Hormone Research in Paediatrics最新文献

{"title":"Novel Insights Large Estrogen and Cortisol Co-Secreting Adrenocortical Tumor in a 17-Year-Old Female: A Case Report and Literature Review.","authors":"Simrat Kaur Veera, Nitsan Shacham, Jessy Epstein, Danielle Wolfe Cohen, Elizabeth Roman, Kristen M Thomas, Marissa Lipton, Brenda Kohn","doi":"10.1159/hrp/adaag014","DOIUrl":"10.1159/hrp/adaag014","url":null,"abstract":"<p><strong>Introduction: </strong>Adrenocortical tumors (ACTs) are rare pediatric tumors which include both benign adrenocortical adenomas (ACAs) and malignant adrenocortical carcinomas (ACCs). The most common presentations of an ACT in children are virilization and/or Cushing's syndrome resulting from tumoral secretion of androgens and cortisol, respectively. Adrenocortical tumors that express high levels of estrogen are extremely rare, and adrenal tumors that co-secrete more than one class of adrenal hormones raise concern for malignancy.</p><p><strong>Case presentation: </strong>We present a case of a 17-year-old female presenting with weight gain, secondary amenorrhea, and acute abdominal pain. She was found to have a large (9.4 cm) right adrenal tumor co-secreting both cortisol and estrogen, which was successfully surgically removed by minimally invasive laparoscopy. Her perioperative course was complicated by severe refractory hypertension requiring multiple antihypertensive medications, and venous thromboses associated with hypercoagulability. Genetic testing revealed no germline driver mutation. Classification of the adrenal tumor as either benign or malignant was discordant when determined by the adult Weiss vs. the pediatric AFIP/Wieneke criteria in this older adolescent.</p><p><strong>Conclusion: </strong>This prismatic case of a rare estrogen-cortisol secreting tumor raises discussion regarding the complexities in the clinical presentation and uncertainties in prognosis of adrenal tumors in adolescents. A literature review showcases 19 case reports published between 1948 and 2025 of estrogen-secreting pediatric ACTs highlighting their rare prevalence. This case stresses the need for a multidisciplinary approach to diagnosis, treatment, and long-term management of this entity in children and adolescents.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrathyroidal Ectopic Thymus: The Trick of the Trade.","authors":"Paolo Cavarzere, Francesco Coccia, Valentina Mancioppi, Rossella Gaudino, Sofia Benamati, Marika Nacci, Franco Antoniazzi, Mirko Trentadue, Costanza Bruno, Claudio Maffeis","doi":"10.1159/hrp/adaag019","DOIUrl":"10.1159/hrp/adaag019","url":null,"abstract":"<p><strong>Introduction: </strong>Intrathyroidal ectopic thymus (IET) is a rare benign entity in children, most often detected incidentally during thyroid or neck ultrasonography. Its sonographic appearance may mimic malignant thyroid nodules, potentially prompting unnecessary diagnostic or surgical interventions. The aim of our study was to describe the occurrence of IET in a tertiary pediatric endocrinology center, defining its clinical, biochemical, and sonographic characteristics and suggesting the best clinical approach.</p><p><strong>Methods: </strong>We retrospectively reviewed all pediatric patients (<18 years) evaluated at our tertiary pediatric endocrinology service between 2015 and 2025 who presented with thyroid nodules classified as EU-TIRADS ≥3 and were subsequently diagnosed with IET based on characteristic imaging findings and stability over time.</p><p><strong>Results: </strong>Twenty-one children with nodules classified as EU-TIRADS ≥3, with a median age of 10.6 (0.55-15) years, were identified. Ten patients (50% males) with a mean age of 6.19 ± 3.93 years were presumed to have IET. All lesions were hypoechoic, well-circumscribed, and demonstrated punctate or linear hyperechogenicities. No lesion showed significant change in size or echotexture during follow-up. Thyroid function was normal in 9 patients, while 1 had subclinical hypothyroidism that resolved during follow-up. None of these 10 patients underwent surgical intervention or fine-needle aspiration biopsy (FNAB).