Thyroid Disease : Euthyroid sick syndrome as a result of Sepsis - The Causes

Euthyroid sick syndrome is defined as a condition of  low T₃ low T₄ syndrome. According ot the study by the Mayo Clinic, in  other word this is the abnormalities of thyroid hormone concentrations seen commonly in a wide variety of nonthyroidal illnesses, resulting in low triiodothyronine, total thyroxine, and thyroid stimulating hormone concentrations(a). Decreased triiodothyronine (T₃) levels are most common. Patients with more severe or prolonged illness also have decreased thyroxine (T₄) levels. Serum reverse T₃ (rT₃) is increased. Patients are clinically euthyroid and do not have elevated thyroid-stimulating hormone (TSH) levels(b). Causes of euthyroid sick syndrome include a number of acute and chronic conditions, including pneumonia, fasting, starvation, sepsis, trauma, cardiopulmonary bypass, malignancy, stress, heart failure, hypothermia, myocardial infarction, chronic renal failure, cirrhosis, and diabetic ketoacidosis and inflammatory bowel disease(c). Others, in the study of classified SES into 3 subgroups according to the different alterations seen in the values of T3, T4, FT3, FT4, TSH, rT3 and TBG suggested that in SES type I the diseases seen, in order of frequency, were: obstructive chronic bronchopneumopathy with acute respiratory failure, diabetic ketoacidosis, neoplasms, ischemic heart disease, cardiac failure, chronic renal failure, liver diseases, acute cerebral vasculopathies, sepsis and collagenopathies. The disease seen in the 2 cases of SES type II was obstructive chronic bronchopneumopathy with acute respiratory failure. In SES type III the diseases seen were, in order of frequency: diabetic ketoacidosis, lung diseases, ischemic heart disease, cardiac failure, peripheral arteriopathies, acute cerebral vasculopathies, neoplasms, liver diseases, acute renal failure(d).
Euthyroid sick syndrome as a result of Sepsis
The Causes of Sepsis
1. Bacteria infection
In the study of Neonates admitted to the neonatal intensive care unit (NICU) at National Taiwan University Hospital (NTUH) between January 2001 and December 2006, found that in n early-onset sepsis, the most common pathogens responsible included group B streptococci (GBS) (36%) and Escherichia coli (E. coli) (26%). GBS was associated with more meningitis involvement but lower incidence of mortality compared with E. coli. The most common causative microorganisms in late-onset sepsis were coagulase-negative staphylococci (CONS) (40%) and Candida (15%). The sepsis-related mortality rates were higher in early-onset sepsis (10%) than in late-onset sepsis (7%)(5).
Other study indicated that Burkholderia cepacia has rarely been reported in Honolulu. Its emergence as a nursing home-acquired pathogen with high mortality rate is concerning. This case report describes a local nursing home patient who was diagnosed with B. cepacia sepsis in 2012(6).

2. Renal infection (Acute pyelonephritis (APN))
IOn the study to assess the risk factors for septic shock by multivariate logistic regression analysis of 69 patients with obstructive APN associated with upper urinary tract calculi who were admitted to the hospital, indicated that patients with obstructive APN associated with upper urinary tract calculi who have decreases in platelet count and serum albumin level should be treated with caution against the development of septic shock(7).

3. Pneumonia
Klebsiella (K.) pneumoniae is a common cause of pneumonia-derived sepsis, according to the study by the University of Amsterdam(8).

4. Bloodstream infection
In the study to determine the independent risk factors on mortality in patients with community-acquired severe sepsis and septic shock, found that in addition to the severity of illness, hypoalbuminemia was identified as the most important prognostic factor in community-acquired bloodstream infection with severe sepsis and septic shock(9).

5. Abdominal infection
In the study to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients, indicated that complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care(10).

6. Dementia in elders
In the  population-based cohort study, in analyzing 41,672 older (≥ 65 years) patients, including 3,487 (8.4%) with dementia, from the first-time admission claim data between 2005 and 2007 for a nationally representative sample of one million beneficiaries enrolled in the Taiwan National Health Insurance Research Database, found that In hospitalized older patients, the presence of dementia increased the risks of acute organ dysfunction, severe sepsis and hospital mortality. However, after intervention using life-support treatments, dementia only exhibited a minor role on short-term mortality(11).

7. Drug-resistant bacteria
In the study to identify the frequency of bacterial isolates in early-onset neonatal sepsis (EONS) and their antimicrobial resistance pattern, found that K. pneumoniae was the predominant causative bacteria of EONS followed by E. cloacae and E. coli. There was a high resistance to ampicillin. Imipenem had the maximum overall activity against the causative bacteria. Continuous surveillance is needed to monitor the changing epidemiology of pathogens and antibiotic sensitivity(12).

8. Weakened immune systems
Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsis-induced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion(13).
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Sources
(a) http://en.wikipedia.org/wiki/Sepsis
(b) http://www.mayoclinic.com/health/sepsis/DS01004 
(c) http://www.ncbi.nlm.nih.gov/pubmed/24082613
(7) http://www.ncbi.nlm.nih.gov/pubmed/24037335
(8) http://www.ncbi.nlm.nih.gov/pubmed/23133376
(9) http://www.ncbi.nlm.nih.gov/pubmed/20149587
(10) http://www.ncbi.nlm.nih.gov/pubmed/23091606
(11) http://www.ncbi.nlm.nih.gov/pubmed/22905169
(12) http://www.ncbi.nlm.nih.gov/pubmed/24019843
(13) http://www.ncbi.nlm.nih.gov/pubmed/24067565