Acute Myocardial Infarction, Euthyroid Sick Syndrome, Ischemic Heart Disease
Conditions
Keywords
Euthyroid Sick Syndrome, low T3 syndrome, deiodases, oxidative stress, ischemic heart disease
Brief summary
The propose of this study is to determine whether N-acetylcysteine is effective in reversing the changes in thyroid hormones seen in critical illness, known as the low T3 syndrome.
Detailed description
The low T3 syndrome or nonthyroidal illness is characterized by low levels of T3, normal or high normal levels of rT3, low or normal levels of T4 and inappropriately normal or low levels of TSH. These changes affect up to 75% of patients and have prognostic implications. Interleukin-6 (IL6) seems to have a causative role in the pathogenesis of nonthyroidal illness. There is evidence that the reduction in serum T3 was inversely associated with serum IL-6, while the rT3 have a positive association. The mechanism of action of cytokines on the metabolism of thyroid hormones has not been determined and the potential role of cytokines on the deiodases has been the focus of research. In a cell culture model study, IL-6 was able to suppress the conversion of T4 to T3 by deiodases type 1 and 2 and stimulate the inactivation of T3 by deiodase type 3, a situation similar to nonthyroidal illness. The use of N-acetylcysteine prevented this alterations, been consistent with the hypothesis that IL6 inhibits the function of the deiodases by increasing the oxygen reactive species and by consuming gluthathione or some gluthathione dependent cofactor. Considering the absence of human studies evaluating the use of N-acetylcysteine in nonthyroidal illness, the aim of this study is to investigate whether NAC has in vivo effect on changes of thyroid hormones.
Interventions
DRUGN-acetylcysteine
in infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours
Sponsors
Hospital de Clinicas de Porto Alegre
Programa de pós-graduação em endocrinologia
Federal University of Rio Grande do Sul
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* diagnosis of acute myocardial infarction with less than 12 hours of evolution * reperfusion therapy (primary angioplasty)
Exclusion criteria
* Thyroid disease * Chronic renal disease with renal replacement therapy * hepatic insufficiency * immunosuppression
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Serum T3 Levels at 48 Hours | 48 hours |
Countries
Brazil
Participant flow
Recruitment details
Consecutive patients with a diagnosis of acute myocardial infarction within 12 hours of evolution who underwent primary percutaneous coronary intervention and were admitted to the emergency and intensive care units of two tertiary hospitals in southern Brazil were recruited.
Pre-assignment details
From the 83 patients enrolled, 15 met one of the following pre-established exclusion criteria: age younger than 18 or older than 80 yrs; primary thyroid disease; use of corticosteroids; chronic renal failure; severe hepatic insufficiency; severe immunosuppression; pregnant women or women undergoing postmenopausal hormone replacement.
Participants by arm
| Arm | Count |
|---|---|
| N-acetylcysteine intra-venous infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours.
N-acetylcysteine: in infusion of 1200 mg of n-acetylcysteine twice a day for 48 hours | 34 |
| no Intervention No intervention / usual care | 33 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
Baseline characteristics
| Characteristic | Total | no Intervention | N-acetylcysteine |
|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 9 | 57.4 years STANDARD_DEVIATION 8.4 | 56.9 years STANDARD_DEVIATION 9.4 |
| FT4 | 1.1 ng/dL STANDARD_DEVIATION 0.2 | 1.1 ng/dL STANDARD_DEVIATION 0.3 | 1.1 ng/dL STANDARD_DEVIATION 0.2 |
| Region of Enrollment Brazil | 67 participants | 33 participants | 34 participants |
| rT3 | 55 ng/dL STANDARD_DEVIATION 7.1 | 55.2 ng/dL STANDARD_DEVIATION 6.1 | 54.7 ng/dL STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 16 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Male | 51 Participants | 24 Participants | 27 Participants |
| T3 | 99.3 ng/dL STANDARD_DEVIATION 17.4 | 98.7 ng/dL STANDARD_DEVIATION 20.7 | 100.4 ng/dL STANDARD_DEVIATION 16.5 |
| T4 | 7.4 mcg/dL STANDARD_DEVIATION 1.5 | 7.4 mcg/dL STANDARD_DEVIATION 1.4 | 7.4 mcg/dL STANDARD_DEVIATION 1.9 |
| TSH | 1.6 mcIU/mL STANDARD_DEVIATION 1.2 | 1.6 mcIU/mL STANDARD_DEVIATION 1.1 | 1.7 mcIU/mL STANDARD_DEVIATION 1.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 34 | 0 / 33 |
| serious Total, serious adverse events | 0 / 34 | 0 / 33 |
Outcome results
Primary
Serum T3 Levels at 48 Hours
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Serum T3 Levels at 48 Hours | 93.5 ng/dL | Standard Deviation 20.1 |
| no Intervention | Serum T3 Levels at 48 Hours | 96.5 ng/dL | Standard Deviation 20.2 |