endemic cretinism
Introduction
Introduction to endemic cretinism Endemic cretinism includes endemic subclinical cretinism caused by iodine deficiency, a neuro-psychiatric syndrome characterized by mental retardation; when iodine deficiency is adequately corrected in the area, Dick disease Or akectin can be prevented. Typical Dick disease usually occurs in severe iodine-deficient areas where there is a swelling of the nail. Local children with urinary iodine below 20 g/L will almost certainly develop Dick disease; when the rate of endemic goiter is greater than 30% There is usually a prevalence of Dick disease; endemic subclinical cretinism occurs in all areas of iodine deficiency, but is more common in areas with moderate or severe iodine deficiency. basic knowledge The proportion of illness: 0.005%-0.006% Susceptible people: no special people Mode of infection: non-infectious Complications: mental retardation
Cause
Cause of endemic cretinism
(1) Causes of the disease
The etiology of endemic cretinism has been relatively clear. It is the result of severe iodine deficiency in the embryonic and neonatal period. In addition to the iodine deficiency theory, there are also genetic problems, autoimmune problems and goiter problems.
Iodine deficiency (35%):
The lack of iodine causes the mother to compete with the fetal thyroid gland for a limited intake of iodide, which in turn affects the thyroid hormone synthesis between the mother and the fetus. The neurological type is mainly caused by severe iodine deficiency in the early stage of the embryo, which damages the growth and development of the nerve. Later, the fetal thyroid gland can synthesize thyroid hormone normally, which can prevent hypothyroidism after birth. The mucinous edema type is based on the early uterine iodine deficiency and the reduction of fetal thyroid hormone synthesis ability.
Genetic factors (25%):
In recent years, domestic studies on the genetics of Dick disease have been studied in many aspects. Most scholars believe that the disease does not conform to the dominant or recessive inheritance of single genes, nor does it find abnormalities in the number or morphology of chromosomes. In short, this issue remains to be seen. further research.
Thyroid-producing substances (20%):
There are many thyroid-induced substances, but the obvious one is cassava. The reason is that cassava contains glucoside, which can form thiocyanate under the action of enzymes in the body.
(two) pathogenesis
The pathogenesis of Dick disease may be related to two factors: the lack of thyroid hormone synthesis and the direct independent effect of iodide deficiency.
1. insufficient synthesis of thyroid hormone
The role of thyroid hormones in physical development (including bone development, sexual development) has been recognized, however, the relationship between thyroid hormone and brain development has been a hot topic in the pathogenesis of Dirk disease.
Dobbing pointed out that there are two main periods in the growth phase of the human brain: the first phase is the proliferative phase of nerve cells, which begins about 12 to 18 weeks of gestation and is completed in the middle of pregnancy. The external environmental factors such as radioactive irradiation, mother Infection is extremely sensitive, and the second phase is the most important period of brain development, which is characterized by brain cell differentiation, migration, myelination, dendritic development, sudden triggering, establishment of neural connections and proliferation of glial cells. In the second trimester, its development peaks before and after birth and lasts for a period of time after birth. This period may last until the age of 2 years, and the first 6 months after birth is the most critical moment of postnatal brain development, about 5 /6 brain development is completed after birth, the second phase is extremely sensitive to nutritional factors and hormone deficiency (including hypothyroidism), a large number of animal experiments confirmed that the effect of thyroid hormone on brain development has a certain time, in During this period of time, hypothyroidism will cause brain development. Once this period of time is added to thyroid hormone, brain developmental disorders can not be corrected (irreversible), so this limited time period is also called During the critical period of development, brain development is performed in a strict and orderly manner. Thyroid hormone is considered to be the "clock" for terminating nerve cell proliferation and stimulating differentiation. During the critical period, thyroid hormone promotes Differentiation and migration of nerve cells, development of neuronal microtubules, extension of axons, branching of dendrites and development of dendritic spines, development of synapses and establishment of neural connections, myelination of axons, neurotransmitters Synthesis (which may affect the synthesis of neuronal synthetases, enzymatic activity, metabolism of mediators), and the development of certain specific neurons (choline, adrenergic, and GABAergic nervous systems) are essential hormones.
Nunez noted that the decrease in synapse formation resulted in increased brain cell death and decreased brain cell number and volume during hypothyroidism. Patel believes that the key role of thyroid hormone in neuronal cell development is to promote its migration and differentiation, while neuronal The effect of proliferation is small. During the critical period, the expression of surface recognition factors in thyroid hormone-sensitive nerve cells is affected by thyroxine deficiency, various cells are not synchronized, and the spatial-temporal relationship between neurons is abnormal. , leading to abnormal nerve pathways or nerve cell stagnation, nerve cells die due to loss of mutual nutrient dominance, so brain cell abnormalities and wrong pathways are one of the mechanisms of irreversible damage caused by thyroid hormone deficiency in critical phase, the central nervous system is the most The fascinating feature is the complex and precise network connection between various neurons. It is the structural basis for accomplishing various behaviors. Modern psychology believes that the material basis of intellectual activity is the dendrites, dendritic spines, and processes in brain tissue. It is related to the level of development of neural connections.
