Subclinical hypothyroidism

Introduction to subclinical hypothyroidism Hypothyroidism (hypothyroidism) is a group of endocrine diseases caused by a variety of thyroid hormone (TH) synthesis, secretion or biological effects. Only serum thyroid stimulating hormone (TSH) levels are mild. Elevated, while serum thyroid hormone (FT4, FT3) levels are normal, patients with no hypothyroidism or only mild hypothyroidism, known as subclinical hypothyroidism (subclinical hypothyroidism), also known as mild Type hypothyroidism, latent hypothyroidism, biochemical hypothyroidism, and decreased thyroid reserve. basic knowledge Sickness ratio: 0.5% Susceptible people: no special people Mode of infection: non-infectious Complications: hypertension, heart failure, angina

The cause of subclinical hypothyroidism

(1) Causes of the disease

The cause of subclinical hypothyroidism is more complicated. Many structural or functional abnormalities can cause thyroid hormone synthesis disorders, causing hypothyroidism, which can be divided into the following four categories:

Primary (thyroid) hypothyroidism has a primary hypothyroidism of approximately 96%, and others are rare, with chronic lymphocytic thyroiditis (CLT, also known as Hashimoto's thyroiditis) being the most common. According to the patient with or without thyroid enlargement, the cause of primary hypothyroidism can be divided into: (1) thyroid gland enlargement: 1 thyroid congenital dysplasia, mostly family tendencies. 2 idiopathic: the cause is unknown, it is said that this disease is the late stage of chronic lymphocytic thyroiditis. 3 after radioactive iodine or thyroidectomy. 4 head and neck tumors after radiation therapy. (2) goiter: 1 thyroid hormone synthesis disorder: caused by autosomal recessive inheritance. 2 due to the mother's iodide or anti-thyroid preparations passed to the fetus. 3 intake of iodine deficiency or natural thyroid-causing substances such as cassava. 4 drugs: anti-thyroid drugs, iodide, phenylbutazone and lithium salts. 5 Chronic lymphocytic thyroiditis: The cause is unknown, may be related to thyroid autoimmune damage, many patients have high titer of peroxidase antibody (TP0-A) and thyroglobulin antibody (TGA), TSH receptor closed type Antibodies may also be one of the causes.

Less common, caused by pituitary disease caused by decreased TSH secretion, such as pituitary tumors, Xi Han disease, pituitary surgery or radiation therapy.

Due to the reduction of thyroid-stimulating hormone releasing hormone (TRH) produced by the hypothalamus, the secretion of TSH in the pituitary is reduced, such as saddle tumor and congenital TRH deficiency.

Thyroid hormones exert biological effects through nuclear receptors. If nuclear receptors are deficient or T3, T4 binding to receptors and post-receptor defects can lead to resistance to thyroid hormones, causing hypothyroidism.

(two) pathogenesis

Subclinical hypothyroidism is due to thyroid hormone synthesis or release disorders, thyroid hormone reduction will inevitably reduce feedback inhibition of TSH, causing elevated TSH, elevated TSH stimulates goiter, hyperplasia and compensatory thyroid hormone release, making Blood thyroid hormones return to normal, but this is normal for thyroid hormones maintained at high TSH levels.

Subclinical hypothyroidism prevention

1. Screening recommendations

It is recommended to screen subclinical hypothyroidism patients (American Thyroid Association) every 5 years in the elderly (American Clinical Endocrine Society) or in people over 35 years of age; especially during pregnancy, infertility and ovulatory dysfunction; and thyroid Family history or personal history of the disease, symptoms or physical examination suggestive of thyroid nodules or hypothyroidism, type 1 diabetes or autoimmune dysfunction in pregnant women need to be screened for subclinical hypothyroidism.

2. Treatment recommendations

Most patients with subclinical hypothyroidism are recommended to use levothyroxine sodium (L-T4) replacement therapy, especially those with anti-thyroid autoantibodies (especially those with TPO-A positive); symptoms suggestive of hypothyroidism; cardiovascular Risk factors for the disease; goiter; pregnant women and patients with infertility and ovulation dysfunction.

3. Follow-up recommendations

For those with mildly elevated TSH in cardiovascular disease; those with TSH 10.0 mU/L; those with negative TPO-A should be followed closely without drug replacement therapy.

