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

• Conditions: Ventricular Fibrillation; Ventricular Flutter; Ventricular Tachycardia; Heart Arrest
• Interventions: Diagnostic Test: TSH determination; Diagnostic Test: FT4 determination; Diagnostic Test: FT3 determination; Diagnostic Test: SPINA-GT; Diagnostic Test: SPINA-GD

• Registration Number: NCT04392258
• Lead Sponsor: Ruhr University of Bochum

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2020-05-07
• Study First Submitted QC: 2020-05-12
• Study First Posted: 2020-05-18
• Study Start: 2021-05-01
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-13
• Last Update Posted: 2021-08-19
• Primary Completion: 2022-06-01
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

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

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Status post resuscitation	TSH determination	Patients or dataset that underwent resuscitation
Status post resuscitation	SPINA-GT	Patients or dataset that underwent resuscitation
Status post resuscitation	SPINA-GD	Patients or dataset that underwent resuscitation
Status post resuscitation	FT4 determination	Patients or dataset that underwent resuscitation
Status post resuscitation	FT3 determination	Patients or dataset that underwent resuscitation

Primary Outcome Measures

Name	Time	Method
TSH response	three hours	Changes in TSH concentration after CPR compared to the value after 24 hours

Secondary Outcome Measures

Name	Time	Method
Prognosis	Through study completion, an average of 1 year	Mortality dependent on pituitary thyrotropic partial function

Trial Locations

Locations (1)

Medizinische Klinik I, Universitätsklinikum Bergmannsheil, Ruhr-Universität Bochum; 🇩🇪 Bochum, NRW, Germany