Hypothyroidism (hypothyroidism) is a pathological condition in which the tissues do not have enough or adequate thyroid hormone action. Hypothyroidism is more common in women than in men, and its prevalence increases with age. The incidence of hypothyroidism in newborns is about 1/7000, and the incidence of hypothyroidism decreases during adolescence and increases after adulthood.
Etiology and pathology
Clinically, it is generally more practical to classify hypothyroidism by age at onset, and it can be divided into the following three types.
① Hypofunction begins in the fetal period or shortly after birth, called cretinism (also known as cretinism);
(2) Hypofunction begins in pre-developmental children, called juvenile hypothyroidism, and in severe cases, called juvenile mucinous edema;
(3) Hypofunction begins in adult life, called hypothyroidism, and in severe cases, called mucinous edema.
(a) Cretinism (cretinism) has two types of endemic and sporadic.
1, endemic cretinism is seen in endemic goiter endemic areas, due to maternal iodine deficiency and insufficient iodine supply to the fetus, resulting in underdevelopment of the thyroid gland and insufficient hormone synthesis. This type of hypothyroidism is extremely harmful to the neurological development of the rapidly growing fetus, especially the brain, resulting in irreversible neurological damage manifested as this syndrome. Some fetuses with iodine deficiency or thyroid hormone deficiency have a tendency to develop cretinism, and its pathogenesis may be related to genetic factors, which is still to be studied.
2. Sporadic cretinism is seen everywhere and its cause is unknown. Since the mother has neither iodine deficiency nor goitre, the causes are presumed to be.
(1) underdeveloped or absent thyroid gland: There are three possibilities.
(1) Defects in the growth and development of the thyroid gland itself in the affected child;
(2) maternal autoimmune thyroid disease during pregnancy, the presence of anti-thyroid antibodies in the serum, through the placenta and into the fetus through the bloodstream to destroy part or all of the fetal thyroid gland;
(3) The mother takes antithyroid drugs or other goiter-causing substances during pregnancy, which hinders fetal thyroid development and hormone synthesis.
(2) Thyroid hormone synthesis disorders: often with a family history, there are five main types of hormone synthesis disorders.
(1) Iodine collection dysfunction of the thyroid gland: this affects the concentration of iodine, and the defect may be due to a disorder of the “iodine pump” involved in the entry of iodine into the cells.
② Disorders of iodine organicization process: Peroxidase defect: This type of thyroid has strong iodine uptake, but the iodide cannot be oxidized to active iodine, resulting in inability to iodize tyrosine. Iodine synthase defect: iodinated tyrosine cannot form mono- and di-iodotyrosine.
(3) Defective iodinated tyrosine coupling: The thyroid gland has produced mono- and di-iodotyrosine coupling disorders, resulting in decreased synthesis of thyroxine (T4) and triiodothyronine (T3).
(4) Defective iodinated tyrosine deiodination: Due to the lack of deiodinase, free mono- and di-iodotyrosine cannot be deiodinated and are present in large amounts in the blood and cannot be reused by the gland, and are excreted in large amounts in the urine, indirectly causing excessive loss of iodine.
⑤ Abnormal thyroglobulin synthesis and breakdown: The iodination of tyrosine residues and the formation of T4 and T3 from iodinated tyrosine residues are carried out in intact thyroglobulin molecules. Abnormalities in thyroglobulin can lead to a decrease in T3, T4 synthesis. It can also produce globulins that are insoluble in butanol and affect the bioefficacy of T4 and T3. Abnormal breakdown of thyroglobulin can increase the level of inactive iodoproteins in the surrounding blood.
(b) The etiology of juvenile hypothyroidism is the same as that of adult patients.
(c) The causes of adult hypothyroidism can be divided into three main categories: thyroid hormone deficiency (thyroprivic), thyrotrophoprivic hormone deficiency (thyrotroprivic), and end-tissue hypothyroidism to thyroid hormone.
