Clinical Pediatric Endocrinology最新文献

Most patients with resistance to thyroid hormone (RTH) test negative in newborn screening (NBS) for congenital hypothyroidism (CH). Here, we present a case of RTH diagnosed through NBS. The patient presented to us after her NBS for CH revealed high TSH (23.4 µIU/mL) and free T4 (FT4) (5.40 ng/dL) levels. Apart from tachycardia, she exhibited no other manifestations related to excess or deficiency of thyroid hormones. A confirmatory test replicated the findings, showing elevated serum TSH levels (35.7 µIU/mL) along with high FT4 levels (5.84 ng/dL). Ultrasonography showed marked thyroid gland enlargement (> +4 SD). Targeted next-generation sequencing of genes associated with genetic thyroid disorders revealed a previously reported THRB variant, p.Gly345Cys. Unexpectedly, two biallelic DUOX2 variants (p.His678Arg and p.Arg1334Trp) were also detected. At her last visit, no significant issues were observed with neurological development, growth, bone maturation, or gastrointestinal symptoms related to thyroid function at the age of 1 year, without treatment for RTH and CH. During follow-up, the TSH and FT4 levels gradually decreased. In conclusion, we report a patient with simultaneous RTH and DUOX2 defects, demonstrating the value of conducting a comprehensive analysis of multiple genes associated with thyroid diseases to better comprehend the pathogenesis in patients with atypical thyroid-related phenotypes.

We report the case of a patient with osteogenesis imperfecta (OI) who developed pulmonary hemorrhage 4 d after pamidronate disodium (PA) administration, despite a relatively stable respiratory status. Bisphosphonates are introduced to reduce osteoclast activity and are now widely used in patients with OI. Bisphosphonates are typically well-tolerated in children, and the standard of care involves cyclic intravenous administration of PA. However, in practice, there is limited experience with the use of PA for severe OI during the neonatal period, and its safety remains uncertain. This report aimed to describe the respiratory events potentially associated with PA in a neonatal patient with OI type 2, suggesting that serious life-threatening complications of pulmonary hemorrhage may occur after PA administration. Further studies are required to assess the relationship between pulmonary hemorrhage and PA administration, aiming to enhance prophylaxis measures.

We conducted a randomized phase 3 study to investigate the efficacy and safety of GH treatment in prepubertal Japanese patients with short stature due to SHOX deficiency. The patients were randomly allocated to the GH-GH group (n = 10), in which the patients were treated with GH (0.35 mg/kg/wk) subcutaneously once daily for 24 mo, or the no-treatment (NT)-GH group (n = 9), in which the patients were untreated for the first 12 mo and then administered the same dosage of GH for the next 12 mo. At month 12, the ∆height standard deviation score (SDS) for chronological age (CA) and serum IGF-1 level were significantly higher in the GH-GH group than those in the NT-GH group. In contrast, bone age (BA) and ΔBA/ΔCA were numerically higher in the GH-GH group but were not statistically significant. At month 24, these parameters were comparable between the two groups. The height velocity was significantly larger in the GH-GH group during the first year and in the NT-GH group during the second year. No serious adverse drug reactions were observed; however, one patient in the GH-GH group exhibited increased insulin resistance at month 24. These results indicated that GH is a promising treatment option for short stature in patients with SHOX deficiency.

Adipsic hypernatremia is typically caused by congenital dysplasia of the hypothalamus and pituitary or brain tumors. However, cases of adipsic hypernatremia without underlying organic abnormalities are rare, and some cases have been reported to be complicated by hypothalamic-pituitary dysfunction. The patient in this case was a 9-yr-old boy who was referred to our hospital because of hypernatremia. His growth chart revealed that he had rapidly become obese since infancy, with growth retardation since the age of seven. His hands and feet were very cold, and he had erythema on his abdomen, indicating possible autonomic dysregulation due to hypothalamic dysfunction. Several hormone load tests showed severe GH deficiency (GHD) and marked hyperprolactinemia (peak: 302.8 ng/mL). Magnetic resonance imaging revealed no organic abnormalities in the hypothalamus and pituitary gland. GH replacement therapy was initiated. Although his growth rate improved, obesity persisted. To the best of our knowledge, this is the first report of adipsic hypernatremia without organic intracranial abnormalities that was treated with GH. Moreover, the patient's prolactin levels were higher than those reported in previous studies. In conclusion, adipsic hypernatremia requires the evaluation of pituitary function and appropriate therapeutic interventions.