</p><p><strong>Conclusion: </strong>IET should be considered in the differential diagnosis of pediatric thyroid nodules especially in the first years of life. Although ultrasonography alone cannot reliably distinguish benign from malignant lesions, recognition of the characteristic imaging pattern of IET, together with clinical and laboratory correlation, can help prevent misdiagnosis of thyroid cancer and avoid unnecessary FNAB.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Luseogliflozin (TS-071) in Japanese Children and Adolescents with Type 2 Diabetes Mellitus: A Multicenter, Randomized, Double-Masked, Placebo-Controlled Phase 3 Study.","authors":"Toru Kikuchi, Hidefumi Nakamura, Hideo Umeuchi, Iwao Kitajima, Hironori Yamasaki, Tatsuhiko Urakami","doi":"10.1159/hrp/adaag009","DOIUrl":"10.1159/hrp/adaag009","url":null,"abstract":"<p><strong>Introduction: </strong>This study evaluated the efficacy and safety of luseogliflozin (TS-071), a sodium-glucose cotransporter 2 inhibitor, in Japanese children and adolescents with type 2 diabetes (T2D).</p><p><strong>Methods: </strong>In this multicenter, randomized, double-masked, placebo-controlled phase 3 trial, patients aged 10-17 years with hemoglobin A1c (HbA1c) levels of 7.0%-12.0%, with or without prior metformin use, were enrolled. Participants were randomized (2:1) to receive luseogliflozin 2.5 mg or placebo for 12 weeks (period I), followed by a 40-week open-label extension (period II), allowing dose escalation to 5 mg.</p><p><strong>Results: </strong>Forty-eight participants were randomized and received luseogliflozin (n = 31) or placebo (n = 17). The primary endpoint - change in HbA1c from baseline at the end of period I - was -1.45% (95% CI, -1.78% to -1.11%) in the luseogliflozin group. The between-group difference in HbA1c change was -1.76% (95% CI, -2.49% to -1.02%). Luseogliflozin maintained efficacy through 52 weeks, with a mean HbA1c change of -0.92% ± 1.74% at the end of period II. Adverse events (AEs) and adverse drug reactions (ADRs) occurred in 85.4% and 29.2% of patients, respectively. No deaths occurred; three serious AEs and one mild hypoglycemic event were reported. Urinary and genital infections were the most frequent ADRs.</p><p><strong>Conclusion: </strong>Luseogliflozin significantly improved glycemic control and was well tolerated, supporting its potential as an effective and safe treatment option for children and adolescents with T2D.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoglycaemia Thresholds in Children with Type 1 Diabetes: Real-Life Practices in the Era of Diabetes Technology.","authors":"Peter William James Delaney, Grant James Smith, Julie Dart, Sarah Black, Barbara Keating, Elizabeth A Davis, Timothy W Jones, Mary Binsu Abraham","doi":"10.1159/hrp/adaag013","DOIUrl":"10.1159/hrp/adaag013","url":null,"abstract":"<p><strong>Introduction: </strong>With an increased use of diabetes technology in type 1 diabetes, there is noted variability in the glucose thresholds at which hypoglycaemia is treated. The study therefore investigated the thresholds for hypoglycaemia treatment on contemporary treatment to capture real-life practices and compared the relationship between glycaemia, hypoglycaemia awareness (HA), and fear of hypoglycaemia (FOH) with their chosen treatment threshold.</p><p><strong>Methods: </strong>Children with type 1 diabetes (parent if child < 12 years) responded to an online survey reporting their chosen glucose thresholds. Clinical and glycaemic data were retrieved from the Western Australian Children's Diabetes Database. Participant groups were defined as treatment at, below, and above the recommended threshold (RT) of less than 3.9 mmol/L.</p><p><strong>Results: </strong>Of 271 respondents (median age: 13.4 years, 98% continuous glucose monitor [CGM]), 54% treated hypoglycaemia at RT, 25% treated above, and 21% treated below. This adoption of glucose thresholds was independent of mode of insulin delivery (p = 0.54). Participants also adjusted thresholds based on day/night (37.3%), presence of active insulin on board (56.1%), and exercise (83.8%), with 96.2% using CGM trend arrows to guide the need for treatment. There was no evidence of a difference in HbA1c, time in range, time below range (TBR), HA, and FOH scores between the three groups (p > 0.05). However, those treating above RT achieved target TBR <3.9 mmol/L (<4%) than other groups (p < 0.05). Three episodes of severe hypoglycaemia occurred: one in the below RT group and two in the RT group.