Journal of Pediatric Endocrinology & Metabolism最新文献

Objectives: Copeptin is secreted in isomolar amounts along with AVP. Its stability makes it a perfect biomarker of AVP deficiency. In children, dynamic GH tests were shown to stimulate copeptin. Here, we retrospectively studied the effect of clonidine on copeptin release.

Methods: This is a monocentric retrospective analysis of donated residual serum samples from 42 children with suspected growth hormone deficiency (GHD) who underwent clonidine stimulation between 2020 and 2023. Copeptin was measured in baseline, 30-, 60-, 90- and 120-min samples by BRAHMS Copeptin proAVP Kryptor immunofluorescence assay.

Results: There were 20 patients with GHD and 22 without; no patient had polyuria-polydipsia syndrome. Median age was 6.7 years (quartiles; 5.6-7.8), and the median height was -2.92 SDS (-3.42 to -2.34). The median baseline level of copeptin was 5.6 pmol/L (3.4-9.6). Median copeptin mildly decreased to 4.5 pmol/L (3.0-10.0) after 30 min; this change was not significant (p=0.45). Thereafter, median values remained low at 4.6, 4.6, and 4.6 pmol/L (60, 90, and 120 min). There was no correlation between baseline copeptin levels and the diagnosis of GHD.

Conclusions: The clonidine stimulation test does not stimulate copeptin release and is not suitable for the assessment of AVP deficiency in children.

Objectives: Homozygous familial hypercholesterolemia (HoFH) is a rare inherited disorder of lipoprotein metabolism associated with significant morbidity and early mortality. The conventional management with lipid-lowering drugs and lipoprotein apheresis is unable to consistently achieve guidelines recommended low-density lipoprotein cholesterol (LDL-C). We aim to describe the efficacy of Evinacumab, a recently approved monoclonal antibody, in lowering LDL-C in an Indian girl with HoFH.

Case presentation: A 16-year-old girl was diagnosed with HoFH at age two years after the appearance of cutaneous and tendo-calcaneus xanthomas. Genetic testing revealed a pathogenic homozygous deletion in the LDL receptor (LDLR) gene. Despite lifestyle measures, a low-fat diet, and maximum doses of atorvastatin and ezetimibe, her average LDL-C level remained 320.3 mg/dL over the past decade. Her caregivers did not accept LDL-apheresis. She also did not respond to Evolocumab therapy. The patient developed progressive calcific aortic stenosis and concentric left ventricular hypertrophy, necessitating aortic valve replacement surgery at age 16 years. The recent addition of Evinacumab to her lipid-lowering drug regimen, resulted in a significant LDL-C reduction of 76.16 %, bringing levels down to 82 mg/dL. These levels were sustained over the last four months.

Conclusions: Evinacumab offers a promising option for managing high-risk and difficult-to-treat HoFH patients. This is the first Indian child receiving Evinacumab for HoFH.

Objectives: The authors sought to assess whether the age of 18 reflects a true pathological inflection point that justifies transitioning between pediatric and adult paradigms of care with differentiated thyroid cancer (DTC).

Methods: A retrospective chart review was conducted for patients aged 12-24 undergoing hemithyroidectomy or total thyroidectomy for papillary or follicular thyroid carcinoma from 2010 to 2020.

Results: A total of 153 patients receiving surgery for DTC were assessed for pathological stage, nodal metastasis, and thyroid neoplasm characteristics. When comparing pathologic tumor staging of patients <18 vs. ≥18 years old, there was a significant relationship between age and pT stage (p=0.009), but not between age and pN stage (p=0.319). However, when comparing patients ≤15 vs. >15 years, there was a significant relationship between age and pT stage (p=0.015) and age and pN stage (p=0.016). Patients ≤15 years of age most commonly had stage pT2 tumors (48.9 %, n=22), whereas most >15 years had stage pT1 tumors (37.9 %, n=41). Of patients whose lymph nodes were analyzed, patients ≤15 years were most likely to have pN1b disease (31.1 %, n=14), while patients >15 years were most likely to have pN0 disease (33.3 %, n=36).

