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Wednesday, 4 December 2013

Thyroid disease: Euthyroid sick syndrome as a result of Sepsis - Misdiagnosis and diagnosis

Euthyroid sick syndrome
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  
 Sepsis is defined as a condition caused by chemicals released into the bloodstream to fight the infection trigger inflammation throughout the body as a result of severe infection(a)(b). according to the study by the University of Utah, sepsis is the commonest cause of admission to medical ICUs across the world. Mortality from sepsis continues to be high. Besides shock and multi-organ dysfunction occurring following the intense inflammatory reaction to sepsis, complications arising from sepsis-related immunoparalysis contribute to the morbidity and mortality from sepsis(c).
Misdiagnosis and diagnosis
D.1. Misdiagosis
1. Delayed diagnosis
There is a report of encountered a case where the diagnosis of malarial infection in a woman with acute puerperal sepsis was significantly delayed(37). Others report a case of Necrotizing fasciitis (NF), a rare polymicrobial infection that can be life-threatening. It is a rapidly progressive inflammatory process affecting the deep fascia, with secondary necrosis of the subcutaneous tissue. Misdiagnosis and delayed treatment can result in death from sepsis, mediastinitis, carotid artery erosion, jugular vein thrombophlebitis, or aspiration pneumonia(38).

2.  Delirium
There is a report of three cases of a 65-year-old woman, admitted for malnutrition, has significant mood-related symptoms that resemble depression, a 50-year-old male, admitted with an abscess, necrotizing fasciitis and sepsis, appears to be suicidal and  61-year-old male, admitted with pneumonia, has auditory hallucinations. All three patients turned out to have a delirium(39).

3. Fatal sepsis
There is a report of  a case of fatal sepsis caused by infection with Klebsiella variicola, which is an isolate genetically related to Klebsiella pneumoniae. The patient's condition was incorrectly diagnosed as common sepsis caused by K. pneumoniae, which was identified using an automated identification system, but next-generation sequencing and the non-fermentation of adonitol finally identified the cause of sepsis as K. variicola(40).

4. Shigella sonnei
There is a report of a case of sepsis, caused by a commensal inactive Escherichia coli, which had been repeatedly misidentified as Shigella sonnei by VITEK 2 compact(41).

D.2. Diagnosis 
According to the study by the Mustafa Kemal University, in cases of severe sepsis and septic shock, lactate clearance early in the hospital course may indicate a resolution of global tissue hypoxia and is associated with decreased mortality rate. Patients with higher lactate clearance after 6 hrs of emergency department intervention have improved outcome compared with those with lower lactate clearance(42).
If you are experience certain symptoms of the above and  your doctor suspects that you have developed Sepsis, after recording the past and present history and completing a physical exam, the tests which your doctor orders may include 
1. The table of sepsis diagnostic criteria
Table 1. Diagnostic criteria for sepsis

[Levy M, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250-6]


Infection, documented or suspected*, and some of the following:
General variables
Fever (> 38.3 °C)
Hypothermia (< 36 °C)
Tachycardia (heart rate > 90/min, or >2 SD above the normal value for age)
Tachypnea (increased respiratory rate)
Altered mental status
Significant edema or positive fluid balance (> 20 mL/kg over 24 hrs)
Hyperglycemia (plasma glucose >120 mg/dL or 7.7 mmol/L) in the absence of diabetes
Inflammatory variables
Leukocytosis (WBC count > 12,000/uL
Leukopenia (WBC count < 4,000/uL
Normal WBC count with > 10% immature forms
Elevated plasma C-reactive protein (CRP)
Elevated plasma procalcitonin (PCT)
Hemodynamic variables
Arterial hypotension
SvO2 (mixed venous oxygen saturation) > 70%
Elevated cardiac index (>3.5 L/min/m2)
Organ dysfunction variables
Arterial hypoxemia
Acute oliguria (reduced urine output)
Creatine increase
Coagulation abnormalities (elevated D-dimer, prolonged PT, reduced protein C)
Ileus (absent bowel sound)
Thrombocytopenia (platelet count < 100,000/uL)
Hyperbilirubinemia
Tissue perfusion variables
Elevated blood lactate
Decreased capillary refill or mottling
(44).

2. The Laboratory tests
The aim is the test is to identify the infectious agent causing the infections. According to the study by the Stanford University School of Medicine, definitive diagnosis depends on cultures of blood or other normally sterile body fluids. Abnormal hematological counts, acute-phase reactants, and inflammatory cytokines are neither sensitive nor specific, especially at the onset of illness. Combinations of measurements improve diagnostic test performance, but the optimal selection of analytes has not been determined. The best-established use of these laboratory tests is for retrospective determination that an infant was not infected, based on failure to mount an acute-phase response over the following 24 to 48 hours(43).
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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 
(37) http://www.ncbi.nlm.nih.gov/pubmed/24032986 
(38) http://www.ncbi.nlm.nih.gov/pubmed/23790808 
(39) http://www.ncbi.nlm.nih.gov/pubmed/23693007 
(40) http://www.ncbi.nlm.nih.gov/pubmed/23449877 
(41) http://www.ncbi.nlm.nih.gov/pubmed/22029193 
(42) http://www.ncbi.nlm.nih.gov/pubmed/15286537 
(43) http://www.ncbi.nlm.nih.gov/pubmed/20569816