Nonthyroidal sick syndrome

Introduction to non-thyroid disease syndrome In hunger or systemic diseases, the concentration of thyroid hormone in the body often drops to the level of hypothyroidism. It has been thought that this is a body compensation and the thyroid function is normal, so it is called normal thyroid disease syndrome (ESS), but In severe disease conditions, severely reduced thyroid hormone (T4) concentrations are associated with increased mortality, so some people believe that it is poorly compensated, so now it tends to use the term without subjective color: non-thyroid disease syndrome (nonthyroidillnesssyndrome) , NTIS). NTIS refers to the effect of acute and chronic nonthyroidillness (NTI) on the functional parameters of normal thyroid gland, and the thyroid itself has no lesions. The change in thyroid hormone is related to the severity and duration of the underlying NTI, regardless of the type of disease. Common in fasting and chronic malnutrition, severe infections, burns, major surgery and trauma, heart, liver, kidney disease or failure. basic knowledge The proportion of illness: 0.0035% Susceptible people: more common in the elderly Mode of infection: non-infectious Complications: varicose veins

Non-thyroid disease syndrome

Acute and chronic diseases

Infectious diseases, fever, acute myocardial infarction, chronic degenerative diseases, chronic diseases such as cirrhosis, chronic kidney disease and renal insufficiency, diabetes and other metabolic diseases, malignant tumors, etc., can cause this disease.

drug

Such as propranolol, propylthiouracil, glucocorticoids, iodine-containing contrast agents.

With low T3 as the main change, the normal type of T4, the so-called low T3 syndrome: mainly due to the inhibition of peripheral 5'-deiodinase activity, decreased activity, and reduced T4 to T3 conversion, but at this time the periphery 5'- Deiodinase activity is normal, resulting in a relative increase in T4 to rT3 conversion.

Low T4 is the main change, the normal type of T3, the so-called low T4 syndrome: low T4 syndrome occurs in relatively critical patients, relatively rapid, the degree of T4 reduction reflects the severity of the disease, is the prognosis One of the important indicators may be related to the following factors: peripheral 5'-deiodinase abnormality; T4 and thyroid hormone binding protein binding inhibition; plasma albumin, thyroid binding globulin decreased, leading to TT4 reduction; liver to thyroid hormone Ingestion and metabolic abnormalities cause a decrease in T4.

High T4 syndrome: rare, mainly elevated serum TT4 levels, common in chronic hepatitis, primary biliary cirrhosis, severe acute intermittent porphyria, etc., may be the patient's serum thyroid-binding globulin (TBG) liter High, partly related to taking iodine-containing drugs.

Age factor

Newborns, the incidence of the elderly is higher, foreigners have reported that the elderly can reach 14%.

Nutritional status

Anorexia, malnutrition, hunger, protein deficiency, etc.

Severe trauma

Anesthesia, after surgery, etc.

Pathogenesis

1. Low T3 syndrome (normal T4, low T3) 5'-monodeiodinase (5'-MDI) causes T4 to switch to T3, rT3 to 3,3'-diiodotyrosine, low T3 syndrome At the time, the inhibition of tissue 5'-MDI can lead to a decrease in T4 to T3, a decrease in the rate of T3 (PR-T3), a delay in rT3 clearance, and a normal rT3 production rate (PR-rT3) per day, blood rT3. Elevation, for a disease, the degree of decline in TT3 blood concentration is related to the severity of the disease. In patients with moderately serious disease, blood TT4 is in the normal range, because the combination of protein and hormone is reduced, the effect on T4 is very high. At T3, the proportion of FT4 increases, KT4 blood concentration and free T4 index often increase. Blood TSH and its response to TRH are generally normal, which is beneficial to reduce energy metabolism and prevent energy consumption in critically ill patients. Protective response.

