Applying precision medicine to the diagnosis and management of endocrine disorders

Abstract

Precision medicine employs digital tools and knowledge of a patient's genetic makeup, environment and lifestyle to improve diagnostic accuracy and to develop individualised treatment and prevention strategies. Precision medicine has improved management in a number of disease areas, most notably in oncology, and it has the potential to positively impact others, including endocrine disorders. The accuracy of diagnosis in young patients with growth disorders can be improved by using biomarkers. Insulin-like growth factor I (IGF-I) is the most widely accepted biomarker of growth hormone secretion, but its predictive value for recombinant human growth hormone treatment response is modest and various factors can affect the accuracy of IGF-I measurements. These factors need to be taken into account when considering IGF-I as a component of precision medicine in the management of growth hormone deficiency. The use of genetic analyses can assist with diagnosis by confirming the aetiology, facilitate treatment decisions, guide counselling and allow prompt intervention in children with pubertal disorders, such as central precocious puberty and testotoxicosis. Precision medicine has also proven useful during the transition of young people with endocrine disorders from paediatric to adult services when patients are at heightened risk of dropping out from medical care. An understanding of the likelihood of ongoing GH deficiency, using tools such as MRI, detailed patient history and IGF-I levels, can assist in determining the need for continued recombinant human growth hormone treatment during the process of transitional care.

Keywords: adolescent; biomarkers; child; early diagnosis; endocrine diagnosis; genetic testing; growth hormone; precision medicine; precocious puberty; transitional care.

Figure 1

Reference intervals for (A) males and (B) females according to the age intervals of six insulin-like growth factor I (IGF-I) immunoassays. Lower limits (2.5th percentile) and upper limits (97.5th percentile) of the normal range are drawn as full lines and means as dotted lines. Data from Chanson et al. (17).

Figure 2

Indications for genetic testing in the diagnosis of central precocious puberty (CPP). Data from Latronico et al. (24). MKRN3, Makorin RING finger protein 3. The dotted arrow indicates the possibility of performing a genetic test (MKRN3 gene analysis) after a normal MRI in children with sporadic CPP.