Hormone Research in Paediatrics最新文献

Introduction: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare disorder characterized by respiratory failure, autonomic dysregulation, and endocrine abnormalities. Some of these patients may also develop neuroendocrine tumors (ROHHAD-NET). The aim of this study was to evaluate the clinical features, biochemical findings, treatments, and outcomes in a cohort of pediatric patients with ROHHAD-NET syndrome followed at a single tertiary center.

Methods: A retrospective review of 10 medical records of patients with ROHHAD-NET syndrome followed between 2007 and 2024 was conducted. Data analyzed included clinical, biochemical, therapeutic interventions and outcomes.

Results: Rapid-onset obesity, observed in all 10 patients, was the first clinical sign with a mean age at onset (MAO) of 5.1 ± 1.8 years. Neurobehavioral disorders were also an early manifestation, occurring in 5 cases with a MAO of 5 ± 1 years. All patients developed respiratory symptoms, with a MAO of 7.4 ± 3 years. Six patients were diagnosed with obstructive sleep apnea syndrome, including 2 with associated alveolar central hypoventilation. Seven patients required ventilatory support. All patients had hypothalamic dysfunction, MAO 6.6 ± 1.3 years. Disorders of water balance were the most frequent manifestation (n = 10), followed by hyperprolactinemia, central hypothyroidism, growth hormone deficiency, adrenal insufficiency, precocious puberty, and hypogonadotropic hypogonadism. Autonomic dysregulation was present in the entire cohort (MAO 6.7 ± 2.3 years), with strabismus as the most common clinical sign (n = 6). Neural crest tumors (ganglioneuromas) were identified in 5 patients, with a MAO of 5.4 ± 1.3 years. Tumor location included the adrenal gland (n = 2) and mediastinum (n = 3). Other clinical findings included thrombocytopenia, celiac disease, enuresis, type 1 and type 2 diabetes, seizures, hypo- and hypertension, and primary hypothyroidism. All patients received symptomatic treatment; 3 also received intravenous immunoglobulin as compassionate therapy, without significant benefit. Three patients died.

Conclusion: High clinical suspicion and early recognition are essential for a prompt diagnosis, timely initiation of respiratory support, and reduction of morbidity and mortality. Larger cohorts are needed for better characterization of this syndrome and to further elucidate its etiology.

Introduction: The gonadal genetics and germ cell tumor (GCT) risk in SRY-negative 46,XX testicular and ovotesticular disorders of sex development (DSD) are poorly understood and debated. This study aimed to investigate the gonadal genetic etiology and evaluate GCT risk in an independent cohort.

Methods: We conducted a retrospective analysis of SRY-negative 46,XX testicular and ovotesticular DSD patients who underwent gonadal biopsy or gonadectomy. Routine next-generation sequencing was performed on peripheral blood samples. In gonadal tissues, quantitative PCR was utilized for SRY gene detection, while whole exome sequencing and whole genome sequencing provided comprehensive genetic analysis. Gonadal histopathological features were assessed through HE staining and immunohistochemical markers.

Results: Thirty-five individuals with SRY-negative 46,XX testicular or ovotesticular DSD were included, comprising 26 ovotesticular and 9 testicular cases. Two pathogenic NR5A1 variants and one SOX3 gene duplication were identified in peripheral blood of 3 out of 34 patients (8.82%). XX/XY chimerism was detected in gonadal tissue of 1 out of 32 patients (3.13%). Notably, no precursor lesions (GCNIS, gonadoblastoma, or undifferentiated gonadal tissue) or GCTs were found. OCT 3/4 positivity was observed in testicular parenchyma of 7 patients (7/35), with these positive germ cells primarily located at the center of the seminiferous cords and showing negative SCF staining.

Conclusion: The risk of GCTs in individuals with SRY-negative 46,XX testicular and ovotesticular DSD remains contentious. This study underscores the importance of comprehensive genetic and histological evaluations of gonadal tissues. Immunohistochemical findings suggest a relatively low GCT risk; however, long-term follow-up is essential for effective patient monitoring.

