 (0.5–1.4) b | 1.0 (0.9–1.2) h | 0.16 |
| 17‐hydroxyprogesterone, nmol/L | 1.3 (1.0–1.6) n | 1.1 (0.6–1.7) c | 1.4 (1.1–1.7) i | 0.19 |
| Luteinizing hormone, U/L | < 0.3 m | < 0.3 d | < 0.3 j | 0.55 |
| Follicle‐stimulating hormone, U/L | 1.3 (1.0–1.6) o | 0.8 (0.6–1.0) e | 1.4 (1.1–1.7) j | 0.004 |
| Estradiol, nmol/L | 0.01 (0.01–0.02) k | N/A | 0.01 (0.01–0.02) k | N/A |
| Testosterone, nmol/L | 0.5 (< 0.1–1.0) f | 0.5 (< 0.1–1.0) f | N/A | N/A |
Note: Values are presented as mean (95% CI). Differences between the girls and boys were analysed using the Mann–Whitney U‐test and statistically significant differences at the level of p‐value less than 0.05 are highlighted with bold.
Abbreviations: DHEAS, dehydroepiandrosterone sulfate; N/A, not available.
n = 18.
n = 14.
n = 17.
n = 12.
n = 11.
n = 13.
n = 60.
n = 40.
n = 48.
n = 52.
n = 23.
n = 78.
n = 64.
n = 65.
n = 64.
Bone age was advanced by approximately 1 year in all children with premature adrenarche, and their predicted adult height was higher than mean parental height, particularly in boys (Table 3). The difference between bone age and chronological age correlated positively with ISO‐BMI (r = 0.342, p = 0.010) and DHEAS concentrations (r = 0.408, p = 0.002) in all children.
TABLE 3.
Bone age, predicted adult height, and mid‐parental height in 70 girls and 21 boys with premature adrenarche.
| All children (n = 91) | Girls (n = 70) | Boys (n = 21) | p | |
|---|---|---|---|---|
| Bone age, SD score | 1.2 (0.9–1.4) a | 1.1 (0.8–1.4) c | 1.4 (0.8–2.1) f | 0.41 |
| Difference between bone age and chronological age, years | 1.0 (0.8–1.3) a | 1.0 (0.7–1.2) c | 1.1 (0.3–1.9) f | 0.89 |
| Predicted adult height, cm | 171.4 (168.8–173.8) b | 167.7 (166.0–169.4) d | 184.7 (180.4–189.0) g | < 0.001 |
| Mid‐parental height, cm | 167.8 (165.8–169.7) b | 164.8 (163.5–166.1) e | 178.8 (175.4–182.2) h | < 0.001 |
| Difference between predicted adult height and mid‐parental height, cm | 3.6 (2.1–5.1) b | 2.9 (1.2–4.7) d | 5.9 (2.6–9.2) g | 0.07 |
Note: Variables are expressed as mean (95% CI). Differences between the girls and the boys were analysed using the Mann–Whitney U‐test and P values less than 0.05 are highlighted in bold. MPH was calculated based on the parents' heights. PAH also took the bone age into account. PAH and BA SDS were calculated by using BoneXpert artificial intelligence system.
Abbreviation: SD, standard deviation.
n = 64.
n = 56.
n = 49.
n = 44.
n = 63.
n = 15.
n = 12.
n = 16.
3.3. Subgroup Analysis According to Bone Age Advancement
Table S1 in supplemental file shows differences in clinical and biochemical variables between the subgroups based on their difference between bone age and chronological age. Children with bone age advancement greater than 1 year had higher DHEAS, BMI, and systolic blood pressure compared to children with less than 1 year of bone age advancement. There were no significant differences in the expression of clinical signs of premature adrenarche between the subgroups. Unlike DHEAS, androstenedione levels were similar between the subgroups.
3.4. Subgroup Analysis According to Weight Status
Table S2 in the supplemental file presents differences in clinical and biochemical variables between the subgroups based on weight classification. Children with overweight and premature adrenarche had more advanced bone age and height SD scores, and higher systolic blood pressure. However, in all subjects, blood pressure tended to rise with greater height. Despite the lack of statistical significance, the DHEAS and androstenedione levels also tended to be higher in children with overweight and premature adrenarche, especially in girls. There were no significant differences in the expression of clinical signs of adrenarche between the subgroups.
