Immobilization-induced hypercalcemia in a patient with renal failure.

SUMMARY: Immobilization-induced hypercalcemia is an uncommon cause of elevated calcium which is usually diagnosed following extensive systemic workup and exclusion of more common etiologies. Previously reported cases have largely described this phenomenon in adolescents and young adults a few weeks to months after the initial onset of immobilization. Metabolic workup tends to demonstrate hypercalcemia, hypercalciuria, and eventual osteoporosis. While the exact mechanism remains largely unclear, a dysregulation between bone resorption and formation is central to the pathogenesis of this disease. Decreased mechanical loading from prolonged bedrest tends to increase osteoclast induced bone resorption while promoting osteocytes to secrete proteins such as sclerostin to reduce osteoblast mediated bone formation. We describe the case of an 18-year-old male who was admitted following intraabdominal trauma. He underwent extensive abdominal surgery including nephrectomy resulting in initiation of dialysis. After 6 months of hospitalization, the patient gradually began developing uptrending calcium levels. Imaging and laboratory workup were unremarkable for any PTH-mediated process, malignancy, thyroid disorder, adrenal disorder, or infection. Workup did reveal significant elevated bone turnover markers which in combination with the clinical history led the physicians to arrive at the diagnosis of immobilization induced hypercalcemia. In order to prevent decreased rates of bone loss, the patient was administered denosumab for treatment. Hypocalcemia followed treatment expectedly and was repleted with supplementation via the patient's total parenteral nutrition. LEARNING POINTS: Immobilization-induced hypercalcemia should remain as a differential diagnosis of patients with prolonged hospitalizations with hypercalcemia. Extensive workup of common etiologies of hypercalcemia should be considered prior to arriving at this diagnosis. Denosumab, while off-label for this usage, offers an effective treatment option for immobilization-induced hypercalcemia though it carries a risk of hypocalcemia especially among patients with renal disease.

Tyrosine Kinase Inhibitors' Newly Reported Endocrine Side Effect: Pazopanib-Induced Primary Adrenal Insufficiency in a Patient With Metastatic Renal Cell Cancer.

Tyrosine kinase inhibitors (TKIs) have been used in the treatment of multiple types of cancer. Pazopanib is one of the TKIs and is considered a first-line treatment for adult patients with metastatic renal cell carcinoma. Many endocrine-related adverse effects have been noted with the use of TKIs including hypothyroidism, vitamin D deficiency, altered bone density, secondary hyperparathyroidism, abnormal glucose metabolism, gynecomastia, and hypogonadism. Subclinical glucocorticoid deficiency and adrenal insufficiency have been reported with the use of TKIs in only a few cases so far; thus, its true prevalence and clinical significance have yet to be fully elucidated. The mechanism is still not fully understood; however, adrenal toxicity with hemorrhage and/or necrosis of the adrenal glands has been observed in studies. In this article, we describe the first reported case of pazopanib inducing primary adrenal insufficiency in a patient with metastatic renal cell carcinoma diagnosed after the exclusion of all other causes of primary adrenal insufficiency.

Expression-Based Cell Lineage Analysis in Drosophila Through a Course-Based Research Experience for Early Undergraduates.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.