-
Clinical Pediatric Endocrinology : Case... 2020
PubMed: 32694892
DOI: 10.1297/cpe.29.131 -
Clinical Pediatric Endocrinology : Case... 2020
Response to the Letter to the Editor of entitled "Nutritional thrift can be associated with precocious puberty and premature adrenarche in children born small for gestational age" by Hüseyin Anıl Korkmaz, Clin Pediatr Endocri (2020) 29: 131-132.
PubMed: 32694893
DOI: 10.1297/cpe.29.133 -
Journal of Pediatric Endocrinology &... Jun 2023Premature adrenarche is often linked to a cluster of endocrine-metabolic risk factors. Our objective was to explore the association of dehydroepiandrosterone sulfate...
OBJECTIVES
Premature adrenarche is often linked to a cluster of endocrine-metabolic risk factors. Our objective was to explore the association of dehydroepiandrosterone sulfate (DHEAS) levels at age 7 with cardio-metabolic traits at ages 10 and 13, independently of adiposity and pubertal stage.
METHODS
Longitudinal study of 603 individuals (301 girls/302 boys) from the Generation XXI birth cohort. DHEAS at age 7 was measured by immunoassay. Anthropometrics, pubertal staging, blood pressure, and metabolic outcomes were evaluated at ages 7, 10, and 13. Pearson correlations between DHEAS and cardio-metabolic traits (insulin, HOMA-IR, triglycerides, LDL-cholesterol, high-sensitivity C-reactive protein, and systolic and diastolic blood pressure) were computed. Path analysis was used to estimate the effect of DHEAS at age 7 on cardiometabolic traits at ages 10 and 13, adjusted for body mass index (BMI) z-score and Tanner stage.
RESULTS
DHEAS at age 7 correlated positively with insulin and HOMA-IR at ages 7 and 10 in both sexes, and at age 13 in girls, but not in boys. In girls, DHEAS levels at age 7 directly influenced HOMA-IR at age 13, controlling for BMI and Tanner stage. In boys, DHEAS at age 7 did not influence HOMA-IR at ages 10 and 13. DHEAS at age 7 did not influence the other cardio-metabolic outcomes analyzed.
CONCLUSIONS
DHEAS levels in mid-childhood have a positive longitudinal association with on insulin-resistance that persists, in girls, but not in boys, at least until age 13. No association was found regarding dyslipidemia, hypertension, or low-grade inflammation.
Topics: Male; Female; Humans; Child; Adolescent; Dehydroepiandrosterone Sulfate; Longitudinal Studies; Birth Cohort; Insulin Resistance; Insulin; Body Mass Index
PubMed: 37141272
DOI: 10.1515/jpem-2022-0593 -
Journal of Research in Medical Sciences... 2020Prolactinoma is a rare tumor of childhood. Clinical presentations of prolactinoma include amenorrhea, delayed puberty, and galactorrhea. For the first time, in this...
Prolactinoma is a rare tumor of childhood. Clinical presentations of prolactinoma include amenorrhea, delayed puberty, and galactorrhea. For the first time, in this case, elevated prolactin levels were associated with unexpected premature pubarche. We describe an 8-year, 7-month-old boy with acne and gradual appearance of pubic hair, corresponding to tanner stage 2. Hormonal tests showed severe hyperprolactinemia (prolactin = 246.8 μg/L and pooled prolactin = 175 μg/L and macroprolactin = 5 μg/L) and mildly elevated level of dehdroepiandrostenedion sulfate (DHEAS) and testosterone. Magnetic resonance imaging (MRI) findings confirmed the presence of a pituitary macroprolactinoma, measuring 14 mm × 12 mm × 8 mm on the right side of the pituitary gland. Cabergoline therapy was commenced (0.5 mg/week) and after 3 months, no evidence of pubarche progression was observed. Prolactin level and tumor size markedly reduced. At the 9-month follow-up visit, a normal MRI was reported. This case highlights that even when facing premature pubarche, careful examination is mandatory, and if no obvious etiology is found for premature pubarche, clinicians should consider prolactinoma.
PubMed: 33824673
DOI: 10.4103/jrms.JRMS_118_20 -
The Australasian Journal of Dermatology Aug 2023Acne vulgaris, a common dermatological condition that affects most adolescents and young adults, can indicate an underlying pathology if present prematurely in...
Acne vulgaris, a common dermatological condition that affects most adolescents and young adults, can indicate an underlying pathology if present prematurely in mid-childhood. Premature acne can be caused by premature adrenarche secondary to non-classical congenital adrenal hyperplasia (NC-CAH), a condition arising from 21-hydroxylase deficiency. This report describes a pair of monozygotic twin brothers with identical premature onset of acne, who were found to have an identical homozygous mutation in the promoter region of the CYP21A2 gene. While it is widely known that NCCAH is associated with genetic changes, the drive behind onset of adrenarche are widely unknown. As such, this report provokes thoughts on whether adrenarche could be influenced by adrenal genetic polymorphisms.
