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Eur J Cardiothorac Surg 2002;22:879-884
© 2002 Elsevier Science NL

Thyroid hormones levels in infants during and after cardiopulmonary bypass with ultrafiltration

R. Bartkowskia*, M. Wojtalika, E. Kormanb, G. Sharmaa, J. Henschkea, W. Mrówczynskia

a Department of Pediatric Cardiac Surgery, K. Marcinkowski University School of Medicine, ul. Fredry 10, 61-701 Poznan, Poland
b Department of Pediatric Endocrinology and Diabetes, K. Marcinkowski University School of Medicine, ul. Fredry 10, 61-701 Poznan, Poland

Received 10 September 2001; received in revised form 5 September 2002; accepted 9 September 2002.

* Corresponding author. ul. Grunwaldzka 167A/29 60-323 Poznan, Poland. Tel.: +48-61-8600-235
e-mail: rbart{at}mp.pl


   Abstract
Top
 Abstract
1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 References
 
Objective: The aim of this study was to find out if infants after cardiopulmonary bypass develop non-thyroidal illness and if illness severity after cardiopulmonary bypass depends on hormone concentration in ultrafiltrate. Methods: Thyroid hormone status was assessed in 20 infants with congenital heart defects undergoing cardiac surgery (age range 7 days–11 months). Blood samples were collected preoperatively, during cardiopulmonary bypass, after cardiopulmonary bypass, and also postoperatively in 1, 2, 3, and 8 day after cardiac surgery. Plasma thyrotropin, thyroxine, free thyroxine, triiodothyronine, free triiodothyronine and reverse triiodothyronine were measured in blood samples and also in ultrafiltrate. Results: All patients had reduction in serum thyrotropin, thyroxine, free thyroxine, triiodothyronine, free triiodothyronine, and elevation of reverse triiodothyronine after cardiac surgery. In all patients we performed ultrafiltration. Patients were divided in to two groups. (with and without prolonged recovery). In the group of patients with prolonged recovery we noticed significantly higher amount of triiodothyronine per kilogram body weight. One of these patients died. The average level of total thyroxine decreased from the level 126 nmol/l before bypass to the minimal level 73 nmol/l after bypass, free thyroxine from the level 18 pmol/l before bypass to the minimal level 12 pmol/l after bypass. The average level of total triiodothyronine decreased from the level 1.54 nmol/l before bypass to the minimal level 0.42 nmol/l after bypass, free triiodothyronine from the level 6.12 pmol/l before bypass to the minimal level 3.21 pmol/l after bypass. The average level of TSH decreased from the level 4.31 mU/l before bypass to the level 0.64 mU/l after bypass. The average level of reverse-triiodothyronine increase from the level 0.83 nmol/l before bypass to the maximal level 1.94 nmol/l after bypass. Conclusions: We conclude that non-thyroidal illness occurs in all infants after cardiopulmonary bypass. The amount of free triiodothyronine that is filtrated during cardiopulmonary bypass may influence postoperative recovery.