Oppenheimer first confirmed that T3 binds to nuclear receptors and plays a role in hormones. T3 is the main active form of thyroid hormone. T3 on the nuclear receptors of surrounding tissues mainly comes from T3 in plasma. Larson found that brain cells and surrounding tissues have The difference is that the nuclear receptor-bound T3 is mainly derived from plasma T4, T4 enters brain cells, and after deiodinase (type II) is converted to T3, it binds to T3 receptor (T3R), and thyroid axis is deficient in iodine. The first to be affected is the decrease of T4, but T3 is normal. Therefore, the surrounding tissue is not affected by T3 normal. The decrease of T4 will directly affect brain development and brain function. Although the activity of type II deiodinase will be compensated in the absence of iodine. Increase, but long-term hypothyroidism, type II deiodinase compensatory failure, decreased enzyme activity, and even decreased brain T3R, so low T4 is directly related to brain development, and it is currently believed that the role of thyroid hormone is mediated through T3R. T3 and T3R combine to form a complex, T3R is activated, converted from non-DNA-binding to DNA-binding, and then interacts with or interacts with certain genes to transcribe or respond to specific genes. The synthesis of white matter plays a regulatory role, T4 decreases, affecting the transcription and translation of genes. T3R is a non-histone in the nucleus. The content of different nerve cells is different. The cerebral cortex, hippocampus and amygdala are the most abundant. Hypothalamus The thalamus, striatum, and olfactory bulb are the second; the cerebellum and brainstem are the least; while the T3R content in nerve cells is 2 to 3 times higher than that of glial cells, so the effect of thyroid hormone on nerve cells is through specific nuclear The receptor T3R exerts its biological effects.
Hypothyroidism caused by iodine deficiency is the basic pathogenesis of Dick disease. Hypothyroidism in different stages of embryonic development and infant development may be related to the pathogenesis of Dick disease.
(1) Fetal hypothyroidism: Fetal hypothyroidism is the main mechanism of brain development after the disease. At present, we can not obtain direct evidence from the development of human embryos to verify the fetal hypothyroidism caused by iodine deficiency. There are two evidences. It can indirectly indicate the presence of fetal hypothyroidism: one is found in aborted fetuses in severe iodine-deficient areas. Fetal hypothyroidism can occur as early as the fourth month of pregnancy, and hormonal hypothyroidism occurs earlier than goiter; another evidence It is the incidence of hypothyroidism in the severely ill areas of the fetus at birth is quite high, some as high as 10% to 30%, which was confirmed in Zaire, India, Tanzania and other wards, so far we do not know the neonatal hypothyroidism To what extent does it truly reflect the presence of fetal hypothyroidism? Amniocentesis may be another way to detect fetal hypothyroidism. Animal experiments have confirmed that fetal hypothyroidism caused by iodine deficiency is the main cause of brain development, Potter is in sheep. At different gestational times, the thyroid gland of the fetus was removed, and the newborn sheep showed a cretin-like change. The earlier the thyroid was removed, the more serious the brain development was, and Potter used low iodine. Feeding the ewes, the T4 decreased at 56 days of gestation, and the goiter appeared at 70 days. The brain development of the born ewes was very similar to that of the thyroids, ie, the wet weight of the brain decreased; the brain DNA and protein content decreased; the brain In the exercise area, the cell density of the visual field and hippocampus increased, and the outer layer of the cerebellum thickened, suggesting cell migration disorder; the Purkinje cell dendritic development disorder, the author also found that the fetal rat hypothyroidism is a brain in the low iodine rat model. The main mechanism of postnatal development, iodine supplementation or thyroid hormone supplementation during the critical period can prevent its occurrence, which proves that fetal hypothyroidism is the main mechanism of brain developmental disorders.
