BSPED2018 Oral Communications Oral Communications 5 (9 abstracts)
New insights into the low dose dexamethasone suppression test in paediatric Cushing’s syndrome (CS)
Ingrid CE Wilkinson 1 , Fiona Riddoch 2 , Lesley A Perry 3 , Lee Martin 4 , Ashley B Grossman 5 , John P Monson 1 , Scott Akker 1 , Martin O Savage 1 , William M Drake 1 & Helen L Storr 1
1Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK; 2Department of Clinical Biochemistry, Barts Health NHS Trust, London, UK; 3Pathology Department, Croydon Health Services, Croydon, UK; 4Department of Paediatric Endocrinology, Royal London Hospital, London, UK; 5Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, 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 (0.5 mg 6 hrly × 48 hrs) comes from a time when biochemical auto analysers 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 hrs. Many clinicians experienced in the assessment of suspected CS consider that ‘normal’ individuals suppress to ≤20 nmol/l and that values of 20–50 nmol/l represent uncertainty. Current sensitivity and specificity are reported as 90% and 100%, respectively for ≤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 82 suspected CS patients, 50 had Cushing’s Disease (CD), 8 had primary pigmented nodular adrenocortical disease (PPNAD) and 24 ‘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 44/50 (88%) CD patients (29 males, median age 13.31 years, range 5.6–17.8) during LDDST. In contrast, cortisol was >20 nmol/l in 49/50 (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 98%(CI95 89.4–100%) and 96% (78.9–99.9%). None of the eight PPNAD patients (four male, median age 12.5 years, range 10.5–16.9) had cortisol levels ≤50 nmol/l during LDDST. Cortisol levels in 23/24 controls (five males, median age 13.9 years, range 4.3–17.0) suppressed to ≤20 nmol/l. One control patient: diagnoses of mosaic turners syndrome; high androgens; hypertension and obesity, suppressed to 22 nmol/l.
Conclusion: Changing the LDDST cut off from ≤50 nmol/l to ≤20 nmol/l improves the sensitivity of the test from 90 to 98% in our paediatric CS patients. This does not greatly reduce the specificity from 100 to 96%. We therefore suggest using serum cortisol of ≤20 nmol/l as a new diagnostic cut off value.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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