</p><p><strong>Conclusion: </strong>Parents and children personalise the glucose thresholds for commencing hypoglycaemia treatment based on the clinical context. Although these thresholds did not increase the time in hypoglycaemia, further studies are needed to evaluate the safe adoption of this approach in clinical care.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyendocrine Metabolic Ovarian Syndrome as the New Name for PCOS: Implications for Paediatric and Adolescent Health Care.","authors":"Selma Feldman Witchel, Sharon E Oberfield, Alexia S Pena, Nicholas Beng Hui Ng, Mahnaz Bahri Khomami, Melanie Cree, Helena J Teede","doi":"10.1159/hrp/adaag010","DOIUrl":"10.1159/hrp/adaag010","url":null,"abstract":"","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perceived Impact of Vosoritide on Health-Related Quality of Life in Children with Selected Genetic Causes of Short Stature: A Qualitative Study of Children and Caregivers.","authors":"Raheem Seaforth, Niusha Shafaei, Kimberly Pitner, Margaret Cho, Beverly Romero, Anna de la Motte, Kelsie Brewer, Roopa Kanakatti Shankar, Andrew Dauber","doi":"10.1159/hrp/adaag004","DOIUrl":"10.1159/hrp/adaag004","url":null,"abstract":"<p><strong>Introduction: </strong>Short stature resulting from genetic conditions is associated with various emotional, physical, and social challenges resulting in significantly lower health-related quality of life (HRQoL). There are minimal qualitative data available on this topic.</p><p><strong>Methods: </strong>We performed a cross-sectional, remote, qualitative interview study targeting children receiving vosoritide for >2 years as part of a clinical trial and their caregivers. Interviews assessed participants' daily experiences of short stature and the impact of vosoritide on HRQoL. Principles of thematic analysis were applied with features from grounded theory-guided coding and analysis of interviews.</p><p><strong>Results: </strong>Twenty-one caregivers and 14 child participants from 20 families were interviewed. Child participants were of ages 8-15 years (M = 10.2). Four conditions were represented in the sample (12 hypochondroplasia, 4 NPR2 mutations, 2 ACAN mutations, 2 Noonan syndrome). At baseline, short stature had significant impacts on physical, social, and daily activity domains. After starting vosoritide, changes were most reported for impacts on daily activities by both caregiver (74%) and child (100%) participants. Most reported were \"improved ability to reach things\" (12 caregivers and 14 children) and \"being more independent/needing less assistance\" (9 caregivers and 5 children).</p><p><strong>Conclusion: </strong>Genetic short stature significantly impacts HRQoL, as reported by both children and their caregivers. Both children and caregivers noted emotional, physical, and social impacts as well as impacts on daily activities. Vosoritide treatment was associated with meaningful improvements in physical impacts and impacts on daily activities.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose Management in Children Living with Type 1 Diabetes: Results from the BETTER Registry.","authors":"Virginie Messier, Mélanie Henderson, Meranda Nakhla, Judith Simoneau-Roy, Meryem Talbo, Domitille Dervaux, Nathalie Kinnard, Andréane Vanasse, Monia Rekik, Rémi Rabasa-Lhoret, Anne-Sophie Brazeau","doi":"10.1159/hrp/adaag016","DOIUrl":"10.1159/hrp/adaag016","url":null,"abstract":"<p><strong>Introduction: </strong>The Behaviors, Therapies, Technologies, and Hypoglycemic Risk in Type 1 Diabetes (BETTER) Registry collects patient-reported outcomes and experiences on individuals living with type 1 diabetes in Canada. The objective of our study was to describe the management of type 1 diabetes reported by parents of children and young adolescents (<14 years of age) enrolled in the BETTER registry.</p><p><strong>Methods: </strong>We conducted a cross-sectional evaluation using self-reported data collected from April 2019 to October 2024. Parents of children and adolescents <14 years self-registered and provided online informed consent. As of October 2024, 699 children and adolescents <14 years of age and living with type 1 diabetes were enrolled.