Hyperthyroidism in children
Introduction
Introduction to hyperthyroidism in children Hyperthyroidism (hyperthyroidism) refers to clinical syndrome caused by excessive secretion of thyroid hormone, often accompanied by goiter, extraocular protrusion and increased basal metabolic rate. Children with hyperthyroidism are mainly found in diffuse toxic thyroid gland. Swelling (Graves disease), about 2% of the fetuses with Graves' disease will have hyperthyroidism after birth, which is caused by the high concentration of thyrotropin receptor stimulating antibody in the mother through the placenta into the fetus. It usually resolves gradually around 3 months after birth. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: arrhythmia, atrial fibrillation, difficulty swallowing, amenorrhea
Cause
Causes of hyperthyroidism in children
(1) Causes of the disease
In addition to diffuse toxic goiter (Graves), other causes of hyperthyroidism can cause chronic lymphatic thyroiditis, subacute thyroiditis, thyroid-adenoma, and McCune Albright syndrome. , thyroid cancer, hyperthyroidism induced hyperthyroidism, excessive secretion of TSH, pituitary adenoma, hypothalamic hyperthyroidism, iatrogenic hyperthyroidism.
Nodular toxic goiter
Also known as Plummer disease, the cause is the same as Graves disease, the thyroid gland is nodular hyperplasia, some can develop into adenoma, some people think that nodules can be caused by "autonomic" hyperfunction.
2. Subacute thyroiditis causes hyperthyroidism
As the thyroid tissue is destroyed by inflammation, thyroid hormone stored in the thyroid gland is released into the blood, and temporary hyperthyroidism occurs.
3. Chronic lymphocytic thyroiditis (Hashimoto's disease)
Hyperthyroidism is also an autoimmune disease of the thyroid gland. When the thyroid tissue is damaged and the vesicle ruptures and the thyroid hormone is released, hyperthyroidism may occur. However, the thyroid pathology has diffuse lymphocytic infiltration, glandular epithelial atrophy and fibrosis. There is hypothyroidism (hypothyroidism), so this hyperthyroidism is also temporary, or pseudo-hyperthyroidism.
4. Iatrogenic hyperthyroidism
Some parents with low-grade children mistakenly believe that taking more medicine can speed up the condition, so taking too many thyroid tablets, so that children with weight loss, palpitations, sweating and other hyperthyroidism, taking lithium carbonate can also cause hyperthyroidism, its mechanism and iodine The compound caused by hyperthyroidism is similar: due to the expansion of the iodine pool in the thyroid gland, the resulting escapement phenomenon, resulting in hyperthyroidism.
5. Iodomethyl hydrazine
It usually occurs after preventing iodine deficiency and generally increasing iodine intake or taking iodine-containing drugs. In the prevention and treatment of iodine deficiency diseases, the incidence of hyperthyroidism is increased. Lebanon reported that since 1995, the national unified iodized salt supplemented iodine, hyperthyroidism The number of patients increased by 2 to 6 times, and the annual incidence increased from 0.02% to 0.07%. In the United States, the rate of remission in patients with Graves has been reduced in recent years. The analysis is related to high iodine diet. The recurrence rate of postoperative hyperthyroidism is lacking in iodine-rich areas. The iodine area is 5 times higher. Iodomethyl guanidine usually occurs 6 months after iodine administration, and the height is 13 months. The clinical manifestations are similar to those of Graves disease. There are few exophthalmos, and there is no thyroid autoantibody in serum, but the rate of thyroid absorption is 131I. Low, high iodine directly leads to damage to thyroid cells, which can induce hyperthyroidism in individuals with genetic susceptibility.
6. Thyroid tumor causes hyperthyroidism
Tumor tissue itself or its metastases can cause hyperthyroidism by ingesting iodine and secreting thyroid hormone.