1. There are two primary and secondary causes of thyroid hormone deficiency due to lesions of the thyroid gland itself.
(1) Primary: The cause is unknown, so it is also called “idiopathic”, which may be related to autoimmune thyroid lesions, and thyroid atrophy occurs more often in this group, accounting for 5% of the incidence of hypothyroidism. Occasionally, it is seen from Graves’ disease and can also be a manifestation of multiple hypoendocrine syndrome (Schmidt’s syndrome).
(2) Secondary: There are more definite causes as follows.
(1) Thyroid destruction: surgical removal of the thyroid gland, or after radioactive iodine or radiation therapy.
(2) Thyroiditis: chronic lymphocytic thyroiditis related to autoimmunity is more frequent in the later stages, while those caused by subacute thyroiditis are rare.
③ Hypofunction with goiter or nodules: chronic lymphocytic thyroiditis is common, occasionally seen in invasive fibrous (Reidel’s) thyroiditis, which may be accompanied by nodular endemic goiter and scattered goiter due to iodine deficiency.
④Extensive intra-glandular lesions: Most commonly seen in advanced thyroid cancer and metastatic tumors, and less commonly in thyroid tuberculosis, amyloidosis, and thyroid lymphoma.
⑤ Drugs: overdose of antithyroid drugs; excessive intake of iodide (organic or inorganic iodine); use of drugs that prevent iodide from entering the thyroid gland, such as potassium perchlorate, thiocyanate, rezosin, p-aminosalicylate sodium (PAS), pautazone, iodine, nitrate, lithium carbonate, etc. Patients with hyperthyroidism are often more sensitive to the inhibitory effects of iodide on thyroid hormone synthesis and release after surgery or 131 iodine treatment. Therefore, hypothyroidism is likely to occur when iodine-containing drugs are taken again.
2, due to thyrotrophic hormone deficiency (thyro-trophoprivic) is divided into pituitary and hypothalamic.
(1) Due to hypopituitarism, thyrotrophic hormone (TSH) secretion is insufficient. This is also known as pituitary (or secondary) hypothyroidism. There are various causes, see “Anterior (glandular) hypopituitarism” for details. In order to avoid confusion with the aforementioned “secondary” thyroid destruction, it is more accurate to call it pituitary hypothyroidism.
(2) It is caused by hypothalamic disorders that lead to insufficient secretion of thyroid hormone-releasing hormone (TRH). This is also known as hypothalamic (or triphasic) hypothyroidism. The trichotillomania is secondary to the pituitary, so it is appropriate to call it hypothalamic.
3, terminal (peripheral) hypothyroidism refers to the terminal tissue thyroid hormone should not disorder. There are two causes.
(1) Due to the presence of thyroid hormone binding antibodies in the blood, thyroid hormone cannot play its normal biological effect;
(2) A decrease in the effect of thyroid hormone on peripheral tissues due to a decrease in the number of thyroid hormone receptors in the peripheral tissues and a decrease in the sensitivity of the receptors to thyroid hormone.
Clinical manifestations
(a) Cretinism has a variety of causes, and the clinical manifestations have commonalities as well as individual characteristics. The common manifestations are: pale skin, thickening, more folds, more scales. The lips are thick, the tongue is large and often extends, the mouth is often open and salivating, the appearance is ugly, the face is pale or waxy, the nose is short and upturned, the nasal bridge is collapsed, the forehead is wrinkled, the stature is short, the limbs are thick and short, the hands are often shovel-shaped, umbilical hernia is common, the heart rate is slow, the body temperature is low, the growth and development are lower than those of the same age, when the adult is often a dwarf.
Special manifestations of various types of cretinism.
1. The degree of congenital thyroid hypoplasia determines how early or late the symptoms appear and their severity. If the gland is completely absent, the above symptoms may appear 1 to 3 months after birth, and the symptoms are more severe, without goiter. If there is still a residual or ectopic gland, most of the typical symptoms appear within 6 months to 2 years of age and may be accompanied by compensatory goiter.
