Euthyroid sick syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Euthyroid sick syndrome is a thyroid hormone disorder in which the levels of T3 (triiodothyronine) and/or T4 (thyroxine) are at abnormal levels, in the setting of a severe underlying illness. The thyroid gland itself is normal. 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 stressful conditions, hypermetabolism, increased energy expenditure, hyperglycemia, and muscle loss takes place. 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. In euthyroid sick syndrome the symptoms of the underlying condition may overlap with features of hypothyroidism. Generally it takes atleast 2-3 weeks for thyroid hormone levels to decline and symptoms of hypothyroidism take even longer to be visible. Common symptoms of hypothyroidism are fatigue, cold intolerance, decreased sweating, hypothermia, coarse skin, weight gain, depression, emotional lability, and attention deficit. The diagnosis of euthyroid sick syndrome is based on clinical presentation and thyroid function tests. Thyroid function tests helps to differentiate between other causes of hypothyroidism and euthyroid sick syndrome. Management of euthyroid sick syndrome includes rapid correction of the underlying disease. Replacement of thyroid hormones in euthyroid sick syndrome is controversial and generally not recommended.^[1][2][3]

In 1960s, the first scientific descriptions on transient alterations in thyroid hormones metabolism were given by several authors who described altered half life of thyroid hormones in athletes under training and with adaptation to cold. In the early 1970s, German and US researchers simultaneously described low T3 syndrome in starvation and shortly thereafter reduced T3 concentrations were observed in critical illnesses requiring intensive care such as in patient’s with tumor or uremia.

Euthyroid sick syndrome may be classified according to the level of thyroid hormones and the severity of the underlying disease into mild, moderate, severe, and recovery phase.

Euthyroid sick syndrome is not a primary thyroid disorder but instead results from changes induced by the nonthyroidal illness. The pathophyisology of euthyroid sick syndrome is multifactorial. It is believed that euthyroid sick syndrome is the result of severe illness and inflammation. 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. Inflammation leads to increased production of cytokines that severely affect genes involved in the production and release of T4 and T3. There is also downregulation of TRH and TSH release from the hypothalamus and pituitary gland respectively. It may be signalled by a decrease in leptin caused by malnutrition. On gross pathology, euthyroid sick syndrome does not appear to be dysfunctional. On microscopic histopathological analysis, euthyroid sick syndrome presents with normal thyroid histology.

Euthyroid sick syndrome can be caused by any serious illness which leads to increased level of cytokines, decreased level of leptin, hyper-metabolism, decreased protein synthesis and decreased level of thyroid-binding globulin. The conditions include sepsis, malignancy, trauma, surgery, burns, bone marrow transplantation, metabolic disorders, and other inflammatory conditions.^[4][5]

Euthyroid sick syndrome must be differentiated from other causes of hypothyroidism on the basis of clinical features and laboratory findings. In euthyroid sick syndrome, serum T3 is decreased more than T4, the T3RU (T3 resin uptake) is high, and TSH is normal or mildly decreased. Various causes of hypothyroidism include primary hypothyroidism, transient hypothyroidism, sub-clinical hypothyroidism, central hypothyroidism (pituitary or hypothaalmic) and peripheral resistance to TSH/TRH.^[6][7][8]

The incidence of euthyroid sick syndrome in intensive care unit (ICU) is approximately 70,000 per 100,000 cases of nonthyroidal illness. The prevalence of euthyroid sick syndrome is estimated to be 40,000 per 100,000 cases of nonthyroidal illness. Euthyroid sick syndrome is more commonly seen in elderly population. There is no racial predilection for euthyroid sick syndrome and both men and women are affected equally.^[9][10][11]

Common risk factors in the development of euthyroid sick syndrome include iodine deficiency, female gender, pregnancy, radiation exposure, elderly, family history of thyroid disease, primary pulmonary hypertension, and infiltrative disease. Less common risk factors are excessive intake of iodine, textile workers, and diabetes mellitus type I.^{[12][13][14][15]}

There is insufficient evidence to recommend routine screening for euthyroid sick syndrome.

If left untreated, patients with euthyroid sick syndrome may progress to develop hypothyroidism or resolve spontaneously with correction of underlying condition. If underlying condition is not treated, the thyroid hormone levels starts to drop after 2-3 weeks of initial illness. The symptoms of hypothyroidism may take some additional weeks to appear. The complications of euthyroid sick syndrome depends upon other organ systems involved and underlying disease(s). The general complications of hypothyroidism as seen in euthyroid sick syndrome include hypothermia, bradycardia, heart failure, dyspnea, myopathy, confusion, apathy and psychosis. Laboratory finding will show increased levels of cholesterol and triglycerides. In addition, patients will have features of organs system involved. The prognosis varies and depends upon extent of the underlying disease at the time of diagnosis. Patients with low T3 (< 2.3 pg/ml) levels may have a longer hospital stay. Mortality rate is as high as 80% when serum T4 value is <3 mcg/dL.