Introduction: In most patients with Turner syndrome (TS) pharmacological pubertal induction (PI) is required to allow the development of female secondary sex characteristics and to reach menarche. The aim of the study was to discuss and assess the process of PI, satisfaction with breast development and side effects of therapy from the patient's and their family's perspective.

Methods: Patients with TS/their caregivers were contacted via social media and encouraged to take part in a 15-question anonymous survey regarding the use of estrogen-progesterone replacement therapy (E-PRT).

Results: A total of 109 participants responded to the survey, 70.6% reported that PI commenced between the ages of 10 and 16. Oral estradiol (E2) was most frequently offered to patients (38.5%) and recommended by 33.9% of respondents. Among the youngest generation transdermal E2 patches were the most frequently utilized method. The most important considerations in choosing a preparation was ease of use (41.3%). Totally, 58.7% of women were satisfied with the development of their breasts, and no form of estrogen therapy proved to be better than others in this respect. The older age at start of treatment was associated with a tendency to poorer satisfaction with breast development. 41.3% of all participants did not report any side effects of hormonal therapy.

Conclusion: The age to initiate puberty pharmacologically and the types of estrogen preparations used for this purpose varied across different age groups, however, with a tendency to mimic physiology and recommended protocols. The timing and mode of PI should aim to maximize intended effects, reduce risks of side effects and be simple to use. The aim should be to meet patients' expectations to ensure that they are not discouraged from taking long-term E-PRT.

Introduction: Thyroid hormones are essential for child development, and untreated hypothyroidism can lead to severe adverse effects, including mental retardation. However, whether thyroid hormone variation within the normal range affects developmental tests is not known. Thus, we aimed to investigate associations between physiological variations in thyroid hormone levels and the results of developmental tests in healthy children.

Methods: This study included 946 children who completed the Bayley Scales of Infant and Toddler Development (BSID) III and 1,467 children who completed the developmental test for children from 6 months to 6 years old (ET 6-6-R). Using regression models, we assessed the association between TSH, FT3, and FT4 and test results as outcomes. In addition, we assessed associations between the subscales and stability across age.

Results: Higher TSH-SDS values were associated with lower ET 6-6-R scores in cognitive development, language development, fine and gross motor skills, with effects between β = -0.13 to β = -0.23 (all ps < 0.05). After adjusting for age, sex, and mother's education, only language development reached significance. FT3 was positively associated with gross motor skills (β = 0.17), fine motor skills (β = 0.26), and cognition (β = 0.15) (ps < 0.05). After adjusting, only fine motor skills remained significant. FT4 showed positive but mostly nonsignificant associations with most subscales. We found no consistent significant associations between BSID scores and thyroid hormones.

Conclusion: The differential results for the developmental tests indicate that the associations are highly specific for particular aspects of development and even developmental stages. Therefore, single measurements have very limited explanatory power.

Introduction: Thanatophoric dysplasia type 1 (TD1) is the most severe form of FGFR3-related skeletal dysplasia, with high perinatal mortality and no approved pharmacologic therapies. Vosoritide, a C-type natriuretic peptide analogue that counteracts FGFR3 overactivation, improves growth in achondroplasia, but its effects in TD1 remain unexplored.

Case presentation: We report the response to vosoritide therapy in a 9-year-old girl with genetically confirmed TD1 (c.2420G>T). Vosoritide was initiated at a dose of 15 µg/kg/day subcutaneously and increased to 30 µg/kg/day after 16 months. Growth velocity, anthropometry, pulmonary function, densitometry, and safety were assessed longitudinally over 28 months. At baseline, height was 78.6 cm (-10.9 SDS) and annual growth velocity (AGV) 1.6 cm/year (-4.7 SDS). After 28 months, height increased by +1.3 SDS and AGV by +2.0 cm/year (+3 SDS from baseline). Lung vital capacity improved by 65%. Serial MRI demonstrated persistent severe foramen magnum stenosis without radiological progression. Adverse events were limited to transient injection-site reactions and mild vasovagal episodes; no major safety concerns emerged.