2. Congenital thyroid hormone synthesis disorder varies depending on the degree of various enzyme deficiencies. Generally, the symptoms are not obvious in the neonatal period, and then compensatory goiter gradually appears, and it is mostly significantly enlarged. Typical hypothyroidism may appear later and may be referred to as goiter cretinism, which may be autosomal recessive. In addition to the symptoms of goiter and hypothyroidism during iodine organic disorders, congenital neurogenic deafness is often present, called Pendred syndrome. These two types are mostly seen in sporadic cretinism, where the mother is not iodine deficient and the thyroid gland is functioning normally, and the fetus is unable to synthesize thyroid hormones itself but can receive compensation from the mother. Therefore, it does not cause serious damage to the nervous system. More than three months after birth, the thyroid hormone given by the mother has been depleted, and due to its own thyroid gland underdevelopment or lack of or due to hormone synthesis disorder, the lack of thyroid hormone in the body is at a very low level, so there are significant symptoms of hypothyroidism, but the impact of intelligence is light.
3. Congenital iodine deficiency is mostly seen in endemic cretinism. As a result of maternal endemic goiter, iodine deficiency during fetal life causes severe and irreversible damage to the fetal nervous system and permanent mental deficiency and hearing and speech impairment after birth in the absence of both fetal and maternal thyroid hormone synthesis, and the generation of enzymes essential for fetal nervous system development (such as uracil nucleoside diphosphate (UDP)) is hindered or their activity is reduced, but after birth the patient’s thyroid In the case of improved iodine supply, the thyroid gland can enhance thyroid hormone synthesis, so the symptoms of hypothyroidism are not obvious, this type is also known as “neurological” cretinism.
4. The mother takes goitre-causing agents or foods (such as cabbage, soybeans, para-aminosalicylic acid, thioureas, rezosin, pau taisong and iodine) during pregnancy, and the goitre-causing substances or drugs in these foods can pass through the placenta and affect the function of the thyroid gland, causing transient goiter or even hypothyroidism after birth. If a large amount of iodine is taken orally during pregnancy for a long period of time, the iodine may pass through the placenta and cause goiter in the newborn, and in huge cases it may cause asphyxia and death of the newborn. During lactation, iodine can also enter the infant through the milk and cause goiter with hypothyroidism.
(The clinical manifestations of juvenile mucinous edema vary according to the age of onset. The onset in young children is similar to that of cretinism except that the physical developmental delay and facial changes are not as significant as those of cretinism. In older children and adolescents, the onset of the disease mostly resembles adult mucinous edema, but is accompanied by varying degrees of growth retardation and delayed puberty.
(C) Adult hypothyroidism and mucinous edema
1. Clinical typing of hypothyroidism (including central-hypothalamic and pituitary hypothyroidism, thyroid hypothyroidism).
(1) Clinical hypothyroidism: In theory, it depends on thyroid hormone, but in practice, the severity and degree of clinical manifestation depends on the urgency of the onset, the speed and degree of hormone deficiency, and it is related to the variability of individual response to thyroid hormone reduction, so severe thyroid hormone deficiency can sometimes have mild clinical symptoms. Therefore, the diagnostic criteria for clinical hypothyroidism should include varying degrees of clinical manifestations and reductions in serum T3 and T4, especially reductions in serum T4 and FT4 as an objective laboratory indicator of clinical hypothyroidism. Clinical hypothyroidism can be divided into heavy and light, the former has obvious symptoms, involving a wide range of systems and often showing mucinous edema, while the latter has milder or atypical symptoms.
(2) Subclinical hypothyroidism: no obvious clinical manifestations: normal serum T3, normal or reduced T4, diagnosis should be confirmed according to TSH measurement or/and TRH test.
Mucinous edema in adults is more common between the ages of 40 and 60, with a male to female ratio of 1:4.5. The onset of the disease is insidious, and the course of the disease develops slowly, and it can take more than 10 years before the symptoms of mucinous edema become apparent. If the cause is unknown, the lesions are mostly complete; if secondary, the lesions are mostly incomplete, and some patients can still recover (e.g., from overdose of hyperthyroidism medication). The onset of the disease is not very insidious when it is caused by surgery or radiation therapy. Early symptoms begin at week 4 and typical symptoms are common after week 8. The earliest symptoms of mucinous edema are decreased sweating, coldness, slow movement, depression, fatigue, drowsiness, mental retardation, poor appetite, weight gain, and constipation. When typical symptoms appear the following manifestations are present.
