Observational and Diagnostical Study on Transient Allostatic Responses of Thyroid Function After Cardiopulmonary Resuscitation

NCT ID: NCT04392258

Last Updated: 2021-08-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-05-01

Study Completion Date

2022-12-31

Brief Summary

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Time-limited adaptive responses of thyroid function are common in the critically ill. About 70% of all patients treated on intensive care units develop a so-called non-thyroidal illness syndrome (NTIS) or TACITUS (thyroid allostasis in critical illness, tumours, uraemia and starvation), which is marked by low serum concentrations of the thyroid hormone T3 and other adaptive reactions of thyroid homeostasis. Occasionally, temporarily elevated concentrations of thyrotropin (TSH) and peripheral thyroid hormones are to be observed, especially after cardiopulmonary resuscitation (CPR). However, the available evidence is limited, although abnormal concentrations of thyroid hormones after CPR have occasionally been reported.

Aim of the planned study is to investigate the thyrotropic (i.e. thyroid-controlling) partial function of the anterior pituitary lobe immediately after CPR. It is intended to evaluate statistical measures of TSH concentration and peripheral thyroid hormones in de-identified datasets (protocol A). Additionally, a prospective sub-study (protocol B) aims at a more precise description of pituitary and thyroid responses by means of serial investigations in routine serum samples, both immediately after CPR and during the course of ongoing treatment. This includes the evaluation of additional possible predictors, too.

Primary endpoint of the study is changed TSH concentration immediately after CPR compared to the TSH value 24 hours later. Secondary endpoint is the relation between thyroid-controlling pituitary function and mortality.

A high proportion of patients undergoing CPR will eventually receive iodinated radiocontrast media (e.g. for computed tomography or coronary angiography). This is one of the reasons why early identifying subjects at high risk for possible iodine-induced thyrotoxicosis is important. Increased oxygen consumption of the heart in hyperthyroidism is one of the reasons for high mortality in thyrotoxicosis. Therefore, accurate diagnosis of alterations in the hypothalamus-pituitary-thyroid (HPT) axis is of paramount importance.

Detailed Description

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Transient allostatic responses of thyroid function are common in the critically ill. About 70% of all patients treated on intensive care units develop a so-called non-thyroidal illness syndrome (NTIS) or TACITUS (thyroid allostasis in critical illness, tumours, uraemia and starvation), which is marked by low serum concentrations of the thyroid hormone T3 and other adaptive reactions of thyroid homeostasis. Occasionally, temporarily elevated concentrations of thyrotropin (TSH) and peripheral thyroid hormones are to be observed, especially after cardio-pulmonary resuscitation (CPR). However, the available evidence is limited, although abnormal concentrations of thyroid hormones after CPR have been reported.

Aim of the planned study is to investigate the thyrotropic partial function of the anterior pituitary lobe immediately after CPR. It is intended to evaluate statistical moments of TSH concentration and peripheral thyroid hormones in de-identified datasets (protocol A). Additionally, a prospective substudy (protocol B) aims at a more precise description of pituitary and thyroid responses by means of serial investigations in routine serum samples, both immediately after CPR and during the course of ongoing in-patient treatment. This also includes the evaluation of additional possible predictors.

Primary endpoint of the study are changed TSH concentrations immediately after CPR compared to the value 24 hours later. Secondary endpoint is the relation between thyrotropic pituitary function and mortality.

A high proportion of patients undergoing CPR will eventually receive iodinated radiocontrast media (e.g. for computed tomography or coronary angiography). This is one of the reasons why early identifying subjects at high risk for possible iodine-induced thyrotoxicosis is important. Increases oxygen consumption of myocardial tissue in hyperthyroidism is one of the reasons for high mortality in thyrotoxicosis. Therefore, accurate diagnosis of alterations in the hypothalamus-pituitary-thyroid (HPT) axis is of paramount importance.

