Original ArticleInfluence of inferior petrosal sinus drainage symmetry on detection of adenomas in Cushing's syndrome
Introduction
MR imaging has been shown to fail to detect adrenocorticotropin-secreting pituitary microadenomas in up to 50% of cases due to their small size, location, and enhancing characteristics [1], [2], [3]. Despite modified protocols using half-dose gadolinium in dynamic MRI imaging [4], spoiled-gradient echo 3D T1 imaging [5], [6], [7], or postcontrast FLAIR imaging [8], accurate localization of otherwise MRI-negative pituitary microadenomas has improved but remains imprecise [9]. Thus under current guidelines BIPSS still represents the gold standard in the diagnostic algorithm for identifying CS in patients with negative or ambiguous MR findings [9], [10]. Bilateral inferior petrosal sinus (IPS) sampling (BIPSS) is highly sensitive and specific in distinguishing Cushing's disease (CD) from ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). However, correct prediction of the adenoma side in patients with CD remained a diagnostic challenge, with reported accuracy ranging from 50–100% [11], [12]. Various explanations for the poor accuracy in lateralization of BIPSS have been published [13], [14], [15]. While variations of the IPS outflow into the jugular vein are frequently encountered [16], data on whether IPS symmetry influences success in prediction of the adenoma side using super-selective BIPSS is scarce.
In this audit of practice, we assessed the influence of drainage patterns on detection of adenomas in ACTH-dependent CS.
Section snippets
Study design
We conducted a retrospective cohort study reviewing records collected in our institutional database from June 1997 to January 2016. Patients met clinical and biochemical inclusion criteria for ACTH-dependent Cushing's syndrome (CS), with negative magnetic resonance imaging (MRI) findings that failed to localize a pituitary microadenoma, which led to the indication of BIPSS. Demographic, laboratory, procedural, interventional, surgical, and histopathologic findings and clinical outcome were
Patients’ characteristics
Clinical and radiological characteristics of patients with BIPSS are presented in supplementary Table 1. Thirty-eight patients (31 women, 7 men) were enrolled in this study. Mean age was 45 ± 15 years, range 7–71 years.
Accuracy of BIPSS in predicting the ACTH source (ectopic vs. central)
The drainage patterns that describe the venous outflow from the petrosal sinus into the jugular vein are reported in supplementary Table 1 and depicted in Fig. 1. On the right side, a type I pattern was recorded in 16 patients (51%), type II in two patients (7%), type III in 10
Discussion
The main findings of this study can be summarized as follows:
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asymmetric IPS drainage patterns are frequently encountered during BIPSS;
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and asymmetric venous outflow does not seem to diminish accuracy in predicting the adenoma side nor does it influence the remission rate from CS.
With a cannulation success rate of 97%, BIPSS correctly predicted the side of the adenoma in 96% of patients with CD. Prediction was improved in symmetric vs. asymmetric drainages, though not significantly (P = 0.42).
Study limitations
The number of patients who underwent BIPSS is relatively small, and statistical uncertainty owing to this small sample size precluded us from undertaking a multivariate analysis of the influence of each venous variant on the accuracy with which the correct side could be predicted. Furthermore, between enrollment of the first study subject in 1997 and enrollment of the most recent patient in 2016 there have been advances in materials used and in treatment options; these may have influenced
Conclusions
With an accurate sampling technique using microcatheters and a clear understanding of the different venous outflow patterns, overall success in prediction of adenoma side is high, even in patients with asymmetric outflow patterns. Nevertheless, asymmetric venous outflow does not seem to significantly influence the accuracy with which the adenoma side can be predicted, nor does it have an influence on the remission rates in patients with CS. Further studies may be needed to establish the
Ethical statement
Ethical standards: The study was approved by the Ethics Committee of the canton of Bern (Kantonale Ethikkommision, KEK, Bern, Switzerland), the organization responsible for research involving humans in Switzerland. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Data sharing statement
The authors agree to share data on request.
Contribution of authors
L.A. contributed to study conception and design, acquisition of data, statistical analysis and interpretation, drafting of the manuscript, critical revision and final approval of the article. EC contributed to study conception and design, interpretation of data, critical revision and final approval of the article. J.G., G.S., P.M., R.H.A., H.R.W., M.M.L., F.K., J.B., L.M., and C.O. contributed to critical revision and final approval of the manuscript.
Disclosure of interest
The authors declare that they have no competing interest.
Acknowledgments
We thank Ms. Anja Giger for the medical illustrations. The assistance of Ms. Jeannie Wurz and Ms. Susan Kaplan in editing the manuscript is highly appreciated.
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