Conclusions: In this sample, separating children and adults at an age of 15, rather than 18, yielded more significant differences in risk of nodal involvement. Markers of invasive histology were more common in patients older than 15, while nodal involvement was more common in patients 15 and under.

Objectives: Graves' disease is the leading cause of hyperthyroidism in children. Only a small percentage of pediatric patients achieve remission with anti-thyroid drug treatment (ATD), and both definitive therapies (thyroidectomy, or radioiodine thyroid ablation) cause lifelong hypothyroidism. Our objective was to evaluate the outcome of patients with pediatric Graves' disease (PGD), treated at a single tertiary center, focusing on response to medical treatment, remission rate, adverse reactions (AR), definitive treatment (DT), and potential predictive factors for remission.

Methods: Data from clinical charts of 130 patients diagnosed with PGD between 2006 and 2021 were collected: epidemiological, clinical, biochemical characteristics, outcome, remission, adverse reactions (AR), and DT were registered. Predictive factors at diagnosis were evaluated for 88 patients diagnosed at our center.

Results: Our patients were 78 % female, 98 % Hispanic, with a median age of 12.7 years (range 1.7-17.3 years). Fourteen (11 %) had Down syndrome. Severe thyrotoxicosis (FT4>5.5 ng/dL) was seen at diagnosis in 66 %. Initially, 129/130 received ATD; during the study, 17 participants (13 %) reached remission, with a median ATD duration of 3.1 years (range 1.3-6.1 years). The chance of remaining hyperthyroid was 65 %. Only one patient relapsed 1.3 years post-ATD. Forty-six percent (59/129) needed DT, 31 % (40/129) were lost to follow-up, and 10 % (11/129) remained on ATD. AR affected 26 % of the patients and most (74 %) occurred within the first 3 months, half of them severe enough to discontinue ATD. No significant predictive factors were identified.

Results: ATD, our first-line treatment, resulted in low remission rates for Hispanic pediatric patients with severe thyrotoxicosis at diagnosis. Poor adherence issues contributed to the indication of DT (46 %) and loss to follow-up (31 %) during the studied period. Based on our findings, DT should be considered at 4 years of ATD in persisting PGD.

Conclusions: ATD, our first line treatment, resulted in low remission rates for Hispanic pediatric patients with severe thyrotoxicosis at diagnosis. Poor adherence issues contributed to the indication of DT (46 %) and loss to follow-up (31 %) during the studied period. Based on our findings, DT should be considered at 4 years of ATD in persisting PGD.

Objectives: Sepiapterin reductase deficiency (SRD) is a rare dopa-sensitive neurotransmitter disorder caused by autosomal recessive mutations in the sepiapterin reductase gene. The triad of paroxysmal stiffening, oculogyric crises, and hypotonia are highly suggestive in some patients. However, in other patients, the clinical picture may be nonspecific and remain under-recognized and misdiagnosed as cerebral palsy.

Case presentation: We present a nine-month-old boy who initially presented with hypotonia and developmental delay, diagnosed as vitamin B12 deficiency. Upon he did not respond to vitamin replacement treatment, he was diagnosed with SRD by whole-exome sequencing (WES). The boy improved dramatically under treatment with L-dopa, 5-hydroxytryptophan and BH4.

Conclusions: We aim to emphasize that SRD can present with nonspecific symptoms, leading to a diagnostic delay for this rare but treatable disease. Moreover, our case is the first to demonstrate the clinical benefit of BH4 add-on treatment. Early intervention is crucial for good outcome and neurodevelopment.

Objectives: Sialidosis type 1 is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in the NEU1 gene, which encodes the sialic acid-degrading enzyme α-neuraminidase. Sialidosis type 1 is a milder form with a late-onset phenotype, characterized by progressive myoclonic epilepsy and ataxia with cherry-red spots. Sialidosis type 2 is an early-onset and more severe form presenting with dysmorphic features, hepatosplenomegaly and cognitive delay. Clinical diagnosis is usually supported by increased urinary bound sialic acid excretion and confirmed by genetic analysis or demonstration of α-neuraminidase enzyme deficiency in cultured fibroblasts. The aim of this study was to present a case of type 1 sialidosis, review the literature, and investigate genotype-phenotype correlations, symptom frequencies, and race-specific mutations in patients diagnosed with type 1 sialidosis.