2. Low T4 syndrome (low T4, low T3) Patients with more severe disease have lower serum T3 and T4, and some patients have more obvious combination of protein and hormone reduction. In other patients, TSH secretion is reduced due to severe disease. Therefore, the sensitive TSH assay can find that the TSH blood concentration is lower than normal, the response to TRH is slow, and the blood concentration of TT4, FT4 and TSH is decreased, suggesting that the pituitary function is inhibited, which may be related to cytokines such as IL-1, IL- 2, IL-6, TNF-, INF- and other effects on the pituitary, although T4 decreased, PR-rT3 decreased, but its degradation was weakened by severe disease, blood rT3 is still elevated, after the underlying disease improved, TSH level It can be elevated until the T4 and T3 blood levels return to normal, and the magnitude of serum T4 reduction correlates with the patient's prognosis.

3. High T4 syndrome Some NTIS patients have elevated serum TT4. These patients have elevated serum TNG, which is common in patients with severe acute intermittent porphyria, chronic hepatitis, and primary biliary cirrhosis. At this time, FT4 is normal, serum TT3 may be normal, FT3 normal low or decreased, serum rT3 increased, with amiodarone or with iodine oral gallbladder contrast agent, serum FT4 is often elevated, these drugs reduce liver uptake of T4 and reduce T4 to T3 conversion, In patients with autonomous thyroid nodules, hyperthyroidism can be induced. The general dose of oral gallbladder contrast agent has less than 24h effect on T4. NTIS patients with elevated serum TT4 and FT4, especially those taking iodine, should be carefully examined for hyperthyroidism. Because the drug or the disease itself has an effect on the conversion of T4 to T3, the serum T3 may be normal or even low, but TT4 may suddenly increase during the disease.

The pathogenesis of NTIS has not been fully elucidated. Studies have shown that the reduction of T3 production in surrounding tissues is not only related to the decrease in 5'-MDI activity and concentration, but also related to the decrease in T4 uptake by tissues. In patients with chronic renal failure, some substances such as 3-carboxyl -4-methyl-5-propyl-2-furanoic acid (CMPF) and indole sulfate are elevated, and bilirubin and free fatty acids (FFA) are increased in other non-thyroid disease patients, Animal studies have confirmed that these substances reduce the uptake of T4 in rat liver, but these substances do not affect TSH secretion. Recently, studies on the pathogenesis of NTIS have focused on cytokines and immune factors, and cytokines have different organisms for different target cells. Role, they can produce autocrine, paracrine and endocrine effects, and these local cytokines interact with immune factors, and the network is a local regulatory system. Usually, cytokines are directed against inflammation, oxidative stress, infection and cell damage. The cytokine acts by binding to a specific cell surface receptor (such as the thyroid gland), usually in the case of non-thyroid severe disease. Hypothalamic - pituitary - thyroid axis cytokines may be mainly derived from circulating blood, but the synthesis of thyroid cells and release of cytokines, may autocrine or paracrine regulation of thyroid function related.

The effects of cytokines and immune factors on TH synthesis and secretion may be primary factors or secondary results of other pathophysiological processes. There are many other factors in the changes of TIS, T4, rT3 and TSH in NTIS serum, including Hypothalamic-pituitary-thyroid axis regulation and TH synthesis, secretion, metabolism, etc., whether low T3 syndrome, low T4 syndrome or high T4 syndrome are often the result of a combination of factors.

Non-thyroid disease syndrome prevention

Because the disease is related to age, the incidence rate is high in newborns and the elderly, and it is reported that the elderly can reach 14%. It is also associated with anorexia, malnutrition, hunger, and protein deficiency. Diseases and acute and chronic diseases such as infectious diseases, fever, acute myocardial infarction, chronic degenerative diseases, chronic diseases such as cirrhosis, chronic kidney disease and renal insufficiency, diabetes and other metabolic diseases, malignant tumors, severe trauma, anesthesia There is a direct correlation between after surgery and so on. Therefore, early detection of early diagnosis is the key to the prevention and treatment of this disease. In the presence of the above diseases, it should be actively treated to avoid increasing the incidence of this disease.

Non-thyroid morbid syndrome complications Complications varicose veins

For those who have this disease in childhood and have FT3, FT4 reduction, there may be developmental disorders of the central nervous system and skeletal development disorders, resulting in mental retardation and short stature. Adults have reduced motor function, lower basal metabolic rate, and can be complicated by obesity. Other complications such as varicose veins, increased risk of cardiovascular disease, and increased risk of diabetes.

