Evaluation of Thyroid Hormone Levels in Full-Term Neonates Presented with Septic Shock

authors found an association between altered thyroid hormone levels and septic shock in neonates and it may be of prognostic importance in septic shock treatment. This study has been conducted to find the relationship between thyroid profile and septic shock in neonates and also to compare the thyroid profile in survivor and non-survivor groups of septic shock patients. Methods: This analytical prospective cohort study was conducted in the NICU of a tertiary care teaching institution in central India. Full-term neonates with late-onset sepsis were included in this study and estimation of thyroid hormones (TSH, T3, T4, fT3, and fT4) was performed. These neonates were divided into those with and without septic shock patients and levels of thyroid hormones were correlated between these patients to find significant relations. The Vasoactive-Inotropic Score (VIS) score was calculated. Results: A total of 195 full-term neonates were included in the study. The mean value of TSH, T3, T4, fT3, and fT4 among neonates with septic shock were 5.27 µg/ml, 80.01 ng/dl, 6.36 µg/dl, 1.40 pg/ml, and 1.40 µg/dl, respectively while the values were 5.29 µg/ml, 94.4 ng/dl, 7.25 µg/dl, 1.84 pg/ml, and 1.43 µg/dl, respectively in septic neonates without shock. This difference was statistically significant except for TSH (p>0.05). The mean value of TSH, T3, T4, fT3, and fT4 among septic shock survivors were 5.27 µg/ml, 80.01 ng/dl, 6.36 µg/dl, 1.40 pg/ml, and 1.40 µg/dl and in septic shock non-survivors were 2.40 µg/ml, 37.33 ng/dl, 3.86 µg/dl, 0.99 pg/ml, and 0.84 µg/dl, respectively (p<0.0001). Only T3 was found to be significantly co-related with VIS in septic shock in all the groups (<0.001). Conclusion: Our study suggests that TSH, T3, T4, fT3, and fT4 levels are significantly low in patients suffering from the septic shock which may vary in the case of TSH. Also, there is a significant decrease in thyroid profile among septic shock non-survivors as compared to survivors. From


Introduction
Neonatal sepsis is a common disease affecting several tissues through pro-and anti-inflammatory responses in the organism [1]. It is characterized by signs and symptoms of infection with or without accompanying bacteremia in the first month of life.
The incidence of neonatal sepsis in the developing world is 10-30% and mortality is around 19% [2].
Neonates with sepsis may present in or progress to septic shock. Initially, it is characterized by cardiovascular dysfunction which eventually requires inotropic support [3]. Septic    The gestational age was assessed from the last menstrual period and the New Ballard Score.
Neonates were also divided according to the presence of shock and the outcome. The demographic information and data on the use of vasoactive drugs, duration of shock, and blood investigation reports were also collected. Relevant investigations were sent for all the neonates including hemoglobin, TLC, ANC, CRP, blood culture, electrolytes, and random blood sugar. Other investigations like chest X-ray, lumbar puncture, urine routine and microscopy, urine for fungal hyphae, urine culture, and arterial blood gas analysis were done when required. In all the included neonates, the thyroid profile was done.
The blood samples collected in the test tube were centrifuged; serum thus obtained was used to estimate T3, T4, and TSH. They were estimated by the chemiluminescence method (using the Immulite1000 Immunoassay system-Siemens) [11].
Neonates who were found to be hypothyroid were excluded from the study and treated for hypothyroidism. Levels of T3, T4, TSH, fT3, and fT4 were compared in the newborn with septic shock with those without septic shock. They were also grouped and compared as survivors and non-      [14]. There are two biologically active thyroid hormones: thyroxine (T4) and 3,5,3'triiodothyronine (T3) [15]. With increasing severity of illness, low total and free T4, and sometimes low TSH, can be observed [14,16]. respectively [11,[17][18][19].
In the present study, a maximum number of cases belonged to the category of low birth babies i.e., 1.5-2.5 Kg (67.69%). The higher prevalence of low birth babies in the study group can be explained as low birth weight is a known risk factor for the development of sepsis and shock. We found an We found that the mean levels of TSH, T3, T4, fT3, and fT4 were lower in septic shock patients than that of without septic shock and the difference was statistically significant except for TSH which is quite similar to the findings of a study done by Yildizdas D et al [21]. where they found that the levels of T3, T4, fT3, fT4 levels of children with septic shock were significantly lower than those of sepsis without shock and control. They also observed low levels of TSH in children with septic shock and children with sepsis without shock, but the difference was not significant [21]. Dutta 25]. We have tried our best to depict the relationship between thyroid hormone with septic shock among full-term neonates but despite our efforts, several limitations are present in our study.
Firstly, we have not investigated the maternal thyroid profile. The maternal thyroid status was assessed based on history and drug intake, so we couldn't assess the exact maternal thyroid status.
Lastly, a larger sample size and serial TSH monitoring are required to establish the clear prognostic significance of the thyroid profile.

Conclusion
Our study suggested a significant decrease in TSH, T3, T4, fT3, and fT4 levels in patients with septic shock as that of patients without septic shock. We also found that there is a significant decrease in thyroid profile among septic shock survivors as compared to the non-survivors and only T3 was found to be significantly co-related with VIS in septic shock among all the patients.
What does this study add to existing knowledge?
The findings of this study regarding the association between thyroid hormone abnormalities and the outcome of patients with septic shock indicated that these abnormalities could be of prognostic value.
Author's contribution SD: Acquisition and interpretation of data, data analysis, drafting the article, and literature review; SJ: Concept, interpretation of data and data analysis, drafting the article, and literature review; AA: Data analysis, manuscript review, manuscript editing, revising the article critically for important intellectual content; JS will act as guarantor. All the authors approved the final manuscript.