Conditions

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Heart Arrest Ventricular Fibrillation Ventricular Flutter Ventricular Tachycardia

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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Status post resuscitation

Patients or dataset that underwent resuscitation

TSH determination

Intervention Type DIAGNOSTIC_TEST

Determination of serum concentration of thyrotropin (TSH)

FT4 determination

Intervention Type DIAGNOSTIC_TEST

Determination of serum free thyroxine (FT4) concentration

FT3 determination

Intervention Type DIAGNOSTIC_TEST

Determination of serum free triiodothyronine (FT3) concentration

SPINA-GT

Intervention Type DIAGNOSTIC_TEST

Calculation of thyroid's secretory capacity (SPINA-GT)

SPINA-GD

Intervention Type DIAGNOSTIC_TEST

Calculation of total deiodinase activity (SPINA-GD)

Interventions

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TSH determination

Determination of serum concentration of thyrotropin (TSH)

Intervention Type DIAGNOSTIC_TEST

FT4 determination

Determination of serum free thyroxine (FT4) concentration

Intervention Type DIAGNOSTIC_TEST

FT3 determination

Determination of serum free triiodothyronine (FT3) concentration

Intervention Type DIAGNOSTIC_TEST

SPINA-GT

Calculation of thyroid's secretory capacity (SPINA-GT)

Intervention Type DIAGNOSTIC_TEST

SPINA-GD

Calculation of total deiodinase activity (SPINA-GD)

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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serum thyrotropin determination serum free T4 determination serum free T3 determination GT Thyroid's secretory capacity LOINC 82368-2 thyroid's incretory capacity GD Sum activity of peripheral deiodinases LOINC 82367-4 deiodination capacity

Eligibility Criteria

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Inclusion Criteria

* Admission after cardiopulmonary resuscitation
* Minimum age of 18 years
* Results of TSH and peripheral thyroid hormone concentrations already available or possibility to reorder these investigations in a post-hoc manner if consent has been obtained (i. e. time interval after venipuncture within the storage period of the central laboratory)
* Inclusion after own consent of the patient after reawakening, via custodian or independent consultant.

Exclusion Criteria

* Missing data on thyroid homeostasis in the first blood specimen (obtained before 3 hours after admission)
* Traumatic brain injury
* Persistent hints for thyroid dysfunction, not explained by non-thyroidal illness syndrome (NTIS) / euthyroid sick syndrome (ESS) / thyroid allostasis in critical illness, tumors, uremia and starvation (TACITUS) in consecutive investigations over several days after resuscitation
* Functionally relevant thyroid or pituitary disorder, as documented in international classification of diseases (ICD) codes.
* Exposure to radiocontrast agents less than 3 months ago
* Therapy with amiodarone (currently or during the previous 3 years)
* Pregnancy
* Known thyroid disease
* Consent not obtained within the routine storage period of the central laboratory
* Post-hoc-exclusion if evidence for true dysfunction the the pituitary or the thyroid became available during the study period.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ruhr University of Bochum

OTHER

Sponsor Role lead

Responsible Party

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PD Dr. Johannes W. Dietrich, MD

Consultant endocrinologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Johannes W Dietrich, M.D.

Role: PRINCIPAL_INVESTIGATOR

Bergmannsheil University Hospitals

Locations

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Medizinische Klinik I, Universitätsklinikum Bergmannsheil, Ruhr-Universität Bochum

Bochum, North Rhine-Westphalia, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Johannes W Dietrich, M.D.

Role: CONTACT

+49-234-302 ext. 6400

Christine Sievers

Role: CONTACT

+49-234-302 ext. 6400

Facility Contacts

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Johannes W Dietrich, M.D.

Role: primary

+49-234-302 ext. 6400

Harald H Klein, M.D.

Role: backup

+49-234-302 ext. 6400

References

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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.

Reference Type BACKGROUND
PMID: 18851740 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23365787 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26279999 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27375554 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28775711 (View on PubMed)

Muller P, Dietrich JW, Lin T, Bejinariu A, Binnebossel S, Bergen F, Schmidt J, Muller SK, Chatzitomaris A, Kurt M, Gerguri S, Clasen L, Klein HH, Kelm M, Makimoto H. Usefulness of Serum Free Thyroxine Concentration to Predict Ventricular Arrhythmia Risk in Euthyroid Patients With Structural Heart Disease. Am J Cardiol. 2020 Apr 15;125(8):1162-1169. doi: 10.1016/j.amjcard.2020.01.019. Epub 2020 Jan 29.

Reference Type BACKGROUND
PMID: 32087999 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33179374 (View on PubMed)

Other Identifiers

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U1111-1251-7468

Identifier Type: OTHER

Identifier Source: secondary_id

DRKS00021695

Identifier Type: REGISTRY

Identifier Source: secondary_id

19-6678-BR

Identifier Type: -

Identifier Source: org_study_id

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