Opportunities for digitally-enabled personalization and decision support for pediatric growth hormone therapy.

Smart technologies and connected health are providing opportunities for improved healthcare for chronic conditions. Acceptance by healthcare professionals (HCPs) and patients is crucial for successful implementation. Evidence-based standards, technological infrastructure and regulatory processes are needed to integrate digital tools into clinical practice.

Intrathyroidal neurofibroma, a case report.

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disease. It is characterized by café-au-lait spots, melanocytic hamartomas of the iris, pseudo-freckles, neurofibromas, and tumor predisposition. The presence of neurofibromas in the thyroid gland is extremely rare.

Characterization of a cohort of patients with hypercalcemia in a tertiary pediatric hospital.

Introduction. Hypercalcemia is infrequent in pediatrics, of diverse etiology, and with multiorgan morbidity. Objective.

ABCD syndrome, an uncommon cause of hypercalcemia in pediatrics.

ABCD syndrome (ABnormal Calcium, Calcinosis, and Creatinine in Down syndrome) is characterized by an association of hypercalcemia, hypercalciuria, nephrocalcinosis, and impaired kidney function in patients with Down syndrome. Only 7 cases have been published worldwide, although it is believed to be underdiagnosed. This report describes 2 new patients with ABCD syndrome and compares them with the cases reported to date.

Exome Sequencing Has a High Diagnostic Rate in Sporadic Congenital Hypopituitarism and Reveals Novel Candidate Genes.

Context: The pituitary gland is key for childhood growth, puberty, and metabolism. Pituitary dysfunction is associated with a spectrum of phenotypes, from mild to severe. Congenital hypopituitarism (CH) is the most commonly reported pediatric endocrine dysfunction, with an incidence of 1:4000, yet low rates of genetic diagnosis have been reported.

Surgical treatment of secondary hyperparathyroidism in children with chronic kidney disease. Experience in 19 patients.

Objectives: Secondary hyperparathyroidism (sHPT) is an important contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). When conservative measures are ineffective, parathyroidectomy is indicated. The aim of our study was to evaluate the efficacy and safety of subtotal parathyroidectomy (sPTX) in pediatric and adolescent patients, and to provide a rationale for considering this aggressive treatment in CKD patients with uncontrolled sHPT.

A Surgical and Clinical Approach to Persistent Müllerian Duct Syndrome: Laparoscopic, Histological, and Molecular Findings.

Background: Persistent müllerian duct syndrome (PMDS) is characterized by the persistence of müllerian duct derivatives in otherwise normally virilized 46,XY males. Biallelic mutations of the anti-müllerian hormone (AMH) and AMH receptor type 2 (AMHR2) genes lead to PMDS type 1 and 2, respectively.

Aim: The aims of the study were to report the clinical, hormonal, and genetic findings in a patient with PMDS and discuss surgical strategies to achieve successful orchidopexy.

Gonadal tumor development in 46,XX disorders of gonadal development.

Background: Differences/disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical.

Objective: The aim of this study is to report the histological characteristics and immunoexpression patterns of gonadal parenchyma in patients with 46,XX testicular and ovotesticular DSD, with a focus on the detection of germ cell malignancies.

Design: Inclusion criteria were SRY-negative 46,XX testicular and ovotesticular DSD with available samples from gonadal biopsy or gonadectomy for the review of histological findings.

Pediatric adrenocortical tumors cohort characteristics and long-term follow-up at a single Argentinian tertiary center.

Unlabelled: Pediatric adrenocortical tumors are rare and heterogeneous endocrine malignancies.

Objectives: To report clinical, biochemical, and histological features, staging, and therapeutic interventions in a cohort of 28 patients treated at a single tertiary center.

Methods: A retrospective review of medical records of children with PACT (diagnosed before <18 years of age) followed between 1987-2018 at Hospital de Pediatría Garrahan, Buenos Aires, Argentina.

Comprehensive Identification of Pathogenic Gene Variants in Patients With Neuroendocrine Disorders.

Purpose: Congenital hypopituitarism (CH) can present in isolation or with other birth defects. Mutations in multiple genes can cause CH, and the use of a genetic screening panel could establish the prevalence of mutations in known and candidate genes for this disorder. It could also increase the proportion of patients that receive a genetic diagnosis.

[Response to lenvatinib in a pediatric patient with respiratory failure associated with papillary thyroid carcinoma].

Papillary thyroid cancer is the most common thyroid tumor in childhood. In advanced stages, it can present with respiratory failure. The treatment of choice is total thyroidectomy and radioactive iodine.

[Atypical presentation of a giant prolactinoma in a 15-year-old boy].

Giant prolactinomas are rare pituitary adenomas characterized by their great local invasion. In this paper, we report a 15-year-old male with left retro-ocular pain and ipsilateral exophthalmos of 4 months of evolution, secondary to a tumour in the base of the skull that invaded the orbit. Hormonal studies revealed serum prolactin of 6913,7 ng/ml (normal value < 20), confirming the diagnosis of giant prolactinoma.

Two novel heterozygous missense variations within the GLI2 gene in two unrelated Argentine patients.

