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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04392258
Other study ID # 19-6678-BR
Secondary ID U1111-1251-7468D
Status Recruiting
Phase
First received
Last updated
Start date May 1, 2021
Est. completion date December 31, 2022

Study information

Verified date August 2021
Source Ruhr University of Bochum
Contact Johannes W Dietrich, M.D.
Phone +49-234-302
Email johannes.dietrich@ruhr-uni-bochum.de
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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.


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 200
Est. completion date December 31, 2022
Est. primary completion date June 1, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Intervention

Diagnostic Test:
TSH determination
Determination of serum concentration of thyrotropin (TSH)
FT4 determination
Determination of serum free thyroxine (FT4) concentration
FT3 determination
Determination of serum free triiodothyronine (FT3) concentration
SPINA-GT
Calculation of thyroid's secretory capacity (SPINA-GT)
SPINA-GD
Calculation of total deiodinase activity (SPINA-GD)

Locations

Country Name City State
Germany Medizinische Klinik I, Universitätsklinikum Bergmannsheil, Ruhr-Universität Bochum Bochum NRW

Sponsors (1)

Lead Sponsor Collaborator
Ruhr University of Bochum

Country where clinical trial is conducted

Germany, 

References & Publications (7)

Aweimer A, El-Battrawy I, Akin I, Borggrefe M, Mügge 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. — View 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. Review. — View 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. — View 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. — View Citation

Dietrich JW, Müller P, Schiedat F, Schlömicher M, Strauch J, Chatzitomaris A, Klein HH, Mügge A, Köhrle 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. — View 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. — View Citation

Müller P, Dietrich JW, Lin T, Bejinariu A, Binnebößel S, Bergen F, Schmidt J, Müller 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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary TSH response Changes in TSH concentration after CPR compared to the value after 24 hours three hours
Secondary Prognosis Mortality dependent on pituitary thyrotropic partial function Through study completion, an average of 1 year
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