(2) maternal hypothyroidism: maternal hypothyroidism is common in areas with iodine deficiency (especially in areas where visceral cretinism predominates). In Zaire, mother hypothyroidism and mucinous cretinism are unique. The specificity, therefore, Delange believes that maternal hypothyroidism is associated with fetal neurodevelopmental disorders, and it has been suggested that children born to mothers with low T4 have lower IQ than normal children, and to what extent mother's hypothyroidism affects fetal brain development. It is not clear that Potter mated the ewes after they had been removed. The examination of the sheep after pregnancy found that the early and middle gestational brain development was backward, but the brain development of the larvae did not differ from the control group at the late pregnancy and at birth. This result suggests that the mother's thyroid function is necessary to maintain fetal brain development, which is obvious in early pregnancy and has little effect in the third trimester. He also found that the ewes and the fetal sheep are simultaneously removed from the thyroid, and the brain development of the offspring is backward. The degree is more serious than that of purely iodine-born lambs. This also indicates the effect of maternal hypothyroidism on the fetus. Mano further confirmed that the low-iodine ewes model was injected in the second trimester without However, DIMIT (3,5-dimethyl-isopropyl-L-thymidine), which has the action of thyroid hormone, results in the correction of the yaw hypothyroidism, but the delivered lamb still appears the same as the low iodine group. The severe brain development is backward (DIMIT can not pass through the placenta), which means that the mother's hypothyroidism has little effect on the fetus. The above experimental results suggest that the mother's hypothyroidism only has a certain influence on fetal brain development in the early pregnancy, and the mechanism may be the mother of early pregnancy. T3, T4 can pass through the placenta, but not in the middle or late stage. The brain development at this time depends mainly on the thyroid function of the fetus itself. In fact, as Escobar puts it, the fetal brain already exists before the fetal thyroid has function. T3R, therefore, the mother's thyroid hormone may affect fetal brain development. In terms of pathogenesis, compared with the importance of fetal hypothyroidism, maternal hypothyroidism is unlikely to be the most important mechanism for the onset of Dick disease. Play a role in the following areas:
1 Before the formation of fetal thyroid function, due to maternal hypothyroidism, the amount of maternal T3, T4 into the fetus is insufficient.
2 When severe iodine deficiency, the mother's thyroid gland still has a good ability to take iodine. The developing fetal thyroid gland is at a disadvantage when competing with the mother to ingest the inorganic iodine of the mother's plasma, thus exacerbating fetal hypothyroidism and iodine deficiency.
3 pregnant women due to increased estrogen levels, liver thyroid hormone binding globulin increased, so that total plasma T3, total T4 increased, while FT3, FT4 decreased, the lack of iodine, this change will be more prominent.
4Coutras confirmed that during normal pregnancy, the iodine clearance rate of the kidney increased and the blood iodine decreased. The loss of endogenous iodine under this physiological condition, such as accompanied by insufficient iodine intake, would aggravate the iodine deficiency of the fetus.
5 During lactation, the mammary gland has the ability to concentrate iodine to ensure the iodine supply of infants and young children. The lactation of the mother during lactation will inevitably affect the supply of iodine to the baby through the milk. In the Zairian ward, it is found that the infant has hypothyroidism after weaning. .
(3) Neonatal hypothyroidism: In areas with normal iodine supply, the incidence of neonatal hypothyroidism is less than 0.02%, mostly sporadic cretinism, and the incidence of neonatal hypothyroidism in low-iodine areas is greatly increased in India. Up to 4% to 15%, Zaire 10% to 30%. In recent years, the number of neonatal TSH in the iodine concentration in the iodized salt is not higher than that in the non-patient area. Undoubtedly affecting brain development, within 2 years of life, is still the critical period of brain development, which is mainly the development of cerebellum, myelination, glial cell proliferation and the establishment of neuronal connections.
(4) transient hypothyroidism or subclinical hypothyroidism: these two hypothyroidism are found in low iodine wards, especially the slight increase in TSH, which also affects brain tissue and organ hypothyroidism, and may also It affects brain development or brain function to a certain extent.
2. The independent role of iodine
This is a controversial point of view. People who hold this view believe that the brain development of the fetus depends mainly on the thyroid function of the fetus itself. The fetal thyroid function is formed after 12 weeks of gestation, so the brain development in the first 3 months of the fetus. May be related to iodine, based on:
1 non-iodine deficiency factors cause congenital hypothyroidism in the fetus, such as sporadic cretinism, the clinical manifestations are significantly different from the disease, the symptoms of deafness and upper motor neuron damage in sporadic disease are not in sporadic cretinism Significant
2 mother throughout the pregnancy hypothyroidism (non-iodine deficiency reasons), the birth of the baby does not appear typical cretinism, or even completely normal;
The development of the 3Corti is between 10 and 18 weeks of gestation, just before the fetal thyroid is formed;
4Firro and Pharoach found that pre-pregnancy injection of iodized oil was more effective than mid-pregnancy injection to prevent the occurrence of Dick disease.