The diagnosis of euthyroid sick syndrome is based on clinical presentation and thyroid function tests. An important part in diagnosing euthyroid sick syndrome is to be able to differentiate between other causes of hypothyroidism and euthyroid sick syndrome. Although the diagnosis of hypothyroidism is mainly a laboratory diagnosis, the coexisting conditions and wide variation in clinical presentation may make the diagnosis difficult. The best initial test is TSH, which in euthyroid sick syndrome can be low, normal, or elevated but not as high as it would be in hypothyroidism. Serum reverse T3 is elevated from inhibition of 5′ monodeiodinase (type I). Patient having severe underlying illness, as in euthyroid sick syndrome, have elevated levels of serum cortisol from underlying stress whereas, patients of hypothyroidism have low serum cortisol from associated hypothalmic/pituitary abnormality.

Obtaining a thorough history contributes in making a diagnosis of euthyroid sick syndrome. Complete history should be obtained regarding past and any newly diagnosed medical conditions, previous history of thyroid disease and current medications. Patients of euthyroid sick syndrome present with serious illness and are febrile with hypermetabolism. In euthyroid sick syndrome the symptoms of the underlying condition may overlap with features of hypothyroidism. Generally it takes atleast 2-3 weeks for thyroid hormone levels to decline and symptoms of hypothyroidism takes even longer period for expression. The common symptoms of hypothyroidism are fatigue, cold intolerance, decreased sweating, hypothermia, coarse skin, weight gain, depression, emotional lability, and attention deficit.

There are no specific physical examination findings associated with euthyroid sick syndrome. The physical examination findings in each patient depends upon the underlying cause of euthyroid sick syndrome such as sepsis, myocardial infarction, pneumonia, chronic renal failure and cirrhosis.

Laboratory findings consistent with the diagnosis of euthyroid sick syndrome include low T3, increased reverse T3 and variable proportions of T4 depending upon the severity of the disease. Patients having reduced concentration of T4 suggests progression of the underlying nonthyroidal illness. Complete thyroid function tests should be done which includes TSH, free T3, total T3, reverse T3, free T4, and total T4.^{[16][5][17][18]}

There are no specific ECG findings associated with euthyroid sick syndrome. However, euthyroid sick syndrome leads to hypothyroidism. The decrease in the levels of thyroid hormones causes decreased activity of the sympathetic nervous system. There can also be deposition of myxoedematous material within the myocardium. ECG in hypothyroidism will present with QT prolongation, first degree AV block, interventricular conduction delay. Severe cases of hypothyroidism will have bradycardia and low QRS voltage.

There are no x-ray findings associated with euthyroid sick syndrome.

There are no CT scan findings associated with euthyroid sick syndrome. However, a CT scan may be helpful in the diagnosis of complications associated with the underlying condition.

There are no MRI findings associated with euthyroid sick syndrome. However, a MRI may be helpful in the diagnosis of complications associated with the underlying condition.

In euthyroid sick syndrome the thyroid gland appears normal. Therefore, there is no role of thyroid ultrasound in euthyroid sick syndrome.

There are no other imaging findings associated with euthyroid sick syndrome.

There are no other diagnostic studies associated with euthyroid sick syndrome.

In euthyroid sick syndrome emphasis is on rapid correction of the underlying disease. Many seriously ill patients have low levels of thyroid hormones but are not clinically hypothyroid and do not require thyroid hormone supplementation. Replacement of thyroid hormones in euthyroid sick syndrome is controversial except, in patients of congestive heart failure where liothyronine (LT3) or levothyroxine (LT4) may be recommended, to improve ventricular performance. Therefore, thyroid hormone therapy is generally not recommended for patients with euthyroid sick syndrome, except possibly those with chronic heart failure.

Surgical intervention is not recommended for the management of euthyroid sick syndrome.

There are no established measures for the primary prevention of euthyroid sick syndrome.

There are no established measures for the secondary prevention of euthyroid sick syndrome.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

In 1960s, the first scientific descriptions on transient alterations in thyroid hormones metabolism were given by several authors who described altered half life of thyroid hormones in athletes under training and with adaptation to cold. In the early 1970s, German and US researchers simultaneously described low T3 syndrome in starvation and shortly thereafter reduced T3 concentrations were observed in critical illnesses requiring intensive care such as in patient’s with tumor or uremia.

