Glucocorticoids remain a critical component of treating many pediatric diseases. According to Aulakh and Singh, in fact, it is estimated 10% of children may require some form of glucocorticoid during their childhood.^[1]

Unfortunately, the chronic use of glucocorticoids in children can have multiple untoward and lasting side effects: stunted growth, suboptimal bone mineralization, delayed puberty, and even impaired neurodevelopment. Despite these problems and the possibility that glucocorticoid-related toxicity has the potential to impact children throughout their adult lives as well as in childhood, research on glucocorticoid toxicity in children is sparse.

This may be for several reasons: a historical lack of a validated measure for this complex problem, the relative absence (until recently) of alternatives to glucocorticoids, reluctance to use “biologic” agents in children, and the mistaken assumption that children may tolerate glucocorticoids well. The assessment of glucocorticoid toxicity in children is complicated further by the need to consider the impact of both age and sex reference ranges.

Glucocorticoid growth impairment was first reported in 1956 by Bloget and colleagues.^[2] Nearly 50 years later, on reviewing the limited data that had become available since 1956, Mushtaq and Ahmed called for “improved awareness and better access to measuring and monitoring” of steroid toxicity and growth impairment.^[3] 

The few papers that have been published tend to focus on how to minimize the side effects of systemic glucocorticoid use in children rather than measuring, monitoring, and evaluating the impacts of glucocorticoid therapy in both the short and longer term.

Mushtaq and Ahmed write that a confounding factor for many studies is that; “a number of childhood conditions that require chronic glucocorticoid therapy may themselves predispose the child to abnormalities of growth and bone health. For instance, poor linear growth and osteoporosis may be presenting features in a child with inflammatory bowel disease.”

The introduction of the pediatric Glucocorticoid Toxicity Index (pGTI) represents an important inflection point in the quest for assessing steroid-toxicity in children and adolescents.^[4] The tool is intended for use in prospective, randomized clinical trials in pediatrics and in pediatric practice, and can in fact be utilized in all clinical disciplines to measure the impact of steroid-toxicity. 

Given the widespread use of steroids and the accelerating pace of immunological drug discovery, this tool represents a significant advance in our ability to evaluate the utility of new pharmacological agents when compared to glucocorticoid treatments, which often are still the mainstay standard of care.

The pGTI is available via a digital platform that is particularly easy to use and integrate into existing systems. It also:

• includes growth as an entirely new domain.
• considers age-related references such as height, and gender-specific reference ranges for blood pressure and for other parameters.
• assesses neurological side effects unique to the pediatric population.
• adjusts domain weights to score those steroid-toxicities that are specific to children.

To learn more about the pGTI, please visit this link.

References

1. Aulakh, R., Singh, S. Strategies for minimizing corticosteroid toxicity: A review. Indian J Pediatr 75, 1067–1073 (2008). https://doi.org/10.1007/s12098-008-0211-6
2. Blodget FM, Burgin L, Iezzoni D,  Gribetz D., Talbot NB., Effects of prolonged cortisone therapy on the statural growth, skeletal maturation and metabolic status of children. N Engl J Med. 1956 Apr 5;254(14):636-41. https://doi.org/10.1056/NEJM195604052541402 
3. Mushtaq T, Ahmed SF. The impact of corticosteroids on growth and bone health. Arch Dis Child. 2002 Aug;87(2):93-6. https://doi.org/10.1136/adc.87.2.93 
4. Paul Brogan, Ray Naden, Stacy P. Ardoin, Jennifer C. Cooper, Fabrizio De Benedetti, Jean-Francois Dicaire, Despina Eleftheriou, Brian Feldman, Jon Goldin, Seth E. Karol, Fiona Price-Kuehne, David Skuse, Constantine A. Stratakis, Nicholas Webb, John H. Stone, The Pediatric Glucocorticoid Toxicity Index, Seminars in Arthritis and Rheumatism, 14 July, 2022 152068, https://doi.org/10.1016/j.semarthrit.2022.152068