Topics: Male; Adolescent; Young Adult; Humans; Child; Twins, Monozygotic; Adrenal Hyperplasia, Congenital; Puberty, Precocious; Acne Vulgaris; Steroid 21-Hydroxylase
PubMed: 37387304
DOI: 10.1111/ajd.14117 -
Frontiers in Endocrinology 2023Most children with non-classic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency are asymptomatic and do not require cortisol replacement therapy...
Most children with non-classic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency are asymptomatic and do not require cortisol replacement therapy unless they develop symptoms of hyperandrogenemia. The current practice is to treat symptomatic children with hydrocortisone aimed at suppressing excess adrenal androgen production irrespective of the child's level of endogenous cortisol production. Once on hydrocortisone therapy, even children with normal cortisol production require stress dosing. Some children with NC-CAH may present with premature adrenarche, growth acceleration, and advanced bone age, but with no signs of genital virilization and normal endogenous cortisol production. In these cases, an alternative therapy to hydrocortisone treatment that does not impact the hypothalamic-pituitary-adrenal axis, but targets increased estrogen production and its effects on bone maturation, could be considered. Aromatase inhibitors (AIs), which block the aromatization of androgen to estrogen, have been used off-label in men with short stature to delay bone maturation and as an adjunct therapy in children with classic CAH. The use of AI as a monotherapy for children with NC-CAH has never been reported. We present three pre-pubertal female children with a diagnosis of NC-CAH treated with anastrozole monotherapy after presenting with advanced bone age, early adrenarche, no signs of genital virilization, and normal peak cortisol in response to ACTH stimulation testing. Bone age z-scores normalized, and all three reached or exceeded their target heights. Monotherapy with anastrozole can be an effective alternative in slowing down bone maturation and improving height outcomes in children with NC-CAH and normal adrenal cortisol production.
Topics: Child; Female; Humans; Adrenal Hyperplasia, Congenital; Anastrozole; Androgens; Estrogens; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Virilism
PubMed: 36936152
DOI: 10.3389/fendo.2023.1101843 -
Journal of the Endocrine Society Oct 2019Premature adrenarche (PA) is associated with childhood overweight and hyperinsulinemia; the long-term cardiometabolic outcome is unknown.
CONTEXT
Premature adrenarche (PA) is associated with childhood overweight and hyperinsulinemia; the long-term cardiometabolic outcome is unknown.
OBJECTIVE
To study cardiometabolic profile in adult women with previous PA.
DESIGN AND PARTICIPANTS
Thirty women with PA and 41 control subjects were followed from prepuberty to young adulthood.
MAIN OUTCOME MEASURES
Prevalence of the metabolic syndrome (MetS) and clinical and biochemical cardiovascular risk factors.
RESULTS
There were no differences in the prevalence of MetS or in any parameters indicating dyslipidemia, hypertension, hepatosteatosis, atherosclerosis, or low-grade inflammation between the study groups. However, prevalence of insulin resistance (IR; = 0.014) and acanthosis nigricans ( = 0.010) was higher in the PA group. Neither fasting glucose nor insulin concentrations differed between the study groups, but HbA1c [adjusted for body mass index (BMI) = 0.011] and Homeostatic Model Assessment of Insulin Resistance ( = 0.044; BMI-adjusted = nonsignificant) were higher in the PA group. Although BMI and fat percentage were comparable between the study groups, the PA group had higher central fat mass than the control group. In the whole study population, MetS and IR were associated with greater adult fat mass, but no prepubertal factors predicting later IR were found.
CONCLUSION
PA does not seem to be associated with MetS, dyslipidemia, hypertension, atherosclerosis, or low-grade inflammation in young adult women. However, some women with PA may be at an increased risk of unfavorable glucose metabolism, which is associated with increased central adiposity at adult age rather than determined by prepubertal factors.
PubMed: 31528825
DOI: 10.1210/js.2019-00193 -
Clinical Endocrinology Mar 2022A nonclassic form of 11β-hydroxylase deficiency (NC11β-OHD) has been reported to cause mild androgen excess symptoms. Currently, the gold standard for biochemical...
OBJECTIVE
A nonclassic form of 11β-hydroxylase deficiency (NC11β-OHD) has been reported to cause mild androgen excess symptoms. Currently, the gold standard for biochemical diagnosis is elevated 11-deoxycortisol (11-DOC) levels after corticotropin stimulation test (ACTHstimT). However, there are no clear 11-DOC level cutoffs. One of the accepted references for 11-DOC levels for the paediatric population was published in 1991 by Lashansky et al. AIM: To determine the correlation between 11-DOC levels measured during ACTHstimT and clinical symptoms attributed to NC11β-OHD.