• In 1543, Andreas Vesalius was the first who provided anatomic description and illustration of the thyroid gland.
• In 1834, Robert Graves was the first who described a syndrome of palpitation, goiter, and exophthalmos.
• In 1895, Adolf Magnus Levy was the first to describe the influence of the thyroid gland and thyroid hormones on the basal metabolic rate.
• In 1949, R. G. Hoskins was the first who described negative feedback of thyroid gland on pituitary, a mechanism he called “servo (feedback) mechanism”.
• In 1960s, the first scientific descriptions on transient alterations in thyroid hormones metabolism were given by several authors who described altered half life of thyroid hormones in athletes under training and with adaptation to cold.^[1][2][3]
• In the early 1970s, German and US researchers simultaneously described low T3 syndrome in starvation and shortly thereafter reduced T3 concentrations were observed in critical illnesses requiring intensive care such as in patient’s with tumor or uremia. ^{[4][5][6][7][8]}
• Modern theories regard the euthyroid sick syndrome as a form of adaptive allostatic response that ensures survival through metabolic adjustment, although allostatic load may confer pathology on its own.^[9][10]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Euthyroid sick syndrome may be classified according to the level of thyroid hormones and the severity of the underlying disease into mild, moderate, severe, and recovery phase.

Euthyroid sick syndrome may be classified according to the level of thyroid hormones and the severity of the underlying disease. 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 is associated with more severe illnesses. On the basis of thyroid hormone levels euthyroid sick syndrome can be categorized into:^{[1][2][3][4][5][6][7]}

Additionally, two phenotypes of euthyroid sick syndrome use to be distinguished, depending on the question if it occurs over short time in acute illness or if it represents a chronic condition (referred to as wasting syndrome)^[3]. In the latter case, concentrations of T3 are even more reduced, and 3,5-T2 concentrations are increased^[6].

Euthyroid Sick Syndrome

Mild euthyroid sick syndrome

Moderate euthyroid sick syndrome

Severe euthyroid sick syndrome

Recovery phase

•Decreased T3 •Normal T4, FT4 and TSH •Increased reverse T3

• Decreased T3 • Normal/decreased FT4 and TSH • Increased reverse T3

• Decreased T3, T4 and TSH • Normal/decreased FT4 • Increased reverse T3

• Normal/decreased T3 • Normal/increased T4, FT4 and TSH • Normal/increased reverse T3

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Euthyroid sick syndrome is not a primary thyroid disorder but instead results from changes induced by the nonthyroidal illness. The cause of euthyroid sick syndrome is multifactorial. It is thought that euthyroid sick syndrome is the result of severe illness and inflammation. During these stress conditions, hypermetabolism occur, that lead to increased energy expenditure, hyperglycemia, and muscle loss. It is speculated, that the body induces some degree of hypothyroidism by inhibiting deiodination of T4 to T3 by the enzyme 5’-monodeiodinase, in order to contain the hypermetabolism. This is an adaptive process by which the body prevents further muscle and calorie loss. Inflammation leads to increased production of cytokines that severely affects genes involved in the production and release of T4 and T3. There is also downregulation of TRH and TSH release from the hypothalamus and pituitary gland respectively. This downregulation may be signalled by a decrease in leptin caused by malnutrition. On gross pathology, euthyroid sick syndrome, does not appear to be dysfunctional. On microscopic histopathological analysis, euthyroid sick syndrome presents with normal thyroid histology.

• 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’-monodeiodinase (type I) which leads to decrease conversion of T4 to T3 and an increase in 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.^{[1][2][3][4][5][6]}
  • 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.
  • During illness, there is also downregulation of TRH and TSH release from the hypothalamus and pituitary gland respectively. It may be signalled by a decrease in leptin caused by malnutrition. Under normal conditions, leptin prevents neuropeptide Y (NPY) and agouti-related protein (AGRP) induced downregulation of TRH.
  • In vitro studies have shown that high concentrations of cytokines severely affect genes involved in the production and release of T4 and T3.
  • Any chronic illness may impair plasma protein binding of thyroid hormones, resulting in reduced levels of total hormones.
• 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.

Pathogenesis of euthyroid sick syndrome include mutation in LEP gene.

