Euthyroid sick syndrome
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Synonyms and keywords: sick euthyroid syndrome; non-thyroidal illness syndrome; low T3 low T4 syndrome
| Euthyroid sick syndrome | |
| ICD-10 | E07.8 |
|---|---|
| ICD-9 | 790.94 |
| MeSH | D005067 |
Overview
Euthyroid sick syndrome is a thyroid hormone disorder where the levels of T3 (triiodothyronine) and/or T4 (thyroxine) are at unusual levels, in the setting of a nonthyroidal illness. Thyroid hormones play a major role in the metabolism, growth and maturation of the human body. Euthyroid sick syndrome is seen in conditions of starvation and critical illness such as sepsis, surgery, severe trauma, burns, metabolic disorders, bone marrow transplantation, and malignancy. During these stress conditions, there occurs hypermetabolism, increased energy expenditure, hyperglycemia, and muscle loss. It is speculated, that the body in order to contain this hypermetabolism induces some degree of hypothyroidism by inhibiting deiodination of T4 to T3 by the enzyme 5’-monodeiodinase. This is an adaptive process by which the body prevents further muscle and calorie loss. Euthyroid sick syndrome presents with low serum T3. Depending upon the severity and duration of the stress inducing condition, the thyroid-stimulating hormone(TSH), thyroxine (T4), and free T4 (FT4) are affected in variable proportions.[1][2][3]
Historical Perspective
Classification
Pathophysiology
T3 (triiodothyronine) is the biologically active form of thyroid hormone. Normally most of the T3 (triiodothyronine) is produced by peripheral deiodination of circulating T4 (thyroxine) by the enzyme 5’-monodeiodinase (type I). In euthyroid sick syndrome there occurs inhibition of the enzyme 5΄-deiodinase (type I) which leads to decrease conversion of T4 to T3 and increased reverse T3 from decreased metabolism. Euthyroid sick syndrome is seen in conditions of starvation and critical illness such as sepsis, surgery, severe trauma, burns, metabolic disorders, bone marrow transplantation, and malignancy. During these stress conditions, there occurs hypermetabolism, increased energy expenditure, hyperglycemia, and muscle loss. It is speculated, that the body in order to contain this hypermetabolism induces some degree of hypothyroidism by inhibiting deiodination of T4 to T3 by the enzyme 5’-monodeiodinase. This is an adaptive process by which the body prevents further muscle and calorie loss. Euthyroid sick syndrome presents with low serum T3. Depending upon the severity and duration of the stress inducing condition, the thyroid-stimulating hormone(TSH), thyroxine (T4), and free T4 (FT4) are affected in variable proportions. The drop in levels of T3 and T4 are more with more severe illnesses. Mortality rate is high when there is a marked decrease in serum T3 and T4.[4][5]
Causes
Drugs leading to decreased 5'monodeiodinase are propranolol (high doses), amiodarone, and glucocorticoid therapy.
Differentiating Euthyroid sick syndrome from Other Diseases
Fasting, starvation, sepsis, trauma, cardiopulmonary bypass, malignancy, heart failure, hypothermia, myocardial infarction, chronic renal failure, cirrhosis, and diabetic ketoacidosis.
Epidemiology and Demographics
Euthyroid sick syndrome is seen in 40-100% patients of nonthyroidal illness.
Age
Euthyroid sick syndrome is more commonly seen in elderly population. People over 65 have more chronic illnesses and have a greater probability of developing euthyroid sick syndrome.
Race
Euthyroid sick syndrome has no racial predilection.
Sex
Euthyroid sick syndrome affects men and women equally.
Risk Factors
Screening
Natural History, Complications, and Prognosis
Natural History
Complications
Prognosis
Diagnosis
Diagnostic Criteria
History and symptom
The common symptoms and signs of clinical hypothyroidism are listed in the table below. The appearance of symptoms depends on the degree of hypothyroidism severity: [6][7][8][9]
| Symptoms | Constituitional | HEENT | Neuromuscular | Other findings |
|---|---|---|---|---|
| More common |
|
|
| |
| Less common |
|
|
|
Physical Examination
Laboratory Findings
Laboratory findings consistent with the diagnosis of euthyroid sick syndrome include
| Euthyroid sick syndrome | Laboratory test |
|---|---|
| Typical euthyroid sick syndrome |
|
| Severe euthyroid sick syndrome |
|
Imaging Findings
Other Diagnostic Studies
In euthyroid sick syndrome the thyroid gland appears normal. Therefore, there is no role of thyroid uptake scan in euthyroid sick syndrome.
Treatment
Medical Therapy
Ill patients may have normal to low TSH depending on the spectrum of illness. Total T4 and T3 levels may be altered by binding protein abnormalities, and medications. Reverse T3 are generally increased signifying inhibition of normal Type 1 enzyme or reduced clearance of reverse T3. Measurement of free T4 and/or free T3 levels will be normal.
Surgery
Prevention
External links
- McIver B, Gorman C (1997). "Euthyroid sick syndrome: an overview". Thyroid. 7 (1): 125–32. PMID 9086580.
References
- ↑ Plank LD, Connolly AB, Hill GL (1998). "Sequential changes in the metabolic response in severely septic patients during the first 23 days after the onset of peritonitis". Ann. Surg. 228 (2): 146–58. PMC 1191454. PMID 9712558.
- ↑ Economidou F, Douka E, Tzanela M, Nanas S, Kotanidou A (2011). "Thyroid function during critical illness". Hormones (Athens). 10 (2): 117–24. PMID 21724536.
- ↑ Harris AR, Fang SL, Vagenakis AG, Braverman LE (1978). "Effect of starvation, nutriment replacement, and hypothyroidism on in vitro hepatic T4 to T3 conversion in the rat". Metab. Clin. Exp. 27 (11): 1680–90. PMID 30020.
- ↑ GRASBERGER, Helmut; GOLCHER, Henriette M.B.; FINGERHUT, Anja; JANSSEN, Onno E. (2002). "Loop variants of the serpin thyroxine-binding globulin: implications for hormone release upon limited proteolysis". Biochemical Journal. 365 (1): 311–316. doi:10.1042/bj20020014. ISSN 0264-6021.
- ↑ Schilling JU, Zimmermann T, Albrecht S, Zwipp H, Saeger HD (1999). "[Low T3 syndrome in multiple trauma patients--a phenomenon or important pathogenetic factor?]". Med. Klin. (Munich) (in German). 94 Suppl 3: 66–9. PMID 10554534.
- ↑ Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Laurberg P (2014). "Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study". Eur. J. Endocrinol. 171 (5): 593–602. doi:10.1530/EJE-14-0481. PMID 25305308.
- ↑ Diaz A, Lipman Diaz EG (2014). "Hypothyroidism". Pediatr Rev. 35 (8): 336–47, quiz 348–9. doi:10.1542/pir.35-8-336. PMID 25086165.
- ↑ Samuels MH (2014). "Psychiatric and cognitive manifestations of hypothyroidism". Curr Opin Endocrinol Diabetes Obes. 21 (5): 377–83. doi:10.1097/MED.0000000000000089. PMC 4264616. PMID 25122491.
- ↑ McDermott MT (2009). "In the clinic. Hypothyroidism". Ann. Intern. Med. 151 (11): ITC61. doi:10.7326/0003-4819-151-11-200912010-01006. PMID 19949140.