Key Words: Thyroid hormone • Congenital • Cardiopulmonary bypass


   1. Introduction
Top
 Abstract
 1. Introduction
2. Material and methods
 3. Results
 4. Discussion
 References
 
Alterations in serum concentrations of total and free triiodothyronine, total and free thyroxine, reverse-triiodothyronine and thyroid-stimulating hormone occur in patients with non-thyroidal illnesses [1]. Usually in non-thyroidal illness low plasma triiodothyronine is noticed, but in more severe illness also low plasma thyroxine is noticed. These abnormalities result from variable, usually reversible, disturbances in the hypothalamo-pituitary-thyroid axis, thyroid hormone binding to serum proteins, tissue uptake of thyroid hormones and thyroid hormone metabolism These changes are caused by the trauma of the surgery, extracorporeal circulation, hypothermia, hemodilution, heparine, and probably by ultrafiltration [2–4]. The mechanism of low total triiodothyronine and high reverse-triiodothyronine is well understood. It is caused by changes in peripheral monodeiodination. The level of 5-monodeiodinase is elevated, and the level of 5'-monodeiodinase is lower than in normal state. That is why monodeiodination from thyroxine to triiodothyronine is lowered, and monodeiodination from thyroxine to reverse-triiodothyronine is elevated. The mechanism of low thyroxine and low thyroid stimulating hormone is connected with alterations in hypothalamo-pituitary-thyroid axis [5]. Some have postulated that these changes represent an adaptive response of the individual to minimize metabolic demands during the stress of non-thyroidal illness. An alternative view is that these changes in thyroid hormone metabolism may contribute to illness rather than result from it.

Alterations in pituitary-thyroid axis play crucial role in non-thyroidal illness, but the mechanism of these changes is only partially understood [9]. Chopra et al. [10] postulated that inhibitors circulating in patients with non-thyroidal illness caused decreased binding of thyroxine to proteins. These changes may be caused by tumor necrosis factor [11] and cytokines such as interleukin-6, which are released during cardiopulmonary bypass [12,13].

Hypothyroidism results in decreased cardiac output as a consequence of diminished heart rate, stroke volume and contractility. And these changes can be dangerous for patients just after cardiopulmonary bypass. Triiodothyronine is an inotropic agent, which can support catecholamines after cardiac surgery. Novitzky et al. proved, that impact of triiodothyronine can support heart function after ischemia and cardiopulmonary bypass [19–21]. Some authors suggest that decreased level of thyroid hormones in non-thyroidal illnesses lowered tissue metabolism, and it is a kind of beneficial adaptation [22,23]. They also suggest that changes in the level of illness severity precede, but do not follow, thyroid alterations in critically ill children [9,14].

The level of dialyzable free triiodothyronine and thyroxine is elevated during cardiopulmonary bypass. Their level after surgery may be influenced by ultrafiltration. Which is used during pediatric bypass to reduce capillary leak and the accumulation of extravascular water associated with bypass [6–8].

The aim of this study was to find out if infants after cardiopulmonary bypass develop non-thyroidal illness and if there is any correlation between recovery after cardiopulmonary bypass and hormone concentration in ultrafiltrate.


   2. Material and methods
Top
 Abstract
 1. Introduction
 2. Material and methods
3. Results
 4. Discussion
 References
 
Thyroid hormone status was assessed in 20 infants (age 7 days–11 months) with congenital heart defect undergoing cardiac surgery between 1998 and 1999 in Department of Pediatric Cardiac Surgery K. Marcinkowski University School of Medicine. Ethics Committee of The K. Marcinkowski University School of Medicine approved this study.

The main clinical data for the patients are summarized in Table 1.


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  		Table 1. The main clinical data for the patients

 
All patients were euthyroid before surgery and were given no drugs that could have influenced thyroid hormone tests. Blood samples were collected:

Plasma thyrotropin, total thyroxine, free thyroxine, total triiodothyronine, free triiodothyronine and reverse-triiodothyronine were measured in blood samples and in ultrafiltrate. Serum was separated from blood by centrifugation and stored at -20 °C until assayed. Serum concentrations of hormones were measured by radioimmunoassays. Plasma thyrotropin were measured by hTSH(125I) SPECTRIA, radioimmunometric method IRMA, produced by ‘Polatom-Swierk’, Poland. Total thyroxine were measured by T4-RIA-PROP MJ-110/F produced by ‘Polatom-Swierk’, Poland. Free thyroxine were measured by FT4 (125I) SPECTRIA produced by ‘Polatom-Swierk’, Poland. Total triiodothyronine were measured by T3-RIA-PROP MJ-109/F produced by ‘Polatom-Swierk’, Poland. Free triiodothyronine were measured by FT3-RIA-CT produced by ‘Polatom-Swierk’, Poland. Reverse triiodothyronine: (REVERSE T3) produced by ‘BioChem ImmunoSystems’

Data were analyzed by two-tailed paired Student's t-test, by Shapiro–Wilk W-test, and than by non-parametric Mann–Whitney U-test (comparing each time value by means of a 0.05 level for significance).


