Retrospective diagnosis of Turner syndrome using electronic health records or screening at initial assessment

The late diagnosis of Turner syndrome (TS) is acknowledged to be one of the major challenges in the management of this multi-system disorder [1]. It is likely that when a positive TS diagnosis is made after referral to a paediatric endocrinology service, the patient has already been seen by a healthcare professional without the correct diagnosis being suspected. Late diagnosis will have negative effects on the treatment of associated comorbidities, such as thyroid disease and delayed puberty, in addition to affecting the prognosis and likely result of the short stature, as growth hormone therapy will by definition be delayed.

See linked news story: Algorithm identifies missed Turner syndrome cases in electronic health records

This article by Alexandrou et al reports data originating from three tertiary paediatric endocrinology referral centres in the USA, namely Louisville, Cincinnati and Washington DC, and describes the ability of algorithm-programmed electronic health records (EHR) to diagnose patients with TS after they have been missed at initial referral and incorrectly labelled as having idiopathic short stature (ISS) [2]. Consequently, the ability of EHRs to expedite a TS diagnosis is certainly encouraging in children who might otherwise have had prolonged incorrect categorisation as ISS.

However, in 2013, an article was published by Sisley et al in the Journal of Pediatrics from the Endocrinology Division of the Cincinnati Children’s Hospital Medical Centre [3] reporting that children with short stature who were healthy and asymptomatic, as assessed by experienced paediatric endocrinologists, and had normal physical examination showed an extremely low positive detection rate from general screening investigations, including karyotype for TS.

The general screening tests had previously been recommended in a Consensus statement following a Workshop organised by the Growth Hormone Research Society, Pediatric Endocrine Society and European Society for Paediatric Endocrinology on management of ISS [4]. The message from the Cincinnati article was that screening tests in such patients were not cost-effective [3]. The article by Alexandrou et al does not cite the Sisley et al report and does not give precise details of the number of patients from Cincinnati who had not received karyotype screening at the time of their initial assessment.

It would appear reasonable to suggest that if the short stature patients had been investigated for TS, as recommended in the 2008 Consensus report [4], those retrieved by the use of EHRs would not have been erroneously labelled as having ISS. The key component of the Sisley et al report is the understanding that expert assessment is required to identify the children who will have a very low pick-up rate of abnormal screening tests. The degree of expertise and experience required is not quantifiable, leading to the interpretation that if in doubt, screening tests can successfully detect such important but potentially latent diagnoses such as TS mosaicism, late-presenting coeliac disease or Crohn’s disease, all of which would benefit from diagnosis as early as possible. The potential retrospective use of EHRs is reassuring, but general screening at initial assessment remains a preferable method of early diagnosis.

  1. Gravholt CH, Andersen NH, Conway GS, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol 2017; 177: G1–70
  2. Alexandrou E, Cabrera-Salcedo C, et al. Algorithm-Driven Electronic Health Record Notification Enhances the Detection of Turner Syndrome. J Pediatr 2019; doi:10.1016/j.jpeds.2019.09.023
  3. Sisley S, Trujillo MV, Khoury J, Backeljauw P. Low incidence of pathology detection and high cost of screening in the evaluation of asymptomatic short children. J Pediatr 2013; 163: 1045–1051
  4. Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. 2007 ISS Consensus Workshop participants. J Clin Endocrinol Metab 2008; 93: 4210–4217