(1) Low basal metabolic rate syndrome: fatigue, slowness of movement, drowsiness, significant memory loss and inattention, abnormal chilliness, absence of sweating and lower than normal body temperature due to poor peripheral blood circulation and reduced energy production.
(2) Mucinous edema face: facial expressions may be described as “indifferent”, “stupid”, “fake mask-like”, “dull”, or even “idiotic”. The cheeks and eyelids are swollen, and the pituitary mucinous edema is sometimes fat and round, as if the face were a full moon. The face is pale, anemic, or yellowish or old ivory-colored. Sometimes there may be cyanosis of the facial skin. The eyelids are often droopy or the fissure is narrowed due to decreased sympathetic tone on the Müller’s muscle. Some patients have mild proptosis, which may be associated with mucinous edema of the retrobulbar tissue in the orbit, but is not a threat to vision. The nose and lips are thickened, the tongue is large and inarticulate, speech is slow and intonation is low. The hair is dry, thinning and fragile, the eyelashes and eyebrows are lost (especially at the tips of the eyebrows), and the male beard grows slowly.
(3) Pale skin or due to mild anemia and thyroid hormone deficiency, the subcutaneous carotene into vitamin A and vitamin A to produce retinal function is reduced, resulting in an increase in plasma carotene content, in addition to anemia pale skin color, so the skin often shows a special waxy yellow, and rough and less luster, dry and thick, cold, scaly and keratinized, especially the hands, arms, thighs for obvious, and can have hyperkeratosis of the skin The skin may be hyperkeratotic. There is non-depressed mucinous edema, and sometimes depressed edema may appear in the lower extremities. The subcutaneous fat is thickened by the accumulation of water, resulting in weight gain in 2/3 of patients. The nails are slow growing, thick and brittle, and often have cracks on the surface. Axillary and pubic hairs are lost.
(4) Mental nervous system: mental retardation, drowsiness, comprehension and memory loss. Visual, auditory, tactile and olfactory senses are dulled, accompanied by tinnitus and dizziness. Sometimes it may be neurotic or may occur delusions, hallucinations, depression or paranoia. In severe cases, there may be mental disorders, such as rigidity, dementia, and lethargy. Patients who have not been treated for a long time and those who have just received treatment are prone to psychosis, and it is generally believed that the psychiatric symptoms are related to decreased metabolism of oxygen and glucose by brain cells. Occasionally, there is a cerebellar syndrome with ataxia and other manifestations. There may also be numbness in the hands and feet, abnormal nociception, characteristic changes in tendon reflexes, the systolic phase of reflexes tends to be agile and lively, while the relaxation phase is delayed, and the Achilles reflex is diminished, greater than 360 msec is good for diagnosis. The knee reflex is mostly normal. The EEG may be abnormal. Protein in the cerebrospinal fluid may increase to 3 g/L.
(5) Muscle and bone: muscle relaxation and weakness, mainly involving shoulder and back muscles, but also may have temporary muscle ankylosis, spasm, pain or cogwheel-like movements, abdominal and dorsal muscles and gastrocnemius may be painful due to spasm, and joints are often painful, and bone density may be increased. In a few cases, muscle hypertrophy may be present. Bone age is often delayed during development.
(6) Cardiovascular system: slow pulse, bradycardia, low heart sound, reduced cardiac output, often half of normal, because the tissue oxygen consumption and cardiac output is reduced in parallel, so myocardial oxygen consumption is reduced, angina pectoris and heart failure rarely occur. However, some patients may have ECG manifestations of myocardial infarction, which may disappear after treatment. Once heart failure occurs, the half-life of digitalis in the body is prolonged, and because of the prolongation of myocardial fibers with mucinous edema, the treatment is often ineffective and easy to poison. Total heart enlargement is more common, often accompanied by pericardial effusion, which can be normalized after treatment. Middle-aged and elderly women may have increased blood pressure. The circulation time is prolonged. Long-term patients are prone to complications of atherosclerosis and coronary artery disease, angina pectoris and arrhythmia.
