Holistic Health Articles and Research Related to Herbal Medicines, Foods and Phytochemicals

Wednesday, 4 December 2013

Multiple myeloma- The Diagnosis

Multiple myeloma, also known as plasma cell myeloma or Kahler’s disease, is a type of abnormal growth of plasma cells collected in the bone marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay by precipitate formation of that can lead to clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). There is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
B. Diagnosis
If you are experience some of the above symptoms, after recording the complete family history and physical examination, the test which your doctor orders may include
1. Standard Blood and urine tests
The aim of the tests are to detect the presence of M proteins of which may be an indication of Multiple myeloma. If M protein is found in the test, additional boold test for beta-2-microglobulin may be necessary for the comfirmation of outcome.
2. Serum Free Light Chain Assays
Free light chain (FLC) assays are important in the diagnosis and monitoring of patients with multiple myeloma (MM). Elevated immunoglobulin free light chain (FLC) level and abnormal FLC ratio are commonly seen in multiple myeloma (MM) and have prognostic implications, accosing to the study by the Division of Hematology, Mayo Clinic, a combination of the risk factors; either abnormal FLC estimate and/or the presence of high-risk IgH translocation, achieved better prognostic stratification. We conclude that patients with IgH translocations have higher FLC levels and abnormal ratios, but the prognostic effect of FLC is only partially explained by translocation status. A system including both these risk factors allows better prediction of outcome(35).
3. Imaging
In multiple myeloma, imaging is required to determine the stage of disease and to anticipate impending bone fractures. According to the study by the Department of Radiology, German Cancer Research Center, modern systems include
a. MRI findings. MRI is most sensitive to both diffuse bone marrow involvement as well as solid plasma cell tumors.
b. Whole-body low-dose CT (WBCT) may replace plain films in the near future, since it is quicker, more sensitive, and is better tolerated by patients. Intramedullary lesions are well seen as long as they are located in long bones where they are surrounded by fat. Diffuse bone marrow infiltration as well as intravertebral lesions, however, are difficult to detect with WBCT in the absence of frank destruction of cancellous bone.
c. PET or PET-CT with 18-fluoro-deoxyglucose (FDG) are insensitive to diffuse bone marrow infiltration, but may help to assess treatment response in solitary or multiple solid plasma cell tumors which have a high FDG uptake before treatment(36).
4. Bone marrow examination
There have been suggestions to eliminate the need for BM examinations as a result of a bone marrow (BM) examination showing less than 5% plasma cells in addition to negative serum and urine immunofixation. In the study to evaluate of patients with multiple myeloma who achieved negative immunofixation in the serum and urine after therapy and found that 14% had BM plasma cells more than or equal to 5%. Adding a requirement for normalization of the serum-free light chain ratio to negative immunofixation studies did not negate the need for BM studies; 10% with a normal serum-free light chain ratio had BM plasma cells more than or equal to 5%. We also found that, on achieving immunofixation-negative status, patients with less than 5% plasma cells in the BM had improved overall survival compared with those with 5% or more BM plasma cells (6.2 years vs 2.3 years, respectively; P = .01)(37).
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

Back to General health http://kylejnorton.blogspot.ca/p/general-health.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(35) http://www.ncbi.nlm.nih.gov/pubmed/20520636
(36) http://www.ncbi.nlm.nih.gov/pubmed/21509684
(37) http://www.ncbi.nlm.nih.gov/pubmed/19641191

