Clinical trial NCT00591032: Approach to a Quantitative Follow-up of Non-thyroidal Illness Syndrome
Official title: Development of Rational and Standardized Diagnostics and Staging for a Differentiated Risk Stratification of Non-thyroidal Illness Syndrome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Euthyroid Sick Syndromes
Non-thyroidal Illness Syndrome
Low T3 Syndrome
TACITUS
Keywords: Critical illness
Euthyroid sick syndromes
Intensive care
Non-thyroidal illness syndrome
Low-T3 syndrome
Lead sponsor: Ruhr University of Bochum
Sponsor class: OTHER
Collaborators: name: Wissenschaftskommission des Universitaetsklinikums Bergmannsheil
name: Private Sponsor (Chantal C. Guilhemotonia-Urban)
First posted: 2008-01-11
Enrollment: 590
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Critically ill patients treated at three intensive care units of the Bergmannsheil university hospitals and that comply with the eligibility criteria.

Brief summary: AQUA FONTIS is a unicentric, multidisciplinary, prospective cross-section and longitudinal study that aims at the development of a more clear-cut diagnostic definition and classification of non-thyroidal illness syndrome (NTIS).

Detailed description: Detailed Description:

Non-thyroidal illness syndrome (NTIS), also referred to as euthyroid sick syndrome (ESS) or thyroid allostasis in critical illness, tumors, uremia and starvation (TACITUS), is a complex endocrine condition that may occur in critically ill patients. It is associated with significantly increased morbidity and mortality.

NTIS is characterised by three components that may occur single or in combination:

1. central hypothyroidism (transient thyrotropic insufficiency)
2. impaired protein binding of thyroid hormones and
3. reduced formation of T3 and increased conversion to rT3 (low-T3-syndrome).

Despite of long lasting research to some of its details NTIS is still poorly characterized in an integrative view. Additionally, it lacks a clinically usable classification.

Given the fact that patients with NTIS are faced with poor prognosis, several studies have been conducted in the past evaluating the question of possible treatment. However, they didn't yield unambiguous results, maybe due to the fact that these studies did not differentiate among the distinct components of NTIS.

Therefore, this study is intended to develop a clear-cut definition and classification of NTIS in order to set a foundation for future therapeutic studies.

This study recruits critically ill patients treated in medical and surgical intensive care units of the Bergmannsheil University hospitals for evaluation of integrative thyrotropic control and follow-up. From these data the correlation of individual prognosis with laboratory-defined components of NTIS will be determined.

This project is intended to:

1. deliver a prognostical aid by providing a differentiated classification,
2. to contribute to a standardised, rational and inexpensive diagnostical procedure and
3. to lay the foundation for future therapeutic trials by identifying subgroups that may benefit from therapy.

Eligibility criteria: Inclusion Criteria:

* Severe illness requiring intensive care
* Stay of at least 24 hours at the ICU

Exclusion Criteria:

* Substituted hypothyroidism or substitution in case of thyroid carcinoma
* Hyperthyroidism that is treated with thyrostatic agents and exhibits a THS level not below the reference region
* Manifest AIDS disease

Primary outcomes:
measure: Assessment of the significance of an innovative physiological index approach (SPINA) in differential diagnosis between NTIS and latent thyrotoxicosis.
timeFrame: Three weeks after admission to ICU (evaluation point 1.5) and additionally on day of discharge from the hospital (evaluation point 1.999)
Secondary outcomes:
measure: Correlation of variables that quantify distinct components of NTIS with independent predictors of evolution, survival or pathophysiological condition and influencing or disturbing factors like medication.
timeFrame: 24 hours (evaluation point 1.1), 72 hours (evaluation point 1.2) and further on weekly (evaluation points 1.3 to 1.5) after admission to the intensive care unit up to the day of discharge from hospital (evaluation point 1.999)
Other outcomes:
Locations:
city: Bochum
country: Germany
facility: Department for medical informatics, biometry and epidemiology, Ruhr-University of Bochum
state: NRW
city: Bochum
country: Germany
facility: Institute of Clinical Chemistry, Transfusion and Laboratory Medicine, Universitätsklinikum Bergmannsheil, Ruhr-Universität Bochum
state: NRW
city: Bochum
country: Germany
facility: Medical Hospital II, Bergmannsheil University Hospitals, Ruhr University of Bochum
state: NRW
city: Bochum
country: Germany
facility: Medizinische Klinik I, Universitätsklinikum Bergmannsheil, Ruhr-Universität Bochum
state: NRW
city: Rheine
country: Germany
facility: Diabetes-Zentrum, Mathias-Spital
state: NRW
city: Kaiserslautern
country: Germany
facility: Abteilung für Laboratoriums- und Transfusionsmedizin, Westpfalz-Klinikum Kaiserslautern
state: RP
Study officials:
affiliation: Medizinische Klinik I, Universitätsklinikum Bergmannsheil, Ruhr-Universität Bochum
name: Johannes W Dietrich, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Diabetes-Zentrum, Mathias-Spital Rheine
name: Steffen Hering, M.D.
role: STUDY_DIRECTOR
affiliation: Medizinische Klinik I, Universitätsklinikum Bergmannsheil, Ruhr-Universität Bochum
name: H H Klein, M.D.
role: STUDY_CHAIR
References:
citation: Dietrich JW, Stachon A, Antic B, Klein HH, Hering S. 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. BMC Endocr Disord. 2008 Oct 13;8:13. doi: 10.1186/1472-6823-8-13.
citation: Dietrich JW, Landgrafe G, Fotiadou EH. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. J Thyroid Res. 2012;2012:351864. doi: 10.1155/2012/351864. Epub 2012 Dec 30.
citation: Dietrich JW, Muller P, Schiedat F, Schlomicher M, Strauch J, Chatzitomaris A, Klein HH, Mugge A, Kohrle J, Rijntjes E, Lehmphul I. Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling. Eur Thyroid J. 2015 Jun;4(2):129-37. doi: 10.1159/000381543. Epub 2015 May 23.
citation: Dietrich JW, Landgrafe-Mende G, Wiora E, Chatzitomaris A, Klein HH, Midgley JE, Hoermann R. Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. Front Endocrinol (Lausanne). 2016 Jun 9;7:57. doi: 10.3389/fendo.2016.00057. eCollection 2016.
citation: Chatzitomaris A, Hoermann R, Midgley JE, Hering S, Urban A, Dietrich B, Abood A, Klein HH, Dietrich JW. Thyroid Allostasis-Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. Front Endocrinol (Lausanne). 2017 Jul 20;8:163. doi: 10.3389/fendo.2017.00163. eCollection 2017.
citation: Dietrich JW, Midgley JEM, Hoermann R. Editorial: "Homeostasis and Allostasis of Thyroid Function". Front Endocrinol (Lausanne). 2018 Jun 5;9:287. doi: 10.3389/fendo.2018.00287. eCollection 2018. No abstract available.
citation: Aweimer A, El-Battrawy I, Akin I, Borggrefe M, Mugge A, Patsalis PC, Urban A, Kummer M, Vasileva S, Stachon A, Hering S, Dietrich JW. Abnormal thyroid function is common in takotsubo syndrome and depends on two distinct mechanisms: results of a multicentre observational study. J Intern Med. 2021 May;289(5):675-687. doi: 10.1111/joim.13189. Epub 2020 Nov 12.