Recent studies, especially Escobar, have confirmed that mother T3, T4 can enter the fetus through the placenta before fetal thyroid formation. This finding changes the traditional view that mother T3, T4 cannot pass through the placenta; but after the fetus forms the thyroid gland, This permeability has declined. According to recent research, fertilized eggs begin to receive maternal thyroid hormone supply on the third day after implantation, so the fetus depends mainly on the mother's T3 and T4 before thyroid function is formed, even if After the formation of fetal thyroid function, the mother's T3 and T4 are still accepted. It is found that 10% of the thyroid hormones in the fetus are born from the mother. Animal experiments also confirm that the development of the inner ear is also dependent on thyroid hormone instead of iodine. Therefore, Hetzel pointed out "There is no evidence that iodine has a direct effect on brain development."
Therefore, it is generally believed that the lack of thyroid hormone synthesis during the critical period of brain development is the main pathogenesis of Dick disease.
Prevention
Endemic cretinism prevention
1. First level prevention
(1) Iodized salt is a simple and effective way to prevent and treat iodine deficiency disorders. The ratio of salt to iodization is 1:50,000, which can effectively prevent the disease of the nail; 1:2 million can prevent the disease, join Potassium iodide in salt is easily oxidized and sublimated. Since 1993, it has been changed to potassium iodate with good stability. In the process of packaging, storage, transportation and consumption of iodized salt, it is necessary to keep the iodized salt dry and package tightly; %; 57.8% in the drawer; 1.9% loss in boiling 2h; 66.1% loss in baking 2h.
(2) Iodized oil injection or oral administration, iodized oil is a long-acting, economical, convenient, and small side-effect prevention and treatment drug, especially suitable for remote, inconvenient transportation, soil and salt interference areas, especially for women of childbearing age, iodization After oil injection, the iodine supply efficiency can reach 3 to 5 years. The oral iodized oil method is simple, the mass is easy to accept, and the control effect is also obvious. The iodine supply efficiency is generally about one and a half years.
(3) Guarantee the amount of iodine required by the human body:
1 group <4 years old normal range 30 ~ 105g / d; suitable amount 70ug / d
24 years old and normal range of 75~225g/d for adults; suitable amount 150ug/d
3 pregnant women, the normal range of lactating mother 150 ~ 300g / d; suitable amount of 200g / d
(4) Women of childbearing age during pregnancy can prevent iodine deficiency during embryonic period (cretinism, subclinical cretinism, neonatal hypothyroidism, neonatal hyperthyroidism and premature birth, stillbirth, congenital malformation).
2. Second level prevention
(1) Monitoring of iodine prevention and treatment:
1 Iodine salt containing iodine monitoring: including iodized salt iodine concentration, packaging, factory sampling, storage and storage, sales points and households in the spot checks, timely correction of problems, reduce iodine losses.
2 Iodized oil injection and oral monitoring: to prevent complications.
3 Disease monitoring: The monitoring point regularly surveys and compares the dynamic changes of the incidence of goiter in the population before and after consumption of iodized salt.
4 iodine metabolism and functional status of pituitary thyroid system, urine iodine determination: urinary iodine increased after iodine addition, group urine iodine determination is meaningful, when urinary iodine <25g / g creatinine, is the criticality of endemic goiter complicated with cretinism Concentration; thyroid absorption 131 iodine rate determination (24h) showed lower than before iodine; serum T3, T4 determination: with iodine increased; serum TSH determination: lower than before iodine supplementation.
5 Determination of children's IQ: no less than 70.
(2) Diagnostic criteria for endemic goiter (1978 China Conference on Prevention and Treatment of Endemic Goiter):
1 living in the goiter area.
2 The thyroid enlargement exceeds the distal end of the thumb or has nodules smaller than the distal end of the thumb.
3 exclude hyperthyroidism, thyroid cancer and other thyroid diseases.
4 ward division criteria (in rural areas).
Lightly ill area: the prevalence of goiter in residents is >3%; the rate of goiter in primary and middle school students aged 7-14 years is >20%; urinary iodine is 25~50ug/g creatinine.
Intensive care area: the prevalence of goiter in residents is >10%; the rate of goiter in primary and middle school students aged 7-14 years is >50%; the urinary iodine is <25ug/g creatinine.
(3) Diagnostic criteria for endemic cretinism (developed in 1980):
1 prerequisites:
A. Born and living in areas with low iodine endemic goiter.
B. There are mental dysplasia, mainly manifested in varying degrees of mental retardation.
2 auxiliary conditions:
A. There are varying degrees of hearing, language and motor neurological disorders.
B. Hypothyroidism, there are different degrees of physical developmental disorders, cretinism image (stupid phase, wide face, wide eye distance, collapsed nose, abdominal bulging, etc.).
