The effects of sampling lateralization on bilateral inferior petrosal sinus sampling and desmopressin stimulation test for pediatric Cushing's disease

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

doi:10.1007/s12020-018-1779-x

Abstract

PurposeBilateral inferior petrosal sinus sampling (BIPSS) is useful for differential diagnosis of adult Cushing’s disease (CD) but may not be so reliable in pediatric cases. The purpose of this study was to evaluate the sensitivity of BIPSS before and after desmopressin stimulation in pediatric CD, and to explore related factors of false-negative results and meanings of sampling lateralization.MethodsWe retrospectively analyzed 16 pediatric CD patients who underwent 17 BIPSS procedures from 2006 to 2017. CD was diagnosed if inferior petrosal sinus (IPS) to peripheral adrenocorticotropic hormone (ACTH) ratio was >2 at baseline or >3 after desmopressin stimulation. Sampling lateralization was yielded if interpetrosal sinus gradient was >1.4. Magnetic resonance imaging (MRI) was conducted. All the patients underwent surgery and the diagnosis was confirmed.ResultsThe sensitivity was 64.7% (11/17) at baseline and 83.3% (10/12) after desmopressin stimulation. After stimulation, BIPSS reached its best sensitivity at 3 min. Sampling lateralization rate was 62.5% and 63.6% before and after stimulation, and the accordant rate with actual tumor lateralization was 50.0% and 42.9%, respectively. The accuracy of MRI in predicting the tumor lateralization was 80.0%. Sampling lateralization rate (81.8% in true-positive, 20.0% in false-negative, p = 0.036) and ACTH at dominant IPS (p = 0.001) was lower among false-negative patients.ConclusionsThe sensitivity of BIPSS in pediatric CD was low at baseline, but increased after desmopressin stimulation. Sampling lateralization cannot accurately indicate the tumor lateralization, but the absence of sampling lateralization with low ACTH at IPS is a hint of false-negative cases in BIPSS.

Highlights

These authors contributed : Shi Chen, Kang Chen.Cushing’s syndrome is the result of chronic elevation of glucocorticoids, which may be exogenous or endogenous
As one of the largest series that systematically reported the use of desmopressin in Bilateral inferior petrosal sinus sampling (BIPSS) for pediatric Cushing’s disease (CD), this study validated that desmopressin stimulation can increase the sensitivity of BIPSS in children and adolescents
The most prominent finding of our study is that BIPSS is not as accurate as reported previously for diagnosis and tumor lateralization in children and adolescents with CD, even in experienced hands, and we suggest that the absence of sampling lateralization before stimulation together with low adrenocorticotropic hormone (ACTH) level at inferior petrosal sinus (IPS) is a potential sign of false negative result in BIPSS

Summary

Introduction

These authors contributed : Shi Chen, Kang Chen. Cushing’s syndrome is the result of chronic elevation of glucocorticoids, which may be exogenous or endogenous. Endogenous Cushing’s syndrome can be caused by adrenocorticotropic hormone (ACTH)-dependent and ACTHindependent forms. ACTH-dependent Cushing’s syndrome is caused by excess secretion of ACTH from the pituitary, which is named Cushing’s disease (CD), or by ectopic secretion of ACTH from neuroendocrine tumors, which is named ectopic ACTH syndrome (EAS), or rarely by ectopic secretion of corticotropin-releasing hormone (CRH) [1]. Since many ectopic ACTH-secreting tumors remain occult for a long time, the differential diagnosis of ACTHdependent Cushing’s syndrome is a challenging issue for clinical management

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