An Optimized Pathway for the Differential Diagnosis of ACTH-Dependent Cushing's Syndrome Based on Low-Dose Dexamethasone Suppression Test.

Kang Chen,Hui Pan,Renzhi Wang,Xiaobo Zhang,Zhaolin Lu,Huijuan Zhu,Shi Chen,Anli Tong,Lin Lu

doi:10.3389/fendo.2021.720823

Abstract

ContextTraditionally, low-dose dexamethasone suppression test (LDDST) was used to confirm the diagnosis of Cushing’s syndrome (CS), and high-dose dexamethasone suppression test (HDDST) was used to differentiate Cushing’s disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS), but some studies suggested that HDDST might be replaced by LDDST. For the differential diagnosis of CS, dexamethasone suppression test was usually combined with other tests such as bilateral petrosal sinus sampling (BIPSS) and pituitary magnetic resonance imaging, but the optimal pathway to incorporate these tests is still controversial.ObjectivesTo develop an optimized pathway for the differential diagnosis of CD and EAS based on LDDST.Design and SettingSingle-center retrospective study (2011–2019).PatientsTwo hundred sixty-nine CD and 29 EAS patients with pathological diagnosis who underwent consecutive low- and high-dose DST.ResultsFor the differential diagnosis of CD and EAS, the area under curve (AUC) of LDDST using urine free cortisol (0.881) was higher than that using serum cortisol (0.685) (p < 0.001) in head-to-head comparison among a subgroup of 108 CD and 10 EAS. The AUC of LDDST (0.883) was higher than that of HDDST (0.834) among all the included patients. With the cutoff of <26%, the sensitivity and specificity of LDDST were 39.4% and 100%. We designed a new pathway in which BIPSS was only reserved for those patients with unsuppressed LDDST and adenoma <6mm, yielding an overall sensitivity of 97.7% and specificity of 86.7%.ConclusionLDDST had similar value to HDDST in differentiating CD and EAS using the specific cutoff point. The pathway that combined LDDST and BIPSS could differentiate CD and EAS accurately.

Highlights

Cushing’s disease (CD) and ectopic ACTH syndrome (EAS) are two main causes of ACTH-dependent Cushing’s syndrome (CS) [1]
While overnight low-dose dexamethasone suppression test (LDDST) can be conducted for outpatients, “standard” 2-day LDDST was usually repeated after hospitalization, most of which were follow by high-dose dexamethasone suppression test (HDDST) immediately in our center
A total of 269 CD patients and 29 EAS patients were included in our study

Summary

Introduction

Cushing’s disease (CD) and ectopic ACTH syndrome (EAS) are two main causes of ACTH-dependent Cushing’s syndrome (CS) [1]. While normal hypothalamus–pituitary– adrenal axis was regulated by negative feedback, the cortisol secretion in CS was partly resistant to excess glucocorticoid, and it was believed that the ectopic tumor has higher autonomy of ACTH secretion compared with the pituitary tumor [1, 3]. Based on these characteristics, low-dose dexamethasone suppression test (LDDST) was designed to diagnose CS and high-dose dexamethasone suppression test (HDDST) to differentiate CD and EAS [4]. It was proposed that LDDST per se may be an alternative for the differential diagnosis of ACTH-dependent Cushing’s syndrome [7, 10, 11], but such viewpoint has not been widely accepted

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