Conclusions: Vosoritide was well tolerated and improved growth velocity and lung function in this long-term TD1 survivor, suggesting therapeutic potential even in severe FGFR3 overactivation. Given TD1's rarity, larger studies and further off-label experience are essential to validate these findings.

Introduction: Associated conditions, especially being born small for gestational age (SGA), have been reported with a higher prevalence in patients with differences in sexual development (DSD) compared to the general population. Our objective was to analyze the prevalence of SGA in a cohort of DSD patients evaluated at a single tertiary pediatric center, and to examine its association with sex chromosome constitution, molecular diagnosis, and clinical phenotype.

Methods: Gestational age, birth weight, and birth length were evaluated to assess prenatal growth and the prevalence of SGA. DSD patients were classified according to karyotype. Among 46,XY DSD patients, perinatal data were further analyzed based on molecular diagnosis and the presence or absence of gonadal dysgenesis.

Results: Overall, 642 DSD patients were included: 202 (31.5%) with chromosomal DSD, 218 (33.9%) with 46,XX DSD, and 222 (34.6%) with 46,XY DSD. SGA prevalence was 30.2%, 7%, and 27.5%, respectively. In the 46,XY DSD group, a molecular diagnosis was achieved in 35% of patients. SGA was more frequent in 46,XY DSD subjects without molecular diagnosis and without gonadal dysgenesis.

Conclusion: A high prevalence of SGA was observed among individuals with sex chromosome DSD, consistent with the literature, whereas a lower prevalence was found among those with 46,XX DSD, as expected in the Latin American population. The frequency of SGA in the 46,XY DSD group reinforces the association between SGA and DSD in the 46,XY DSD, particularly in patients without a clear molecular diagnosis and without specific disorders of undervirilization. Factors involved in early embryonic growth, development, and gonadal differentiation may mediate the association between being born SGA and DSD in humans. Further studies are needed to clarify the etiological diagnosis.

Introduction: Patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency require lifelong glucocorticoid treatment, often at supraphysiologic doses, which increases their risk for obesity starting in early childhood and osteoporosis later in life. While obesity and inflammation have been shown to negatively impact bone health in the general population, the relationship between bone mineral density (BMD) and abdominal adiposity in youth with CAH remains unclear. We examine the association between BMD, adiposity, inflammation, and adrenal androgens in youth with CAH.

Methods: Thirty-five youth with CAH (12.33 ± 3.20 years; 12 males) and 38 age- and sex-matched controls (12.70 ± 2.83 years; 14 males) underwent dual-energy X-ray absorptiometry for BMD, MRI for abdominal adiposity (visceral adipose tissue [VAT] and subcutaneous adipose tissue [SAT]), and bone age X-ray. Linear regression models assessed associations between whole body and lumbar spine areal BMD height-adjusted Z-score (LS aBMD_HAZ), adiposity, hormones, and inflammatory markers, adjusting for GC dose and BMI-z.

Results: Adiposity measures were significantly higher in CAH patients (SAT, VAT, total % body fat, Ps <0.01). LS aBMD_HAZ negatively correlated with SAT (β = -1.21; 95% CI: -2.17, -0.24; p = 0.014), VAT (β = -0.38; 95% CI: -0.77, 0.02; p = 0.061), and total % body fat (β = -0.63; 95% CI: -1.23, -0.03; p = 0.039) in youth with CAH, independent of BMI-z and GC dose. In controls, only VAT (β = -0.39; 95% CI: -0.77, -0.01; p = 0.044) was negatively associated with LS aBMD_HAZ. Areal BMD_HAZ remained within normal limits for both groups, but in CAH patients, LS aBMD_HAZ declined with age. No associations were found between BMD_HAZ and adrenal hormones or MCP-1.

