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

NCT04392258 | Unknown

• 3 other identifiers: 19-6678-BRU1111-1251-7468DRKS00021695
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Arrest; Ventricular Fibrillation; Ventricular Flutter; Ventricular Tachycardia

Keywords

thyroid; homeostasis; allostasis; resuscitation; allostatic load; critical illness; TACITUS; NTIS; Circulatory arrest

Outcome Measures

Primary Outcomes (1)

• TSH response

  Changes in TSH concentration after CPR compared to the value after 24 hours

  three hours

Secondary Outcomes (1)

• Prognosis

  Through study completion, an average of 1 year

Study Arms (1)

Status post resuscitation

Patients or dataset that underwent resuscitation

Diagnostic Test: TSH determination; Diagnostic Test: FT4 determination; Diagnostic Test: FT3 determination; Diagnostic Test: SPINA-GT; Diagnostic Test: SPINA-GD

Interventions

TSH determination DIAGNOSTIC_TEST

Determination of serum concentration of thyrotropin (TSH)

Also known as: serum thyrotropin determination

Status post resuscitation

FT4 determination DIAGNOSTIC_TEST

Determination of serum free thyroxine (FT4) concentration

Also known as: serum free T4 determination

Status post resuscitation

FT3 determination DIAGNOSTIC_TEST

Determination of serum free triiodothyronine (FT3) concentration

Also known as: serum free T3 determination

Status post resuscitation

SPINA-GT DIAGNOSTIC_TEST

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

Also known as: GT, Thyroid's secretory capacity, LOINC 82368-2, thyroid's incretory capacity

Status post resuscitation

SPINA-GD DIAGNOSTIC_TEST

Calculation of total deiodinase activity (SPINA-GD)

Also known as: GD, Sum activity of peripheral deiodinases, LOINC 82367-4, deiodination capacity

Status post resuscitation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

De-identified datasets (protocol A) or patients (protocol B) admitted to an intensive care unit after cardiopulmonary resuscitation (CPR)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruhr University of Bochum: lead

Study Sites (1)

Medizinische Klinik I, Universitätsklinikum Bergmannsheil, Ruhr-Universität Bochum

Bochum, North Rhine-Westphalia, D-44789, Germany

RECRUITING

Related Publications (7)

• 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.

  PMID: 18851740 BACKGROUND

• 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.

  PMID: 23365787 BACKGROUND

• 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.

  PMID: 26279999 BACKGROUND

• 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.

  PMID: 27375554 BACKGROUND

• 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.

  PMID: 28775711 BACKGROUND

• 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.

  PMID: 32087999 BACKGROUND

• 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.

  PMID: 33179374 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum aliquots are stored for postponed determination of non-classical thyroid hormones including but not limited to thyronamines, 3,5-diiodothyronine (3,5-T2) and reverse T3 (rT3).

MeSH Terms

Conditions

Heart Arrest; Ventricular Fibrillation; Ventricular Flutter; Tachycardia, Ventricular; Thyroid Diseases; Critical Illness

Interventions

Thyroid Function Tests

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Tachycardia; Cardiac Conduction System Disease; Endocrine System Diseases; Disease Attributes

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Endocrine; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Johannes W Dietrich, M.D.

  Bergmannsheil University Hospitals

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Johannes W Dietrich, M.D.

CONTACT

+49-234-302; johannes.dietrich@ruhr-uni-bochum.de

Christine Sievers

CONTACT

+49-234-302; christine.sievers@bergmannsheil.de

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant endocrinologist

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: May 18, 2020
• Study Start: May 1, 2021
• Primary Completion: June 1, 2022
• Study Completion: December 31, 2022
• Last Updated: August 19, 2021

Record last verified: 2021-08

Locations

DE (1)