3.5. Subgroup Analysis According to Age at Diagnosis
Differences in clinical and biochemical variables between the subgroups based on their age at diagnosis are depicted in Table S3 (supplemental file). Children diagnosed before the age of six had lower DHEAS concentrations (Figure 2) and were taller than children diagnosed after the age of six. Girls diagnosed earlier also tended to have higher birth length and less advanced bone age. Boys diagnosed earlier had lower BMI SD scores and ISO BMI values than those diagnosed later.
FIGURE 2.
Scatterplot illustrating the relationship between age at diagnosis and dehydroepiandrosterone sulfate (DHEAS).
4. Discussion
This retrospective study, conducted using patient records from a single university hospital, gathered and analysed all premature adrenarche diagnoses from 2014 to 2023. Its purpose was to provide an overview of children's characteristics and find associations between premature adrenarche‐related variables. The results followed our hypothesis that Finnish children with premature adrenarche would express typical characteristics of the condition. This study was the first Finnish premature adrenarche study based on patient registry data and provided a broader view of the characteristics of Finnish children with premature adrenarche.
The percentage of girls in the study is consistent with previous premature adrenarche studies, with most studies having the limitation of a small number of boys, as premature adrenarche typically appears more often in girls [8]. The children with premature adrenarche, especially girls, were born earlier and smaller than average Finnish children [25]. The prevalences of being born preterm (14%/18% for boys/girls, respectively) or small for gestational age (21%/7%) were higher than expected. However, it should be noted that gestational age and birth size measurements were not available for all children. Previously, the association between being born SGA and earlier timing of adrenarche has been reported in some studies [4, 13], but not in all [27, 28]. These varying findings between different study cohorts may be explained, for example, by differing postnatal growth patterns, which appear to be a significant factor modulating later development independently of birth size [3].
Clinical signs of androgen action appeared in a similar order in boys and girls. Adult‐type body odour was the most common and typically the first sign of premature adrenarche. Axillary and pubic hair were the rarest clinical signs of premature adrenarche, appearing later than other signs. The most significant differences were in the appearance of oily and axillary hair, with the girls expressing more of both. These findings are consistent with previous studies on Finnish children with premature adrenarche [8]. Four girls (6%) and two boys (10%) did not express clinical signs of androgen action, and they were diagnosed with premature adrenarche based on their DHEAS levels being over one μmol/L in addition to their increased weight, height, and bone age. The fraction of overweight and obese subjects was higher in our study (42% in both boys and girls), especially in girls, than in the general child population in Finland (37% in boys and 23% in girls) [29].
Children with premature adrenarche had elevated DHEAS values, congruent with the definition of premature adrenarche. These values were in the typical range for Tanner P stage 1–2 and Tanner B/G stage 1 [26]. Elevated androstenedione values also match the literature on premature adrenarche [1, 7, 12, 21, 30], and were in the typical range for Tanner B/G stage 1 [26]. DHEAS levels tended to rise with increased difference between bone age and chronological age and ISO BMI, as well as with age, corresponding well with prior studies [10, 11, 15, 17]. 17‐hydroxyprogesterone values were low, suggesting the low risk of having non‐classical congenital adrenal hyperplasia as a cause of premature adrenarche in these children. Testosterone levels in boys were prepubertal, with the upper limit of the normal range of Tanner G1 stage being 1.0 nmol/L [26].
Our subjects showed growth patterns typical for premature adrenarche, with moderate bone age advancement and increased weight and height at diagnosis. This growth and weight gain pattern is comparable to what has been seen in the previous premature adrenarche cohorts [5]. It is also similar to the previous findings of increased early growth rate and weight gain associated with an earlier timing of adrenarche [3, 4, 5]. Bone age advancement was approximately one year in all children. Children with premature adrenarche and more advanced bone age often exhibit a more pronounced phenotype of adrenarche [10, 11, 14], with higher weight and androgen levels. It has been speculated that the earlier height gain associated with bone age advancement in premature adrenarche might shorten adult height. Our subjects with a greater difference between bone age and chronological age had higher DHEAS concentrations and BMI SD score values. Their predicted adult height was taller than mid‐parental height, particularly in boys. Predicted adult height also fell within the average height range according to Finnish growth references [25]. It indicates that premature adrenarche does not significantly alter adult height, as shown in most other studies about premature adrenarche [13, 14, 15, 16]. These findings from us and others question the need for routine measurement of bone age in children with premature adrenarche, or at least in those children with mild phenotypes of premature adrenarche. However, rapid advancement in growth, premature pubarche, and other clinical signs than premature pubarche at an early age (under 6 years) should remain indications for bone age measurement.