7. Newborn hyperthyroidism
The presence of LATS in the blood of pregnant women with hyperthyroidism can be transmitted to the fetus through the placenta, rarely due to mutations in the TSH receptor. Due to the mutation of the TSH receptor, the extracellular TSH binding region of the receptor is antigenic and usually occurs temporarily. Can be prolonged for several years, the light is asymptomatic without treatment, the severe performance is extremely irritating, irritating, hunger, skin flushing, breathing and heart rate, exophthalmos, goiter, sometimes jaundice, liver swelling Big, need treatment.
8.TSH increased type of hyperthyroidism
Also known as TSH toxicity, blood T3, T4 and TSH are increased, can have the following reasons:
(1) pituitary tumors: increased secretion of TSH, or ectopic tumors secrete TSH-like substances, such as lung cancer, hydatidiform mole.
(2) Selective pituitary arrhythmia: a type of thyroid dysfunction, inherited, blood T3 is elevated, blood T4 is also high, but the pituitary does not have a negative feedback response, blood TSH is still increased, while other tissues in the body Blood T3 and T4 still react to cause hyperthyroidism.
(3) Familial hyperthyroidism: defective anterior pituitary, lack of 5' deiodinase in TSH cells, T3 reduced T3, T3 nuclear receptors are not fully saturated, negative feedback on TSH secretion is reduced, so TSH secretion Still more, blood T3, T4 is still high, causing hyperthyroidism, also known as pituitary TSH secretion syndrome, treated with T3, hyperthyroidism can be alleviated.
9. Hyperthyroidism combined with other diseases
Can coexist with other endocrine diseases or autoimmune diseases, such as multi-endocrine gland autoimmune syndrome, can be combined with idiopathic Addison disease, hypoparathyroidism, diabetes, pernicious anemia, myasthenia gravis, lupus erythematosus, Rheumatoid arthritis, etc., can also be seen in Down syndrome and multiple fibrous dysplasia.
10.T3 toxic hyperthyroidism
Only blood T3 is increased, and blood T4 is normal, often seen in early or recurrence of hyperthyroidism.
11.T4 toxicity
Hyperthyroidism only has blood T4 increased, while blood T3 is normal. It is currently considered that T3 toxicosis and T4 toxicosis are not independent diseases, but some stages of hyperthyroidism can show simple blood T3 or high blood T4, or recovery process after treatment. The above results appear, and the total T3 or total T4 height is not necessarily hyperthyroidism. Free T3 (FT3) and free T4 (FT4) should be investigated. If there is an increase, hyperthyroidism can be diagnosed.
(two) pathogenesis
1. The pathogenesis of Graves disease
Graves disease is an autoimmune disease, which is the most common type of autoimmune thyroid disease in children, accounting for about 95%. Although domestic and foreign scholars have conducted a lot of research on the pathogenesis of Graves disease, it has not yet been fully elucidated. Most of them are concentrated in In the study of humoral immunity, the recently studied thyroid stimulating hormone receptor antibody (TRAb) plays an important role in the pathogenesis of Graves disease. The TSH receptor is an autoantigen and induces the production of autoantibodies. TRAb is a group of polyclonal antibodies. (TSAb) and blocking (TBII).
Two kinds of antibodies, in Graves' disease, mainly dominated by excitatory antibodies. When combined with TSH receptors, they stimulate thyroid follicular cells to proliferate and produce a large amount of thyroid hormones, causing increased catabolism and sympathetic excitation in cells. The aspect is characterized by the abnormality of the suppressor T cell clone, the function of which is obviously reduced, causing immunoregulatory disorder, and the inhibition of the helper T cells and the sensitized effector cells is released, so that the latter attacks the thyroid tissue cells, and the helper T cells assist the B cells. It is transformed into plasma cells and produces a large amount of thyroid stimulating antibodies and causes disease. The untreated Graves disease TRAb in adults can be as high as 83% to 100%, and 93% in children. The TRAb positive rate decreases with the improvement of treatment, if TRAb remains for a long time. When negative, it can reduce the recurrence of hyperthyroidism, and the TRAb of the relapsed patient is increased again.