</p><p><strong>Results: </strong>Children had a mean age of 8.8 ± 3.1 years old with a diabetes duration of 2.3 ± 2.7 years, 44.9% were female, and 85.0% were of European ancestry. More than 80% used a continuous glucose monitoring system and 38.3% used an insulin pump. Most recent HbA1c ≤7% was reported by 15.9% of participants. At least 1 episode of level 2 hypoglycemia (glucose levels <3.0 mmol/L, with ability to self-treat) in the last month was reported by 72.5% of participants, with a median number of episodes (interquartile range) of 5 (2, 10). The occurrence of level 3 hypoglycemia (low glucose, requiring help from another person, use of glucagon, hospitalization, or loss of consciousness) in the last 12 months was reported by 8.6% of participants. Among these, the median number of episodes was 1 (1, 3).</p><p><strong>Conclusion: </strong>Our results indicate that, despite a wide use of continuous glucose monitoring, the occurrence of hypoglycemia is still high and the proportion of children and adolescents reaching the HbA1c target is low.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent Elevation of Thyroid-Stimulating Hormone despite Levothyroxine Therapy Revealing Autoimmune Adrenal Insufficiency in an Adolescent with Autoimmune Thyroiditis: A Case Report and Review of Literature.","authors":"Janvi Biju, Sabitha Sasidharan Pillai","doi":"10.1159/hrp/adaag015","DOIUrl":"10.1159/hrp/adaag015","url":null,"abstract":"<p><strong>Introduction: </strong>Autoimmune thyroiditis (AIT) or Hashimoto thyroiditis is the most common cause of acquired hypothyroidism in the developed nations, and these patients are at increased risk for other autoimmune conditions, including autoimmune adrenal insufficiency (AAI). Routine screening for AAI is not recommended in asymptomatic children with AIT. The coexistence of AAI and AIT establishes the diagnosis of autoimmune polyglandular syndrome type 2 (APS-2), a rare disorder that is predominantly diagnosed in adults, with limited data available in pediatric patients. We report an adolescent male with AIT who was subsequently diagnosed with AAI during evaluation for persistently elevated thyroid-stimulating hormone (TSH) levels despite reported adherence to levothyroxine therapy. We performed a literature review on pediatric patients with AIT and AAI and identified 20 patients from 19 published case reports.</p><p><strong>Case presentation: </strong>An adolescent male was diagnosed with AIT at 12 years 10 months of age. Six months later, he developed hypothyroidism and was started on levothyroxine. Despite reported adherence, TSH levels remained above target, necessitating progressive dose escalation to 125 µg daily (2.2 µg/kg/day) over the subsequent 16 months. At that time, he reported intermittent headaches, dizziness, and fatigue. Growth parameters and vital signs remained normal, although retrospective review revealed hyperpigmentation over the preceding 2 years. Laboratory evaluation demonstrated sodium 128 mEq/L (136-143 mEq/L), potassium 6.7 mEq/L (3.8-4.9 mEq/L), cortisol 0.3 μg/dL (3.6-17.0 μg/dL), aldosterone < 1 ng/dL (ref. 4-48 ng/dL), renin 10.0 ng/mL/h (0.25-5.82 ng/mL/h), adrenocorticotropic hormone 1,184 pg/mL (9-57 pg/mL), and positive 21-hydroxylase antibodies, confirming the diagnosis of AAI. He was treated with intravenous fluids, stress-dose hydrocortisone, and fludrocortisone, followed by maintenance glucocorticoid and mineralocorticoid replacement. Thyroid function subsequently normalized with continued levothyroxine therapy.</p><p><strong>Conclusions: </strong>Our case highlights the importance of considering AAI in children with AIT who have persistent elevation of TSH despite levothyroxine therapy, particularly when accompanied by suggestive clinical features or biochemical abnormalities. Although persistently elevated TSH is nonspecific and may have multiple explanations, including variable adherence or absorption, recognition of coexisting AAI is essential to avoid delayed diagnosis and potentially life-threatening adrenal crisis.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Slipped Capital Femoral Epiphysis during Vosoritide Therapy for Short Stature: A Case Series.","authors":"Roopa Kanakatti Shankar, Matthew E Oetgen, Benjamin D Martin, Niusha Shafaei, Kimberly Pitner, Andrew Dauber","doi":"10.1159/hrp/adaag011","DOIUrl":"10.1159/hrp/adaag011","url":null,"abstract":"<p><strong>Introduction: </strong>Vosoritide is a C-type natriuretic peptide analog approved for treatment of children with achondroplasia with established safety and efficacy. We report slipped capital femoral epiphysis (SCFE) as a treatment-emergent serious adverse event in two prospective clinical trials of vosoritide for individuals with genetic forms of short stature.