Clinical trial NCT01501110: Effects of N-acetylcysteine on Low T3 Syndrome
Official title: Evaluation of the Effects of N-acetylcysteine on Thyroid Hormone Levels in the Low T3 Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Myocardial Infarction
Euthyroid Sick Syndrome
Ischemic Heart Disease
Keywords: Euthyroid Sick Syndrome
low T3 syndrome
deiodases
oxidative stress
ischemic heart disease
Lead sponsor: Federal University of Rio Grande do Sul
Sponsor class: OTHER
Collaborators: name: Hospital de Clinicas de Porto Alegre
name: Programa de pós-graduação em endocrinologia
First posted: 2011-12-29
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Serum T3 Levels at 48 Hours
timeFrame: 48 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande do Sul
city: Porto Alegre
country: Brazil
facility: Instituto de Cardiologia
state: Rio Grande do Sul
Study officials:
affiliation: Federal University of Rio Grande do Sul
name: Josi Vidart
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal University of Rio Grande do Sul
name: Ana maia
role: STUDY_DIRECTOR
References:
citation: Wajner SM, Goemann IM, Bueno AL, Larsen PR, Maia AL. IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells. J Clin Invest. 2011 May;121(5):1834-45. doi: 10.1172/JCI44678. Epub 2011 Apr 11.
citation: Boelen A, Kwakkel J, Fliers E. Beyond low plasma T3: local thyroid hormone metabolism during inflammation and infection. Endocr Rev. 2011 Oct;32(5):670-93. doi: 10.1210/er.2011-0007. Epub 2011 Jul 26.
citation: Maia AL, Goemann IM, Meyer EL, Wajner SM. Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease. J Endocrinol. 2011 Jun;209(3):283-97. doi: 10.1530/JOE-10-0481. Epub 2011 Mar 17.
citation: Bello G, Pennisi MA, Montini L, Silva S, Maviglia R, Cavallaro F, Bianchi A, De Marinis L, Antonelli M. Nonthyroidal illness syndrome and prolonged mechanical ventilation in patients admitted to the ICU. Chest. 2009 Jun;135(6):1448-1454. doi: 10.1378/chest.08-1816. Epub 2009 Mar 2.
citation: Koenig RJ. Modeling the nonthyroidal illness syndrome. Curr Opin Endocrinol Diabetes Obes. 2008 Oct;15(5):466-9. doi: 10.1097/MED.0b013e32830eb838.
citation: Vidart J, Wajner SM, Leite RS, Manica A, Schaan BD, Larsen PR, Maia AL. N-acetylcysteine administration prevents nonthyroidal illness syndrome in patients with acute myocardial infarction: a randomized clinical trial. J Clin Endocrinol Metab. 2014 Dec;99(12):4537-45. doi: 10.1210/jc.2014-2192.