The nail resistance is closely related to heredity. Among the patients with hyperthyroidism, about 15% of the patients have the same disease, and nearly half of the relatives are positive for anti-thyroid antibodies. Beijing Children's Hospital analyzed 368 cases of Graves disease, with a family history of 21.4. %, Hassan reported 4 pairs of twins with hyperthyroidism, patients with their relatives HLA, some types of alleles increased frequency, related diseases such as Addison disease, insulin-dependent diabetes, myasthenia gravis, systemic lupus erythematosus, The incidence of rheumatoid arthritis, vitiligo, idiopathic thrombocytopenic purpura and pernicious anemia is increased, histocompatibility antigen (HLA) is associated with the onset of hyperthyroidism, and Arid et al. have shown the frequency of occurrence of HLA-D in Caucasian Graves disease. It is higher than HLA-B8; Yanagawa et al found that American white Graves disease and HLA-DQA10501 gene have genetic susceptibility. The frequency of HLA-B46, DRB9, DQB1-030303 in Chinese male patients in Hong Kong is significantly increased. Genetic studies indicate that Graves disease may be Multi-gene disease, 34% of genes are related to environmental factors, such as mental stimulation, mood swings, excessive ideological burden, and puberty and sensation Dyeing and so on are all related to the induction of this disease.
2. Pathological changes
Graves disease thyroid gland is symmetrically enlarged, follicular cells increase, from cuboid to columnar, the gelatin in the follicle is lost or only a small amount of very lightly stained colloid, there is a large number of rows arranged between the epithelium and the gel. Foam, blood vessels increased significantly, lymphoid tissue also increased, a large number of lymphocytes infiltrated, under the electron microscope, the Golgi hypertrophy in the follicular cells, the inner pulp network and nucleoprotein increased, the microvilli increased and became longer, and the secretion was active. In terms of histochemistry, the peroxidase activity of follicular cells was enhanced, the cytoplasmic ribonucleic acid increased, the alkaline phosphatase activity of interstitial capillary endothelial cells was enhanced, and the glial droplets positive for PAS staining appeared in the cytoplasm.
3. Pathophysiological changes
Hyperthyroidism in patients with hyperthyroidism is closely related to thyroid autoantibodies. A variety of thyroid autoantibodies can be detected in vivo. It is reported that 80% to 100% of patients can detect TSH receptor antibody (TSHRAb), which is immune to thyroid stimulation. Globulin, which stimulates thyroid function, increases thyroid uptake by thyroid, cAMP-mediated thyroid hormone synthesis and increased thyroglobulin synthesis, promotes protein synthesis and cell growth, and treats antibodies with TSHR after treatment with hyperthyroidism. As the disease rises, the disease gradually eases.
Some other anti-thyroid antibodies, such as thyroglobulin antibody (TGAb), thyroid microsomal antibody (TMAb) or thyroid peroxidase antibody (TPOAb), may also be found in some hyperthyroid cases. These antibodies may also be present in some normal individuals. However, its specificity is not as good as the TSH receptor antibody.
At present, it is believed that the mechanism of invasive exophthalmia of Graves disease is that anti-thyroid antibody and anti-eye muscle antibody bind to extraocular muscle and fibroblasts in the orbit and produce toxic reaction. It is also believed that infiltrative exophthalmos is deposited in the orbital muscle. - An anti-thyroglobulin immune complex that causes an inflammatory response of the immune complex.
In a few cases, there are nodules (including adenomas) in the thyroid gland, which are called nodular gonads with hyperfunction.