C. Different degrees of hypothyroidism (mucus edema, dry skin, delayed X-ray and delayed healing of the epiphysis, decreased plasma PBI, elevated serum T4, TSH).
Anyone with one or more of the necessary and auxiliary conditions and who can rule out birth injury, encephalitis, meningitis and drug poisoning can be diagnosed with Dick disease.
3. Third level prevention
Thyroid powder preparation therapy: It has extremely obvious effect on the treatment of patients with gelatinous goiter. Adults take oral thyroid tablets 60-120mg per day, combined with potassium iodide 10mg, 3 months for one course of treatment, generally 2 to 4 courses, treatment interval For half a month, the curative goiter and cystic hypertrophic nodular goiter are better.
Complication
Endemic cretinism complications Complications, mental retardation
Endemic cretinism occurs in areas where goiter is prevalent. In the embryonic stage, iodine-induced stagnation is absent. In areas where iodine is absent, many adults suffer from iodine deficiency and cause goiter. After 4 months of pediatric embryo, the thyroid gland has been able to synthesize thyroxine. However, the mother lacks iodine, and the iodine deficiency provided to the fetus is bound to cause insufficient synthesis of thyroxine in the fetal period, which seriously affects the development of the fetal central nervous system, especially the brain. If iodine is not supplemented in time, it will cause irreversible damage to the nervous system and cause mental retardation.
Symptom
Symptoms of endemic cretinism common symptoms craniofacial deformity facial expression apathy lower body lower than upper sluggish thyroid function constipation goiter gait instability
Clinical manifestation
(1) mental retardation (mental retardation): This is a syndrome, a special term for mental illness. Its diagnostic criteria are: onset before the age of 18; IQ below 70; different levels of social adaptation, The mental symptoms of Dick disease are actually mental retardation. Generally, IQ is less than 50 cretinism, and 50-69 is subclinical cretinism. Mental retardation is the main feature of Dick disease. Serious cases are idiots, life. Can not take care of themselves; light can work, but can not engage in technical labor; subclinical cretinism (Aktin) primary school is difficult to graduate, visceral cretinism mental retardation is lighter than the nerve type, showing slow thinking, IQ Slightly higher than the neurological type, but in terms of mental retardation, there is no essential difference between the two types of cretinism.
(2) Deaf-mutism: Hearing and speech disorders are very prominent. Statistics on 80 cases of Dyke disease in Chengde: 95% have hearing impairment, of which 26.2% are all sputum; 97.5% have speech disorders, of which dumb 46.3%, after iodine supplementation or treatment with thyroid tablets, the hearing improved slightly, and the visceral type was obvious, which may be related to the improvement of mucous edema in the inner ear.
(3) squint (squint): This is caused by damage to the cranial nerves, more common in neurotype cretinism, is a common strabismus or spastic strabismus.
(4) Neuro-motor dysfunction: Motor dysfunction is caused by damage to the nervous system. In general, neurological nerve damage and dyskinesia are more prominent and more obvious than visceral type.
Cone system lesions: the following limbs are most prominent, muscle tension is enhanced, tendon reflexes, pathological reflexes (such as: Babinski sign, Gordon sign, Chadock sign, Hoffmann sign positive), severe lower extremity spastic diplegia, According to the statistics of 80 cases of cretinism in Chengde, 76.2% of people with movement disorder can have special gait, gait instability, dragging, duck step, and some cause. The muscle tension is unbalanced and causes deformity. For example, the ankle joint is drooping, and the legs are scissor-like. In severe cases, they cannot stand and can only crawl on the ground.
Extrapyramidal lesions: Muscle rigidity is mainly caused by the flexors of the extremities, with the proximal end (shoulders and hips) being more pronounced, showing a mild flexion and anteversion posture. When performing passive exercise, it shows rigidity, similar to the performance of Parkinson's disease. However, there is no clonic, and some patients also show positive release inhibition, such as sucking reflex and eyebrow percussion reflex.
(5) goiter: more common in neurotype cretinism, the prevalence of goiter is 12% to 66%, mostly mild swelling; visceral cretinism rarely has goiter, most of the thyroid atrophy or Very small, some completely atrophy, this patient often requires thyroxine replacement therapy.
(6) Growth and development backwardness: Physical retardation or backwardness is caused by hypothyroidism, mainly as follows:
1 Short stature: The more severe iodine deficiency, the shorter the body is, the more obvious it is. The cretin cretinism is more obvious. Many patients are only 1.2-1.4 m high in adulthood. The neurological patients are mostly stunted, but may eventually be close to normal. The short stature is characterized by long bone developmental disorders, so the lower part of the patient is smaller than the upper part, and the length of the patient is smaller than the finger spacing. The patient with visceral swelling is short in limbs, short in the neck, and shorter in fingers and toes.
