ESPE Yearbook of Paediatric Endocrinology

J Endocrinol Invest 48(Suppl 1) (2025) 7-19.PMID: 39347909

Brief Summary: Cushing’s syndrome (CS) is characterized by prolonged and excessive exposure to glucocorticoids, resulting in significant morbidity and mortality. The authors reviewed literature published between 1970 to 2023, and summarize current screening strategies and updates in biochemical testing and imaging. They propose a pragmatic, stepwise diagnostic approach.

Although rare, paediatric CS is associated with significant morbidity. Early and accurate recognition is essential to reduce the complications. The classification of Cushing’s syndrome (CS) is determined by its etiology, which can be categorised: pituitary (Cushing’s disease, CD), ectopic ACTH secretion, or adrenal origin. It is imperative and sometimes challenging to differentiate between non-neoplastic hypercortisolism (NNH), often caused by psychiatric conditions, obesity, or extreme physical stress, as initial screening tests may yield false positives [1, 2].

The authors endorse current consensus guidelines recommending late-night salivary cortisol (LNSC), 24-hour urinary free cortisol (UFC), and 1-mg dexamethasone suppression test (DST) as initial tools [2]. The authors highlight the limitations and advantages of each: UFC requires multiple samples due to high variability; DST may yield false positives due to altered dexamethasone metabolism; LNSC is advantageous for being non-invasive. Measurement of dexamethasone levels is recommended in children to reduce false positives. The use of LC-MS/MS assays, which allow the quantification of cortisol and cortisone, is proposed to enhance the identification of endogenous cortisol production, and to reduce the occurrence of false-positive results.

The authors maintain that MRI remains the standard imaging modality for CD, with spoiled gradient-recalled acquisition in the steady state MRI enhancing adenoma detection being a key advancement. Functional imaging techniques with new molecules (e.g., 68Ga-DOTATATE PET/CT for small tumours, 11C-metomidate PET/CT for adrenal lesions) offer promise but require further validation. In many cases, a non-invasive approach using 3 to 4 biochemical and imaging modalities may obviate the need for bilateral inferior petrosal sinus sampling (BIPSS).

In conclusion, early suspicion, and proper use of LNSC, UFC and DST improves diagnostic accuracy. A non-invasive, stepwise approach may reduce reliance on BIPSS in selected cases.

References: 1. Findling, J.W. and H. Raff, Recognition of nonneoplastic hypercortisolism in the evaluation of patients with cushing syndrome. Journal of the Endocrine Society, 2023. 7(8): p. bvad087.2. Fleseriu, M., et al., Consensus on diagnosis and management of Cushing’s disease: a guideline update. The lancet Diabetes & endocrinology, 2021. 9(12): p. 847–875.