Enhancing Cushing's disease diagnosis: exploring the impact of desmopressin on ACTH gradient during BIPSS

Tobias Skrebsky de Almeida; Ticiana da Costa Rodrigues; Fabíola Costenaro; Leandro Armani Scaffaro; Maurício Farenzena; Fernando Gastaldo; Mauro Antônio Czepielewski

doi:10.3389/fendo.2023.1224001

Enhancing Cushing's disease diagnosis: exploring the impact of desmopressin on ACTH gradient during BIPSS

Front Endocrinol (Lausanne). 2023 Aug 3:14:1224001. doi: 10.3389/fendo.2023.1224001. eCollection 2023.

Authors

Tobias Skrebsky de Almeida^{1

2}, Ticiana da Costa Rodrigues^{1

2

3}, Fabíola Costenaro^{1

2}, Leandro Armani Scaffaro⁴, Maurício Farenzena⁴, Fernando Gastaldo⁵, Mauro Antônio Czepielewski^{1

3}

Affiliations

¹ Postgraduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
² Endocrinology Division, Hospital Moinhos de Vento, Porto Alegre, Brazil.
³ Endocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
⁴ Radiology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
⁵ Department of Radiology, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.

Abstract

Introduction: The differential diagnosis between Cushing's disease (CD) and ectopic ACTH syndrome (EAS) is complex, and bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold-standard test. However, BIPSS with corticotropin-releasing hormone (CRH) stimulation is rarely available.

Objective: This retrospective cohort study aimed to assess the accuracy of the inferior petrosal sinus to peripheral ACTH gradient (IPS:P) before and after desmopressin stimulation for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS), applying different cutoff values.

Methods: A total of 50 patients (48 with CD and 2 with EAS) who underwent BIPSS were included in this study. The sensitivity and specificity of IPS:P in BIPSS before and after desmopressin stimulation were evaluated. Various cutoff values for IPS:P were examined to determine their diagnostic accuracy.

Results: Using the traditional IPS:P cutoff, the sensitivity was 85.1% before stimulation, 89.6% after stimulation, and a combined sensitivity of 91.7%. Applying cutoff values of IPS:P >1.4 before and >2.8 after stimulation, the sensitivity was 87.2% and 89.6%, respectively, with a combined sensitivity of 91.7%. Receiver operating characteristic (ROC) curve analysis determined optimal cutoff values of 1.2 before stimulation and 1.57 after stimulation, resulting in a sensitivity of 93.6% and 93.8%, respectively, with a combined sensitivity of 97.9%. Specificity remained at 100% throughout all analyses. Among the 43 patients who responded positively to stimulation, 42 (97.7%) did so within the first three minutes, and all 43 (100%) did so within the first five minutes. None of the assessed clinical variables predicted the ACTH response to stimulation in BIPSS with statistical significance.

Discussion: ACTH stimulation with desmopressin during BIPSS improves the accuracy of IPS:P, making it a valuable tool for investigating ACTH-dependent Cushing's syndrome. Considering the low risk of complications, we recommend the use of desmopressin stimulation during BIPSS for the differential diagnosis of ACTH-dependent CS.

Keywords: ACTH; Cushing’s disease; Cushing’s syndrome; bilateral inferior petrosal sinus sampling; desmopressin; ectopic ACTH syndrome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ACTH Syndrome, Ectopic* / diagnosis
Adrenocorticotropic Hormone / metabolism
Cushing Syndrome* / diagnosis
Deamino Arginine Vasopressin / pharmacology
Humans
Petrosal Sinus Sampling
Pituitary ACTH Hypersecretion* / diagnosis
Retrospective Studies

Substances

Adrenocorticotropic Hormone
Deamino Arginine Vasopressin

Grants and funding

This work was supported by the Research Incentive Fund (FIPE) of Hospital de Clínicas de Porto Alegre and the Postgraduate Program in Medical Sciences: Endocrinology (PPG ENDO) from Universidade Federal do Rio Grande do Sul.