Multiple myeloma- Misdiagnosis

Multiple myeloma, also known as plasma cell myeloma or Kahler’s disease, is a type of abnormal growth of plasma cells collected in the bone marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay by precipitate formation of that can lead to clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). There is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
A. Misdiagnosis
1. Spinal epidural metastasis
There is a report of a 42-year-old man presented with a one-month history of upper back pain and a two-week history of progressive spastic paraparesis. Thoracic spinal MRI showed an epidural mass with spinal cord compression at T6-8 but no bony involvement. The patient underwent T6-8 laminectomy for decompression. Lumbosacral MRI and CT scans revealed bony abnormalities on the sacrum and left posterior iliac bone. Immunohistochemical studies confirmed the diagnosis of multiple myeloma (MM)(28).
2. Orbital mass
There is a report of a case of a 28-year-old African-American woman presented with new onset of left exophthalmos and diplopia with initially vomputed tomography of the head showed a solitary mass in the left orbit, But excisional biopsy revealed a diffuse infiltrate composed of exclusively λ-restricted monotypic plasma cells based on morphology and immunohistochemistry, consistent with a plasma cell neoplasia. A subsequent staging bone marrow biopsy showed involvement of the bone marrow by λ-restricted monotypic plasma cells, consistent with a plasma cell myeloma. Serum protein electrophoresis and immunofixation studies on the peripheral blood showed a monoclonal band of IgE-λ; thus, an IgE-λ plasma cell myeloma(29).
3. Acute liver diseases
According to the study by St. Vincent’s Comprehensive Cancer Center, there is a report of a case of a 55-year-old woman with MM who presented with painless jaundice, mild pruritus, and abnormal liver function tests resembling acute cholestatic hepatitis without the stigmata of chronic liver disease, but clinical manifestations of liver involvement in multiple myeloma (MM) are uncommon. Rare cases of MM present as acute liver disease(30).
4. Pituitary mass lesion
there is a report of a case of a 71-year-old female patient affected by an extramedullary IgG-lambda multiple myeloma presenting as a pituitary mass lesion. The diagnostic approaches confirmed the diagnosis of multiple myeloma and describe treatment outcome after therapy, according to the study by Medizinische Klinik Campus Innenstadt, Klinikum der LMU(31).
5. Intrasellar plasmacytoma
Plasmacytomas are unusual causes of a sellar mass. Occasionally, they can be misdiagnosed as a nonfunctioning adenoma because of radiological and clinical similarities. there is a report of a 70-year-old woman presented with a recurrent hypophysial mass. Initial diagnosis of a nonfunctioning pituitary adenoma was later overruled by a repeat biopsy, which showed a plasmacytoma. The tumor stained positively for CD138 and kappa light chain(32).
6. Pituitary adenoma
There is a report of a case of multiple myeloma which presented as a solitary intrasellar tumor. The initial radiographic and light microscopic findings were interpreted as being consistent with pituitary adenoma. Subsequently, when systemic disease developed and a bone marrow biopsy demonstrated multiple myeloma(33),
7. Chromophobe adenoma
62-year-old woman presenting with intracranial lesion eroding the sella with compression of optic chiasma was found to have plasmacytoma of the pituitary area. At the time of initial surgery, the patient had no biochemical, immunologic or marrow findings of multiple myeloma. The intracranial tumor was interpreted initially as chromophobe adenoma on light microscopy, but the diagnosis of plasmacytoma was established by electron microscopic examination of the tumor(34).
8. Etc.
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

Back to General health http://kylejnorton.blogspot.ca/p/general-health.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(28) http://www.ncbi.nlm.nih.gov/pubmed/22898195
(29) http://www.ncbi.nlm.nih.gov/pubmed/23084304
(30) http://www.ncbi.nlm.nih.gov/pubmed/18021472
(31) http://www.ncbi.nlm.nih.gov/pubmed/22851185
(32) http://www.ncbi.nlm.nih.gov/pubmed/18726062
(33) http://www.ncbi.nlm.nih.gov/pubmed/3791987
(34) http://www.ncbi.nlm.nih.gov/pubmed/445346