• LEP gene mutation:^{[7][8][9][10]}
  • The LEP gene encodes for leptin.
  • Normally, α-MSH stimulates TRH gene expression.
  • Leptin enhances this effect of α-MSH on TRH gene expression.
  • Leptin also decreases neuropeptide Y (NPY) and agouti-related protein (AGRP) induced decrease in TRH gene expression.
  • Any chronic illness or starvation can lead to decrease in leptin production.
  • Patients who have a defective LEP or leptin receptor due to genetic mutations and who develop chronic illness later in life show reduced TRH secretion and features of euthyroid sick syndrome.^[11][12][13]

Euthyroid sick syndrome is seen with starvation and severe illness such as:^[14][15]

• Sepsis
• Malignancy
• Trauma
• Surgery
• Burns
• Bone marrow transplantation
• Other inflammatory conditions
• Metabolic disorders
• Any major condition of:
  • Cardiovascular system: Myocardial infarction
  • Respiratory system : Pneumonia
  • Genitourinary system: Chronic renal failure
  • Gastrointestinal system: Cirrhosis

In euthyroid sick syndrome the thyroid gland appears normal on gross pathology.

On microscopic histopathological analysis, euthyroid sick syndrome presents with normal thyroid histology.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Euthyroid sick syndrome can be caused by any serious illness which leads to increased level of cytokines, decreased level of leptin, hyper-metabolism, decreased protein synthesis and decreased level of thyroid-binding globulin. The conditions include sepsis, malignancy, trauma, surgery, burns, bone marrow transplantation, metabolic disorders, and other inflammatory conditions.

Euthyroid sick syndrome can be caused by any serious illness which leads to increased level of cytokines, decreased level of leptin, hyper-metabolism, iodine containing contrast medium, decreased protein synthesis and decreased level of thyroxin-binding globulin. The conditions include:^[1][2][3]

• Sepsis
• Malignancy
• Trauma
• Surgery
• Burns
• Bone marrow transplantation
• Metabolic disorders
• Other Inflammatory conditions
• Any major condition of:
  • Cardiovascular system: Myocardial infarction
  • Respiratory system : Pneumonia
  • Genitourinary system: Chronic renal failure
  • Gastrointestinal system: Cirrhosis

• The following table summarize the effect of various drugs on thyroid hormones level:

↓ Hormone secretion	↓ T4	↓ TSH	↓ 5′ monodeiodinase	↑ Breakdown of thyroid hormones	Thyroid binding globulin
					Increased	Decreased
Lithium Amiodarone	Aluminum hydroxide Ferrous sulphate Sucralfate	Dopamine Octreotide Glucocorticoids	Propylthiouracil Amiodarone Propranolol (high dose)	Phenobarbital Rifampin Phenytoin Carbamazepine	Estrogens Tamoxifen Fluorouracil Methadone Heroin	Androgens Anabolic steroids Glucocorticoids Furosemide Mefenamic acid Salicylates

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Euthyroid sick syndrome must be differentiated from other causes of hypothyroidism on the basis of clinical features and laboratory findings. In euthyroid sick syndrome, serum T3 is decreased more than T4, the T3RU (T3 resin uptake) is high, and TSH is normal or mildly decreased. In primary hypothyroidism, serum T4 is decreased more than T3, the T3RU (T3 resin uptake) is low, and TSH is increased. Other causes of hypothyroidism include transient hypothyroidism, sub-clinical hypothyroidism, central hypothyroidism (pituitary or hypothalamic) and peripheral resistance to TSH/TRH.

Euthyroid sick syndrome must be differentiated from other causes of hypothyroidism on the basis of history and symptoms and laboratory findings:^[1][2][3]

Disease			History and symptoms			Laboratory findings							Additional findings
			Fever	Goiter	Pain	TSH	Free T4	T3	T3RU	Thyroglobin	TRH	TPOAb
Euthyroid sick syndrome		Mild	+	–	–	Normal	Normal	↓	↑	–	Normal	–	Additional findings of underlying condition
		Moderate	+	–	–	Normal /↓	Normal /↓	↓	↑	–	Normal/↓	–
		Severe	+	–	–	↓	N/↓	↓	↑	–	↓	–
Primary hypothyroidism	Autoimmune		+	+/- Diffuse	–	↑	↓	Normal/↓	Normal	Normal/↑	Normal	↑	May be accompanied by other autoimmune diseases
	Thyroiditis		+	+/-	+	↑	↓	Normal	Normal	Normal/↑	Normal	Normal	Infectious thyroiditis associated with neck pain
	Others		–	+/-	–	↑	↓	Normal	Normal	Normal/↑	Normal	Normal	History of hyperthyroidism Drug history
Transient hypothyroidism			+/-	–	+/-	↑	↑	Normal	Normal	↑	Normal	Normal	May present primarily with hyperthyroidism
Subclinical hypothyroidism			–	–	–	↑	Normal	Normal	Normal	↑	Normal	Normal/↑	Asymptomatic
Central Hypothyroidism	Pituitary		+	–	–	Normal/↓	Normal/↓	Normal/↓	↓	Normal	Normal	Normal	Other pituitary hormone deficiencies signs
	Hypothalamus		+	–	–				↑	Normal	↓	Normal	Other pituitary hormone deficiencies signs
Resistance to TSH/TRH			–	–	–	↑	Normal/↓	Normal/↓	Normal	Normal	↑/↓	Normal	Rare