Case presentation: We report herein a family of four Turkish siblings affected with sialidosis type 1 associated with a homozygous variant, c.403G>A p. (Asp135Asn), in the NEU1 gene. A systematic literature review on sialidosis type 1 was carried out, by the PubMed database was searched using keywords included sialidosis and/or NEU1 gene. We selected case reports or series that included genetically confirmed type 1 sialidosis from 1996 to 2023. So far, nearly genetically confirmed 80 patients from unrelated 65 families, more than 40 NEU1 disease causing mutations, have been identified in patients with sialidosis type 1. Among the reported mutations, missense variants are the most common, and few nonsense, frameshift, exonic duplications or small deletions have been reported. c.239C>T p. (Pro80Leu) variant in Chinese and Japanese patients, c.649G>A p. (Val217Met) variant in Japanese patients, c.880C>T p. (Arg294Cys) variant in Indian patients, c.629C>T p. (Pro210Leu) variant in Ecuadorian patients, c.982G>A p. (Gly328Ser) variant in Italian patients, and c.403G>A p (Asp135Asn) and c.625del p. (Glu209Serfs*94) variants in Turkish patients were found higher.

Conclusions: Race-specific variants were found with higher percentages in certain populations.

Objectives: Exocrine pancreatic insufficiency has been demonstrated in type 1 diabetes (T1D); lower concentrations of pancreatic enzymes have been associated with metabolic risk (MR). Influence of puberty and MR factors on serum concentrations of amylase and lipase remain unexplored in Indian youth with T1D. 1) To characterize and predict determinants of serum amylase and lipase concentrations in adolescents/youth with T1D. 2) To assess relationship between amylase, lipase, and prevalence of MR.

Methods: Cross sectional, observational study on 291 (155 girls) adolescents/youth (10-24 years) with T1D. History, examination, body composition, biochemistry (glycated hemoglobin [HbA1c], thyroid stimulating hormone [TSH], lipids).

Results: Mean age, diabetes duration and HbA1c were 15.3, 7.0 years and 10.0 ± 2.1, respectively. Relative risk of lower amylase/higher lipase concentrations (9.5 %) was 1.42 and 1.34, respectively, though these did not reach statistical significance. In pubertal participants, amylase was lower and lipase higher; association was not found with MR. Higher TSH and lower serum calcium were significantly associated with higher lipase (p<0.001).

Conclusions: We have characterized amylase and lipase concentrations across puberty; poor glycemic control tended to be associated with lower amylase and higher lipase, though these findings did not reach statistical significance. Amylase and lipase concentrations should be monitored in Indian adolescents with T1D, particularly in those with poor metabolic control, puberty, uncontrolled hypothyroidism, or reduced calcium intake, while further longitudinal and larger studies are needed to generalize these findings.

Objectives: Limited data are available on the hormonal response of children to venepuncture or intravenous cannulation (IVC). Catecholamines (epinephrine (E) and norepinephrine (NE)) have been traditionally recognized as stress hormones. Copeptin, the carboxyl-terminus of the arginine vasopressin (AVP) precursor peptide, is also a known marker for stressful stimuli, including myocardial infarction, critical illness, and sepsis. We aimed to measure the above stress markers in response to IVC in the pediatric population.

Methods: We measured plasma E, NE and serum copeptin concentrations in 100 children aged 5-17 years undergoing endocrine testing. Labs were drawn 1-3 min (min) after placement of IV cannula (baseline or 0 min) and then re-measured 20 min later (+20 min) while subjects rested in a quiet room.