(7) Digestive system: poor appetite, anorexia, abdominal distension, constipation, bulging bowel, and even megacolon and paralytic intestinal obstruction. 50% of patients have lack of gastric acid or no gastric acid due to the presence of anti-gastrin antibodies. SGOT, LDH and CPK may be increased in liver function.
(8) Respiratory system: The combination of obesity, mucinous edema, pleural effusion, anemia and poor circulatory system function can lead to shortness of breath and reduced diffusion of carbon dioxide in the alveoli, resulting in respiratory symptoms and even carbon dioxide anesthesia.
(9) Endocrine system: adrenocortical function is generally lower than normal, blood and urine cortisol are reduced, ACTH secretion is normal or reduced, ACTH excitatory response is delayed, but there is no clinical manifestation of hypoadrenocorticism, such as this disease with primary autoimmune hypoadrenocorticism and diabetes mellitus is called multiple hypoendocrine syndrome (Schmidt syndrome). In chronic and severe cases of the disease, reduced pituitary and adrenal function may occur, and these conditions may be accelerated during stress or rapid thyroid hormone replacement therapy.
In chronic patients with this disease, the pituitary gland is often enlarged, and primary hypothyroidism, due to increased TSH, may be accompanied by increased prolactin and thus overflow, but the mechanism of hyperprolactinemia in this disease has not been elucidated. Sympathetic nerve activity is reduced in thyroid hormone deficiency and may be associated with a reduced plasma cyclic adenosine response to epinephrine, a normal secretion rate and plasma concentration of epinephrine, and a corresponding increase in the function of norepinephrine. β-adrenergic receptors may be reduced in hypothyroidism. Plasma clearin concentration, urinary 5-hydroxyindoleacetic acid excretion rate is normal. Androstenolone excretion is decreased. The rate of insulin degradation is decreased and the patient has increased insulin sensitivity.
(10) Urinary system and water-electrolyte metabolism: decreased renal blood flow, delayed excretion of phenol red test, glomerular basement membrane thickening may appear a small amount of proteinuria, poor water diuretic test, water diuretic effect can not be corrected by cortisone but by thyroid hormone. Na+ exchange is increased and hyponatremia may occur, but K+ exchange is often normal. Serum Mg2+ may be increased, but the rate of exchanged Mg2+ and urinary Mg2+ excretion is decreased.
(11) Hematologic system: Hematopoietic function is inhibited by thyroid hormone deficiency, erythropoietin is reduced, iron and vitamin B12 absorption is impaired by gastric acid deficiency, and excessive menstruation causes mild to moderate normochromic or hypochromic microcytic anemia in 2/3 of the patients, and pernicious anemia (macrocytic) in a minority (about 14%). Sedimentation may be increased. The deficiency of factor VIII and IX leads to a weakened coagulation mechanism of the body, so it is prone to bleeding tendency.
(12) Coma: The most serious manifestation of mucinous edema, mostly seen in the elderly who have not been treated for a long time. Most of them develop in winter when it is cold. Cold and infection are the most common causes, and other causes such as trauma, surgery, anesthesia, and sedation can contribute to it. The coma is often preceded by a history of drowsiness, with flaccid limbs, absent reflexes, low body temperature (below 33°C), shallow and slow respiration, bradycardia, weak heart sounds, reduced blood pressure, and shock, and may be accompanied by cardiac and renal failure, which is often life-threatening.
Laboratory tests
(A) Indirect basis
1, hemoglobin and red blood cell reduction is often mild or moderate anemia, hypohemoglobin small red blood cell type, normal red blood cell type, large red blood cell type can occur.
2.Prolonged Achilles tendon reflex time is often greater than 360mS, and in severe cases, it can be 500-600mS.
3, basal metabolic rate is often reduced in -35% to -45%, sometimes up to -70%.