2 sexual development backward: neurological patients are mild, manifested as external genitalia and secondary sexual development retardation, menstrual menarche is late, but later sexual development can still be close to maturity, most can be married to childbearing, as long as iodine deficiency is corrected, the children born Can be completely normal, visceral cretinic disease development is very significant, secondary sexual development is very poor, male no beard, no pubic hair, mane, male signs are not prominent; female breast development is poor, no pubic hair and mane, genital It is a child-type, male testicle is small, cryptorchidism; women often show primary amenorrhea, even if menstruation is irregular, the amount is small, patients with visceral type can not give birth.
3 cretin disease face: due to hypothyroidism, facial facial features development backward, severe cases of embryonic appearance, typical face includes: head large, short, face; eye cracks are horizontal, wide eye distance; collapsed nose The nose is thick and the nostrils are facing forward; the lips are thick and tongue-shaped, often with a mouth-like tongue, flowing; the ears are large, the ear shells are particularly soft, the nasal cartilage is also soft; the hair is sparse, the skin is dry and dull; the expression is sluggish, or a silly image Or smirking (Figure 3).
4 Infants and children with growth retardation: anterior iliac crest closure; late teething, poor dentin; starting, standing, walking time is significantly later than children of the same age; bone X-ray examination found bone age behind.
(7) Hypothyroidism: mainly seen in patients with visceral type, the neurological type is not obvious, the main performance is:
1 mucinous edema, non-finger edema, loose skin, poor elasticity, edema tissue often blocky, mostly distributed in the neck, abdomen, waist and hips, face and limbs.
2 muscle development is poor, slack, weakness, often accompanied by umbilical hernia, abdominal wall hernia or inguinal hernia.
3 The skin is rough and dry, and the nails are thin and soft; the skin mucosa is often grayish white, with less sweat and less sebaceous gland secretions.
4 severe cases of low body temperature, fear of cold, blood pressure, pulse, breathing are lower than normal; less eating, more constipation; Achilles tendon reflex relaxation time.
5 spirits are sluggish, slow-moving, expressionless or indifferent.
2. Clinical classification The clinical manifestations of Dick disease are divided into heavy, medium and light, and the extremely light type is Aktin. This classification is mainly based on the indexing method of mental retardation (Table 1).
This kind of indexing method is mainly based on the level of IQ. In addition, it should be based on the patient's clinical performance and comprehensively judged by six aspects. They are: living ability, labor ability, Language understanding, computing power, speech ability and listening.
Severe: no basic living ability, can not take care of themselves, can not wear clothes, eat; can not engage in labor; do not understand the language; no concept of number; dumb or can only simply pronounce or speak a single word; full or behind the 1m There is a reaction when you shout.
Moderate: Have basic living ability, such as self-care and urinating, can dress and eat; participate in simple labor; can only understand words or simple words; can only do simple addition and subtraction or physical addition and subtraction; can only say simple A few words ("half language"); at the back of 1m, ordinary voice can be heard.
Mild: Being able to take care of daily life independently, but having difficulty in helping others; doing ordinary housework or rough work in the field; being able to understand simple words, but having difficulty understanding; abstract computing is difficult; can say simple sentences, but the language is not clear; Generally speaking, you can hear it, and you can hear it by speaking in a small voice at 1m.
3. Clinical classification According to the patient's clinical manifestations, the disease is divided into the following three types:
(1) Neurotype: This is the most common type. The vast majority of cretinism in China and the world is neurological, with prominent mental retardation and neurological syndrome (hearing, speech and motor neurological disorders) as the main manifestations. The main features are mental retardation and nerve injury syndrome, which is mainly caused by nerve damage. The patient is mainly characterized by severe mental retardation; hoarseness; nerve damage and manifestation of motor dysfunction (such as hip, knee flexion, deformation, thigh) The skeletal development is lighter and the height is close to normal; there is goiter, but the thyroid function is not obvious (Figure 1).
(2) Mucinous edema type (abbreviated as visceral type): The main manifestations of hypothyroidism characterized by mucinous edema (including short stature or dwarf, sexual developmental disorder and cretinism), only found in parts of South Asia And iodine-deficient areas such as Zaire in Africa; in China only in the northwestern regions, namely Xinjiang, Qinghai, Gansu, Ningxia and Inner Mongolia, the main features of this type are obvious hypothyroidism, mucinous edema and growth. Developmental retardation (dwarf), bone age development is obviously backward, sexual development is backward, typical cretinism face, mental retardation, but lighter than nerve type (Figure 2).