Several heterozygous GLI2 gene mutations have been reported in patients with isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD) with or without other malformations. The primary aim of this study was to analyze the presence of GLI2 gene alterations in a cohort of patients with IGHD or MPHD and ectopic/absent posterior pituitary. The coding sequence and flanking intronic regions of GLI2 gene were amplified and directly sequenced from gDNA of 18 affected subjects and relatives.

Five new cases of 46,XX aromatase deficiency: clinical follow-up from birth to puberty, a novel mutation, and a founder effect.

Context: Aromatase is the key enzyme for estrogen biosynthesis and is encoded by the CYP19A1 gene. Since 1991, several molecular CYP19A1 gene alterations associated with aromatase deficiency have been described in both sexes.

Objective: The objective of the study was to detect CYP19A1 mutations in five aromatase-deficient 46,XX patients, to describe the clinical follow-up from birth to puberty and to perform haplotype analysis associated with the high-frequency c.

A novel missense mutation in the HSD3B2 gene, underlying nonsalt-wasting congenital adrenal hyperplasia. new insight into the structure-function relationships of 3β-hydroxysteroid dehidrogenase type II.

Context: 3βHSD2 is a bifunctional microsomal NAD+-dependent enzyme crucial for adrenal and gonad steroid biosynthesis, converting Δ5-steroids to Δ4-steroids. 3βHSD2 deficiency is a rare cause of congenital adrenal hyperplasia caused by recessive loss-of-function HSD3B2 mutations.

Objective: The aim was to define the pathogenic consequences of a novel missense mutation in the HSD3B2 gene.

Three novel IGF1R mutations in microcephalic patients with prenatal and postnatal growth impairment.

Background: IGF1R gene mutations have been associated with varying degrees of intrauterine and postnatal growth retardation, and microcephaly.

Objective: To identify and characterize IGF1R gene variations in a cohort of 28 Argentinean children suspected of having IGF-1 insensitivity, who were selected on the basis of the association of pre/postnatal growth failure and microcephaly.

Methods: The coding sequence and flanking intronic regions of IGF1R gene were amplified and directly sequenced.

Preserved fertility in a patient with a 46,XY disorder of sex development due to a new heterozygous mutation in the NR5A1/SF-1 gene: evidence of 46,XY and 46,XX gonadal dysgenesis phenotype variability in multiple members of an affected kindred.

In humans, steroidogenic factor 1 (NR5A1/SF-1) mutations have been reported to cause gonadal dysgenesis, with or without adrenal failure, in both 46,XY and 46,XX individuals. We have previously reported extreme within-family variability in affected 46,XY patients. Even though low ovarian reserve with preserved fertility has been reported in females harboring NR5A1 gene mutations, fertility has only been observed in one reported case in affected 46,XY individuals.

Effectiveness of rhGH treatment on final height of renal-transplant recipients in childhood.

Background: Growth retardation is a considerable clinical problem in children with chronic kidney disease (CKD). Optimization of metabolic and nutritional parameters does not always lead to improved growth. Recombinant human growth hormone (rhGH) treatment has been used to improve height.

Steroid 21-hydroxylase gene mutational spectrum in 454 Argentinean patients: genotype-phenotype correlation in a large cohort of patients with congenital adrenal hyperplasia.

Objective: To report genotype-phenotype correlation in a large cohort of patients.

Context: Study of the CYP21A2 gene in 866 unrelated chromosomes of 21-hydroxylase deficiency in Argentinean patients with classic and nonclassic (NC) forms of congenital adrenal hyperplasia (CAH).

Methods: Eleven most common mutations were analysed by allele-specific polymerase chain reaction, restriction fragment length polymorphism (RFLP) or southern blot analysis.

Three new SF-1 (NR5A1) gene mutations in two unrelated families with multiple affected members: within-family variability in 46,XY subjects and low ovarian reserve in fertile 46,XX subjects.

Background: Three novel heterozygous SF-1 gene mutations affecting multiple members of two unrelated families with a history of 46,XY disorders of sex development (DSD) and 46,XX ovarian insufficiency are described.

Methods: clinical and mutational analysis of the SF-1 gene in 9 subjects of two families.

Results: family 1 had 2 affected 46,XY DSD subjects.

Two novel mutations of the TSH-beta subunit gene underlying congenital central hypothyroidism undetectable in neonatal TSH screening.

Context: Patients with TSH-beta subunit defects and congenital hypothyroidism are missed by TSH-based neonatal screening.

Objective: Our objective was to report the molecular consequences of a novel splice-junction mutation and a novel missense mutation in the TSH-beta subunit gene found in two patients with congenital central hypothyroidism and conventional treatment-resistant anemia.

Results: Patient 1 had a homozygous G to A nucleotide change at the 5' donor splice site of exon/intron 2.

A new DAX-1 mutation in a family with a case of neonatal adrenal insufficiency and a sibling with adrenal hypoplasia and sudden death at 3 years of age.

Adrenal hypoplasia congenita (AHC) is a hereditary disorder that leads to adrenal insufficiency and hypogonadotropic hypogonadism (HHG) in childhood. The gene responsible for the X-linked form of AHC, DAX1 (dosage-sensitive sex-reversal, AHC, on the X-chromosome, gene 1)/NR0B1, encodes for a nuclear factor which lacks the characteristic zinc finger DNA-binding domain that is highly conserved in nuclear receptors. Deletions and point mutations in the DAX1 gene have been described in more than 70 AHC families.