4. If the cause of lipid begins in the thyroid gland, cholesterol is often greater than 300mg/dl. If the cause begins in the pituitary gland or hypothalamus, cholesterol is mostly normal or low, but in infants with cretinism, there may be no hypercholesterolemia. Triglycerides are elevated, LDL is elevated, and HDL-cholesterol is decreased.
5. Increased blood carotenoids.
6. Phosphocreatine kinase (CPK) lactate dehydrogenase (LDH) is increased, 17-ketosteroids, 17-hydroxycorticosteroids are decreased. The glucose tolerance test shows a flat curve and delayed insulin response.
7. Calcium and phosphorus measurements showed normal serum calcium and phosphorus, decreased urinary calcium excretion, normal fecal calcium excretion, normal fecal and urinary phosphorus excretion, and decreased blood AKP in infants and young adults with this disease.
The electrocardiogram shows low voltage, sinus bradycardia, low or inverted T waves, and occasionally a long P-R interval (A-V conduction block) and an increase in QRS wave duration.
X-ray examination of thyroid hormone is important for the early diagnosis of cretinism because of its role in the growth and maturation of bone, especially in relation to the latter. The butterfly saddle is often round and enlarged in children over 7 years of age and can be reduced after treatment: in children under 7 years of age, the butterfly saddle shows delayed maturation, a semicircular shape, a pointed posterior bed projection and a flattened saddle node. The cardiac shadow is often diffusely enlarged bilaterally on chest radiographs, and wave photography and ultrasonography show pericardial effusion, which can be completely recovered after treatment.
10, EEG examination of certain cretinism has diffuse abnormal EEG, low frequency, rhythmic irregularities, paroxysmal bilateral Q waves, no a wave, showing central brain dysfunction.
(II) Direct basis
The most useful test is serum TSH, which can be elevated in thyroid hypothyroidism, and low or even undetectable in pituitary or hypothalamic hypothyroidism, which can be accompanied by low secretion of other anterior pituitary hormones. Regardless of the type of hypothyroidism, serum total T4 and FT4 are mostly low. Serum T3 can be measured in the normal range in mild cases, but it can be reduced in severe cases. In some patients with clinically asymptomatic or asymptomatic subclinical hypothyroidism, serum T3 and T4 can be normal. This is the result of compensatory feedback from increased TSH secretion after the decrease of T3 and T4 secretion by the thyroid gland. Some patients have normal serum T3 and reduced T4, which may be due to the relatively increased synthesis of biologically active T3 by the thyroid gland under TSH stimulation or iodine deficiency, or the increased conversion of T4 to T3 in the surrounding tissues. Therefore, a decrease in T4 and a normal T3 can be considered as one of the indicators for an earlier diagnosis of hypothyroidism. T4 is routinely measured in newborns with cord blood as a screening test for cretinism. In addition, in patients with severe diseases and normal thyroid function and in elderly normal individuals, serum T3 can be reduced, so T4 concentration is more important than T3 concentration for diagnosis.
Since total T3 and T4 can be affected by TBG, free T3 and T4 (FT3 and FT4) can be measured to assist in diagnosis.
2. Plasma protein-bound iodine (plasmaproteinboundiodine, PBI) is often measured below normal in hypothyroid patients, mostly below 3 to 4 μg/dl.
3. The rate of 131 iodine uptake by the thyroid gland is significantly lower than normal, often with a low flat curve, while the urinary excretion of 131 iodine increases.
4. The measurement of serum thyroid stimulating hormone (TSH) is extremely important for hypothyroidism, and is greater than T4 and T3. Its normal value is 0-4μu/ml, with 10μu/ml as the high limit (2± 1ng/ml in our hospital). If the disease is caused by destruction of the thyroid gland itself, TSH is significantly elevated, often >20μu/ml. If <10μu/ml and the blood concentration of thyroid hormone is reduced, it means that the TSH reserve function of the pituitary gland is reduced and it is secondary to hypothalamic or pituitary hypothyroidism, but depending on the severity of the hypothalamic-pituitary condition, TSH can be normal, low or significantly reduced.
