RESUMEN
Background: Puberty suppression is a standard of care for gender-affirming therapy in gender-diverse youth. Leuprolide acetate is a gonadotropin-releasing hormone agonist (GnRHa) commonly used for pubertal suppression. There are concerns that GnRHa agents prolong the rate-corrected QT interval (QTc) when used as androgen deprivation therapy in management of prostate cancer; however, there is a paucity of literature regarding the effect of leuprolide acetate on QTc intervals in gender-diverse youth. Aim: To determine the proportion of gender-diverse youth with QTc prolongation on leuprolide acetate therapy. Methods: A retrospective chart review of gender-diverse youth initiated on leuprolide acetate between July 1, 2018 and December 31, 2019 was conducted at a tertiary care pediatric hospital in Alberta, Canada. Youth aged 9-18 years were included if a 12-lead electrocardiogram was completed after initiating leuprolide acetate. The proportion of adolescents with clinically significant QTc prolongation was assessed, defined as QTc >460 milliseconds (ms). Results: Thirty-three pubertal youth were included. The cohort had a mean age of 13.7 years (standard deviation [SD] 2.1) and 69.7% identified as male (assigned female at birth). The mean post-leuprolide acetate QTc was 415 ms (SD 27, range 372-455). Twenty-two (66.7%) of youth were prescribed concomitant medications, including QTc-prolonging medications in 15.2%. None of the 33 youth on leuprolide acetate had QTc prolongation. Only 24.2% patients had a borderline QTc (QTc 440-460 ms). Conclusion: No gender-diverse youth on leuprolide acetate demonstrated clinically significant QTc prolongation.
RESUMEN
Plexiform neurofibroma (PN) involvement of the external genitalia in patients with neurofibromatosis type I (NF1) is a rare cause of nonhormonal clitoromegaly. We present a 3-year-old female with known NF1 who presented with clitoromegaly. She was identified with an extensive pelvic mass involving the bladder wall, perineum, labia, clitoris, rectum, and sacral foramina. A partial cystectomy was performed, and histopathology was consistent with PN. She has been initiated on a mitogen activated protein kinase enzyme kinase inhibitor, trametinib, which has been effective in achieving partial radiographic response of the bladder mass over 5 months. Additionally, she has experienced clinical response to trematinib with resolution of urinary urgency and frequency since initiating treatment.
RESUMEN
The incretin hormone glucagon-like peptide-1 (GLP-1) has received enormous attention during the past three decades as a therapeutic target for the treatment of obesity and type 2 diabetes. Continuous improvement of the pharmacokinetic profile of GLP-1R agonists, starting from native hormone with a half-life of ~2-3 min to the development of twice daily, daily and even once-weekly drugs highlight the pharmaceutical evolution of GLP-1-based medicines. In contrast to GLP-1, the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) received little attention as a pharmacological target, because of conflicting observations that argue activation or inhibition of the GIP receptor (GIPR) provides beneficial effects on systemic metabolism. Interest in GIPR agonism for the treatment of obesity and diabetes was recently propelled by the clinical success of unimolecular dual-agonists targeting the receptors for GIP and GLP-1, with reported significantly improved body weight and glucose control in patients with obesity and type II diabetes. Here we review the biology and pharmacology of GLP-1 and GIP and discuss recent advances in incretin-based pharmacotherapies.