What Is Subclinical Hypothyroidism?

Subclinical hypothyroidism is usually asymptomatic, however, about 30% of patients show some symptoms, which can 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%). Hypothyroidism due to surgery, radiotherapy, and other reasons is generally free of goiter, while other causes are often accompanied by goiter. It is worth noting that there is a dose-dependent effect between symptoms and thyroid hormones.

Subclinical hypothyroidism

Hypothyroidism (hypothyroidism, referred to as hypothyroidism) is a group of endocrine diseases caused by insufficient synthesis, secretion, or biological effects of thyroid hormone (TH) caused by multiple reasons. Only the level of serum thyroid stimulating hormone (TSH) is slightly elevated, while the level of serum thyroid hormone (FT4, FT3) is normal, and the patient has no hypothyroidism or only mild hypothyroidism, which is called subclinical hypothyroidism hypothyroidism (referred to as subclinical hypothyroidism), also known as mild hypothyroidism, latency hypothyroidism, biochemical hypothyroidism, and reduced thyroid reserve. This type of patient is usually found during a routine physical examination or at the time of consultation due to some non-specific symptoms or hypercholesterolemia. Elevated serum TSH due to other reasons, such as: recently adjusted levothyroxine dose due to failure to reach steady state, especially in patients with poor compliance; inpatients with serum TSH during recovery from severe disease or recovery from destructive thyroiditis Transient elevations, including subacute thyroiditis and postpartum thyroiditis after viral infections; untreated primary adrenal insufficiency; patients treated with recombinant human TSH injections; and the presence of heterophilic antibodies against mouse proteins, which Antibodies can cause false elevated TSH in some tests. Although central hypothyroidism (usually hypothalamic) may cause a slight increase in serum TSH concentration (due to the presence of biologically inactive TSH molecules in the circulation), serum FT4 concentration in these patients is usually significantly reduced.

Subclinical hypothyroidism symptoms and signs

1. Neurobehavioral abnormalities and neuromuscular dysfunctions such as depression, memory loss, cognitive impairment, and various neuromuscular symptoms occur in patients with subclinical hypothyroidism. Can also be manifested as skeletal muscle abnormalities, including elevated serum creatine phosphate kinase (CPK) and lactic acid. Despite normal thyroid function, the offspring of pregnant women with subclinical hypothyroidism still experience slower intellectual development.

2. Impact on cardiopulmonary function Myocardial density measurement found abnormalities in the myocardium; in resting and exercise states, myocardial contraction and diastolic function of patients with subclinical hypothyroidism were slightly affected; under exercise load, cardiac output, maximum arterial flow decline. Pulmonary function was measured as reduced vital capacity. The effect of subclinical hypothyroidism on cardiopulmonary function is slight. Although there are differences compared with those with normal thyroid function, it is important whether this difference causes serious clinical damage.

3. Risk factors for cardiovascular disease Because subclinical hypothyroidism is often accompanied by an increase in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and a decrease in high-density lipoprotein cholesterol (HDL-C), It is widely regarded as a risk factor for cardiovascular disease. Studies have found that for every 1mU / L increase in TSH level, TC increases by 0.09 to 0.16mmol / L, and the relationship between TSH and LDL-C is closer in patients with insulin resistance. Patients with subclinical hypothyroidism can show abnormal vascular endothelial dysfunction, such as impaired blood flow-mediated and endothelium-dependent vasodilation. Recent studies have found that the prevalence of aortic sclerosis and myocardial infarction is higher in patients with subclinical hypothyroidism.

Subclinical hypothyroidism medication

Possible outcomes of untreated subclinical hypothyroidism include: cardiac insufficiency or adverse cardiac endpoints (including atherosclerotic disease and cardiovascular mortality), elevated TC and LDL-C, symptoms of systemic hypothyroidism or Neuropsychological symptoms, and progress to clinical symptomatic hypothyroidism.

The treatment of patients with subclinical hypothyroidism should be determined according to the specific circumstances of the patient. Antithyroid antibody-positive patients, even if their blood lipids are normal, need to be treated because they are more likely to develop clinical hypothyroidism. However, even in the absence of antithyroid antibodies, elevated serum TSH levels are associated with an increased prevalence of clinical hypothyroidism. For patients with a TSH concentration of 4.5 to 10 mU / L, the correlation between subclinical hypothyroidism and symptoms of systemic hypothyroidism or cardiac insufficiency has not been determined. There is currently no population-based study, but the risk of clinical hypothyroidism may progress. Higher than those with TSH 4.5mU / L. Although conventional levothyroxine treatment is not recommended, thyroid function needs to be followed every 6 to 12 months to monitor TSH levels; those with TSH 10mU / L have clinical type A The risk of reduction is increased, and treatment is recommended to improve symptoms and reduce LDL-C levels. 14% to 21% of patients after treatment with levothyroxine can avoid clinical hypothyroidism. In addition, pregnant women and infertile women with ovulation disorders also need treatment.