Non-thyroid morbid syndrome symptoms common symptoms hypoproteinemia slow response polydipsia hepatosplenomegaly varicose liver function abnormality spider sputum polyuria

Thyroid function syndrome is an acute stress condition in the body. Chronic severe disease has a low level of serum T3 or T4, and rT3 level is increased. The TSH of most patients is normal. This is the adaptive change of the body. Generally, NTIS is not available. The obvious clinical symptoms are mainly the clinical manifestations of the primary disease and the changes in the indicators of thyroid function tests.

Infectious diseases may have fever, increased white blood cell count, systemic poisoning symptoms; nephrotic syndrome may have facial edema, massive proteinuria, hypoproteinemia, etc.; patients with chronic renal failure may have facial edema, hypertension, anemia, BUN and elevated serum creatinine; liver disease patients with yellow skin stains, spider mites, liver palm, varicose veins, hepatosplenomegaly, abnormal liver function; diabetic patients may have more drink, more urine, more food, weight loss, fatigue , blood glucose and glycosylated hemoglobin increased; myocardial infarction patients may have a history of coronary heart disease, myocardial enzymology changes, ECG changes; other heart, lung disease has its own clinical manifestations and signs; patients with malignant tumors may have local and metastatic symptoms, tumors Marker elevation, imaging changes and histopathological evidence; infectious diseases such as malaria, typhoid, encephalitis, meningitis, etc. have specific sources of infection and characteristic clinical manifestations; drug-induced patients have a history of taking drugs, more common The drugs include glucocorticoids, dopamine, propranolol, etc. Other stress conditions include history of trauma, history of surgery, and history of toxic exposure in poisoned patients.

Low T3 syndrome thyroid function test may show serum TT3, FT3 decreased, TT4, FT4 normal, TSH normal, rT3 increased, the degree of T3 decline is related to the severity of the disease, and the prognosis of the disease, severe disease may appear low T4 Syndrome, thyroid function test can show serum TT4, FT4 decreased, TT3, FT3 also decreased, TSH normal or decreased, rT3 can be increased, the degree of T4 decline is significantly related to the severity of the disease, and can be used as a disease prognosis One of the indicators, high T4 syndrome is rare in clinical, accounting for about 1%. Thyroid function tests may show elevated serum TT4, normal FT4, normal TT3, normal or decreased FT3, and elevated rT3.

Examination of non-thyroid morbid syndrome

1. Low T3 syndrome thyroid function test is generally normal T4 (TT4, FT4), low T3 (TT3, FT3), rT3 is elevated, it should be noted that the T4 of severe patients can also be reduced, the patient's TSH and T4 are normal, according to this Can be differentiated from hypothyroidism.

2. Low T4 syndrome serum T4 decreased, can be accompanied by T3 decreased, TSH is normal, attention to severe cases of TSH can also be reduced, and the response to TRH is slow, indicating pituitary hypothyroidism, but the patient's rT3 level is high, in After the basic lesions are improved, TSH, T4, and T3 can all return to normal. Care should be taken to avoid misdiagnosis as hypothyroidism.

3. Partial application of dopamine and glucocorticoids may cause a decrease in serum TSH levels in NTIS, which is related to drug inhibition.

4. During pregnancy, due to increased secretion of estrogen in the body, TT4 is elevated, FT4, FT3, rT3 and TSH are normal, and attention should be paid to the difference between high T4 syndrome.

5. 2% to 3% of patients with low T3 syndrome and low T4 syndrome may have obvious TSH abnormalities (TSH>20mU/L, TSH<0.01mU/L), and attention should be paid to hyperthyroidism and hypothyroidism. Identification.

In the case of comorbidities, the corresponding myocardial enzymology examination and electrocardiogram examination can be performed.

