Paediatric Endocrinology: Before and Beyond ‘Ringing the Bell’

Ringing the bell…

Many cancer centres have adopted a naval tradition of bell ringing to signify ‘when the job is done’ at the completion of treatment. Despite global disparities [1, 2], the childhood cancer cure rates have improved, and the population of ageing survivors is increasing [3]. However, the majority experience cancer- and treatment-related effects requiring life-long care [3]. The most prevalent severe chronic health conditions include endocrine disorders, subsequent neoplasms, and cardiovascular disease [4].

In 2006, an expert panel met in Italy to produce the Erice Statement, updated a decade later: ‘the long-term goal of the cure and care of a child with cancer is that they become a resilient and autonomous adult with optimal health-related quality of life, accepted in society at the same level as their age peers’ [5, 6].

I had the opportunity to reflect on two decades of Australian and Canadian ‘Paediatric Endocrine Oncology’ experience with an enthusiastic group of Australian and New Zealand paediatric endocrinology trainees. The themes were (i) acute endocrinology (ii) chronic endocrinology (‘within care’ and ‘after care’), (iii) late effects surveillance, more aptly and positively described as ‘Aftercare’ or ‘Survivorship’ and (iv) endocrinology within childhood cancer genetic predisposition syndromes. I shared reflections relevant to before and beyond ‘ringing the bell’, with a selection included below.

Know their story…

A child approaching pubertal age with a history of acute lymphoblastic leukaemia (ALL) is referred. The child's story: an early infantile diagnosis, a poor short-term prognosis and an uncertain journey ahead. The parents' stories convey their differing approaches: a 10-year division of cognitive load, one cure and one care.

Know their story before…

An adolescent girl with a craniopharyngioma is experiencing the challenging sequelae of hypothalamic obesity and learning difficulties [7, 8]. A short duration before: high levels of academic and sporting achievement. Familial expectations of these outcomes persist.

Sticky notes…

These colourful, small pieces of paper with a re-adherable strip of glue are found peppered across workplaces and homes. Covering text- and notebooks, they were the clue to another adolescent's short-term memory struggles.

My first ‘aftercare’ experience in the early 1990s was a preschool-age boy with microcephaly and cognitive impairment after treatment for high-risk ALL [9]. Modern treatments differ, but deficits in neurocognitive functioning persist [10].

Shifting goals…

The safety of growth hormone is continually monitored [11]. The parents whose son is rehabilitating from surgery for brain tumour progression are less focused, so too are their clinicians, on growth velocity. Move forward a few years: tall family, secondary school, twin towering above and younger sibling's height overtaking. The culmination is a family's shifted goal and focus directed to questions about replacing the deficient growth hormone.

Shifting endocrinology…

The dynamic shift of hormone production is influenced by the interplay of tumour and its treatment over time. The milestone of achieving pubertal age after concerted efforts to suppress the hypothalamic tumour-induced precocious puberty is then so often thwarted by acquired tumour- and treatment-induced deficits in the hypothalamic–pituitary–gonadal axis.

Have your ‘antennae’ up…

During an earlier career phase, adolescents with ALL were experiencing an improved prognosis, but emerging with intractable joint pain. The osteonecrosis diagnoses were initially late as this pain preceded any clues on plain skeletal radiographs. Awareness grew with respect to risk factors (e.g., glucocorticoid type and dose in treatment protocols) and early diagnosis (Magnetic Resonance Imaging if persistent joint pain, especially in older adolescents). Treatment protocols were adjusted yet there are limited effective treatment options for symptomatic disease [12].

Embrace learning…

Recent research indicates that a considerable proportion of childhood cancers is due to germline or mosaic mutations in cancer predisposition genes [13, 14]. With an expanding number of genes recognised, the relevance to paediatric endocrinologists is increasingly complex [11, 15-18].

As treatments emerge, so too must we learn of any resultant endocrinopathies. This is exemplified by tyrosine kinase inhibitors affecting growth and immune checkpoint inhibitors' association with thyroid dysfunction [19, 20]. We shall also observe if new treatment modalities such as proton beam radiation therapy in the region of the pituitary gland ameliorate endocrine sequelae [21].

Patient and disease…

Precision-guided treatment informed by comprehensive molecular profiling affords the opportunity for significantly improved outcomes for children with high-risk cancers [22]. Similarly, individualised psychosocial support is encouraged [23]. Reflecting on the words of William Osler (1849–1919), in addition to knowing ‘what kind of disease the patient has’, he emphasised the importance to ‘know what kind of patient the disease has’ [24].

Beyond ‘Ringing the Bell’ and beyond paediatric endocrinology, increased awareness of ‘accelerated ageing’, the accelerated onset of ageing-related diseases [25-28], further highlights the evolving needs and complexity of survivorship care.

The author declares no conflicts of interest.