(3) Mixed type: It has the main features of the above two types, both obvious nerve damage and obvious hypothyroidism, but some prefer neurological type, while others tend to have more visceral type. In the visceral area with visceral type, more mixed types can be found, but in the cerebral area, the mixed type is less common.
The above is the classification criteria for endemic cretinism, but subclinical cretinism is not classified.
Examine
Local cretinism check
1. Urine iodine is generally low, and Dick disease is generally found in areas with severe iodine deficiency. The urinary iodine level of residents is usually below 20 g/g creatinine, and the prevalence of thyroid is above 30%. This area is often accompanied by Dick disease. popular.
2. Hormone examination: patients with visceral type showed typical hypothyroidism, ie TT4, FT4, FT4I decreased; TSH increased; T3, FT3 decreased, a small number of patients were normal, and neurological patients varied, generally speaking, visceral type To be light, TT4, FT4 are mostly reduced, a few are normal; TSH is elevated, some are normal; FT3, TT3 are more normal, and some are compensatory.
3. Iodine absorption rate: The neurogenic cretinism is an iodine starvation curve; while the visceral iodine absorption rate is not obvious, and some even decrease, which does not mean that iodine nutrition is good, but due to thyroid atrophy.
4. Anti-thyroid antibody: serum anti-microsomal antibody (TMAb), anti-thyroglobulin antibody (TGAb), anti-second glial antibody (TC2-Ab) are negative, but thyroid growth inhibition of visceral cretinism The increase of immunoglobulin (TGII), Tangte's examination of Xinjiang visceral cretinism confirmed that 66.7% of patients with visceral type had TGII, and 55.6% of patients also had immunoglobulins that inhibit IGF-1 (IGF- 1 insulin-like growth factor), Boyages also found by B-ultrasound, TGII-positive patients have thyroid atrophy.
5. X-ray examination: bone development retardation is an important manifestation, which is characterized by poor bone age, osteophyte dysplasia and delayed ossification center. These changes are associated with decreased serum T4 and elevated TSH, especially in patients with visceral type. Often accompanied by a saddle enlargement or deformation.
6. Hearing and vestibular function tests: The damage of hearing and vestibular function is the most serious neurological type. The radionuclide cerebral blood flow imaging examination shows that in patients with hearing impairment, the cerebral blood flow in the temporal lobe is reduced.
7. EEG examination: Most patients are abnormal, with wave, wave increase, brain wave rhythm slow and low potential as the main features, reflecting brain development backwardness.
8. Brain CT examination: There are many domestic reports, but there are lack of diagnostic features, including ventricular dilatation; brain atrophy (cortical sulcus widening, etc.); brain, cerebellar dysplasia; increased intracranial calcification, Basal ganglia, caudate nucleus, lenticular nucleus are common, and some calcification also occurs in the cortex and cerebellum. Brain CT changes are often positively correlated with damage and signs of the nervous system.
Diagnosis
Diagnosis and diagnosis of endemic cretinism
Diagnostic criteria
The diagnostic criteria developed by the Health Standards Committee and issued by the Ministry of Health are as follows:
1. Diagnostic Principles Those who have the following prerequisites and have one or more of the supplementary conditions can be diagnosed as Dick or Aktin after eliminating the disease caused by iodine deficiency. .
2. Diagnostic criteria
(1) Prerequisites:
1 Epidemiology: Patients must be born and live in an iodine deficiency ward.
2 clinical manifestations: there are varying degrees of mental retardation, mainly manifested in varying degrees of mental retardation (lower), IQ (IQ) of Aceting disease is 55 to 69, IQ of Dick disease is below 54 (including 54) .
(2) Auxiliary conditions:
1 Nervous system disorders: motor neurological disorders (cone system and extrapyramidal system), including varying degrees of spastic paralysis, gait and posture abnormalities, Dick patients showed obvious, and these typical clinical signs did not exist in Aktin patients. However, there may be mild nervous system damage, manifested as psychomotor disorders and/or motor skills disorders, and Dick's disease has hearing impairment: Aktin, which may have extremely mild hearing impairments, such as audiometry, hearing The threshold is raised, and there is an abnormality in the high frequency or low frequency.
Dick disease has speech disorders (dumb or speech disorder); Aktin, a very mild speech disorder or normal.
2 thyroid dysfunction: Dick disease has physical developmental disorders; akectin, no or mild physical developmental disorders.
Dick disease has the following different degrees of cretinism (the appearance of mental retardation), such as: stupid, smirk, wide eye distance, nose collapse, soft ear, abdominal bulging, umbilical hernia, etc.; The above performance, but the degree of bone age development and bone healing may be poor.
