Endocrinopathies in Inherited Leukodystrophies: A Scoping Review of Reported Frequencies, Diagnostic Strategies, and Treatment

Leukodystrophies are a diverse group of inherited disorders affecting central nervous system white matter, with onset from infancy to adulthood. Although neurological symptoms dominate, endocrine dysfunctions are increasingly recognized as significant contributors to disease course. These can arise directly from genetic mutations or secondarily due to hypothalamic–pituitary or peripheral gland involvement. This scoping review focuses on leukodystrophies associated with hormonal abnormalities, summarizing current diagnostic approaches, preventive strategies, and treatment options. Literature from PubMed/MEDLINE and Embase (1991–May 2026) was analysed, including original research, reviews, meta-analyses, and case reports. Endocrinopathies commonly observed include adrenal insufficiency, hypogonadism, growth hormone deficiency, hypothyroidism, and diabetes mellitus. Disorders such as X-linked adrenoleukodystrophy, POLR3-related leukodystrophy, vanishing white matter disease, and Aicardi–Goutières syndrome show distinct hormonal involvement patterns. Early detection and timely hormone replacement can improve growth, development, metabolic stability, and quality of life, while preventing severe complications. Diagnosis integrates clinical evaluation, hormonal testing, neuroimaging, and advanced molecular analyses, including whole-exome or whole-genome sequencing. Effective management requires a multidisciplinary approach combining supportive care, endocrine replacement, and selected disease-modifying therapies. Understanding the interplay between neurological and endocrine features is crucial for optimizing care and improving long-term outcomes.