</p><p><strong>Case report: </strong>We report 5 participants from two investigator-initiated, single center, phase II, prospective, open label clinical trials of vosoritide (NCT04219007 Basket trial including patients with RASopathies, Aggrecan mutations (ACAN) and NPR2 deficiency and NCT05849389 in girls with Turner syndrome) who developed SCFE. In the basket trial, SCFE was observed in 2/12 participants with ACAN mutations, 1/11 with RASopathy but not in the 7 participants with NPR2 mutations or 24 with hypochondroplasia. In the Turner syndrome trial, 2/5 participants receiving vosoritide developed SCFE. All 5 participants who developed SCFE had received >12 months of treatment and presented with the rare valgus type of SCFE.</p><p><strong>Conclusion: </strong>Vosoritide treatment may be associated with a higher risk of SCFE in some individuals with genetic forms of short stature such as Turner syndrome and Aggrecan mutations. The causal mechanisms and contributory factors to the predisposition for valgus deformities noted with vosoritide therapy in children with these genetic conditions warrant further study.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenal Androgens, Estrone, and Insulin-Like Growth Factor 1 Are Associated with Thelarche without Gonadotropin Activation in Girls.","authors":"Saija Burtsov, Anna Viitasalo, Sonja Soininen, Merja R Häkkinen, Seppo Auriola, Aino Mäntyselkä, Raimo Voutilainen, Jarmo Jääskeläinen, Timo A Lakka","doi":"10.1159/hrp/adaag012","DOIUrl":"10.1159/hrp/adaag012","url":null,"abstract":"<p><strong>Introduction: </strong>Although a well-known phenomenon, the hormonal mechanism of thelarche in the absence of gonadotropin activation remains unclear. To reveal the biological mechanisms of such thelarche, we assessed serum concentrations of several hormones potentially related to breast development, as well as clinical signs of androgen action.</p><p><strong>Methods: </strong>A population-based sample of 175 girls aged 9-11 was divided into those without thelarche (Tanner breast stage 1) and those with thelarche (Tanner breast stage ≥2). The girls were further categorized based on basal serum luteinizing hormone (LH) using a cut-off of 0.3 IU/L. This resulted in three groups: 114 girls with low LH without thelarche, 32 girls with low LH and thelarche, and 29 girls with higher LH and thelarche. Serum concentrations of sex steroids and insulin-like growth factor-1 (IGF-1) and clinical signs of androgen action were assessed at ages 7-9 and 9-11 years.</p><p><strong>Results: </strong>Girls with low LH and thelarche had higher levels of dehydroepiandrosterone sulfate (DHEAS) (0.80 vs. 0.60 µmol/L, p = 0.03 at 7-9 years; 0.97 vs. 0.72 µmol/L, p = 0.03 at 9-11 years), testosterone (0.18 vs. 0.14 nmol/L, p = 0.02; 0.27 vs. 0.22 nmol/L, p = 0.02), estrone (14.5 vs. 11.5 pmol/L, p = 0.02; 24.3 vs. 18.2 pmol/L, p = 0.002), and IGF-1 (28.6 vs. 23.6 nmol/L, p = 0.001; 35.9 vs. 31.1 nmol/L, p = 0.006) than girls with low LH without thelarche. Differences in DHEAS, testosterone, and IGF-1 diminished after further adjustment for body fat percentage. Girls with low LH and thelarche also had more clinical signs of androgen action at both ages than girls with low LH without thelarche. There were no statistically significant differences in hormonal concentrations at 7-9 years between girls with low LH and thelarche and those with higher LH and thelarche. However, at 7-9 years, girls with low LH and thelarche had more signs of androgen action than girls with higher LH and thelarche. At 9-11 years, girls with higher LH and thelarche had higher hormonal concentrations except for DHEAS than girls with low LH and thelarche.</p><p><strong>Conclusion: </strong>Thelarche with low LH is associated with elevated DHEAS, testosterone, estrone, and IGF-1 concentrations, which is partly explained by BF%, suggesting that aromatization of adrenal androgens to estrogens in adipose tissue is one hormonal mechanism of thelarche in girls without gonadotropin activation.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}