Study protocol

The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome

Johannes W Dietrich¹ , Axel Stachon² , Biljana Antic³ , Harald H Klein¹ and Steffen Hering¹

¹Medical Hospital 1, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, NRW, Germany

²Institute of Clinical Chemistry, Transfusion and Laboratory Medicine, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, NRW, Germany

³Klinik für Innere Medizin, Evangelisches Krankenhaus Hattingen, Hattingen, NRW, Germany

author email corresponding author email

BMC Endocrine Disorders 2008, 8:13doi:10.1186/1472-6823-8-13

Published:	13 October 2008

Abstract

Background

Non-thyroidal illness syndrome (NTIS) is a characteristic functional constellation of thyrotropic feedback control that frequently occurs in critically ill patients. Although this condition is associated with significantly increased morbidity and mortality, there is still controversy on whether NTIS is caused by artefacts, is a form of beneficial adaptation, or is a disorder requiring treatment. Trials investigating substitution therapy of NTIS revealed contradictory results. The comparison of heterogeneous patient cohorts may be the cause for those inconsistencies.

Objectives

Primary objective of this study is the identification and differentiation of different functional states of thyrotropic feedback control in order to define relevant evaluation criteria for the prognosis of affected patients. Furthermore, we intend to assess the significance of an innovative physiological index approach (SPINA) in differential diagnosis between NTIS and latent (so-called "sub-clinical") thyrotoxicosis.

Secondary objective is observation of variables that quantify distinct components of NTIS in the context of independent predictors of evolution, survival or pathophysiological condition and influencing or disturbing factors like medication.

Design

The approach to a quantitative follow-up of non-thyroidal illness syndrome (AQUA FONTIS study) is designed as both a cross-sectional and prospective longitudinal observation trial in critically ill patients. Patients are observed in at least two evaluation points with consecutive assessments of thyroid status, physiological and clinical data in additional weekly observations up to discharge. A second part of the study investigates the neuropsychological impact of NTIS and medium-term outcomes.

The study design incorporates a two-module structure that covers a reduced protocol in form of an observation trial before patients give informed consent. Additional investigations are performed if and after patients agree in participation.

Trial Registration

ClinicalTrials.gov NCT00591032