Conclusion: Adiposity negatively impacts BMD in CAH youth, independent of BMI and GC dose, potentially increasing the risk of osteoporosis in adulthood. Further research is needed to explore strategies to mitigate these effects.

Introduction: The rate of malignancy (ROM) among pediatric studies using the Bethesda System is 39.5% and 41.5% for atypia of undetermined significance/follicular lesion of undetermined significance and for suspected follicular neoplasm, respectively. Data reported on the basis of Bethesda System showed lower ROM in adults with indeterminate nodules (30.5% and 28.9%, respectively). Studies on adults based on the Italian Society of Anatomic Pathology and Cytology (SIAPEC) classification, report a ROM of 4-20.8% for TIR3a and 28-60.3% for TIR3b category, showing greater sensitivity in detecting malignancy. To date, very few performance data are available about SIAPEC classification in pediatric age.

Methods: Multicentre retrospective data were collected from 44 pediatric subjects with thyroid nodules.

Results: The distribution of cytological categories after fine-needle aspiration biopsy (FNAB) was 26 TIR3a and 18 TIR3b. Surgical approach was performed in 8/26 subjects with TIR3a and 18/18 subjects with TIR3b with a total ROM of 53.8% (12.5% for TIR3a, 72.8% for TIR3b). Total FNAB accuracy for the indeterminate cytologic category was 77%.

Conclusion: The reported data seem to confirm a greater sensitivity of SIAPEC classification to identify malignancy within the indeterminate category also in pediatric age and not only in adulthood. This finding may orient clinicians toward clinical follow-up for the indeterminate TIR3a group and toward surgical approach with total thyroidectomy in the indeterminate TIR3b group, although this indication should be confirmed in further national multicenter studies including larger cohorts.

Background: Inequities in the clinical care and health outcomes of youth and young adults (YYAs) with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) are well-established. Systemic and institutional racism and barriers, as well as implicit biases underlie these inequities in the USA.

Summary: This article offers a broad overview and analysis of disparities in clinical care and outcomes among YYAs with T1D and T2D, framed within an ethical context. We argue that achieving ethical care requires centering assessments of patient and family needs within the realities of their lived experiences, as well as structural barriers and challenges. We examine the impact of structural racism and implicit bias on clinical care and explore how factors such as non-English language communication, literacy, numeracy, nutrition, school nursing services, access to diabetes technology and medications, and insurance disparities influence diabetes management and outcomes. The article concludes with a call to action and concrete recommendations to address and reduce these inequities.

Key messages: Clinicians can play a pivotal role in reducing diabetes-related healthcare disparities by adopting an ethical approach that centers upon lived experiences of YYA with diabetes thereby identifying opportunities for more equitable care.

Growth hormone (GH) therapy is a cornerstone in managing pediatric growth disorders, yet individual responses vary significantly despite standardized protocols. This variability underscores the need for a comprehensive predictive framework to guide clinical decisions and optimize outcomes. Key determinants of growth response include the underlying diagnosis and degree of GH sensitivity, with conditions like severe GH deficiency typically responding better than disorders such as idiopathic short stature, small for gestational age, or Turner syndrome. Patient-specific factors - including age at treatment initiation, bone age delay, mid-parental height, and auxological parameters - further shape therapeutic outcomes. Definitions of poor response remain debated, typically relying on first-year height gain or height velocity metrics. A suboptimal response should prompt reassessment of the diagnosis and therapeutic strategy. Emerging therapies offer promising alternatives and adjuncts aimed at improving adherence, targeting specific etiologies, and enhancing outcomes. Despite early success, these interventions require further validation regarding long-term efficacy, safety, and cost-effectiveness. Together, these innovations reflect a broader shift toward mechanism-driven, personalized therapy in pediatric endocrinology.