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

Study Overview
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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.

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

Conditions
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Heart Arrest, Ventricular Fibrillation, Ventricular Flutter, Ventricular Tachycardia

Intervention / Treatment
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* Diagnostic Test: TSH determination
* Diagnostic Test: FT4 determination
* Diagnostic Test: FT3 determination
* Diagnostic Test: SPINA-GT
* Diagnostic Test: SPINA-GD


Participation Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Status post resuscitation<br>Patients or dataset that underwent resuscitation | Diagnostic Test: TSH determination<br>* Determination of serum concentration of thyrotropin (TSH)<br>* Other names: serum thyrotropin determination;Diagnostic Test: FT4 determination<br>* Determination of serum free thyroxine (FT4) concentration<br>* Other names: serum free T4 determination;Diagnostic Test: FT3 determination<br>* Determination of serum free triiodothyronine (FT3) concentration<br>* Other names: serum free T3 determination;Diagnostic Test: SPINA-GT<br>* Calculation of thyroid's secretory capacity (SPINA-GT)<br>* Other names: thyroid's incretory capacity;Diagnostic Test: SPINA-GD<br>* Calculation of total deiodinase activity (SPINA-GD)<br>* Other names: deiodination capacity;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TSH response | Changes in TSH concentration after CPR compared to the value after 24 hours | three hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prognosis | Mortality dependent on pituitary thyrotropic partial function | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allostatic load, critical illness, TACITUS, thyroid, homeostasis, allostasis, resuscitation, NTIS, Circulatory arrest