ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Best Pract Res Clin Endocrinol Metab. 2020:101418. PMID: 32414619.

Cushing’s syndrome (CS) is the constellation of signs and symptoms resulting from excessive exposure to cortisol (1). While exogenous CS is relatively common, endogenous CS accounts for only 2.3 to 3.2 new cases per million per year; 10% of these present in children (2–4). Endogenous CS is caused by either ACTH-dependent sources (pituitary or ectopic) or ACTH-independent (adrenal) hypercortisolemia.

This review summarizes current knowledge regarding the genetics of CS, reviewing well-established genetic causes (e.g. mutations in MEN1, GNAS or TP53 ), as well as novel genes implicated in its pathogenesis. Moreover, the authors categorize known CS genes by disease types (Cushing’s disease, ACTH-independent CS or ectopic CS) together with their accompanying phenotypic features. They also provide recommendations on genetic screening in CS cases and discuss the appropriate techniques during clinical management. They highlight the need for careful review of the patient’s personal and family history for clues to a specific genetic syndrome, as well as the importance of understanding the diagnostic value of genetic testing and its value to guide treatment options. In summary, this article provides an overview of the various genetic mechanisms underlying hypercortisolemia in CS and provides helpful guidance on the use of genetic testing.

References:

1. Lacroix A, Feelders RA, Stratakis CA, et al. Cushing’s syndrome. Lancet 2015; 386(9996): 913e27.

2. Wengander S, Trimpou P, Papakokkinou E, et al. The incidence of endogenous Cushing’s syndrome in the modern era. Clin Endocrinol (Oxf) 2019; 91(2): 263e70.

3. Lindholm J, Juul S, Jorgensen JO, et al. Incidence and late prognosis of cushing’s syndrome: a population-based study. J Clin Endocrinol Metab 2001; 86(1): 117e23.

4. Stratakis CA. An update on Cushing syndrome in pediatrics. Ann Endocrinol (Paris) 2018; 79(3): 125e31.