Multiple myeloma- Diseases associated to Multiple myeloma

Multiple myeloma, also known as plasma cell myeloma or Kahler’s disease, is a type of abnormal growth of plasma cells collected in the bone marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay by precipitate formation of that can lead to clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). There is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
B. Diseases associated to Multiple myeloma
1. Bone diseases
Multiple myeloma is a plasma cell malignancy characterized by the frequent development of osteolytic bone lesions. According to the study by the University of Pittsburgh, and Division of Hematology/Oncology, Veterans Administration Pittsburgh Healthcare System, Research and Development, the multiple myeloma-induced bone destruction is a result of the increased activity of osteoclasts that occurs adjacent to multiple myeloma cells. This activity is accompanied by suppressed osteoblast differentiation and activity, resulting in severely impaired bone formation and development of devastating osteolytic lesions(22).
2. Bilateral ovarian involvement
Extramedullary spread of multiple myeloma is extremely rare. There is a report of a case of bilateral ovarian involvement in plasma cell myeloma of a 48-year-old Persian woman who experienced constitutional symptoms, bone pain and flashing for one year. Her condition showed multiple myeloma with lytic lesions of the skull, plasma cell infiltration in bone marrow and positive light chain lambda type in serum(23).
3. Gaucher’s disease
There is a report of a case of the evolution of a monoclonal gammopathy of undetermined significance to multiple myeloma in a patient with Gaucher’s disease of a 64-year-old woman who, 12 years after receiving a diagnosis of Gaucher’s disease with concurrent monoclonal gammopathy of undetermined significance, developed worsening thrombocytopenia and bone pain(24).
4. Acetabular osteolysis
There is a report of a case of 71 year old man was operated in December 2005 with a total uncemented hip arthroplasty. Immediate evolution was favourable but at 4 months postoperatively he came with the complaints of left back pain irradiating in the left thigh. X-rays revealed the presence of a lytic lesion around the acetabulum with secondary dispalcement of the acetabular cup. Further investigations ruled out infection and confirmed the presence of multiple myelom(25).
5. Paget Disease (PD)
Although the Coexistence of Paget Disease (PD) and symptomatic Multiple Myeloma (MM) has rarely been described, there is a report of a 73 years old man with a diagnosis of Paget Disease (PD) and symptomatic Multiple Myeloma (MM). PD mimics many of the features of bone destructive process in MM, making differential diagnosis more complicated. In addition, the presence of serious muscolo-skeletal and metabolic complications in both diseases makes management of patients difficult, worsening the prognosis(26).
6. Multiple myeloma associated precursor diseases
Multiple myeloma and chronic lymphocytic leukaemia share common biological and clinical features including the presence of defined precursor conditions (monoclonal gammopathy of undetermined significance and monoclonal B-cell lymphocytosis respectively), according to the study by the National Institutes of Health, Bethesda(27).
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

Back to General health http://kylejnorton.blogspot.ca/p/general-health.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(b) http://www.ncbi.nlm.nih.gov/pubmed/18251580
(c) http://www.ncbi.nlm.nih.gov/pubmed/22073517
(22) http://www.ncbi.nlm.nih.gov/pubmed/17996587
(23) http://www.ncbi.nlm.nih.gov/pubmed/22845423
(24) http://www.ncbi.nlm.nih.gov/pubmed/9341594
(25) http://www.ncbi.nlm.nih.gov/pubmed/17918494
(26) http://www.ncbi.nlm.nih.gov/pubmed/23205256
(27) http://www.ncbi.nlm.nih.gov/pubmed/18021086