1. Use levothyroxine sodium (L-T4) replacement therapy, starting with small doses. The initial dose is generally 0.05 0.075 mg / d (patients with coronary heart disease and elderly patients should start with a smaller dose, 0.0125 0.025 mg / d), and gradually increase the amount until the serum TSH reaches a normal level. Levothyroxine sodium (L-T4) has a slow and long-lasting effect, with a half-life of about 8 days. After starting treatment and after changing the dose, serum TSH levels are measured every 6 weeks; once TSH levels are stable, TSH is measured once a year; if progressive hypothyroidism occurs, the dose of levothyroxine sodium needs to be increased.

Treatment has three benefits:

(1) It can significantly improve the symptoms, mood and cognition of patients.

(2) Prevent its development into clinical hypothyroidism. Epidemiological data show that 4.3 to 14.3 patients need to be treated in order to prevent 1 patient from developing into clinical hypothyroidism, which is similar to other preventive medical measures such as statins for hyperlipidemia.

(3) Improve the abnormal lipid profile, reduce TC and LDC-C to varying degrees, and reduce the risk of death from cardiovascular disease. A recent meta-analysis showed that by treating subclinical hypothyroidism, TC and LDL- C decreased by 0.2 mmol / L and 0.26 mmol / L, respectively, but HDL-C did not change significantly. In patients with higher cholesterol levels (6.21mmol / L) and in patients with subclinical hypothyroidism due to inadequate treatment of clinical hypothyroidism, TC decreased more significantly.

2. Due to the skewed distribution of serum TSH values in the population, most individuals have normal TSH at the lower limit; even TSH at the normal upper limit will cause TC to increase, and TC will decrease as TSH levels decrease after L-T4 replacement therapy; Even normal high-limit TSH will show vascular endothelial dysfunction, so the optimal target range for TSH treatment is 0.5 to 2.0 mU / L.

3. For those who have symptoms of hypothyroidism with a TSH of 4.5 to 10 mU / L, the physician can give experimental treatment of levothyroxine sodium for several months, while monitoring the improvement of hypothyroidism symptoms, and continue treatment if the symptoms improve significantly.

4. The normal range of serum T3 and T4 concentrations is large. Patients have different needs and sensitivities to thyroid hormones in different living environments and labor intensity. Treatment should emphasize the principle of individualization. To avoid over-treatment, causing adverse consequences such as hyperthyroidism, atrial fibrillation and osteoporosis.

5. Clinical hypothyroidism When subclinical hypothyroidism occurs during treatment with levothyroxine sodium, the drug dose needs to be adjusted so that TSH is within the reference range. The speed of dose adjustment depends on the patient's age and concomitant disease. A slight increase in TSH in patients who feel good, especially those with arrhythmia or other heart diseases, does not require drug dose adjustment.

Subclinical hypothyroidism diet health care

The diet should be light, pay attention to hygiene, and match the diet reasonably.

Preventive care for subclinical hypothyroidism

1. Screening recommendations recommend screening subclinical hypothyroidism patients (American Thyroid Association) every 5 years in the elderly (American Clinical Endocrinology Association) or in people older than 35 years; especially pregnant women, infertility and abnormal ovulation ; And women with a family or personal history of thyroid disease, symptoms or physical examination suggesting thyroid nodules or hypothyroidism, type 1 diabetes, or autoimmune disorders who wish to conceive should be screened for subclinical hypothyroidism.

2. Treatment recommendations It is recommended that most patients with subclinical hypothyroidism use levothyroxine sodium (L-T4) replacement therapy, especially those with positive antithyroid autoantibodies (especially TPO-A positive); there are indications of hypothyroidism Symptoms; risk factors for cardiovascular disease; goiter; pregnant women and patients with infertility and ovulation disorders.

3. Follow-up recommendations For elderly patients with cardiovascular disease with a slight increase in TSH; those with TSH 10.0 mU / L; patients with TPO-A negative should be closely followed up without drug replacement therapy.