Bone age advancement may be influenced by obesity, possibly due to its effects on peripheral steroid metabolism and aromatisation of androgens to oestrogens in adipose tissue [11, 15, 17]. Children with premature adrenarche and overweight also tend to show a more pronounced phenotype of premature adrenarche and possibly have an increased risk of abnormal glucose metabolism [19]. Consistent with previous studies, children who were overweight and had premature adrenarche had higher bone age and height SD scores than children with normal weight and premature adrenarche [10, 11, 15, 17]. DHEAS and androstenedione levels also tended to be higher in overweight children.
There are also possible differences in phenotypes regarding the timing and strength of adrenarche. Some children exhibit clinical signs of adrenarche significantly earlier than others, indicating the importance of early life factors in the development of adrenarche [2]. Very early presentation of clinical signs could be explained by an earlier and faster tempo of underlying zona reticularis development and androgen production or by differences in steroid metabolism and androgen action in target tissues. Children diagnosed before the age of six had lower DHEAS concentrations, though still elevated for age [2, 26]. They also had a higher height SD score than children diagnosed later, which is consistent with the findings that children with premature adrenarche use more of their growth potential earlier compared to children without premature adrenarche [9, 13, 14]. Girls with an early diagnosis also tended to have higher birth length and less advanced bone age, while the boys diagnosed earlier had lower BMI SD score than the boys diagnosed later.
All these differences in our subgroup analyses suggest heterogeneity in the etiological factors behind the development of premature adrenarche. There might also be different subgroups with different long‐term outcomes among children with premature adrenarche. This view was also discussed in a recent adrenarche review [21] and supported by other researchers who speculated that there might be different premature adrenarche subgroups based on weight status and insulin sensitivity [30].
4.1. Strengths and Limitations
Although our findings are consistent with those of previous studies, a key strength of the present study lies in its use of a comprehensive and standardised bone age dataset from a relatively large cohort of children with premature adrenarche. The limitations were the small number of boys, as in other premature adrenarche studies, and the small number of data points in certain variables. As this was a cross‐sectional retrospective registry study, we lacked longitudinal clinical or biochemical follow‐up data, including final achieved adult height. Similarly, no information on adverse outcomes in adulthood was available. As our dataset consisted primarily of Caucasian children, our study might not apply as accurately to children of other ethnicities. Because premature adrenarche is considered a benign condition in most cases and mild clinical signs of androgen production are easily overlooked, children with premature adrenarche with a milder phenotype are not usually evaluated in specialised care in Finland. This might have led to the exclusion of many children with premature adrenarche from our dataset. The data were also collected only from a single centre providing secondary and tertiary care.
5. Conclusion
Finnish children with premature adrenarche evaluated in our hospital expressed typical characteristics of premature adrenarche, with advanced bone age, higher androgen levels, and increased height and weight at diagnosis. However, there were slight differences in the characteristics of the children owing to the differences in body composition, age at diagnosis, bone age advancement, and hormone levels. Predicted adult height seems normal, raising questions about the necessity of routine bone age assessment for all patients with premature adrenarche. More extensive follow‐up studies on premature adrenarche are needed to better understand the condition's underlying factors and variable presentation. Given that premature adrenarche is often a normal variant, longitudinal follow‐up studies are especially needed to identify subgroups and biomarkers that may predict an elevated risk of adverse long‐term outcomes.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Table S1: Differences in clinical and biochemical variables between the subgroups based on their bone age and chronological age difference (BA‐CA).
Table S2: Differences in clinical and biochemical variables between the subgroups based on their weight classification.
Table S3: Differences in clinical and biochemical variables between premature adrenarche subgroups based on their age at diagnosis.
Acknowledgement
Open access publishing facilitated by Ita‐Suomen yliopisto, as part of the Wiley ‐ FinELib agreement.
Funding: The authors received no specific funding for this work.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1: Differences in clinical and biochemical variables between the subgroups based on their bone age and chronological age difference (BA‐CA).
Table S2: Differences in clinical and biochemical variables between the subgroups based on their weight classification.
Table S3: Differences in clinical and biochemical variables between premature adrenarche subgroups based on their age at diagnosis.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.