Multiple myeloma- The Complications

Multiple myeloma, also known as plasma cell myeloma or Kahler’s disease, is a type of abnormal growth of plasma cells collected in the bone marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay by precipitate formation of that can lead to clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). There is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
A. Complications
1. Deteriorated quality of life
patients with MM reported a mean decrease (e.g., worsening) between baseline and 1-yr follow-up scores for: quality of life (mean, 68 vs. 55, respectively, P < 0.001; 74% of patients had a deteriorated score)(17).
2. Immue dysfucntion
Mesenchymal stem cells (MSCs), a key regulator for immunomodulatory function, have decreased osteogenic potential in MM patients opf that can lead to impaied immunity. According to the study by the Second Affiliated Hospital of Soochow University, T cells from normal donors possessed the ability to promote osteoblastic differentiation of ND-MSCs, but this ability of T cells both directly from MM patients and co-cultured with MM-MSCs was impaired which in turn lose the ability to stimulate osteogenesis of MSCs(18).
3. Osteogenesis imperfecta
Osteogenesis imperfecta (OI) also known as brittle bone disease, is a congenital bone disorder that causes extremely fragile bones.There is a report of a case of osteogenesis imperfecta with multiple fractures already from childhood, myelomatosis was diagnosed at the age of 52 years as a result of a serum M-component (IgG, lambda), Bence Jones proteinuria, myeloma cells in the bone marrow, and osteolytic skeletal lesions of that can lead to erosion of bone mass and fractures. She died 10 months later. A partial postmortem examination of a larger bone lesion confirmed the diagnosis.(19).
4. Renal insufficiency
Renal insufficiency is an independent risk factor in MM. An impaired renal function in light chain associated disorders may be caused by myeloma cast nephropathy (MCN) but also by AL-amyloidosis (AL-A) and monoclonal immundeposition disease (MIDD), according to the study by Heinrich Braun Klinikum Zwickau(20).
5. Anemia
Anemia is a common complication in patients with multiple myeloma (MM) and occurs in more than two thirds of all patients as MM can inetrfere with the production of normal blood cells. According to the study by Department of Medicine I, Wilhelminenspital, the most frequent underlying pathophysiological mechanism is anemia of chronic disease (ACD), relative erythropoietin (EPO) deficiency (due partly to renal impairment) and myelosuppressive effects of chemotherapy, but many other factors may account for or contribute to anemia in myeloma(21).
6. Pseudomonas endocartiditis
There is a report of a case of a is reported a rare case in a 73-year-old man with multiple myeloma who developed endocarditis due to pseudomonas(21a).
Etc.
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

Back to General health http://kylejnorton.blogspot.ca/p/general-health.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(b) http://www.ncbi.nlm.nih.gov/pubmed/18251580
(c) http://www.ncbi.nlm.nih.gov/pubmed/22073517
(17) http://www.ncbi.nlm.nih.gov/pubmed/22762785
(18) http://www.ncbi.nlm.nih.gov/pubmed/21199732
(19) http://www.ncbi.nlm.nih.gov/pubmed/472657
(20) http://www.ncbi.nlm.nih.gov/pubmed/23392999
(21) http://www.ncbi.nlm.nih.gov/pubmed/16163188
(21a) http://www.ncbi.nlm.nih.gov/pubmed/23386092

Multiple myeloma- The Risk Factors

Multiple myeloma, also known as plasma cell myeloma or Kahler’s disease, is a types of abnormal growth of plasma cells collected in the bone marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay by precipitate formation of that can lead to clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). There is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
B. Risk Factors
1. Age
The risk of Multiple myeloma increase with Age and multiple myeloma (MM) is the second most common hematological malignancy in China. According to the study by the Beijing Chaoyang Hospital, Capital Medical University, in the retrospectively analyzed study of 264 newly diagnosed MM patients from the Beijing Chaoyang Hospital showed that the median patient age was 59 years (range, 28-84) and the most common monoclonal protein (42%) was the IgG subtype(12).
2. Gender
In the study to to characterize gender disparities in myeloma, showed that
a. Genetic lesions (13q- trisomy 1q, and an IGH)
Disparities were found in the prevalence of primary genetic lesions with immunoglobulin heavy chain gene (IGH) translocations being more common in women (50% of female patients vs. 38% of male patients, P < 0.001).
b. Hyperdiploidy
Hyperdiploidy is being more common in men (50% female vs. 62% male, P < 0.001)(13).
3. Excess body weight
Excess body weight is a risk factor for multiple myeloma. According to the stdy by the National Institute of Environmental Medicine suggested that excess risk of multiple myeloma (MM) among obese persons could be the result of altered circulating levels of adipokines, polypeptide hormones with pro- and anti-inflammatory properties secreted by adipose tissue as adiponectin may play an important role in obesity-related myelomagenesis(14).
4. Body build or nutritional status
In an exploratory study conducted of common clinical conditions as predictors of subsequent cancer in 143,574 outpatients of a health maintenance organization (in California, USA), suggest that body build or nutritional status may be involved in the development of MM by mechanisms that are presently unknown(15).
5. Race
Epidemiological data have suggested that African Americans (AA) are twice as likely to be diagnosed with multiple myeloma (MM) as compared to European Americans (EA)(16).
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

