Vitamin D receptor hypermethylation as a biomarker for pediatric adrenocortical tumors.

Objective: Pediatric adrenocortical tumors (pACT) display complex genomic backgrounds, lacking robust prognostic markers and targeted therapeutic options. Vitamin D3 receptor (VDR) promoter hypermethylation and underexpression were reported in adrenocortical carcinomas from adult patients. In this study, we aimed to investigate VDR expression levels and methylation status in pACT and their clinical and prognostic significance. Design: Retrospective cross-sectional study enrolling pediatric patients with ACT from two tertiary referral institutions. Methods: We evaluated clinicopathological features, VDR mRNA (qPCR) and protein (immunohistochemistry) expression, and VDR-wide methylation of ACT samples from 108 pediatric patients. Fourteen pediatric and 32 fetal and postnatal normal adrenals were used as controls. Results: Unlike in pre- and post-natal normal adrenals, most pACT lacked nuclear VDR expression and had reduced mRNA levels, especially the carcinomas. Unsupervised analysis of VDR methylation data revealed two groups of pACT with distinct disease features and outcomes. Tumors with high VDR methylation presented lower mRNA levels, and the respective patients presented advanced disease and reduced disease-free and overall survival. Conclusions: VDR has a role in normal adrenocortical development and homeostasis, which is impaired during tumorigenesis. VDR hypermethylation and underexpression may be both predictive and prognostic biomarkers for pACT.

A two-year follow-up of asfotase alfa replacement in a patient with hypophosphatasia: clinical, biochemical, and radiological evaluation.

Hypophosphatasia (HPP) is a rare disease with a high mortality rate in its severe forms. It is caused by mutations within the gene encoding the tissue-nonspecific alkaline phosphatase (TNSALP), an enzyme responsible for bone mineralization. In 2015, the Food and Drug Administration approved the use of asfotase alfa, the first medication showing benefit in the treatment of HPP. We describe a case with a 2-year follow-up of the first Brazilian child treated with asfotase alfa. A 5-year-old boy, born to consanguineous parents, was diagnosed with HPP at the age of 20 months. During prenatal ultrasonography, polyhydramnios and shortening of long bones were detected. After birth, he presented delayed motor development, repeated respiratory infections, and bone deformities. At the age of 2 years and 8 months, he started walking and had already lost his primary teeth. He had reduced levels of alkaline phosphatase (ALP), elevated levels of pyridoxal 5'-phosphate (PLP), and a p.Ala33Val (c.98C>T) missense mutation in homozygosis in the TNSALP gene. His parents and sister also had reduced ALP levels, high PLP levels, and the same mutation in heterozygosis. His father and sister were healthy, and his mother was diagnosed with rickets in childhood, which resulted in short physical stature and lower limb deformities. The patient was started on asfotase alfa at the age of 2 years and 10 months. After 2 years of treatment, he improved his motor skills, had no further episodes of severe respiratory infection, and showed improved radiological findings of rickets, without any severe side effect.

New glycemic metrics and traditional clinical and laboratory profiles of children and adolescents with type 1 diabetes mellitus in an outpatient follow-up.

INTRODUCTION: This study evaluated the demographic, clinical, and laboratory data - including traditional (as glycated hemoglobin, HbA1c) and new glycemic metrics (as time in range, TiR) - and the complications present in children and adolescents (CA) in outpatient follow-up, as well as their possible associations. METHODS: This retrospective observational study's data were compiled from the CA's medical records with T1DM (n = 78) being followed up at the Pediatric Endocrinology Service of the Federal University of Uberlândia. RESULTS: The average participants' age was 10.2 years (1-16), most of them (55%) being male, with a diagnosis time of 4.5 years (1-13), and a body mass index of 18 kg/m2. The group had HbA1c levels of 9.6% and an estimated average glycemia of 229.5 ± 103 mg/dL. TiR was 25% (7-54%); the short- (CV%) and medium-term (ΔHbA1c) glycemic variability was 45.7% and 1.5%, respectively. Approximately 10% had diabetes ketoacidosis in the last year of follow-up, about 6% had chronic complications, such as nephropathy or retinopathy, and 20% had some other associated autoimmune disease. 49% of the participants reported regular physical activity. CONCLUSION: The high values of HbA1c and glycemic variability amplitude, short TiR, and the early presence of chronic complications reveal that the treatment did not reach its goal in this population. Better education of patients and their families about the disease and greater adherence to intensive insulin treatment can optimize the control of diabetes in pediatric patients.

Intracranial compound odontome.

An exceedingly rare case of an extragnathic odontome is described arising within the brain. A 10-year-old boy complained of progressive frontal headache for 5 years. Axial computerized tomography the head revealed a solid, calcified lesion with well-defined borders localized in the sellar and suprasellar region composed of multiple calcified structures resembling teeth. The diagnosis was compound odontome. Physical examination and blood analysis revealed hypopituitarism. The patient was submitted for radical tumour resection. He developed persistent diabetes insipidus, hypothyroidism and adrenal insufficiency for which appropriate replacement therapy has been necessary. This case demonstrates that an odontogenic lesion may arise in brain tissues due to the embryological relationship between primordial stomodeum and Rathke's pouch. Its development could be associated with endocrine disturbances.