DESIGN
A retrospective study including all paediatric patients who underwent ACTHstimT at Shamir Medical Center between 2007 and 2015. Clinical data were collected from the patients' medical files. Outcome measures included the number of patients with hyperandrogenism signs and predefined elevated 11-DOC cut-off levels according to Lashansky for sex and age, and according to commercial kit cut-offs.
RESULTS
Data were complete at presentation for 136 patients. Long-term clinical data were documented for 98 patients, mean follow-up duration of 3.1 years (1.37-5.09). There was no statistically significant difference in the number of cases with elevated 11-DOC according to both cut-offs and early puberty, premature adrenarche nor acne. Follow-up data demonstrated no statistically significant difference in the number of cases with elevated 11-DOC levels among patients with compromised final adult height, polycystic ovarian syndrome or hyperandrogenism.
CONCLUSIONS
Basal and corticotropin stimulated 11-DOC levels were not significantly elevated above the 1.5 times cut-offs according to paediatric-specific norms or the commercial assay in paediatric individuals with possible clinical suspicion of NC11β-OHD.
Topics: Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Child; Cortodoxone; Female; Humans; Hyperandrogenism; Male; Mixed Function Oxygenases; Puberty, Precocious; Retrospective Studies
PubMed: 34596265
DOI: 10.1111/cen.14597 -
Hormone Research in Paediatrics Mar 2024Children with premature adrenarche (PA) have increased adrenal androgen concentrations and earlier pubertal development than their peers. Early sexual maturation and...
INTRODUCTION
Children with premature adrenarche (PA) have increased adrenal androgen concentrations and earlier pubertal development than their peers. Early sexual maturation and exposure to androgens have both been associated with an increased risk for neuropsychological adversities in adulthood. Such adversities would presumably influence the experienced health-related quality of life (HRQoL) of those affected.
METHODS
A longitudinal case-control cohort study, in which 30 PA girls and 40 age-matched controls were followed from childhood to young adult age. The main outcome measure was the total 15D HRQoL score. In addition, we assessed specific dimensions of the questionnaire, the subjects' relationship statuses and living arrangements.
RESULTS
There were no differences between the groups in the overall 15D scores (PA, 0.956 (0.052); control, 0.947 (0.055); p 0.482), or on any dimension of this instrument.
CONCLUSION
The study suggests that a history of PA does not lead to impaired HRQoL in adult age.
PubMed: 38471476
DOI: 10.1159/000538283 -
Frontiers in Endocrinology 2020An increase of serum dehydroepiandrosterone (DHEA) sulfate (DHEAS) is observed in premature adrenarche and congenital adrenal hyperplasia. Very high DHEAS levels are...
An increase of serum dehydroepiandrosterone (DHEA) sulfate (DHEAS) is observed in premature adrenarche and congenital adrenal hyperplasia. Very high DHEAS levels are typical for adrenal tumors. Approximately 74% of DHEAS is hydrolyzed to DHEA by the steroid sulfatase (STS). The reverse reaction is DHEA sulfation. Besides these two enzyme reactions, the DHEAS transported through the cell membrane is important for its distribution and excretion. We present a female adolescent with overweight and a very high DHEAS. The presence of a DHEAS-producing tumor was rejected using ultrasonography, Magnetic Resonance Tomography (MRT), and dexamethasone suppression. STS deficiency was suspected. Sequence analysis revealed a heterozygous nonsense mutation which predicts a truncation of the carboxyl region of the STS that is implicated in substrate binding. No partial gene deletion outside exon 5 was detected by multiplex ligation-dependent probe amplification. The bioassay revealed normal enzyme activity in the patient's leukocytes. A defect of transporter proteins was suggested. Both efflux [multidrug-resistance protein (MRP)2 and breast cancer-resistance protein (BCRP)] and uptake [organic anion-transporting polypeptide (OATP) and organic anion transporter (OAT) carriers] transporters were studied. Sequence analysis of exons revealed a heterozygous Q141K variant for BCRP. A novel heterozygous nonsense mutation in the gene and a known heterozygous missense variant in the gene were found. The heterozygous nonsense mutation in the gene is not supposed to be responsible for STS deficiency. The BCRP variant is associated with reduced efflux transport activity only in its homozygous state. The combination of the two heterozygous mutations could possibly explain the observed high levels of DHEAS and other sulfated steroids.
Topics: Adolescent; Case-Control Studies; Codon, Nonsense; Dehydroepiandrosterone Sulfate; Female; Humans; Multidrug Resistance-Associated Protein 2; Pediatric Obesity; Prognosis; Steryl-Sulfatase; Young Adult
PubMed: 32435230
DOI: 10.3389/fendo.2020.00240