Australasian Paediatric Endocrine Group: tests, treatments and procedures clinicians and consumers should question

Numerous hormones, such as growth hormone and testosterone, are subject to circadian rhythms. Relying on random measures of these hormones is therefore of limited diagnostic utility as their levels may peak and plateau at particular times throughout the day. Unless adjustments are made to take account of these circadian rhythms then random readings will not be sufficiently informative.

Supporting evidence

  • Ayling R. More guidance on growth hormone deficiency. J Clin Pathol 2004; 57(2):123–5.
  • Brambilla DJ, Matsumoto AM, Araujo AB, et al. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. The Journal of Clinical Endocrinology and Metabolism 2009; 94(3):907–13. 
  • Hawkes C, Grimberg A. Measuring growth hormone and insulin-like growth factor-I in infants: what is normal? Pediatr Endocrinol Rev 2013; 11(2):126–46.

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There is no consensus protocol on bone-age assessment of younger children and infants, particularly those under the age of two. Skeletal growth and maturation is most rapid in infants and toddlers, so accurate bone-age assessment in these children is challenging.

Of the bone-age measurement techniques available, there is a major inadequacy with one of the most used methods: the limited change in the appearance of the ossification centres of the hand/wrist change in the first months of life. A recent survey found much lower rates of confidence in the accuracy of this technique when applied to the one-to-three-year-old group. Although a recently reported and validated bone-age measurement technique based on fibular shaft length was found to outperform other methods, it still yielded significant errors when applied to infants (i.e. under one year).

Supporting evidence

  • Breen MA, Tsai A, Stamm A, et al. Bone age assessment practices in infants and older children among Society for Pediatric Radiology members. Pediatr Radiol 2016; 46:1269. 
  • Tsai A, Stamoulis C, Bixby SD, et al. Infant bone age estimation based on fibular shaft length: model development and clinical validation. Pediatr Radiol 2016; 46:342–56.

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Particularly given its low sensitivity, insulin-like growth factor binding protein 3 (IGFBP-3) does not significantly contribute to the diagnosis of childhood short stature resulting from growth-hormone deficiency (GHD), which can lead to the under identification of GHD. It should therefore not be used as a routine measure for the workup and diagnosis of children with short stature. However, IGFBP-3 testing may have a role, along with IGF-1 testing, as an auxiliary diagnostic index for provocative testing.

Supporting evidence

  • Boquete HR, Sobrado PG, Fideleff HL, et al. Evaluation of diagnostic accuracy of insulin-like growth factor (IGF)-I and IGF-binding protein-3 in growth hormone-deficient children and adults using ROC plot analysis. J Clin Endocrinol Meta 2003; 88:4702–8.
  • Cianfarani S, Liguori A, Boemi S, et al. Inaccuracy of insulin-like growth factor (IGF) binding protein (IGFBP)-3 assessment in the diagnosis of growth hormone (GH) deficiency from childhood to young adulthood: association to low GH dependency of IGF-II and presence of circulating IGFBP-3 18-kilodalton fragment. J Clin Endocrinol Metab 2005; 90(11):6028–34. 
  • Shen Y, Zhang J, Zhao Y, et al. Diagnostic value of serum IGF-1 and IGFBP-3 in growth hormone deficiency: a systematic review with meta-analysis. Eur J Pediatr 2015; 174(4):419–27.

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While there is some evidence that the use of GnRH agonists can achieve improvements in height in females with early puberty, it is also associated with the development of polycystic ovary syndrome (PCOS) in adolescence and risks compromising bone health. Its use outside of clinical trials is not recommended. Given that the treatment duration must also be lengthy for its benefits to be manifested, its use is not recommended to augment height in adolescents with short stature and normally timed puberty.

Supporting evidence

  • Chiavaroli V, Liberati M, D'Antonio F, et al. GnRH analog therapy in girls with early puberty is associated with the achievement of predicted final height but also with increased risk of polycystic ovary syndrome. Eur J Endocrinol 2010; 163(1):55–62. 
  • Dunkel L. Treatment of idiopathic short stature: effects of gonadotropin-releasing hormone analogs, aromatase inhibitors and anabolic steroids. Horm Res Paediatr 2011 ;76 Suppl 3:27–9. 
  • Wit M, Visser-van Balen H, Kamp GA, et al. Benefit of postponing normal puberty for improving final height. European Journal of Endocrinology 2004; 151:S41–5.
  • Yanovski JA, Rose SR, Municchi G, et al. Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature. N Engl J Med 2003; 348(10):908–17.

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Aromatase inhibitors are used as adjuvant therapy for breast cancer. There is growing acceptance of their use to increase the adult height of children with short stature and some evidence that aromatase inhibitors can at least improve short-term growth outcomes. One recent clinical trial of aromatase inhibitors used in paediatric patients found them to be safe and effective. Even so, there is still little evidence overall that this treatment improves final adult height or is sufficiently safe. A 2015 Cochrane review found a significant proportion of pre-pubertal boys undergoing this treatment suffered mild morphological abnormalities of their vertebrae. More evidence is needed to demonstrate safety and efficacy of aromatase inhibitors before they can be routinely prescribed to promote growth in children with short stature.

Supporting evidence

  • Diaz-Thomas A, Shulman D. Use of aromatase inhibitors in children and adolescents: what's new? Curr Opin Pediatr 2010; 22(4):501–7. 
  • Mauras N, Ross JL, Gagliardi P, et al. Randomized trial of aromatase inhibitors, growth hormone or combination in pubertal boys with idiopathic short stature. J Clin Endocrinol Metab 2016; 6:jc20162891.
  • McGrath N, O'Grady MJ. Aromatase inhibitors for short stature in male children and adolescents. Cochrane Database of Systematic Reviews 2015; 10:CD010888.
  • Wit JM, Hero M, Nunezs SB. Aromatase inhibitors in paediatrics, Nature Reviews Endocrinology 2012; 8:135–47.

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A working group of lead clinicians from APEG brainstormed an initial list of 11 low-value practices in paediatric endocrinology and a preliminary review of the evidence for each was undertaken. An online survey was developed based on these 11 recommendations along with a summary of the evidence for each, and circulated to APEG members for their feedback. For each recommendation, respondents were asked to assign a score from 1 to 5 (where 1 = strongly disagree and 5 = strongly agree) on two criteria: ‘The recommendation is evidence based’ and ‘The recommendation is relevant to paediatric endocrinology in Australasia’. Based on the recommendations which received the highest average total scores, and after a final in-depth review of the related evidence, the final top five were chosen and approved by APEG.

Last reviewed 25 September 2017