Pathological causes of subclinical hypothyroidism

The causes of subclinical hypothyroidism are more complex, and many structural or functional abnormalities can cause thyroid hormone synthesis disorders and hypothyroidism. It can be divided into the following 4 categories:

1. Primary (thyroid) hypothyroidism accounts for about 96% of primary hypothyroidism, and the others are rare. Among them, chronic lymphocytic thyroiditis (CLT, also known as Hashimoto's thyroiditis) is the most common.

According to the patients with or without goiter, the etiology of primary hypothyroidism can be divided into:

(1) The thyroid is not enlarged:

Congenital dysplasia of the thyroid gland is more familial.

Idiopathic: The cause is unknown, and it is said that this disease is the late stage of chronic lymphocytic thyroiditis.

After radioiodine or thyroidectomy.

After radiotherapy for head and neck tumors.

(2) Goiter:

Thyroid hormone synthesis disorder: caused by autosomal recessive inheritance.

Caused by fetal iodide or antithyroid preparation passed to the fetus.

intake of iodine deficiency or natural goiter-causing substances such as cassava.

Drugs: caused by anti-thyroid drugs, iodide, butepine and lithium salts.

Chronic lymphocytic thyroiditis: The etiology is unknown and may be related to thyroid autoimmune damage. Many patients have high titers of peroxidase antibody (TP0-A) and thyroglobulin antibody (TGA), TSH receptor blocking type Antibodies may also be one of the causes.

2. Secondary (pituitary) hypothyroidism is less common and is caused by pituitary disease that reduces TSH secretion, such as caused by pituitary tumors, Sheehan's disease, pituitary surgery, or radiation therapy.

3. Tertiary (hypothalamic) hypothyroidism is rare. It is caused by the reduction of thyroid-stimulating hormone-releasing hormone (TRH) produced by the hypothalamus, which reduces the secretion of TSH in the pituitary, such as tumors on the saddle and congenital TRH deficiency .

4. Peripheral resistance to thyroid hormones (RTH) Thyroid hormones exert biological effects through nuclear receptors. If nuclear receptors are lacking or T3, T4 binds to the receptors, and postreceptor defects can lead to peripheral thyroid hormones. Effect of resistance, causing hypothyroidism.

Diagnosis of subclinical hypothyroidism

Subclinical hypothyroidism needs to be distinguished from iron deficiency anemia, aplastic anemia, chronic nephritis, nephrotic syndrome, chronic renal failure, primary adrenal insufficiency, obesity, and normal thyroid morbid syndrome. And laboratory tests can be identified. In addition, there is a need for intermittent adherence with thyroxine therapy, as well as the recovery of some severe non-thyroid diseases. Heterophilic antibodies to mouse proteins (this antibody can cause false elevated TSH in some tests) ), And TSH receptor inactivation caused by mutation caused by TSH increased.

1. Normal thyroid sick syndrome (normal thyroid sick syndrome) Some acute or chronic non-thyroid diseases can affect the production or metabolism of thyroid hormones through different pathways, clinical manifestations of low metabolism and low sympathetic nervous response, such as cold, Weakness, edema, loss of appetite, constipation and other manifestations. Serum T3 and / or T4 are measured to be low, which is easily misdiagnosed as hypothyroidism. Simple T3 depression is called low T3 syndrome, and severe cases can also show low T4, called low T4 syndrome.

When the body is severely wasted, chronically hungry, chronic diseases and serious infections, myocardial infarction and other diseases, the 5'-deiodinase activity in the body decreases, and the 5-deiodinase activity increases, so that the conversion of T4 to T3 in the body is reduced, and the conversion to rT3 is increased. The thyroid hormone test found that T4 and T3 decreased, but TSH did not increase, of which T3 decreased more significantly. When the primary disease is cured, T4 and T3 return to normal, which is different from the general clinical hypothyroidism. , The latter TSH is elevated. In acute myocardial infarction, T3 decreases by 50% within 3 to 4 days. However, TSH does not increase, and when the primary disease is cured, T3 returns to normal. It is very important to distinguish low T3 syndrome or low T4 syndrome, because their serum T3 and T4 decline is a protective measure for the body. Artificially taking thyroid hormone preparations to increase the body's metabolic rate will inevitably exacerbate the primary disease. Condition.

2. Chronic nephritis patients with hypothyroidism due to sodium retention show 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 cannot be obtained correctly Diagnosis and treatment. Patients with chronic renal insufficiency of nephritis often show abnormal measurement of thyroid hormones, mainly due to a decrease in serum T3, which is a protective response to reduce the body's metabolic rate. Nephritis edema is mostly concave. Hypothyroidism is mostly non-concave. Both hypothyroidism and nephritis have serosal exudate, but the plasma protein of hypothyroidism is normal, while the plasma protein of nephritis is low. In addition to edema, patients with hypothyroidism are often accompanied by poor metabolism, such as fear of cold, low appetite, rough skin, slow heart rate, constipation, and nephritis proteinuria. As long as the hypothyroidism is considered clinically, the laboratory test is not difficult to make a differential diagnosis.