Subclinical hypothyroidism complications Complications, hypertension, heart failure, angina

The mental development of the offspring of the subclinical hypothyroidism is still slowing down. It can cause high blood pressure, heart failure, and angina.

Subclinical hypothyroidism Symptoms Common symptoms Myxedema, tired face, dry skin, slow response, heart enlargement, myocardial infarction

Subclinical hypothyroidism is usually asymptomatic, however, about 30% of patients show some symptoms, which may still indicate the presence of subclinical hypothyroidism, such as dry skin (28%), poor memory (24%), and unresponsiveness (22%). ), muscle weakness (22%), fatigue (18%), muscle cramps (17%), chills (15%), eyelid edema (12%), constipation (8%), hoarseness (7%), due to Surgery, radiotherapy and other reasons caused by hypothyroidism are generally no thyroid enlargement, and other causes are often accompanied by goiter, it is worth noting that there is a dose-dependent effect between symptoms and thyroid hormone.

1. Neurobehavioral abnormalities and neuromuscular dysfunction

Such as depression, memory loss, cognitive impairment and a variety of neuromuscular symptoms in the subclinical hypothyroidism patients, can also be manifested as skeletal muscle abnormalities, including serum creatine phosphokinase (CPK) and elevated lactate, etc., although The mental development of the offspring of pregnant women with normal thyroid function and subclinical hypothyroidism is still slowing down.

2. Effects on cardiopulmonary function

Myocardial density was found to be abnormal in myocardium; myocardial systolic and diastolic function were slightly affected in patients with subclinical hypothyroidism at rest and exercise; under exercise load, cardiac output, maximum aortic flow decreased, and lung function was measured as Decreased lung capacity, subclinical hypothyroidism has a milder effect on cardiopulmonary function, although there is a difference compared with normal thyroid function, but it is important that this difference produces serious clinical damage.

3. Risk factors for cardiovascular disease

Because subclinical hypothyroidism is often accompanied by elevated serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), as well as a decrease in high-density lipoprotein cholesterol (HDL-C), is widely considered to be a cardiovascular disease. Risk factors, some studies have found that for every 1mU / L increase in TSH level, TC increased by 0.09 ~ 0.16mmol / L, and the relationship between TSH and LDL-C is more closely in patients with insulin resistance, subclinical hypothyroidism patients can behave For vascular endothelial dysfunction, such as blood flow mediated and endothelium-dependent vasodilation, the latest study found that patients with subclinical hypothyroidism have a higher prevalence of arteriosclerosis and myocardial infarction.

Subclinical hypothyroidism

Hormone determination

Subclinical hypothyroidism FT4, FT3 normal (or mildly decreased FT4, mild hypothyroidism, decreased FT4 in the early stage of hypothyroidism, FT4 is more sensitive than FT3), elevated serum high-sensitivity TSH (sTSH) and hypersensitive TSH (uTSH) The normal reference range of serum TSH is 0.45~4.5mU/L. If sTSH5.0mU/L, FT4, TP0-Ab and thyroglobulin antibody (TGAb) should be added to identify subclinical hypothyroidism or autoimmune at an early stage. Diagnosis of thyroid disease, subclinical hypothyroidism has a persistently high titer of TGAs, and TPO-Ab or TSH combined with inhibitory immunoglobulin (TBII) predicts a greater likelihood of progression to clinical hypothyroidism in the future.

2. Determination of blood components

May be associated with mild, moderate normal cell normal pigmented anemia; blood TC is often elevated, HDL-C is decreased, triglyceride (TG) and LDL-C, apolipoprotein B (Apo-B), homocysteine (Hcy), blood carotene, blood AST, LDH and CPK increased, occasionally hypoglycemia, blood prolactin (PRL) can be elevated.

3. ECG changes

There may be low voltage, sinus bradycardia, T wave low or inverted, prolonged PR interval, atrioventricular separation, prolonged QT interval, myocardial contractility and ejection fraction decreased, left ventricular contraction time prolonged.

4. Thyroid radionuclide scanning

Is the best way to find ectopic thyroid (post-hyoid bone, posterior sternum, mediastinal thyroid, ovarian thyroid, etc.), contralateral thyroid deficiency in the contralateral thyroid gland due to functional compensation and enhanced imaging, radionuclide scanning Functional evaluation of thyroid and thyroid nodules also has a certain significance.

