Cardiometabolic outcomes in girls with premature adrenarche: a longitudinal analysis of typical vs. exaggerated presentations
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Gülcan Seymen
,
Murat İmal
Abstract
Objectives
To evaluate cardiometabolic risk factors in girls with premature adrenarche (PA), with a specific focus on outcomes based on adrenal androgen levels (typical vs. exaggerated adrenarche).
Methods
Eighty-four girls with PA were followed from diagnosis to mid-puberty. Clinical, biochemical, and hormonal parameters were assessed at both time points. Participants were stratified based on dehydroepiandrosterone sulfate (DHEAS) levels: typical PA (40–130 μg/dL) and exaggerated adrenarche (>130 μg/dL). Age- and sex-matched controls (n=58) were included for pubertal comparisons.
Results
At baseline, 25 % of PA girls were overweight/obese, and 22 % had elevated HOMA-IR. Exaggerated adrenarche was present in 19 % of subjects. By puberty, overweight/obesity prevalence rose to 33.3 %, with significant increases in fasting insulin, HOMA-IR, and declines in insulin sensitivity indices (QUICKI, FGIR). Comparisons with controls revealed significantly higher BMI, waist circumference, and insulin resistance among PA girls. However, there were no significant metabolic differences between exaggerated and typical PA groups, except for a higher waist circumference in the exaggerated group.
Conclusions
Elevated mid-childhood DHEAS does not independently predict worsened metabolic outcomes by puberty. Baseline adiposity, not androgen level, is the principal determinant of insulin resistance and cardiometabolic risk in PA. Lifestyle interventions targeting weight management are crucial in mitigating future risk.
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Research ethics: The study was approved by the Institutional Review Board of Kocaeli University, Turkey (Approval No: KOU KAEK 2015/13), and conducted in accordance with the Declaration of Helsinki (as revised in 2013).
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Informed consent: Informed consent was obtained from all individuals included in the study, or their legal guardians or wards.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: None declared.
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Data availability: Not applicable.
References
1. Voutilainen, R, Jääskeläinen, J. Premature adrenarche: etiology, clinical findings, and consequences. J Steroid Biochem Mol Biol 2015;145:226–36. https://doi.org/10.1016/j.jsbmb.2014.06.004. PMID: 24923732.Suche in Google Scholar PubMed
2. Rosenfield, RL, Lipton, RB, Drum, ML. Thelarche, pubarche, and menarche attainment in children with normal and elevated body mass index. Pediatr 2009;123:84. https://doi.org/10.1542/peds.2008-0146.Suche in Google Scholar PubMed
3. Güven, A, Cinaz, P, Bideci, A. Is premature adrenarche a risk factor for atherogenesis? Pediatr Int 2005;47:20–5. https://doi.org/10.1111/j.1442-200X.2004.02006.x. PMID: 15693861.Suche in Google Scholar PubMed
4. Ibáñez, L, Potau, N, Chacón, P, Pascual, C, Carrascosa, A. Hyperinsulinaemia, dyslipemia and cardiovascular risk in girls with a history of premature pubarche. Diabetologia 1998;41:1057–63. https://doi.org/10.1007/s001250051030.Suche in Google Scholar PubMed
5. Vuguin, P, Linder, B, Rosenfeld, RG, Saenger, P, DiMartino-Nardi, J. The roles of insulin sensitivity, insulin-like growth factor I, and IGF-binding proteins-1 and -3 in the hyperandrogenism of African–American and Caribbean Hispanic girls with premature adrenarche. J Clin Endocrinol Metab 1999;84:2037–42. https://doi.org/10.1210/jcem.84.6.5722.Suche in Google Scholar PubMed
6. Denburg, MR, Silfen, ME, Manibo, AM, Chin, D, Levine, LS, Ferin, M, et al.. Insulin sensitivity and the insulin-like growth factor system in prepubertal boys with premature adrenarche. J Clin Endocrinol Metab 2002;87:5604–9. https://doi.org/10.1210/jc.2002-020896.Suche in Google Scholar PubMed
7. Mathew, RP, Byrne, DW, Linton, MF, Vaughan, DE, Fazio, S, Russell, WE. Evidence of metabolic syndrome in lean children with premature pubarche at diagnosis. Metabol 2008;57:733–40. https://doi.org/10.1016/j.metabol.2008.01.010.Suche in Google Scholar PubMed
