ESPE Abstracts (2018) 89 P-P1-015

New Insights into Low Dose Dexamethasone Suppression Test in Paediatric Cushing's Syndrome

Ingrid C E Wilkinsona, Lee Martinb, Ashley B Grossmana,c, John P Monsond, Scott Akkera, Martin O Savagea, William M Drakea & Helen L Storra

aCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; bDepartment of Paediatric Endocrinology, Royal London Hospital, London, UK; cOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK; dCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, First Floor, John Vane Science Centre, Charterhouse Square, London, UK

Background: The Low dose dexamethasone suppression test (LDDST) is an important investigation for suspected Cushing’s Syndrome (CS). The traditional definition of normal suppression of serum cortisol to ≤50 nmol/l during the LDDST (0.5 mg 6 hrly × 48 h) comes from a time when biochemical autoanalysers did not routinely detect very low values. Previous studies reported 5.1–8.3% of patients with Cushing’s Disease (CD) suppressed to <50 nmol/l at 48 h during LDDST. Many clinicians experienced in the assessment of suspected CS consider that ‘normal’ individuals should suppress to ≤20 nmol/l during a LDDST and that LDDST values of 20–50 nmol/l represent a range of uncertainty. Current sensitivity and specificity is reported as 90% and 100% for a cut off of ≤50 nmol/l.

Methods: We reviewed a retrospective cohort of paediatric patients referred to our centre with suspected CS between 1982 and 2018.

Results: Of 70 suspected CS patients, 49 had Cushing’s Disease (CD), 7 had Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and 14 ‘control’ subjects, in whom the diagnosis of CS was excluded following detailed biochemical evaluation and prolonged clinical/auxological follow-up. The serum cortisol remained >50 nmol/l in 42/49 (86%) CD patients (29 males, median age 13.22 years) during LDDST. In contrast, cortisol during LDDST was >20 nmol/l in 48/49 (98%) CD patients. One patient with cortisol ≤20 nmol/l during LDDST had a high clinical suspicion of CD and investigations including bilateral simultaneous inferior petrosal sinus sampling confirmed this. The sensitivity and specificity of a LDDST cut off value of ≤20 nmol/l is 97.96% (95% CI 89.15%–99.95%) and 100% (76.84%–100%). None of the 7 PPNAD patients (four male, median age 12.2 years) had cortisol levels of ≤50 nmol/l during LDDST. Cortisol levels in all 14 controls (three males, median age 12.7 years) suppressed to ≤20 nmol/l during LDDST.

Conclusion: Whilst the numbers are small, changing the LDDST cut off from ≤50 nmol/l to ≤20 nmol/l improves the sensitivity of the test from 85.71% to 97.96% in our paediatric CD patients. This does not adversely affect the specificity which remains 100%. We therefore suggest using serum cortisol of ≤20 nmol/l as a new diagnostic cut off value.

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