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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2013

Open Access 01-12-2013 | Research

ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent aberrant in vivo and in vitroresponses to hormonal stimuli and coupling of arginine-vasopressin type 1a receptor to 11β-hydroxylase

Authors: Johannes Hofland, Leo J Hofland, Peter M van Koetsveld, Jacobie Steenbergen, Wouter W de Herder, Casper H van Eijck, Ronald R de Krijger, Francien H van Nederveen, Maarten O van Aken, Johannes W de Groot, Thera P Links, Frank H de Jong, Richard A Feelders

Published in: Orphanet Journal of Rare Diseases | Issue 1/2013

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Abstract

Background

Adrenal Cushing’s syndrome caused by ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) can be accompanied by aberrant responses to hormonal stimuli. We investigated the prevalence of adrenocortical reactions to these stimuli in a large cohort of AIMAH patients, both in vivo and in vitro.

Methods

In vivo cortisol responses to hormonal stimuli were studied in 35 patients with ACTH-independent bilateral adrenal enlargement and (sub-)clinical hypercortisolism. In vitro, the effects of these stimuli on cortisol secretion and steroidogenic enzyme mRNA expression were evaluated in cultured AIMAH and other adrenocortical cells. Arginine-vasopressin (AVP) receptor mRNA levels were determined in the adrenal tissues.

Results

Positive serum cortisol responses to stimuli were detected in 27/35 AIMAH patients tested, with multiple responses within individual patients occurring for up to four stimuli. AVP and metoclopramide were the most prevalent hormonal stimuli triggering positive responses in vivo. Catecholamines induced short-term cortisol production more often in AIMAH cultures compared to other adrenal cells. Short- and long-term incubation with AVP increased cortisol secretion in cultures of AIMAH cells. AVP also increased steroidogenic enzyme mRNA expression, among which an aberrant induction of CYP11B1. AVP type 1a receptor was the only AVPR expressed and levels were high in the AIMAH tissues. AVPR1A expression was related to the AVP-induced stimulation of CYP11B1.

Conclusions

Multiple hormonal signals can simultaneously induce hypercortisolism in AIMAH. AVP is the most prevalent eutopic signal and expression of its type 1a receptor was aberrantly linked to CYP11B1 expression.
Appendix
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Metadata
Title
ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent aberrant in vivo and in vitroresponses to hormonal stimuli and coupling of arginine-vasopressin type 1a receptor to 11β-hydroxylase
Authors
Johannes Hofland
Leo J Hofland
Peter M van Koetsveld
Jacobie Steenbergen
Wouter W de Herder
Casper H van Eijck
Ronald R de Krijger
Francien H van Nederveen
Maarten O van Aken
Johannes W de Groot
Thera P Links
Frank H de Jong
Richard A Feelders
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2013
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-8-142

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