Diagnosis and diagnosis of non-thyroid morbid syndrome

Diagnostic criteria

The diagnosis of NTIS is mainly determined by the performance, degree, laboratory examination and follow-up observation of thyroid hormone changes in the primary disease. If the above-mentioned primary cause of low T3 syndrome exists, serum TT3 is decreased, FT3 is normal or decreased, serum rT3 is elevated, serum TSH and TT4 are normal, FT4 is increased or normal, free T4 index is often increased, and generally low T3 syndrome can be diagnosed. If the patient has severe consumptive diseases (such as cirrhosis, renal insufficiency, burns, severe infection) , long-term hunger, anorexia nervosa, major surgery, malignant tumors, etc.), blood TT3, TT4, FT3 level decreased, FT4 normal or decreased, blood TSH normal or low, rT3 normal or elevated, TBG normal or low TRH stimulation test is normal or unresponsive, can be diagnosed as low T3 or low T4 syndrome, some patients in the acute phase of the disease, serum TT4 increased, FT4 increased or normal, TT3 may be normal, FT3 normal low or lower Normal, elevated serum rT3 should be suspected of high T4 syndrome (common in older women, mostly with a history of taking iodine), but should be differentiated from T4 hyperthyroidism.

Differential diagnosis

1. Primary or secondary hypothyroidism In NTIS, thyroid dysfunction is quite common, its severity predicts the patient's prognosis, serum T3 is low, indicating cirrhosis, advanced congestive heart failure and other serious systemic diseases. Increased mortality (the same significance for lower T4), and patients with low serum T4 and concomitantly reduced blood T3 had the worst prognosis.

It is obvious that patients with NTIS have difficulty in diagnosing thyroid disease. At this time, serum TT4 and TT3 may be normal in patients with hyperthyroidism. However, serum FT4 and FT3 still have diagnostic value. Serum TSH is undetectable (<0.10U/ml) in hyperthyroidism, but TSH in patients with only 7% or less in NTIS is undetectable. It is common in patients treated with dopamine and glucocorticoids. In NTIS, clinical hypothyroidism is also difficult to diagnose. If TSH is above 25-30U/ml, it is highly likely Primary hypothyroidism, about 12% of NTIS patients with TSH above normal, less than 3% of NTIS patients with TSH above 20U/ml, NTIS patients who did not use TSH secretion drugs, serum FT4 strongly suggested hypothyroidism below normal However, rT3 is not helpful in the diagnosis of hypothyroidism. The level of TSH in secondary hypothyroidism may be low, normal or mildly elevated. If NTIS patients have no pituitary or hypothalamic disease, blood cortisol is often elevated or normal. PRL and gonadotropin are normal. On the contrary, if blood cortisol and gonadotropin are decreased and PRL is elevated, it supports central (pituitary or hypothalamic) injury. It is best to review after acute NTIS recovery in the diagnosis of thyroid disease. Thalamus-pituitary Gland axis function.

Although the serum T3 is low in NTIS, many scholars believe that the thyroid function of these patients is normal, because most patients with normal serum TSH, some data suggest that the synthesis, secretion, regulation and role of TSH in NTIS are abnormal, when NTIS At the time of recovery, a temporary increase in serum TSH indicates that TSH is inhibited at NTIS, which is stressful with NTIS, with cortisol, elevated catecholamine levels, and heat exhaustion. The normal thyroid function in NTIS is explained as follows: 1TH The level of low time is short and not serious; 2 the clinical mild hypothyroidism is not sensitive; 3 the body tissue is more sensitive to T3; 4 the body has active TH other than T3 (sulfate-T3); 5 low T3 has less effect on TSH; 6NTIS The number of T3 receptors and affinity increase.

2. T4 type hyperthyroidism Most patients with hyperthyroidism, although serum T3 and T4 are increased, but the increase of serum T3 concentration is more obvious than serum T4, suggesting that the thyroid gland release more T3 and the distal tissue will transform T4 into T3, T4 type hyperthyroidism It refers to a type of hyperthyroidism in which serum T4 is significantly increased, and serum T3 is generally normal. T4 type hyperthyroidism is mainly seen in elderly people who have been exposed to excessive iodine, elderly patients or elderly patients, and long-term hospitalization is more common. Excessive iodine intake causes the gland to synthesize more T4. If there is no history of excessive iodine intake, it is suggested that the T4 transformation into T3 is inhibited in peripheral tissues, while the serum rT3 is elevated in high T4 syndrome, and TSH can be identified normally.

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