Back to General health http://kylejnorton.blogspot.ca/p/general-health.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(b) http://www.ncbi.nlm.nih.gov/pubmed/18251580
(c) http://www.ncbi.nlm.nih.gov/pubmed/22073517
(12) http://www.ncbi.nlm.nih.gov/pubmed/23420708
(13) http://www.ncbi.nlm.nih.gov/pubmed/21680536
(14) http://www.ncbi.nlm.nih.gov/pubmed/23007407
(15) http://www.ncbi.nlm.nih.gov/pubmed/7999970
(16) http://www.ncbi.nlm.nih.gov/pubmed/23422747

Multiple myeloma- The Causes

Multiple myeloma, also known as plasma cell myeloma or Kahler’s disease, is a types of abnormal growth of plasma cells collected in the bone marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can causes kidney problem but also interference with the Roche automated total bilirubin assay by precipitate formation of that can lead to clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). there is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).

A. Causes
1. Monoclonal gammopathy of undetermined significance (MGUS)
Monoclonal gammopathy of undetermined significance (MGUS) has been associated with an increased risk of smoldering multiple myeloma (SMM. Strong evidence showed that multiple myeloma is consistently preceded by a precursor state at the molecular level, there is urgent need to better understand mechanisms that regulate transformation from precursor to full-blown multiple myeloma(7).
2. Genetic abnormalities
a. Dysregulation of c-myc Gene
Dysregulation of c-myc by translocation to the switch regions of the IgH locus occurs in most murine plasmacytomas. Translocations involving 14q32 have been reported in 20-40% of abnormal karyotypes from human multiple myeloma (MM), and involve a variety of loci(8).
b. Gene (IgH)
Chromosome translocations involving the immunoglobulin heavy chain gene (IgH) on 14q32 are a seminal event in the pathogenesis of many B-cell malignancies. According to the study by the New York Presbyterian Hospital-Weill Medical College of Cornell University, , Recurrent Ig translocations identify at least three distinct molecular subtypes of myeloma(9).
c. Chromosome translocations
(11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (FGFR3 and MMSET), and 16q23 (c-maf))
Four chromosomal partners appear to account for the majority of primary IgH translocations: 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (FGFR3 and MMSET), and 16q23 (c-maf). They are mediated primarily by errors in IgH switch recombination and less often by errors in somatic hypermutation, with the former dissociating the intronic and 3′ enhancer(s), so that potential oncogenes can be dysregulated on each derivative chromosome (e.g., FGFR3 on der14 and MMSET on der4). Secondary translocations, which sometimes do not involve Ig loci, are more complex, and are not mediated by errors in B cell specific DNA modification mechanisms(10).
d. Cytogenetic alteration and/or hyperdiploidy
At diagnosis, 96% of cases with multiple myeloma versus 77% of monoclonal gammopathy of undetermined significance cases showed at least one cytogenetic alteration and/or hyperdiploidy(11).
3. Etc.
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

Back to General health http://kylejnorton.blogspot.ca/p/general-health.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(b) http://www.ncbi.nlm.nih.gov/pubmed/18251580
(c) http://www.ncbi.nlm.nih.gov/pubmed/22073517
(7) http://www.ncbi.nlm.nih.gov/pubmed/21411440
(8) http://www.ncbi.nlm.nih.gov/pubmed/9308253
(9) http://www.ncbi.nlm.nih.gov/pubmed/10707795
(10) http://www.ncbi.nlm.nih.gov/pubmed/11607813
(11) http://www.ncbi.nlm.nih.gov/pubmed/22929983

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