5. Trans-T3 (rT3) is reduced in thyroid and central hypothyroidism and may be increased in peripheral hypothyroidism.
6. Thyroid stimulating hormone (TSH) excitation test to understand the response of the thyroid gland to TSH stimulation. If the rate of 131 iodine uptake does not increase after TSH, it suggests that the lesion originates in the thyroid gland and therefore does not respond to TSH stimulation.
7.Thyroid hormone-releasing hormone test (referred to as TRH excitation test) is described in “Thyroid Function Measurement”. If the TSH is normal or low, but after the TRH stimulation causes an increase and a delayed response, it indicates that the lesion is in the hypothalamus. If the TSH is low to low, normal or slightly high and the TSH in the blood does not increase or shows a low (weak) response after TRH stimulation, the lesion is in the pituitary gland or the TSH storage function of the pituitary gland is reduced. If TSH is originally high and becomes more pronounced after TSH stimulation, the lesion is in the thyroid gland.
If the cause is related to autoimmunity, anti-thyroglobulin and anti-microsomal antibodies can be measured in the blood.
Diagnosis and differentiation
Early diagnosis of cretinism is extremely important. Conditions should be created to include serum thyroid hormone and TSH as routine tests for newborns. In order to avoid or minimize permanent mental retardation, treatment should be started as early as possible, so early diagnosis must be sought. The diagnosis of cretinism in infants is difficult, but careful observation of growth, development, appearance, skin, diet, sleep, stool and other aspects should be made, and relevant laboratory tests should be performed if necessary. Due to the special appearance of cretinism, attention should be paid to differentiate it from congenital dementia (Tongue-stretching dementia called Down’s syndrome).
Mucinous edema is not difficult to diagnose in typical cases, but early mild cases and atypical cases are often confused with anemia, obesity, edema, nephrotic syndrome, hypometabolic rate syndrome, menstrual disorders, hypopituitarism, etc., which require thyroid function measurements for differentiation. The diagnosis of end-stage hypothyroidism is sometimes not easy. The main laboratory feature is that the patient has clinical signs of hypothyroidism and the serum T4 concentration is increased. Some patients may also have characteristic facial features, deafness, and stippled epiphyses. There is no goitre.
Treatment
(a) The earlier the treatment of cretinism, the better the outcome. Initially, triiodothyronine 5 μg every 8 hours and L-thyroxine sodium (T4) 25 μg/d were given orally in the nascent stage of cretinism, and after 3 days, T4 increased to 37.5 μg/d. After 6 days, T3 was changed to 2.5 μg every 8 hours. Over the course of treatment T4 was gradually increased to 50 μg per day while T3 was gradually reduced to discontinuation. Or T4 treatment alone, the first amount of 25μg/d after the first 25μg/d weekly increase 25μg/d, after 3-4 weeks to 100μg/d, and then into a slow increase, so that serum T4 to maintain 9-12μg/dl, such as clinical efficacy is not satisfactory, the dose can be slightly increased. Infants and children aged 9 months to 2 years require 50 to 150 μg T4 per day, and thyroid hormone should be increased if their skeletal growth and maturation are not accelerated. Although TSH values are helpful to know whether treatment is appropriate, it is more effective to know how well hypothyroidism is being treated from clinical symptom improvement than to measure serum T4. Treatment should be continued for life.
(b) Treatment of juvenile mucinous edema is the same as in older children with cretinism.
(c) Adult mucinous edema is treated significantly with thyroid hormone replacement therapy and requires lifelong administration. The drug preparations used are synthetic thyroid hormones and thyroid proteins obtained from the thyroid gland of animals.
1. Thyroid tablets are commonly used, starting with small doses of 15-30 mg daily, with a final dose of 120-240 mg. Having used up to 240 mg and not seeing any effect consider whether the diagnosis is correct or whether it is peripheral hypothyroidism. The dose should be reduced to an appropriate maintenance dose of approximately 90-180 mg daily when the treatment is effective and the symptoms improve and the pulse rate and basal metabolic rate return to normal. If there are palpitations, arrhythmia, tachycardia, insomnia, irritability, excessive sweating and other symptoms during the treatment, the dosage should be reduced or suspended.