Prevention
Prevention of hyperthyroidism in children
At present, domestic and foreign data have confirmed that diffuse toxic goiter is related to some allele types of HLA-II antigen, autoimmune. It is believed that the cause of Graves disease may be due to the immune monitoring and regulation function of TS cells in patients. Sexual defects, but the exact mechanism needs to be further clarified. Genetic factors plus adverse environmental factors, such as mental stimulation, mood swings, excessive ideological burden, and puberty development, infection, etc. can induce the disease, and have spread in iodine-deficient areas in recent years. After the consumption of iodized salt, the incidence of onychomycosis has an increasing trend.
When subjected to stress such as mental stimulation and infection, the immune stability in the body is destroyed, and the "forbidden strain" cells are out of control, which results in the proliferation of B cells that produce TSI (thyroid-stimulating immunoglobulin), which is secreted by the help of TH cells. A large number of autologous antibodies, TSI, cause disease, and the incidence of trauma and family history is higher.
Therefore, it is necessary to prevent and control various infections, including vaccination, strengthen nutrition, enhance physical fitness, etc., and pay attention to timely detection of psychological problems, timely psychological treatment and other preventive measures, especially the prevention of iatrogenic hyperthyroidism.
Complication
Complications of hyperthyroidism in children Complications, arrhythmia, atrial fibrillation, dysphagia, amenorrhea
Often feel palpitations, severe cases can have arrhythmia, atrial fibrillation; neck discomfort, pressure, dysphagia; slow puberty, menstrual disorders, amenorrhea and menorrhagia; children rarely see hyperthyroidism, severe with shock. Shock is a clinical syndrome characterized by acute and effective circulating blood volume caused by various serious pathogenic factors, with neuro-humoral factor imbalance and acute circulatory disorder. These pathogenic factors include major bleeding, trauma, poisoning, burns, asphyxia, infection, allergies, and heart pump failure.
Symptom
Symptoms of hyperthyroidism in children Common symptoms Susceptible appetite abnormality thin eyeballs prominent fatigue Hongmai attention is not concentrated Goiter hypothermia high metabolism group
Most children develop puberty, <5 years old are rare, children with hyperthyroidism clinical process are very different, the general symptoms gradually worsen, the symptoms start to the diagnosis time is generally 6 to 12 months, the symptoms of the initial onset of the disease is not obvious Slow progress, often showing emotional instability, lack of concentration in class, irritability, hyperactivity and inattention, and other minor behavioral changes. Typical symptoms and signs have the following manifestations:
1. Sympathetic excitability increases basal metabolic rate increases such as weight loss, hyperhidrosis, heat loss, low fever, increased appetite, increased stool frequency, sleep disturbance and easy fatigue, etc., because the sympathetic nervous system is too excited, the heart rate is accelerated, and the temper is irritable. Older children often feel palpitations, severe cases can have arrhythmia, atrial fibrillation, and often have small and rapid tremors in both hands.
2. All children have different degrees of thyroid enlargement, generally left and right symmetry, soft texture, smooth surface, clear boundary, can move up and down with swallowing action, sometimes audible on swollen thyroid To systolic murmurs or convulsions and tremors, nodular enlargement can vary in size, hard, single or multiple nodules, sometimes patients with neck discomfort, pressure, difficulty swallowing, may have adolescence Slow development, menstrual disorders, amenorrhea and less menstruation.
3. Eye changes are unique manifestations of hyperthyroidism. Because the eyeballs are often gaze-like, they are not often blinking, and the upper eye is contracted. When the eye is down, the upper eyelid cannot fall immediately with the eyeball, and the upper eyelid is difficult to valgus. Also includes widening of the eyelids, eyelid edema, conjunctival edema, corneal congestion and so on.
4. Others may have adolescent sexual development, menstrual disorders, amenorrhea and less menstruation.
Examine
Examination of hyperthyroidism in children
Mainly measured total blood T3 (TT3), total T4 (TT4), free T3 (FT3), free T4 (FT4) and hypersensitive TSH can be diagnosed. In the early stage of hyperthyroidism, when the clinical symptoms are mild, T3 rises first. In the future, T4 will increase and typical clinical symptoms will appear. In the early stage of recurrence of hyperthyroidism, T3 will increase first, and then T4 will increase. When the symptoms of hyperthyroidism are not fully controlled, only T3 can be seen, and T3 is recognized. Hyperthyroidism is important for early diagnosis of hyperthyroidism and recurrence of hyperthyroidism.
