Transient synovitis associated with leuprolide depot (Lupron).

Summary: A 6.6-year-old female presented to endocrinology with precocious puberty for evaluation and management. Workup was initiated, and a diagnosis of central precocious puberty was confirmed.

Targeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy.

The RET (REarranged during Transfection) gene, which encodes for a transmembrane receptor tyrosine kinase, is an established oncogene associated with the etiology and progression of multiple types of cancer. Oncogenic RET mutations and rearrangements resulting in gene fusions have been identified in many adult cancers, including medullary and papillary thyroid cancers, lung adenocarcinomas, colon and breast cancers, and many others. While genetic RET aberrations are much less common in pediatric solid tumors, increased RET expression has been shown to be associated with poor prognosis in children with solid tumors such as neuroblastoma, prompting an interest in RET inhibition as a form of therapy for these children.

Abnormal thyroid function: an unusual presentation of pituitary stalk interruption syndrome.

Summary: An 11-year-old girl with past medical history of septic shock and multi-organ failure at age 5 presented to her primary care doctor with concern for pallor of the lips. Laboratory studies demonstrated low free thyroxine (T4) and normal thyroid-stimulating hormone (TSH). A referral to endocrinology was made where the patient was evaluated, and laboratory evaluation was repeated.

Insights into the cellular pathophysiology of familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis (fHLH) encompasses a group of rare inherited immune dysregulation disorders characterized by loss-of-function mutations in one of several genes involved in the assembly, exocytosis, and function of cytotoxic granules within CD8+ T cells and natural killer (NK) cells. The resulting defect in cytotoxicity allows these cells to be appropriately stimulated in response to an antigenic trigger, and also impairs their ability to effectively mediate and terminate the immune response. Consequently, there is sustained lymphocyte activation, resulting in the secretion of excessive amounts of pro-inflammatory cytokines that further activate other cells of the innate and adaptive immune systems.

Digenic Inheritance: Evidence and Gaps in Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder characterized by the inability to properly terminate an immune response. Familial HLH (FHLH) and related immune dysregulation syndromes are associated with mutations in the genes , and , all of which are required for the assembly, exocytosis, and function of cytotoxic granules within CD8+ T cells and natural killer (NK) cells. Loss-of-function mutations in these genes render the cytotoxicity pathway ineffective, thereby failing to eradicate immune stimuli, such as infectious pathogens or malignant cells.