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

The incidence of euthyroid sick syndrome in intensive care unit (ICU) is approximately 70,000 per 100,000 cases of nonthyroidal illness. The prevalence of euthyroid sick syndrome is estimated to be 40,000 per 100,000 cases of nonthyroidal illness. Euthyroid sick syndrome is more commonly seen in elderly population. There is no racial predilection for euthyroid sick syndrome and both men and women are affected equally.

• The incidence of euthyroid sick syndrome in intensive care unit (ICU) is approximately 70,000 per 100,000 cases of nonthyroidal illness.^[1]
• The incidence of euthyroid sick syndrome in hospitalized patients is 11,000 per 100,000 cases of nonthyroidal illness.

• The prevalence of euthyroid sick syndrome is estimated to be 40,000 per 100,000 cases of nonthyroidal illness.^[2]

• 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.^[3]

• Euthyroid sick syndrome has no racial predilection.

• Euthyroid sick syndrome affects men and women equally.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Common risk factors in the development of euthyroid sick syndrome include iodine deficiency, female sex and pregnancy, radiation exposure, elderly, family history of thyroid disease, primary pulmonary hypertension, and infiltrative disease. Other less common risk factors are excessive intake of iodine, textile workers, and diabetes mellitus type I.

Common risk factors in the development of euthyroid sick syndrome includes:^{[1][2][3][4][5]}

• Iodine deficiency
• Female sex and pregnancy
• Radiation exposure
• Elderly
• Family history of thyroid disease
• Primary pulmonary hypertension
• Infiltrative disease

Less common risk factors in the development of euthyroid sick syndrome includes:

• Excessive intake of iodine
• Textile workers
• Diabetes mellitus type I

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

There is insufficient evidence to recommend routine screening for euthyroid sick syndrome.

There is insufficient evidence to recommend routine screening for euthyroid sick syndrome.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

If left untreated, patients with euthyroid sick syndrome may progress to develop hypothyroidism or resolve spontaneously with correction of underlying condition. If underlying condition is not corrected, the thyroid hormone levels starts to drop after 2-3 weeks of initial illness. The symptoms of hypothyroidism may take some additional weeks before they start to appear. The complications of euthyroid sick syndrome depends upon other organ systems involved and underlying disease. The general complications of hypothyroidism as seen in euthyroid sick syndrome include hypothermia, bradycardia, heart failure, dyspnea, myopathy, confusion, apathy and psychosis. Laboratory findings will show increased levels of cholesterol and triglycerides. In addition, patients will have features of organs system involvement. The prognosis varies and depends upon extent of the underlying disease at the time of diagnosis. Patients with low T3 (< 2.3 pg/ml) levels may have a longer hospital stay. Mortality rate is as high as 80% when serum T4 value is <3 mcg/dL.

If left untreated, patients with euthyroid sick syndrome may either progress to:^[1]

• Hypothyroidism: If the underlying condition is not corrected, thyroid hormone levels starts to drop after 2-3 weeks of initial illness. The symptoms of hypothyroidism may take some additional weeks before they start to appear. The common symptoms of hypothyroidism include fatigue, cold intolerance, decreased sweating, hypothermia, coarse skin, and weight gain

If the patient is treated of the underlying condition, thyroid hormones gradually return to normal level and symptoms of hypothyroidism subside.

The complications of euthyroid sick syndrome depends upon the other organ systems involved and underlying disease. The general complications of hypothyroidism as seen in euthyroid sick syndrome include:^[2][3]

• Hypothermia
• Bradycardia
• Heart failure
• Dyspnea
• Confusion
• Apathy
• Psychosis
• Increased serum cholestrol & triglycerides

Depending on the extent of the underlying disease at the time of diagnosis, the prognosis may vary. Patients with low free T3 (< 2.3 pg/ml) levels may have a longer hospital stay and higher rates of intensive care unit admission. Mortality rate is as high as 80% when serum T3 is extremely low and/or T4 value is <3 mcg/dL.^{[4][5][6][7][8]}

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