Overnight dexamethasone suppression test: a valuable measure of medical treatment efficacy in ACTH-dependent Cushing’s Syndrome  

S. Goulopoulou*^a (Dr), A. Michou^a (Dr), E. Divaris^a (Dr), G. Kourkouta^a (Dr), M. Kita^a (Dr), Z. Efstathiadou^a (Dr)

^a Department of Endocrinology, Hippokration General Hospital, Thessaloniki, GREECE

* sophiagoul@hotmail.com

Introduction

Monitoring the response to medical treatment of Cushing’s syndrome (CS) is quite challenging and mainly based on remission of clinical signs and symptoms, improvement of metabolic parameters and on measurements of 24h urinary free cortisol (UFC) and basal plasma cortisol levels.

Most treatment efficacy studies are based on UFC, which however is subject to wide variation and could lead to inconclusive results.

On the other hand, the restoration of the negative feedback of corticotropes, as reflected by ODST, when cortisol levels decline to normal, could be used as a more reliable marker of response to medical treatment, serving as a biological index of exposure to glucocorticoids at the pituitary tissue level.

Aim

We have studied the role of ODST as a marker of response to medical treatment in ACTH-dependent CS.

Methods

Seven patients with ACTH-dependent Cushing’s syndrome (1 ectopic), on medical treatment were studied.

Data on 24h UFC, ODST and morning plasma cortisol were collected retrospectively, along with data of the metabolic profile and the clinical signs and symptoms of each individual subject.

Results

In 6 patients, pharmacotherapy with steroidogenesis inhibitors or pasireotide was the primary treatment and in 1 patient, metyrapone was initiated 7 years post-pituitary surgery due to recurrent disease. Six patients received metyrapone, 1 ketoconazole and one patient daily pasireotide.

While on treatment, all 7 patients normalized UFC with a reduction range of 37-128%. Similarly, all patients showed a reduction in post-dexamethasone cortisol levels by 52-91%. Three patients completely normalized post-dex cortisol levels (<1.8mcg/dl), and another three showed a significant (>50%) decrease with levels of 5-6.9mcg/dl.

Interestingly, normalization of ODST was associated with complete clinical response.

Conclusions

In this preliminary study, ODST emerges as a useful “biochemical” and at the same time “biological” marker of treatment efficacy in Cushing’s disease, counteracting the variability of UFC measurements.

References:

1. Frederic Castinetti, Lynnette K Nieman et al. Approach to the patient treated with stereoidogenesis inhibitors. J.Clin Endocrinol Metab 2021 Jul; 106(7): 2114-2123.

2.Leonie H.A.Broersen, Meghna Jha et al. Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis. Pituitary. 2018; 21(6): 631-641.

The author has declared no conflict of interest.