Recent Advances in the Diagnosis and Treatment of Paediatric Endocrine Disorders

Abstract

The discovery, synthesis and administration of hormones revolutionised the medical management of endocrine disorders in the first half of the 20th century. Kocher revolutionised thyroid surgery in the late 1800s and early 1900s [1], Banting and Best are credited with the synthesis of insulin in 1920 [2, 3], and steroids were first administered to patients with congenital adrenal hyperplasia (known as adrenogenital syndrome at the time) in the 1950s [4, 5]. Nobel Prizes were awarded for these and other discoveries that furthered endocrinology knowledge and treatment [6]. Although these hormonal replacements were life-saving, clearly further advancements are required to truly manage these conditions.

Here we present a collection of narrative reviews on recent advances in paediatric endocrinology, including the management of paediatric thyroid cancer, screening for type 1 diabetes and the use of burosumab in X-linked hypophosphataemic rickets.

The management of paediatric thyroid cancer has traditionally relied on extrapolation from adult data, but childhood disease behaves differently from adult thyroid cancer. Paediatric differentiated thyroid cancers are more widely metastatic at diagnosis than adults; however, the mortality rate is much lower. The first guideline for the management of paediatric thyroid cancer was published by the American Thyroid Association in 2015 [7]. Vanderniet et al.'s review focuses on developments in the understanding and management of paediatric thyroid cancer since the publication of this guideline [8]. Important conclusions are drawn, including the importance of paediatric-specific data, optimal sonographic and cytological diagnostics, use of advanced genomic techniques to prognosticate and make management decisions, consideration of familial cancer syndromes and that management recommendations are rapidly evolving due to the accumulation of new knowledge. Furthermore, interdisciplinary input is required for optimal management of this rare condition and may include paediatric endocrinologists, surgeons, oncologists, geneticists, pathologists, radiologists and nuclear medicine physicians. As we enter the age of advanced therapeutics, there are new targeted molecular therapies available for some forms of paediatric thyroid cancer that can reduce the burden of traditional treatment such as radioactive iodine.

Approximately 30% of children and adolescents present with diabetic ketoacidosis (DKA) at the diagnosis of type 1 diabetes [9]. There are potential long-term consequences of DKA, in addition to the acute metabolic decompensation. Clinical type 1 diabetes mellitus is defined as a random plasma glucose level ≥ 11.1 mmol/L or a fasting plasma glucose of ≥ 7.0 mmol/L, which signifies irreversible damage to the insulin-producing beta cells. However, it is now well recognised that the onset of beta cell autoimmunity and destruction precedes this. Clinical type 1 diabetes is now labelled as stage 3 diabetes, with stages 1 and 2 being pre-symptomatic phases. Stage 1 denotes the presence of islet autoantibodies, and stage 2 includes this plus evidence of biochemical dysglycaemia. Pre-symptomatic diabetes may be diagnosed through the detection of islet autoantibodies and offers the opportunity to educate children and families prior to the onset of stage 3, symptomatic diabetes mellitus, and therefore the avoidance of DKA presentations. Narayan et al. discuss the stages of type 1 diabetes, screening methods and programmes and the potential to treat those with stage 1 or 2 diabetes with new disease-modifying agents which may delay the onset of stage 3 diabetes [10].

X-linked hypophosphataemia (XLH) is a form of dominantly inherited rickets with a significant impact on quality of life. Affected individuals may have a range of clinical features including short stature, leg bowing, pain, craniosynostosis, dental disease, hearing impairment and many other impacts. Mutations in PHEX result in increased FGF23 expression, which causes renal phosphate wasting and inhibits the activation of vitamin D. Traditionally, it has been treated with phosphate and activated vitamin D replacement, which are suboptimal in the management of this condition [11]. Sandy et al. discuss XLH and a new monoclonal antibody that has been developed for the management of this condition, known as burosumab [12]. Burosumab is given as a fortnightly (in children) or monthly (in adults) subcutaneous injection and was listed on the Pharmaceutical Benefits Scheme in Australia in 2022; however, it is not yet available in New Zealand. Burosumab has been shown to be transformative for both children and adults with XLH, with improved exercise capacity, skeletal growth, mobility and fracture healing, as well as reduced pain and stiffness. Sandy et al. explore some of the lesser understood clinical manifestations such as dental disease, hearing impairment and nephrocalcinosis, which may be related to conventional therapy, and discuss whether burosumab is expected to affect these characteristics.

As we enter the second quarter of the 21st century, we look forward to continual evolution in the management of paediatric endocrine conditions, improving the quality of life for affected individuals and their families. We hope you find value in this collection.

The authors declare no conflicts of interest.