8. de Ferran, K, Paiva, IA, Garcia, LS, Gama, MP, Guimarães, MM. Isolated premature pubarche: report of anthropometric and metabolic profile of a Brazilian cohort of girls. Horm Res Paediatr 2011;75:367–73. https://doi.org/10.1159/000324107.Suche in Google Scholar PubMed
9. Kaya, G, Yavaş Abalı, Z, Baş, F, Poyrazoğlu, S, Darendeliler, F. Body mass index at the presentation of premature adrenarche is associated with components of metabolic syndrome at puberty. Eur J Pediatr 2018;177:1593–601. https://doi.org/10.1007/s00431-018-3211-1.Suche in Google Scholar PubMed
10. Ibáñez, L, DiMartino-Nardi, J, Potau, N, Saenger, P. Premature adrenarche – normal variant or forerunner of adult disease? Endocr Rev 2000;21:671–96. https://doi.org/10.1210/edrv.21.6.0416.Suche in Google Scholar PubMed
11. Cook, S, Weitzman, M, Auinger, P, Nguyen, M, Dietz, WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third national health and nutrition examination survey, 1988–1994. Arch Pediatr Adolesc Med 2003;157:821–7. https://doi.org/10.1001/archpedi.157.8.821. PMID: 12912790.Suche in Google Scholar PubMed
12. Bundak, R, Furman, A, Günöz, H, Darendeliler, F, Baş, F, Neyzi, O. Body mass index references for Turkish children. Acta Paediatr 2006;95:194–8. https://doi.org/10.1080/08035250500334738. PMID: 16449026.Suche in Google Scholar PubMed
13. Neyzi, O, Furman, A, Bundak, R, Günöz, H, Darendeliler, F, Baş, F. Growth references for Turkish children aged 6 to 18 years. Acta Paediatr 2006;95:1635–41. https://doi.org/10.1080/08035250600652013. PMID: 17129974.Suche in Google Scholar PubMed
14. Hatipoğlu, N, Ozturk, A, Mazicioğlu, MM, Kurtoglu, S, Seyhan, S, Lokoglu, F. Waist circumference percentiles for 7- to 17-year-old Turkish children and adolescents. Eur J Pediatr 2008;167:383–9. https://doi.org/10.1007/s00431-007-0502-3. PMID: 17487506.Suche in Google Scholar PubMed
15. Marshall, WA, Tanner, JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303. https://doi.org/10.1136/adc.44.235.291. PMID: 5785179; PMCID: PMC2020314.Suche in Google Scholar PubMed PubMed Central
16. Kurtoğlu, S, Hatipoğlu, N, Mazıcıoğlu, M, Kendirci, M, Keskin, M, Kondolot, M. Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods. J Clin Res Pediatr Endocrinol 2010;2:100–6. https://doi.org/10.4274/jcrpe.v2i3.100. PMID: 21274322; PMCID: PMC3005684.Suche in Google Scholar PubMed PubMed Central
17. Ten, S, Maclaren, N. Insulin resistance syndrome in children. J Clin Endocrinol Metab 2004;89:2526–39. https://doi.org/10.1210/jc.2004-0276. PMID: 15181020.Suche in Google Scholar PubMed
18. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents (National Heart, Lung, and Blood Institute). Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatr 2011;128:S213–256. https://doi.org/10.1542/peds.2009-2107C. PMID: 22084329; PMCID: PMC4536582.Suche in Google Scholar PubMed PubMed Central
19. Zimmet, P, Alberti, KG, Kaufman, F, Tajima, N, Silink, M, Arslanian, S, et al.. IDF Consensus Group. The metabolic syndrome in children and adolescents: an IDF consensus report. Pediatr Diabetes 2007;8:299–306. https://doi.org/10.1111/j.1399-5448.2007.00271.x. PMID: 17850473.Suche in Google Scholar PubMed
20. Utriainen, P, Jääskeläinen, J, Romppanen, J, Voutilainen, R. Childhood metabolic syndrome and its components in premature adrenarche. J Clin Endocrinol Metab 2007;92:4282–5. https://doi.org/10.1210/jc.2006-2412. PMID: 17698912.Suche in Google Scholar PubMed
21. Corvalán, C, Uauy, R, Mericq, V. Obesity is positively associated with dehydroepiandrosterone sulfate concentrations at age 7 years in Chilean children of normal birth weight. Am J Clin Nutr 2013;97:318–25. https://doi.org/10.3945/ajcn.112.037325. PMID: 23283497; PMCID: PMC3545681.Suche in Google Scholar PubMed PubMed Central
22. Liimatta, J, Utriainen, P, Laitinen, T, Voutilainen, R, Jääskeläinen, J. Cardiometabolic risk profile among young adult females with a history of premature adrenarche. J Endocr Soc 2019;3:1771–83. https://doi.org/10.1210/js.2019-00205.Suche in Google Scholar
