Tailored use of belatacept in adolescent kidney transplantation.

Adolescent transplant recipients are at risk for nonadherence, development of de novo donor-specific antibody (dnDSA), and allograft loss. Belatacept, a selective T cell costimulatory blocker, is associated with reduced dnDSA, improved renal function, and prolonged allograft survival when compared to calcineurin inhibitor-based regimens in adults; however, its use in children is scant. Three adolescents were initiated on belatacept between August 2017 and September 2018 at the time of kidney transplantation. Selection criteria included age ≥ 14 and EBV IgG + serostatus. Intraoperative alemtuzumab and methylprednisolone were given as induction therapy. Tailored maintenance therapy included steroid-free belatacept and sirolimus for two patients. One patient was initially maintained steroid-free on belatacept and belimumab, an inhibitor of B cell activating factor to treat concurrent systemic lupus erythematous; steroids were added subsequently. Renal function, biopsy-proven rejection, dnDSA, allograft survival, infection, nonadherence, and proteinuria were monitored. Renal function was 86, 73, 52 mL/min/1.73 m2 at 20, 20, and 8 months, respectively. There was 100% adherence to therapy and no development of dnDSA. All patients had treatable infections. One developed steroid-responsive acute cellular rejection. Belatacept-based regimens can be tailored for adolescent recipients with good short-term clinical outcomes.

Successful Management of Cushing Syndrome From Ectopic ACTH Secretion in an Adolescent With Osilodrostat.

A previously healthy 11-year-old male was found to have a mass in the pancreatic head after several months of abdominal pain and jaundice. Pathology was consistent with a World Health Organization grade 2 pancreatic neuroendocrine tumor. He developed refractory hypertension and was found to have Cushing syndrome from ectopic ACTH secretion, with oligometastatic liver disease. He underwent surgical resection of the pancreatic tumor and metastases. Postoperatively, his Cushing syndrome resolved, but it reemerged 1 year later in the setting of disease recurrence. He was not a candidate for bilateral adrenalectomy. Ketoconazole therapy was inadequate and he was started on metyrapone, lanreotide, cabergoline, and spironolactone. Although this regimen was well-tolerated, his Cushing syndrome recurred 4 months later as his metastatic disease burden increased. Osilodrostat was begun and the dose was gradually increased in response to his uncontrolled Cushing syndrome. Osilodrostat resulted in rapid improvement and eventual normalization of his urinary free cortisol at a dose of 18 mg twice daily. He had no adverse effects. This rare case highlights the successful off-label use of osilodrostat, a medication intended for refractory Cushing disease in adult patients, in a pediatric patient with Cushing syndrome caused by ectopic ACTH secretion.

Disrupted Circadian Rhythm of Epinephrine in Males With Youth-Onset Type 2 Diabetes.

Context: Blood pressure and plasma catecholamines normally decline during sleep and rapidly increase in early morning. This is blunted in adults with type 2 diabetes (T2D). Objective: We hypothesize that increased sympatho-adrenal activity during sleep differentiates youth with T2D from nondiabetic obese youth and lean youth. Methods: Fasting spot morning and 24-hour urines were collected in obese adolescents with and without T2D, and normal-weight controls. Fractionated free urine catecholamines (epinephrine, norepinephrine, and dopamine) were measured, and the ratio of fasting spot morning to 24-hour catecholamines was calculated. Results: Urinary 24-hour catecholamine levels were comparable across the 3 groups. Fasting morning epinephrine and the ratio of fasting morning/24-hour epinephrine were higher in youth with T2D (P = 0.004 and P = 0.035, respectively). In males, the ratio of fasting morning/24-hour epinephrine was also higher in youth with T2D (P = 0.005). In females, fasting morning norepinephrine and the ratio of fasting morning/24-hour dopamine were lower in obese youth with and without T2D (P = 0.013 and P = 0.005, respectively) compared with lean youth. Systolic blood pressure was higher in diabetic participants than other groups; males trended higher than females. Conclusion: Circadian rhythm in catecholamines is disrupted in youth-onset T2D, with a blunted overnight fall in urinary epinephrine in males. Conversely, fasting morning norepinephrine and dopamine levels were lower in obese females with or without T2D. Higher nocturnal catecholamines in males with T2D might associate with, or predispose to, hypertension and cardiovascular complications. Lower catecholamine excretion in females with obesity might serve an adaptive, protective role.