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Frontiers in Endocrinology 2023Prader-Willi syndrome (PWS) is a rare genetic disorder resulting from lack of expression of the paternally derived chromosome 15q11-13, associated with several... (Review)
Review
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 β-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.
Topics: Female; Humans; Prader-Willi Syndrome; Diabetes Mellitus, Type 1; Adrenal Hyperplasia, Congenital; Human Growth Hormone; Obesity
PubMed: 37124733
DOI: 10.3389/fendo.2023.1148318 -
Clinical Pediatric Endocrinology : Case... 2022We aimed to determine the prevalence of early puberty in girls with premature pubarche and analyze the time interval between their pubarche and succeeding thelarche....
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.
PubMed: 35002065
DOI: 10.1297/cpe.2021-0042 -
EClinicalMedicine Dec 2021Extremely tall children (defined as height SDS (HSDS) ≥+3) are frequently referred to specialized healthcare for diagnostic work-up. However, no systematic studies...
BACKGROUND
Extremely tall children (defined as height SDS (HSDS) ≥+3) are frequently referred to specialized healthcare for diagnostic work-up. However, no systematic studies focusing on such children currently exist. We investigated the aetiology, clinical features, and auxological clues indicative of syndromic tall stature in extremely tall children subject to population-wide growth monitoring and screening rules.
METHODS
Subjects with HSDS ≥+3 after three years of age born between 1990 and 2010 were identified from the Helsinki University Hospital district growth database. We comprehensively reviewed their medical records up to December 2020 and recorded underlying diagnoses, auxological data, and clinical features.
FINDINGS
We identified 424 subjects (214 girls and 210 boys) who fulfilled the inclusion criteria. Underlying growth disorder was diagnosed in 61 (14%) patients, in 36 (17%) girls and 25 (12%) boys, respectively (P=0•15). Secondary causes were diagnosed in 42 (10%) patients and the two most frequent secondary diagnoses, premature adrenarche, and central precocious puberty were more frequent in girls. Primary disorder, mainly Marfan or Sotos syndrome, was diagnosed in 19 (4%) patients. Molecular genetic studies were used as a part of diagnostic work-up in 120 subjects. However, array CGH or next-generation sequencing studies were seldom used. Idiopathic tall stature (ITS) was diagnosed in 363 (86%) subjects, and it was considered familial in two-thirds. Dysmorphic features or a neurodevelopmental disorder were recorded in 104 (29%) children with ITS. The probability of a monogenic primary growth disorder increased with the degree of tall stature and deviation from target height.
INTERPRETATION
A considerable proportion of extremely tall children have an underlying primary or secondary growth disorder, and their risk is associated with auxological parameters. Clinical features related to syndromic tall stature were surprisingly frequent in subjects with ITS, supporting the view that syndromic growth disorders with mild phenotypes may be underdiagnosed in extremely tall children. Our results lend support to comprehensive diagnostic work-up of extremely tall children.
FUNDING
Päivikki and Sakari Sohlberg Foundation, Foundation for Pediatric Research, and Helsinki University Hospital research grants.
PubMed: 34849478
DOI: 10.1016/j.eclinm.2021.101208 -
Journal of the Endocrine Society Mar 2023Premature adrenarche (PA) may predispose to some adverse long-term health outcomes. Cardiorespiratory fitness (CRF) is one of the strongest factors known to predict...
CONTEXT
Premature adrenarche (PA) may predispose to some adverse long-term health outcomes. Cardiorespiratory fitness (CRF) is one of the strongest factors known to predict overall health, but no data exist on the CRF of women with a history of PA.
OBJECTIVE
To study if hyperandrogenism in childhood resulting from PA leads to a measurable difference in CRF between young adult PA and control women.
METHODS
A total of 25 women with PA and 36 age-matched controls were followed from prepubertal age until adulthood. Anthropometric measurements, body composition, biochemical, and lifestyle factors were assessed. The main outcome measure was maximal cycle ergometer test result at the mean age of 18.5 years. We also assessed prepubertal predicting factors for CRF with different linear regression models.
RESULTS
Though prepubertal children with PA were taller and heavier than their non-PA peers, there were no significant differences in height, body mass index, body composition, or physical activity in young adulthood. We observed no significant differences in any of the parameters of the maximal cycle ergometer test, including maximal load ( = .194) or peak oxygen consumption ( = .340). Hemodynamic responses of the groups were similar. None of the examined models or prepubertal factors significantly predicted CRF at adult age.
CONCLUSION
This study suggests that hyperandrogenism in childhood/adolescence resulting from PA does not have a significant impact on adulthood CRF.
PubMed: 37077523
DOI: 10.1210/jendso/bvad041 -
Journal of Ovarian Research Nov 2023Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the... (Meta-Analysis)
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.
Topics: Female; Humans; Anti-Mullerian Hormone; Follicle Stimulating Hormone; Inhibins; Observational Studies as Topic; Puberty, Precocious
PubMed: 37996919
DOI: 10.1186/s13048-023-01302-2 -
Hormone Research in Paediatrics 2021Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal...
BACKGROUND
Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal serum luteinizing hormone (LH) ≥0.3 IU/L or LH-releasing hormone (LHRH)-stimulated LH ≥5 IU/L). Stimulation testing is the diagnostic gold standard but is time-consuming and costly. Serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are increased in girls with CPP.
OBJECTIVE
The aim of the study was to assess the utility of serum IGF-1 and IGFBP-3 in identifying CPP in girls aged 6-8 years.