23. Ribeiro, FA, Resende, EAMR, Silva, APD, Tomé, JM, Palhares, HMDC, Borges, MF. Metabolic and hormonal assessment of adolescent and young adult women with prior premature adrenarche. Clinics 2019;74:e836. https://doi.org/10.6061/clinics/2019/e836. PMID: 31241662; PMCID: PMC6558997.Suche in Google Scholar PubMed PubMed Central
© 2025 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Original Articles
- Spatiotemporal associations between incidence of type 1 diabetes and COVID-19 vaccination rates in children in Germany – a population-based ecological study
- Continuous glucose monitoring evidence of celiac disease in type 1 diabetes
- Impact of race and delayed adoption of diabetes technology on glycemia and partial remission in type 1 diabetes
- Immunogenetic profiling of type 1 diabetes in Jordan: a case-control study on HLA-associated risk and protection
- Annual case counts and clinical characteristics of pediatric and adolescent patients with diabetes in Kenyatta National Hospital, Nairobi, Kenya. A 14 year retrospective study
- Real-world effectiveness of sodium glucose transporter 2 inhibitors among youth with type 2 diabetes
- Investigation of the association between nitric oxide synthase gene variants and NAFLD in adolescents with obesity
- Cardiometabolic outcomes in girls with premature adrenarche: a longitudinal analysis of typical vs. exaggerated presentations
- A disease that is difficult to predict: regional distribution and phenotypic, histopathological and genetic findings in McArdle disease
- Causal analysis of uterine artery pulsatility index-related proteins and the risk of precocious puberty in girls: a Mendelian randomization study
- Case Reports
- Understanding rickets in osteopetrosis via a case: mechanisms and treatment implications
- A case of JAGN1 mutation presenting with atypical diabetes and immunodeficiency
- Compound heterozygous ROBO1 gene variants in a neonate with congenital hypopituitarism, dysmorphic features and midline abnormalities: a case report and review of the literature
- Phenotypic variation among four members in a family with DAX1 deficiency
- MMP13-related metaphyseal dysplasia: a differential diagnosis of rickets
- Congress Abstracts
- JA-PED | Annual Meeting of the German Society for Pediatric and Adolescent Endocrinology and Diabetology (DGPAED e. V.)
Artikel in diesem Heft
- Frontmatter
- Original Articles
- Spatiotemporal associations between incidence of type 1 diabetes and COVID-19 vaccination rates in children in Germany – a population-based ecological study
- Continuous glucose monitoring evidence of celiac disease in type 1 diabetes
- Impact of race and delayed adoption of diabetes technology on glycemia and partial remission in type 1 diabetes
- Immunogenetic profiling of type 1 diabetes in Jordan: a case-control study on HLA-associated risk and protection
- Annual case counts and clinical characteristics of pediatric and adolescent patients with diabetes in Kenyatta National Hospital, Nairobi, Kenya. A 14 year retrospective study
- Real-world effectiveness of sodium glucose transporter 2 inhibitors among youth with type 2 diabetes
- Investigation of the association between nitric oxide synthase gene variants and NAFLD in adolescents with obesity
- Cardiometabolic outcomes in girls with premature adrenarche: a longitudinal analysis of typical vs. exaggerated presentations
- A disease that is difficult to predict: regional distribution and phenotypic, histopathological and genetic findings in McArdle disease
- Causal analysis of uterine artery pulsatility index-related proteins and the risk of precocious puberty in girls: a Mendelian randomization study
- Case Reports
- Understanding rickets in osteopetrosis via a case: mechanisms and treatment implications
- A case of JAGN1 mutation presenting with atypical diabetes and immunodeficiency
- Compound heterozygous ROBO1 gene variants in a neonate with congenital hypopituitarism, dysmorphic features and midline abnormalities: a case report and review of the literature
- Phenotypic variation among four members in a family with DAX1 deficiency
- MMP13-related metaphyseal dysplasia: a differential diagnosis of rickets
- Congress Abstracts
- JA-PED | Annual Meeting of the German Society for Pediatric and Adolescent Endocrinology and Diabetology (DGPAED e. V.)