   3. Results
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
4. Discussion
 References
 
All patients demonstrated reduction in serum thyrotropin, total and free thyroxine, total and free triiodothyronine, and elevation of reverse triiodothyronine after cardiac surgery. Two patients died

The average level of total thyroxine (Fig. 1) decreased in the beginning of cardiopulmonary bypass from the level 127 nmol/l before bypass, to 65 nmol/l during bypass (difference is statistically significant P<0.05), and then increased to 111 nmol/l after bypass (difference is statistically significant P<0.05). The average level of thyroxine decreased in the day 0 (100 nmol/l), 1 (76 nmol/l), and 2 (74 nmol/l). We noticed increasing in 8th day 131 nmol/l) (difference is statistically significant (P<0.05) between level in day 2 and 8, but there is no significance between level after bypass and day 0, and between day 1 and 2).



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  		Fig. 1. The level of total thyroxine (T4), total triiodothyronine (T3) and reverse triiodothyronine.

 
The average level of free thyroxine (Fig. 2) did not change significantly in the beginning of cardiopulmonary bypass from the level 18 pmol/l before bypass, to 18 pmol/l during bypass (difference is not statistically significant), and then increased to 19 pmol/l after bypass (difference is not statistically significant). The average level of free thyroxine decreased in the day 0 (17 pmol/l), day 1 (13 pmol/l), and day 2 (13 pmol/l). We noticed increasing in 8th day (19 pmol/l) (differences are statistically significant (P<0.05) between level in day 0 and 1, and between levels in day 2 and 8, but there is no significance between level in day 1 and 2).



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  		Fig. 2. The level of free thyroxine (fT4) and free triiodothyronine (fT3).

 
The average level of total triiodothyronine (Fig. 1) decreased in the beginning of cardiopulmonary bypass from the level 1.54 nmol/l before bypass, to 0.84 nmol/l during bypass (difference is statistically significant P<0.05), and then increased to 1.25 nmol/l after bypass (difference is statistically significant P<0.05). The average level of triiodothyronine decreased in the day 0 (0.81 nmol/l), and in day 1 (0.42 nmol/l) (differences are statistically significant P<0.05). We noticed increasing in 2nd (0.48 nmol/l) and 8th day (1.31 nmol/l) (differences are statistically significant (P<0.05) between level in day 2 and 8, but there is no significance between level in day 1 and 2).

The average level of free triiodothyronine (Fig. 2) increased in the beginning of cardiopulmonary bypass from the level 6.12 pmol/l before bypass, to 7.02 pmol/l during bypass (difference is statistically significant P<0.05), and then slightly increased to 7.06 pmol/l after bypass (difference is not statistically significant). The average level of free triiodothyronine decreased in the day 0 (5.27 pmol/l), day 1 (3.23 pmol/l), and day 2 (3.21 pmol/l). We noticed increasing in 8th day (5.8 pmol/l) (differences are statistically significant (P<0.05) between level in day 0 and 1, and between levels in day 2 and 8, but there is no significance between level in day 1 and 2).

The average level of TSH (Fig. 3) decreased in the beginning of cardiopulmonary bypass from the level 4.31 mU/l before bypass, to 1.46 mU/l during bypass (difference is statistically significant P<0.05), and then increased to 2.43 mU/l after bypass (difference is statistically significant P<0.05). The average level of TSH decreased in the day 0 (0.64 mU/l), and in the day 1 we noticed increasing (0.67 mU/l) which was not statistically significant. We noticed statistically significant increasing in 2nd day (1.87 mU/l) and in 8th day (3.65 mU/l) (P<0.05).



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  		Fig. 3. The level of TSH.

