Update on diagnostic and therapeutic challenges of central hypothyroidism among childhood cancer survivors

Context: Following the exposure to toxic therapeutic agents employed in the treatment of malignancies, endocrine complications can affect up to 40–60% of childhood cancer survivors (CCS), with central hypothyroidism (CeH) being a relevant adverse event observed in this population. Given the long-standing uptrend in the number of CCS due to advances in antineoplastic and support therapies, the issue of treatment-related endocrine disorders, including CeH, has become an increasingly relevant topic. Methods: Pubmed search carried out using an ad-hoc query string in January 2025. Main results: The pathophysiology of CeH in CCS is primarily related to damage to the hypothalamic-pituitary-thyroid axis, often caused by the synergetic detrimental effect of antineoplastic treatments. Understanding the pathogenesis and the specificities of iatrogenic CeH is crucial to improve the clinical management of CCS. Due to the often subtle and paucisymptomatic nature of CeH in its early stages, regular, life-long thyroid screening is essential to prompt timely diagnosis. Indeed, early identification of CeH allows for appropriate thyroid hormone replacement, which is crucial for preventing long-term metabolic and developmental complications and to improve the quality of life of these patients. Conclusions: This review aims to enhance awareness among healthcare providers regarding the critical importance of timely detection of CeH and its specificities among CCS, in order to better understand the pathogenesis of treatment-related CeH and to outline evidence-based strategies for the diagnosis and treatment of CeH in this vulnerable population.