1. The normal value of blood TT4 is 54-167 pmol/L, the normal value of FT4 is 10-30 pmol/L, and the TT4 and FT4 increase in hyperthyroidism.
2. The normal value of blood TT3 is 0.8-2.6 pmol/L, and the normal value of FT3 is 3.5-10 pmol/L. FT3 is more important in the diagnosis of hyperthyroidism, and often only FT3 is increased in early hyperthyroidism.
3. TSH reduction in hyperthyroidism can be measured by ultra-sensitive TSH kit to 0.02mU / L, continuous low TSH can make hyperthyroidism diagnosis.
4. Basal metabolic rate (BMR) The normal value is ±15%. The determination of children over 5 years old is more meaningful. The hyperthyroidism BMR>15%. Because of the popularity of thyroid function measurement, BMR has been rarely measured.
5. TRH excitatory test intravenous thyroid stimulating hormone releasing hormone (TRH), 7g / kg, before the injection and 15, 30,90,120min after the injection of blood TSH, normal 30min TSH increased by 5 ~ 40mU / L, hyperthyroidism Excessive T3 inhibition, TSH secretion, TSH is not increased or lower than normal, but if you can do ultra-sensitive TSH measurement, you can replace this test.
6. Determination of anti-thyroglobulin antibody (TGAb) and anti-thyroid microsomal antibody (TMAb) in order to determine whether it is caused by Hashimoto's disease, determination of various excitatory or inhibitory thyroid antibodies to observe the therapeutic effect and the possibility of recurrence .
7. Thyroid scan to understand the size of the thyroid, the nature of the nodules, to exclude tumors, cysts and so on.
8. Thyroid B ultrasound can show the size of the thyroid, showing nodules, cysts and so on.
Diagnosis
Diagnosis and diagnosis of hyperthyroidism in children
diagnosis
According to clinical symptoms, laboratory tests can make a diagnosis. Typical Graves disease is determined by serum thyroxine. If the total T3 and free T3 are increased and the TSH level is low, the diagnosis can be established. If possible, the thyroid antibody can be further tested.
Differential diagnosis
1. Lymphocytic thyroiditis (Hashimoto's disease) may present hyperthyroidism symptoms in the early stage of the disease, but most of them are transient. After follow-up, the detection of TGAb and TMAb can help to distinguish with Graves disease, but it is impossible to distinguish between the two. Simultaneous children, when the thyroid can reach the nodules or the serum T3 value is extremely high, thyroid ultrasound and / or radionuclide scanning should be performed to correctly diagnose nodular goiter and identify cancer; Children with mild swelling and mild hyperthyroidism should consider the possibility of subacute thyroiditis (caused by viral infection). If necessary, consider radionuclide scanning and fine needle aspiration cytology.
2. Newborn hyperthyroidism is rare, mostly temporary, common in pregnant women with hyperthyroidism or hypothyroidism, the presence of thyroid receptor-stimulated immunoglobulin or long-acting thyroid stimulant (LATS) in the blood, delivered through the placenta For infants, very few are caused by TSH receptor gene activating mutations. Most newborns have hyperthyroidism at birth, which is characterized by exophthalmos, thyroid enlargement, irritability, hyperactivity, tachycardia, shortness of breath, and severe Heart failure occurs, blood T3, T4 increase, TSH decline, these symptoms after 6 to 12 weeks, with the reduction of thyroid-stimulated immunoglobulin levels in the body.
3. Simple goiter occurs mostly in adolescence, normal heart rate, normal stool frequency, normal FT3, FT4, T3, T4, and can be done with hypersensitive TSH or TRH stimulation if necessary.