Results: Between 0 and 20 min, the median (IQR) NE (n=99) changed from 349 (244, 482) pg/mL to 253 (184, 348) pg/mL (p<0.001); E (n=54) changed from 57 (43, 116) pg/mL to 57 (38, 96) pg/mL (p=0.024); Copeptin changed from 9.4 (6.3, 15.2) pmol/L to 9 (5, 13) pmol/L (p<0.001). The mean decrease (delta) was 106 pg/mL for NE (28 %, p<0.001), 16 pg/mL for E (18 %, p=0.042) and 2.7 pmol/L for copeptin (17 %, p=0.012). There was no correlation between the decrease (expressed as a percentage) in NE vs. E, E vs. copeptin, and NE vs. copeptin.

Conclusions: Our data suggest that the stress of IVC induces a rapid increase in NE, E, as previously described, as well as copeptin levels. The copeptin decrement, concordant with the catecholamine trend in the minutes after IVC, supports this peptide (and AVP) as a rapid response marker of stress, and has unclear practical implications for copeptin measurements in evaluating fluid and sodium metabolism disorders in children.

Objectives: Kallmann syndrome (KS) is a rare genetic disorder marked by hypogonadotropic hypogonadism and either anosmia or hyposmia. It exhibits genetic heterogeneity, with mutations identified in only 30 % of cases, involving various genes such as KAL1, FGFR1, FGF8, CHD7, and SOX10. Here, we present a case of gonadotropin deficiency associated with KS, observed in both a mother and her daughter, the latter conceived through assisted reproductive technology using the mother's ovum.

Case presentation: A 12-year-old female presented with short stature and lack of growth over the past year. Initial laboratory testing revealed mildly elevated TSH (8.348 uIU/mL), normal free T4 (0.9 ng/dL), and positive thyroid antibodies, including elevated TPO (629 IU/mL). Her growth hormone peak response to stimulation testing was 12.8 ng/mL, and GnRH stimulation indicated a peak LH value of 1.78 mIU/mL and a peak FSH value of 2.83 mIU/mL, consistent with hypogonadotropic hypogonadism (HH). Genetic testing identified a novel heterozygous variant in the SOX10 gene, predicted to be damaging, and also present in her mother, who had Kallmann syndrome. The patient was initiated on low-dose estrogen therapy with estradiol patches to stimulate growth and pubertal development.

Conclusions: This case highlights the transmission of a novel SOX10 mutation in a mother-daughter pair through assisted reproductive technology, bypassing the typical infertility-related barriers to genetic inheritance in KS. The autosomal dominant inheritance pattern observed in this family emphasizes the importance of genetic counseling when reproductive assistance is considered. This case also suggests that SOX10 mutations may contribute more broadly to the pathogenesis of KS and related HH.

Objectives: Immune checkpoint inhibitors (ICIs) are emerging treatment options for children with brain tumors, who are already at risk for developing endocrinopathies due to tumor location and treatment. Endocrine ICI-related adverse effects (irAEs) are common in adults but poorly characterized in the pediatric population. The aims of this study were to determine in pediatric brain tumor patients in a single institution (1) if endocrine surveillance took place before and after ICIs were initiated, and (2) the occurrence of endocrine irAEs.

Methods: This is a retrospective chart review of 22 pediatric brain tumor patients treated with ICIs at Children's Hospital Los Angeles between 2010 and 2022. We analyzed endocrine laboratory results, patient demographics, and treatment course.

Results: Most patients (82 %) received surveillance in at least one endocrine system before ICI treatment - all had thyroid function tested (100 %) whereas non-thyroid endocrine functions were seldomly assessed (6-22 %). Only those patients with surveillance prior to treatment had ongoing surveillance after ICI initiation - 100 % for thyroid function and 17-39 % for other endocrine systems. Hypothyroidism was the only endocrine problem diagnosed after ICI initiation, in two patients (9 %). Of note, most patients (68 %) expired during or shortly after ICI treatment.

Conclusions: This is one of the first institutional surveys of pediatric ICIs in a high-volume pediatric brain tumor center. Thyroid surveillance commonly occurred in pediatric patients, revealing diagnoses of hypothyroidism, which is consistent with adult data. However, little information is available for non-thyroid endocrine conditions, reflecting the need for comprehensive and systematic endocrine surveillance.