Chronic inflammatory conditions, such as juvenile idiopathic arthritis, are associated with growth failure. Growth failure appears to be correlated with both the effects of inflammation and negative effects of glucocorticoids (used as therapeutic option) on the growth hormone axis and locally on the growth plate and bone metabolism. In the last decade, the introduction of biologics has changed the disease course regarding consequences and outcomes. Anyway in some cases, treatment with biologics has failed in restoring normal growth in patients with juvenile idiopathic arthritis; in contrast, several studies have reported improved height velocity and growth rate in patients with juvenile idiopathic arthritis treated with growth hormone. This study aimed to evaluate the impact of growth hormone treatment on the growth and pubertal development in juvenile idiopathic arthritis patients through a narrative review of the literature over the last four decades.

Noonan syndrome is a congenital disorder characterized by distinctive facial appearance, congenital heart defects, short stature, and skeletal dysplasia. Although boys with Noonan syndrome frequently exhibit cryptorchidism, a mild form of 46,XY disorders of sex development (DSD), they barely manifest more severe genital abnormalities. Here, we report a boy with ambiguous genitalia, short stature, and non-specific dysmorphic features. He had no cardiac abnormalities or skeletal dysplasia. His score in the Noonan syndrome diagnostic criteria (36 of 157 points, 23%) was lower than the cutoff for diagnosis (50%). Whole-exome sequencing identified a de novo heterozygous variant (c.922A>G: p.Asn308Asp) in PTPN11 and a maternally inherited hemizygous variant (c.1439C>T: p.Pro480Leu) in FLNA. The PTPN11 variant was a known causative mutation for Noonan syndrome. FLNA is a causative gene for neurodevelopmental and skeletal abnormalities and has also been implicated in 46,XY DSD. The p.Pro480Leu variant of FLNA was assessed as deleterious by in silico analyses. These results provide evidence that whole-exome sequencing is a powerful tool for diagnosing patients with atypical disease manifestations. Furthermore, our data suggest a possible role of digenic mutations as phenotypic modifiers of Noonan syndrome.

Several studies have reported an association between age at menarche and the onset of type-1 diabetes mellitus (T1DM). This review compared the age at menarche in patients who had menarche after T1DM diagnosis with that of patients who were healthy and/or had menarche before T1DM diagnosis. Searches were conducted using four databases. The outcome was the age at menarche of patients who had menarche after T1DM diagnosis and patients who were healthy and/or had menarche before T1DM diagnosis. A qualitative analysis was performed using the JBI (Joanna Briggs Institute) Critical Appraisal. Quantitative analysis of the mean differences was performed using Revman 5.4 tool. A total of 1952 studies were obtained from the initial search. The final results were 13 articles that met the inclusion criteria for the qualitative assessment and eight for the quantitative assessment. Eight studies included 1030 patients who had menarche after being diagnosed with T1DM and 1282 patients who were healthy and/or had menarche before T1DM diagnosis. The meta-analysis showed a cumulative effect on a mean difference of 0.87 (95% CI: 0.75; 0.99, p-value < 0.00001), indicating a later age at menarche in patients who had menarche after T1DM diagnosis. The age at menarche was later in patients who had menarche after T1DM diagnosis compared to healthy subjects and those who had menarche beforehand.

The objectives of this study were to (1) compare peak expiratory flow (PEF), physical activity (PA), and core performance among normal-weight, overweight, and obese adolescents and (2) explore the relationships between PEF, physical activity, core performance, and anthropometric measurements across these groups. Ninety adolescents aged 10-13 yr were categorized based on BMI: normal weight (n = 30, 5th to < 85th percentile, BMI-Z score -2 to < 1), overweight (n = 30, 85th to < 95th percentile, BMI-Z score 1 to < 2), and obese (n = 30, > 95th percentile, BMI-Z score > 2). PEF and percent-predicted values of PEF (PEF% pred) values were calculated. Waist and neck circumferences were measured. Physical activity levels were assessed using the Physical Activity Questionnaire for Older Children (PAQ-C), from which total and subscores were derived. Core performance was evaluated through modified push-up (MPU) and sit-up tests. The PEF% pred and PAQ-C scores showed no significant differences between groups (p > 0.05). However, MPU repetition rates were significantly lower in obese adolescents compared to overweight (p = 0.019) and normal-weight peers (p < 0.001). There was a significant correlation between PEF% pred and PAQ-C total scores (p = 0.014), as well as out-of-school subscores (p = 0.039) in overweight adolescents. Similarly, PEF% pred was linked to MPU repetitions in obese adolescents (p = 0.029). Obese adolescents exhibited decreased core performance relative to their overweight and normal-weight counterparts, which correlated with the PEF% pred. Physical activity was associated with PEF% pred exclusively in overweight adolescents.