5. Molecular biology examination

Congenital hypothyroidism, the etiology of familial hypothyroidism depends on molecular biology, and the corresponding analytical methods can be selected according to clinical needs.

6. Pathological examination

If necessary, biopsy or needle aspiration can be used to take thyroid tissue or cells for pathological examination to assist diagnosis.

Diagnosis and diagnosis of subclinical hypothyroidism

diagnosis

The patient had no hypothyroidism or only mild hypothyroidism, serum thyroid hormone was normal (FT4 may be slightly decreased), and only TSH was elevated, which can be diagnosed as subclinical hypothyroidism.

1. Since the half-life of T4 is 7 days, the half-life of T3 is 1 day, and the half-life of TSH is no more than 1 hour. If the TSH is elevated, it indicates that the circulating thyroid hormone is insufficient, and it does not indicate that the increase of TSH causes the thyroid hormone to be compensated. Including TH resistance syndrome).

2. Because subclinical hypothyroidism is usually asymptomatic, even if there are symptoms suggestive of hypothyroidism, due to lack of specificity, easy to be missed or misdiagnosed as other diseases, in any of the following cases, you should think of subclinical hypothyroidism Possibly: unexplained fatigue, chills; intractable, moderate anemia; unresponsive, memory loss; unexplained edema and weight gain; intractable constipation; dyslipidemia, especially blood TC, elevated LDL-C Increased CPK, etc.; heart enlargement, heart failure manifestation and heart rate is not fast, or with decreased myocardial contractility and increased blood volume.

3. If repeated determination of serum TSH and FT4 is within the normal range, the symptoms and signs of hypothyroidism should be evaluated, the history of hyperthyroidism (radiation, partial resection), goiter or family history of thyroid disease; need to review Blood lipid profile; pregnant women or women who wish to have a pregnancy in particular need to pay attention.

Differential diagnosis

Subclinical hypothyroidism needs to be differentiated from iron deficiency anemia, aplastic anemia, chronic nephritis, nephrotic syndrome, chronic renal failure, primary adrenal insufficiency, obesity, normal thyroid morbid syndrome, etc. And laboratory tests can be identified, in addition, there is a need for intermittent refractory compliance with thyroxine treatment, as well as some serious non-thyroid disease recovery period, there are anti-mouse protein heterophilic antibodies (this antibody in some tests It can cause an increase in the TSH caused by a decrease in the TSH receptor caused by the mutation.

1. Normalthyroid sick syndrome with normal thyroid function

Some acute or chronic non-thyroid diseases can affect the production or metabolism of thyroid hormone through different ways, clinical manifestations of low metabolism and low sympathetic response, such as cold, fatigue, edema, loss of appetite, constipation, etc., determination of serum T3 And (or) T4 is low, easy to be misdiagnosed as hypothyroidism, simple T3 is called low T3 syndrome, and severe cases can also show low T4, called low T4 syndrome.

When the body is severely thin, chronic hunger, chronic diseases and serious infections, myocardial infarction and other diseases, the body's 5'-deiodinase activity decreases, while 5-deiodinase activity increases, which reduces the conversion of T4 to T3 in the body and increases the conversion to rT3. Thyroid hormone was found to be T4, T3 decreased, but TSH did not increase, and T3 decreased more obviously. When the primary disease was cured, T4 and T3 returned to normal, which is different from the common clinical primary hypothyroidism. The latter TSH is elevated. In acute myocardial infarction, T3 is reduced by 50% within 3 to 4 days, but TSH is not elevated. When the primary disease is cured, T3 returns to normal, and low T3 syndrome or low T4 syndrome is identified. The signs are very important, because their serum T3, T4 decline is a protective measure of the body, artificially added thyroid hormone preparation to improve the body's metabolic rate, will inevitably exacerbate the condition of the primary disease.