Dick disease often has clinical thyroid dysfunction (hypothyroidism), such as mucinous edema, dry skin, dry hair; serum T3 is normal, compensatory increase or decrease, T4, FT4 is lower than normal, TSH is higher than normal; Acetin, generally no clinical low performance, but can appear hormonal hypothyroidism, that is: serum T3 normal, T4, FT4 normal lower limit or decrease, TSH can be increased or above the normal upper limit.
3. Diagnostic considerations
(1) When diagnosing Dick disease, attention should be paid to the exclusion of birth injury, neonatal asphyxia, encephalitis, meningitis, epilepsy, drug poisoning, etc. caused by mental retardation caused by brain damage; otitis media, drugs (such as streptomycin, Qing Hearing or speech disorder caused by cerulein, so when the patient has the above-mentioned necessary conditions, but can not rule out other diseases that cause similar symptoms of the disease, it should be considered as a suspicious patient with Dick disease, to be further diagnosed.
(2) When diagnosing icytin, other causes should be excluded, such as malnutrition, zinc deficiency, and cultural background may affect intelligence; otitis media or other drugs that damage the auditory nerve may affect hearing; and factors affecting bone age and physical development. You should exclude them one by one to diagnose ictin.
(3) The diagnosis of mental retardation can be based on the intelligence test method. Those who are 5 years old or older (including 5 years old) are recommended to use the Chinese Raven test; 4 years old (including 4 years old) are recommended to use the Chinese Denver Development Screening Scale or other Develop a scale of developmental quotient (DQ).
(4) For the diagnosis of psychomotor disorders or motor skills disorders, it is recommended to use multiple measures of comprehensive assessment or use the complete mental exercise test scale.
Note: The IQ rating is based on the Raven and Wechsler tests (=100, s=15).
Differential diagnosis
In the epidemic area of the genital area, it is not difficult to diagnose sputum, dumb, dementia, neuromotor dysfunction, and poorly developed physiology. The difficulty in identification is mainly the dysplasia with no thyroid or hypothyroidism. How to distinguish patients with other mental retardation and deaf-mute patients (not caused by iodine deficiency) (Table 2).
1. Sporadic cretinism: These patients have very prominent mucinous edema and other hypothyroidism symptoms, mental retardation, delayed ossification center, but generally no obvious hoarseness, thyroid iodine absorption rate is almost zero, almost no obvious Muscular dyskinesia, thyroid nucleus shows thyroid deficiency or ectopic, and generally no symptoms of pyramidal tract damage, these can be identified.
2. The sequelae of brain damage caused by acquired factors: such as birth injury, encephalitis, meningitis, brain trauma, poisoning factors, etc., their identification mainly depends on detailed medical history, and those with a clear history can be excluded from the diagnosis of gram disease.
3. Congenital type (Down syndrome): This patient has no hoarseness and no hypothyroidism. There are often small ear malformations, small finger deformities and traversing hands. Chromosome examination can clearly diagnose, that is, 21 trisomy, therefore, easy Identification.
4. Pendred syndrome: The syndrome has obvious goiter and congenital deafness, but there is no hypothyroidism, no mental retardation, and physical development is normal.
5. Pituitary pygmy: The patient showed symmetry, proportional body short, normal intelligence, hearing and language barrier-free, normal thyroid function, which can be identified with Dick disease.
6.Laruence-Moon-Biedl syndrome: a rare autosomal recessive hereditary, with low mental retardation and sexual organ dysplasia, but the following three symptoms are unique to this syndrome and can be distinguished from Dick disease: obesity, more Finger (toe) or finger (toe) malformation and retinitis pigmentosa.
7. Phenylketonuria: a common autosomal recessive disorder with symptoms within 4 to 6 months after birth, yellow (yellow hair), white (skin white), stupid (intellectually low), stinky (Beat and smell have odor) and other four characteristics, urine iron oxide test is positive, blood phenylalanine concentration increased.
8. Mucopolysaccharidosis (constrained by slip): autosomal recessive inheritance, short stature, developmental delay, mental, hearing and language barriers. The point of differentiation is that the disease has hepatosplenomegaly and the fingers are curved. "Special face: such as: ugly, nose lifted, nostril upturned, the lower edge of both ears is lower than the binocular level, the tongue is large and thick, the neck is short, the rib X-ray film is ribbon-like, the spine is tongue-like, urine Mucopolysaccharide is positive, and most children die around 10 years old.
9. Galactose hematuria: autosomal recessive inheritance, feeding difficulties or refusal to eat weeks to months after birth, mental retardation, liver, cataract, urine mucic acid test positive.
