Phase 3 Trial of a Small-volume Subcutaneous 6-Month Duration Leuprolide Acetate Treatment for Central Precocious Puberty.

Context: Gonadotropin-releasing hormone agonists (GnRHas) are standard of care for central precocious puberty (CPP). A 6-month subcutaneous injection has recently been approved by the Food and Drug Administration.

Objective: Determine efficacy, pharmacokinetics, and safety of 6-month 45-mg subcutaneous leuprolide acetate for CPP.

A Randomized Safety and Efficacy Study of Somavaratan (VRS-317), a Long-Acting rhGH, in Pediatric Growth Hormone Deficiency.

Context: Somavaratan (VRS-317) is a long-acting form of recombinant human GH under development for children and adults with GH deficiency (GHD).

Objectives: To determine the optimal somavaratan dose regimen to normalize IGF-1 in pediatric GHD and to evaluate safety and efficacy of somavaratan over 6 months.

Design: Open-label, multicenter, single ascending dose study followed by 6-month randomized comparison of 3 dosing regimens.

Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial.

Context And Objective: The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy.

Design: This was a phase 3, prospective, open-label study.

Setting And Participants: Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month histrelin implant during a long-term extension phase.

Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor.

Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15 years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li-Fraumeni syndrome.

Results of a second year of therapy with the 12-month histrelin implant for the treatment of central precocious puberty.

Background. Gonadotropin releasing hormone analogs (GnRHas) are standard of care for central precocious puberty (CPP). The histrelin subcutaneous implant is safe and effective in the treatment of CPP for one year.

Remission of congenital diabetes insipidus after eight years.

Septo-optic dysplasia (SOD) (De Morsier's syndrome) is a complex developmental disorder marked by variable and often incomplete formation of cranial midline structures, resulting in absence of the septum pellucidum, optic nerve hypoplasia, and hypothalamic-pituitary dysfunction. We describe a patient with SOD who manifested symptoms in the early neonatal period with severe deficiencies of multiple pituitary hormones including anti-diuretic hormone (ADH). Her congenital diabetic insipidus (DI), consequence of an anatomic defect, can be argued to be of the most severe type.

Adrenocorticotropin-secreting pancreatoblastoma.

We present a 3-year-old child with Cushing's syndrome due to an ACTH-secreting metastatic pancreatoblastoma. This malignancy is a rare cause of Cushing's syndrome, particularly at pediatric age. We describe her course including the use of ketoconazole to alleviate hypercortisolemia.

Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial.

Context: GnRH analog (GnRHa) therapy for central precocious puberty (CPP) typically involves im injections. The histrelin implant is a new treatment that provides a continuous slow release of the GnRHa histrelin.

Objective: The objective of the study was to investigate the safety and efficacy of the subdermal histrelin implant for the treatment of CPP in treatment naive and previously treated children.

A familial missense mutation in the hinge region of DAX1 associated with late-onset AHC in a prepubertal female.

Mutations in the DAX1 (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita (AHC) critical region on the X chromosome gene 1; NR0B1) cause X-linked AHC, a disease characterized by primary adrenal failure in infancy and hypogonadotropic hypogonadism. All known missense mutations impair DAX1 repression of steroidogenic factor 1 (SF1) transactivation and have been localized to the putative ligand binding domain. Here, an asymptomatic father and his late-onset AHC daughter were both shown to share a novel DAX1 mutation (C200W), the first missense mutation identified in the hinge region of DAX1.

Onset of acquired autoimmune hypothyroidism in infancy: a presentation of delayed gross-motor development and rhabdomyolysis.

We report the case of a 23-month-old girl who presented with poor growth and delayed attainment of gross-motor milestones. Elevated creatine phosphokinase (CPK) indicated rhabdomyolysis, ultimately attributed to severe, acquired autoimmune hypothyroidism. Growth data and bone-age suggest the onset of hypothyroidism occurred at or before 12 months of age.

Micropenis with testicular regression, low LH levels, and poor androgen and HCG responses: a distinct syndrome?

We report three boys, including two brothers, with micropenis and poor phallic growth in response to both exogenous human chorionic gonadotropin (HCG) and testosterone therapy in the newborn period. They exhibited low neonatal testosterone levels that failed to respond to HCG stimulation. These boys displayed a unique gonadotropin profile with reduced luteinizing hormone levels and elevated follicle-stimulating hormone levels.

Agenesis of the mesencephalon and metencephalon with cerebellar hypoplasia: putative mutation in the EN2 gene--report of 2 cases in early infancy.

Congenital absence of the midbrain and upper pons is a rare human malformation. We describe two unrelated infants with this anomaly and cerebellar hypoplasia who were born at term but died in early infancy from lack of central respiratory drive. MRI in both cases disclosed the lesions during life.