 
The average level of reverse-triiodothyronine (Fig. 1) decreased in the beginning of cardiopulmonary bypass from the level 0.83 nmol/l before bypass, to 0.47 pmol/l during bypass, and to 0.83 pmol/l after bypass (differences are statistically significant P<0.05), and then increased to 1.7 pmol/l in day 0 (difference is statistically significant (P<0.05) and than increased in the 1st day to 1.92 pmol/l (difference is not statistically significant). The average level of reverse-triiodothyronine decreased significantly in the 2nd (1.4 pmol/l) and in the 8th day (0.87 pmol/l), (differences are statistically significant P<0.05).

In all patients we performed ultrafiltration. Patients were divided in to two groups. (with and without prolonged recovery). In the group of patients with prolonged recovery we noticed significantly (P<0.05) higher amount of triiodothyronine per kilogram body weight (0.027 pg) (Fig. 4) . In group of patients without prolonged recovery the average amount of free triiodothyronine in ultrafiltrate was 0.003 pg.



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  		Fig. 4. The average amount of triiodothyronine in ultrafiltrate (in patients with or without intensive care treatment).

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
References
 
All patients demonstrated significant reduction in serum thyrotropin, total and free thyroxine, total and free triiodothyronine, and elevation of reverse triiodothyronine after cardiac surgery. These changes are connected with non-thyroidal illness.

We have noticed the relationships between serum TSH, total triiodothyronine, total thyroxine and reverse triiodothyronine changes during recovery from severe hypothyroxinemia after cardiopulmonary bypass. We found, that levels of all hormones increased during recovery, but the rise of TSH preceded the rise of the other hormones. It may suggest, that cardiopulmonary bypass suppresses TSH release. It means that alterations in pituitary-thyroid axis play also important role in non-thyroidal illness.

Thyroxine, and triiodothyronine are the hormones, which are secreted by the thyroid gland, but thyroxine is also converted into triiodothyronine in the peripheral tissues. It is known that level of 5-monodeiodinase is elevated, and the level of 5'-monodeiodinase is lowered in non-thyroidal illness. That is why monodeiodination from thyroxine to triiodothyronine is lowered, and monodeiodination from thyroxine to reverse-triiodothyronine, which is biologically inactive, is elevated. We observed it after bypass. When the level of triiodothyronine was low, the level of reverse triiodothyronine was high. The rapid decrease of triiodothyronine, and slow decrease of thyroxine were not beneficial. Triiodothyronine, which suppresses releasing of TSH, is converted in the pituitary gland from thyroxine [14]. Higher level of thyroxine causes lower level of TSH and, as a consequence, lower level of triiodothyronine.

Alterations, which we noticed during bypass (decreased level of total thyroxine, total triiodothyronine, reverse triiodothyronine, TSH, only small decrease of free thyroxine and increase of free triiodothyronine), are connected with heparinization and hemodilution. Elevated level of free thyroxine and free triiodothyronine comparing to lower levels of other hormones, are connected with heparinization, which causes impaired serum protein binding of thyroid hormones [15–18]. These hormones are dialyzable and were found in ultrafiltrate.

It is obvious that proper thyroid function is very important for cardiovascular system. Hypothyroidism could be dangerous especially just after cardiopulmonary bypass. Hypothyroidism can causes decreased heart rate, output, contractility and increased systemic vascular resistance. In patients, who lose higher amount of triiodothyronine we noticed prolonged recovery after cardiopulmonary bypass. It means that triiodothyronine replacement therapy may be beneficial.

We conclude that non-thyroidal illness occurs in all infants after cardiopulmonary bypass.

The amount of free triiodothyronine that is filtrated during cardiopulmonary bypass may influence postoperative recovery.


   Footnotes
 
Presented at the joint 15th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 9th Annual Meeting of the European Society of Thoracic Surgeons, Lisbon, Portugal, September 16–19, 2001.


   References
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 References
 

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