METHODS
The study was a single-center retrospective study. Girls with confirmed CPP (n = 44) and isolated premature precocious adrenarche/ precocious thelarche (PA/PT, n = 16) had baseline biochemical profiling and LHRH stimulation testing. Serum IGF-1 and IGFBP-3 results were converted to standard deviation scores (SDS). Correlations were calculated and receiver operating characteristic curves were plotted.
RESULTS
Girls with CPP had higher basal and peak LH, IGF-1 SDS, and growth velocity (p < 0.05). IGF-1 SDS correlated positively with basal and peak LH (p < 0.05). IGF-1 SDS (1.75-2.15) differentiated CPP and PA/PT with 89% sensitivity and 56% specificity (basal LH) and 94% specificity and 55% sensitivity (peak LH). IGFBP-3 SDS did not differ between groups or by CPP parameters.
CONCLUSIONS
In clinical practice, IGF-1 SDS may be an additional tool for identifying CPP in girls aged 6 to 8 years when baseline clinical and laboratory diagnostic criteria are inconclusive, possibly avoiding more time-consuming and costly procedures.
Topics: Child; Female; Follicle Stimulating Hormone; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Luteinizing Hormone; Puberty, Precocious; Retrospective Studies; Sensitivity and Specificity
PubMed: 34098553
DOI: 10.1159/000516361 -
Journal of the Endocrine Society Feb 2021
PubMed: 33381669
DOI: 10.1210/jendso/bvaa166 -
Frontiers in Endocrinology 2022Wiedemann-Steiner Syndrome (WSS) is a genetic disorder associated with an array of clinical phenotypes, including advanced bone age and short stature....
CONTEXT
Wiedemann-Steiner Syndrome (WSS) is a genetic disorder associated with an array of clinical phenotypes, including advanced bone age and short stature. 11-ketotestosterone (11KT) is a member of the group known as 11-oxygenated C19 androgens that are implicated in premature adrenarche.
CASE DESCRIPTION
Case 1: The patient is a 3 year and 11-month-old female diagnosed with WSS due to deletion of detected on CGH microarray. At two years and 11 months, imaging revealed an advanced bone age. We obtained an 11KT level on this patient. 11KT in case 1 was elevated at 26.3 ng/dL, while the normal reference range is 7.3-10.9 ng/dL and the reference interval for premature adrenarche is 12.3-22.9 ng/dL, The repeat 11KT at follow up (chronological age 4 years and 6 months) was still elevated at 33.8 ng/dL Case 2: A second child with WSS and a 5kb intragenic deletion was evaluated at 11 months of age; his 11KT was 4.5 ng/dL.
CONCLUSIONS
The elevated 11KT may indicate maturational changes related to increasing adrenal gland androgenic activation and may explain the advanced bone age seen in some patients with WSS. To our knowledge, this is the first case report that describes 11KT as a bioactive androgen potentially causing bone age advancement in WSS. Lack of elevation of 11KT in the second child who is an infant suggests increasing androgenic precursors and metabolites related to premature adrenarche may need to be longitudinally followed.
Topics: Female; Humans; Androgens; Abnormalities, Multiple; Intellectual Disability
PubMed: 36263329
DOI: 10.3389/fendo.2022.1004114 -
Practical Laboratory Medicine Aug 2022Androstenedione (ASD) is a biomarker used in the diagnostic workup of hyperandrogenism, congenital adrenal hyperplasia, premature adrenarche, and polycystic ovary...
UNLABELLED
Androstenedione (ASD) is a biomarker used in the diagnostic workup of hyperandrogenism, congenital adrenal hyperplasia, premature adrenarche, and polycystic ovary syndrome (PCOS). The Elecsys ASD competitive electrochemiluminescence immunoassay (Roche Diagnostics, Indianapolis, IN) is a new assay recently available in the US.
OBJECTIVE
This study evaluated the analytical and clinical performance of the Elecsys ASD assay.
DESIGN & METHODS
We evaluated the linearity/analytical measuring range (AMR), precision, and accuracy of the Elecsys ASD assay on the cobas e601 analyzer. ASD was measured in serum/plasma in the Elecsys ASD, Immulite (Siemens Medical Solutions USA, Inc. Malvern, PA), and LC-MS/MS assays. Reference intervals (RI) were evaluated across genders, menopausal status, and in children. Statistical analysis was performed using EP evaluator and R program.
RESULTS
The Elecsys ASD assay had a linear response across the AMR. The intra- and inter-assay coefficients of variation at various concentrations were ≤4.5%. The Elecsys ASD assay had a mean difference of -0.04 ng/mL (-1.7%) with the LC-MS/MS assay, whereas the Immulite assay had a mean difference of 1.17 ng/mL (66%) and -1.22 ng/mL (-38%) compared to the LC-MS/MS and Elecsys ASD assays, respectively. The Roche recommended RIs for healthy men (0.280-1.52 ng/mL) and postmenopausal women (0.187-1.07 ng/mL) were successfully verified. The RIs for children were adopted from published data. For pre-menopausal women, a RI of <1.60 ng/mL was established. The ASD concentrations in women with and without PCOS overlapped.
CONCLUSIONS
The Elecsys ASD assay has superior comparability to the LC-MS/MS assay than the Immulite assay.
PubMed: 35620064
DOI: 10.1016/j.plabm.2022.e00279 -
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