Endocrine Abstracts

Introduction: In children, BRAF (e.g. dabrafenib) and MEK (e.g. trametinib) inhibitors are used to treat a range of tumours including low-grade gliomas, Langerhans cell histiocytosis (LCH), and plexiform neurofibromas. However, the ubiquitous nature of the BRAF/MAPK/MEK pathway in various physiological processes means that these treatments are not without their own side effects such as renal tubulopathies (causing hyponatraemia) and hyperglycaemia.

Aim: To describe the endocrine dysfunction observed in a cohort of children treated with BRAF and MEK inhibitors at Great Ormond Street Hospital, the largest paediatric centre in the UK utilising these treatments.

Methods: Electronic data for patients treated with dabrafenib and trametinib from January 2019 to May 2022 were collected. Outcomes included patient weight, BMI, BMI SDS, blood glucose, insulin and HbA1c concentrations and the presence of hyponatraemia (< 135 mmol/l).

Results: A total of 55 patients (28 males, 27 females) on dabrafenib (n=25) and trametinib (n=42) were included for analysis. The median age was 9.64 years old. The most common indications for treatment was low-grade glioma (n=35). Growth hormone deficiency was the most noted co-morbidity (n=10), followed by precocious puberty (n=9). Nine patients had at least one hyponatraemic episode during treatment of whom three had coexisting central diabetes insipidus. The mean minimum sodium for all patients during treatment was 136.3 mmol/l. A total of 6 patients were diagnosed with a form of glucose dysregulation (e.g. insulin resistance, type 2 diabetes), of whom four were diagnosed during treatment, all with hypothalamo-pituitary lesions.

Discussion and Conclusion: Whilst the use of BRAF and MEK inhibitors herald a new era in targeted molecular treatment for various tumours, it is also important to recognise and monitor for unique endocrine side effects in patients on these treatments.