3. Anemia About 25% to 30% of patients with hypothyroidism show anemia. There are many reasons for anemia. Patients with hypothyroidism are more common in women, often accompanied by heavy menstrual flow and long menstrual periods, leading to excessive blood loss. At the same time, loss of appetite, nutrition Deficiency and gastric acid deficiency worsen anemia. Anemia is very common in middle-aged women and is not taken seriously. Patients with anemia often have symptoms of cold, loss of appetite, and fatigue, so many hypothyroidisms are often misdiagnosed as anemia for a long time without an accurate diagnosis. And treatment. Primary hypothyroidism is low in thyroid hormone and TSH is elevated, and the differential diagnosis is not difficult. 5% to 10% of patients with primary hypothyroidism exhibit large cell anemia due to folic acid deficiency. When the effect of iron treatment is not good, the possibility of large cell anemia should be considered.

4. Serous membrane effusion hypothyroidism occurs due to slow lymphatic reflux, increased capillary permeability, hydrophilicity of mucin and mucopolysaccharides in the serosa, and TSH stimulation of adenosine in the serosa. Acid cyclase activity, which increases the secretion of hyaluronidase, causing ascites, pericardial effusion, pleural effusion, and joint effusion. Serous membrane effusion can

Subclinical hypothyroidism examination method

Laboratory inspection:

1. Hormone determination: The subclinical hypothyroidism FT4 and FT3 are normal (or the FT4 is slightly decreased, and the initial stage of mild hypothyroidism and hypothyroidism is mainly FT4 decline, and FT4 is more sensitive than FT3). uTSH) increased. 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 determine the early subclinical hypothyroidism or autoimmune thyroid. Diagnosis of the disease. Subclinical hypothyroidism with persistently high titers of TGAb, TPO-Ab, or TSH-binding inhibitory immunoglobulin (TBII) is highly predictive of future progression to clinical hypothyroidism.

2. Determination of blood composition can be accompanied by mild and moderate normal cell normal pigment anemia; blood TC often increases, HDL-C decreases, triacylglycerol (TG) and LDL-C, apolipoprotein B (Apo-B), Homocysteine (Hcy), blood carotene, blood AST, LDH and CPK increased. Occasionally, hypoglycemia may increase PRL.

Other auxiliary checks:

1. ECG changes may have abnormalities such as low voltage, sinus bradycardia, low or flat T wave, prolonged PR interval, atrioventricular separation, and prolonged QT interval. Myocardial contractility and ejection fraction decreased, and left ventricular contraction time prolonged.

2. Thyroid radionuclide scanning is the best method to find ectopic thyroid (back hyoid, sternum, mediastinal thyroid, ovarian thyroid, etc.). The contralateral thyroid of congenital one-lobe thyroid deficiency is manifested by functional compensation. Like enhancement. Radionuclide scanning is also of significance for the functional evaluation of thyroid and thyroid nodules.

3. Molecular biology examination The diagnosis of congenital hypothyroidism and familial hypothyroidism depends on molecular biology examination. Corresponding analysis methods can be selected according to clinical needs.

4. Pathological examination If necessary, thyroid tissue or cells can be obtained by biopsy or needle aspiration for pathological examination to assist diagnosis.

Complications of subclinical hypothyroidism

The sub-clinical hypothyroidism of pregnant women still slows the intellectual development of their offspring.

Prognosis of subclinical hypothyroidism

Studies of the natural history of subclinical hypothyroidism have shown that 57% of patients are still subclinical hypothyroidism, 34% of patients develop clinical hypothyroidism, and 9% of patients return to normal thyroid function. The predictive factors for the development of clinical hypothyroidism are: antithyroid autoantibody positive; serum TSH greater than 20mU / L; Graves' disease receiving radionuclide therapy; head and face tumor receiving radiotherapy.

Pathogenesis of subclinical hypothyroidism

Subclinical hypothyroidism is due to obstacles to the synthesis or release of thyroid hormones. The reduction of thyroid hormones will necessarily reduce the feedback inhibition of TSH, which will cause the rise of TSH. Elevated TSH stimulates goiter, hyperplasia, and increased release of compensatory thyroid hormones. Blood thyroid hormone returned to normal, but this is normal thyroid hormone maintained at high TSH levels.