2. Chronic nephritis

Hypothyroidism patients with pale sodium retention showed pale skin, edema, anemia, high blood pressure and elevated blood cholesterol. Some patients are also associated with urinary protein positive, so they are often considered to be kidney disease, and they are not diagnosed and treated correctly. Nephritis patients with chronic renal insufficiency often show abnormalities in thyroid hormone determination, mainly serum T3 decline, which is the protective response of the body to reduce metabolic rate. Nephritis edema is mostly concave, and hypothyroidism is mostly non-concave. There is serosal effusion in hypothyroidism and nephritis, but the plasma protein of hypothyroidism is normal, and the plasma protein of nephritis is low. In addition to edema, hypothyroidism patients are often accompanied by cold, low appetite, rough skin and slow heart rate. , constipation and other metabolically low performance, and nephritis proteinuria is obvious, as long as the hypothyroidism is considered clinically, laboratory examination is not difficult to differentiate diagnosis.

Anemia

About 25% to 30% of patients with hypothyroidism show anemia. The causes of anemia are various. Patients with hypothyroidism are more common in women, often with more menstrual flow, longer menstrual period, leading to excessive blood loss, loss of appetite, undernutrition and stomach acid. Lack of anemia is more serious, and anemia is very common in middle-aged women, and it is not taken seriously. Anemia patients are often accompanied by symptoms such as cold, loss of appetite, fatigue, etc., so many hypothyroidism is often misdiagnosed as anemia for a long time. Without accurate diagnosis and treatment, the thyroid hormone with primary hypothyroidism is low, and TSH is elevated. The differential diagnosis is not difficult. 5% to 10% of patients with primary hypothyroidism have large folic acid deficiency. Cellular anemia, when the effect of iron treatment is not good, should consider the possibility of large cell anemia.

4. Serous effusion

The cause of serous effusion in hypothyroidism is due to slow lymphatic reflux, increased capillary permeability, hydrophilicity of serosal mucin and mucopolysaccharide, and TSH stimulates adenylate cyclase activity in the serosal cavity. Increase the secretion of hyaluronidase, causing ascites, pericardial effusion, pleural effusion and joint cavity effusion, serous effusion can appear alone, or two or more appear, hypothyroidism occurs in serous effusion Often misdiagnosed as tuberculosis, malignant tumors, uremia, pericarditis and connective tissue disease, hypothyroidism in the serous effusion with high protein content, low cell count, high cholesterol content and immunoglobulin content, treatment of diuretics Insensitive, in patients with unexplained serous effusion, thyroid hormone should be measured, except for the possibility of hypothyroidism.

5. Idiopathic edema

The fibroblasts of hypothyroidism patients secrete hyaluronic acid and mucopolysaccharide, which are hydrophilic, block lymphatic vessels, cause mucinous edema, and most of them show non-concave edema. Patients often have symptoms because they are not specific, and they cannot be found for a long time. , was misdiagnosed as idiopathic edema.

6. Pituitary tumor

Long-term hypothyroidism patients, especially children, the pituitary can be increased, sometimes misdiagnosed as pituitary tumors; primary hypothyroidism long-term blood T4 decline, pituitary TSH cells hypertrophy, resulting in increased saddle, some women due to menstruation Disorders and lactation, laboratory tests found that prolactin was slightly elevated, misdiagnosed as pituitary prolactin secretory tumor, patients with hypothyroidism due to elevated TRH, TRH stimulation of prolactin (PRL) effect is stronger than TSH stimulation effect, especially in In some women after abortion and childbirth, it is not difficult to identify pituitary tumors and hypothyroidism by measuring thyroid function. Sometimes patients with hypothyroidism are swollen by hands and feet, with thick lips and thick tongues, hoarseness, increased hands and feet, and increased saddles. Will be misdiagnosed as pituitary growth hormone secretory tumor, but hypothyroidism patients with normal serum growth hormone levels, hypothyroidism patients with cold, constipation, slow heart rate and other symptoms are different from acromegaly, hormone determination can be differential diagnosis.

7. Depression

Patients with hypothyroidism occur more frequently in the elderly. With the increase of age, the prevalence of hypothyroidism also increases. The symptoms of elderly patients are not specific, the progress of the disease is slow, and it is not easy to be found. It is cold, dull and loss of appetite. Symptoms such as depression, poor sleep and depression are diagnosed as senile depression. Elderly people with depression should consider the possibility of hypothyroidism. Patients with hypothyroidism who are treated with anti-depression alone cannot achieve satisfactory results.

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