2. Sodium L-thyroxine (T4) or triiodothyronine (T3) T4100μg or T320～25μg is equivalent to 60mg of dry thyroid tablets. should start with a small dose, T4 twice daily, 25μg orally each time, and then increase 50μg every 1~2 weeks, the final dose is 200~300μg, but the general daily maintenance amount is about 100~150μg T4 The daily dose of T3 is 60 to 100 μg. T3 is faster and stronger than T4 and dry thyroid preparations, but the duration of action is shorter, and as replacement therapy dry thyroid tablets and T4 are superior to T3. Due to the unstable biological potency of dry thyroid preparations, T4 tablets are superior for treatment.
3, T4 and T3 mixed preparations T4 and T3 in a 4:1 ratio into a combination or tablet, the advantage is that it has a similar effect to endogenous thyroid hormone.
The initial dose can be slightly larger and the dose can be increased more rapidly for younger people without heart disease. For example, dry thyroid tablets can be started at 60mg per day and then increased by 60mg per day after 2 weeks to the required maintenance dose.
4. Thyroid extract, USP and purified porcine thyroglobulin have been used clinically.
The dose should be reduced as appropriate in elderly patients. In patients with a history of coronary or other heart disease and psychiatric symptoms, thyroid hormone should be started in smaller doses and increased more slowly. For example, dry thyroid tablets should be started at 15 mg daily and only increased by 15 mg every two weeks or more until an appropriate maintenance dose is reached. If it causes angina attacks, arrhythmias or psychiatric symptoms, the dose should be promptly reduced.
Since the normal range of serum T3 and T4 concentrations is large, the severity of hypothyroidism varies, and the demand and sensitivity to thyroid hormones are not uniform, so treatment should be individualized.
In patients with hypopituitarism and severe disease, thyroid hormone therapy should be started after corticosteroid replacement therapy in order to prevent adrenocortical insufficiency.
Peripheral hypothyroidism can be treated with higher doses of T3 if treatment is difficult.
In patients with anemia, iron, folic acid, vitamin B12 or liver preparations should be given. Gastric acid levels must be noted in the fashion of iron therapy and must be supplemented if low.
In patients with cardiac symptoms, digitalis is generally not necessary unless there is congestive heart failure. Cardiac signs and ECG changes can gradually disappear after the application of thyroid preparations.
Patients with mucinous edema are sensitive to insulin, sedatives and anesthetics, which can induce coma, so it should be used with caution.
Treatment of mucinous edema coma.
1, thyroid preparations because of thyroid tablets and T4 action is too slow, so it is necessary to use the rapid action of triiodothyronine (T3). At the beginning, it is best to use intravenous preparations (D, L-triiodothyronine), 40 to 120 μg for the first time, and 5 to 15 μg of T3 every 6 hours by sedation until the patient is awake and changed to oral administration. If this form is not available, triiodothyronine tablets can be finely grinded with water and given intranasally every 4-6 hours at 20-30 μg each time; in the absence of fast-acting preparations, T4 can be used, with the first dose of 200-500 μg intravenously, and later 25 μg intravenously every 6 hours or 100 μg orally daily. The first dose of T4200μg and T350μg intravenously, and then T4100μg and T325μg intravenously daily, can also be used dry thyroid tablets, once every 4-6 hours, 40-60mg each time, the dose can be slightly larger for newborns, and then decreasing depending on the improvement of the disease, with heart disease, it is appropriate to start with a smaller amount, 1/5 to 1/4 of the general dosage.
2. Administer oxygen, keep the airway open, and if necessary, tracheotomy or intubation to ensure adequate gas exchange.
3.Keep warm, keep warm by increasing the bedding and room temperature, etc. The room temperature should be gradually increased to avoid a sudden increase in oxygen consumption to the detriment of the patient.
4.Adrenocorticotropic hormone, hydrocortisone 50~100mg every 4~6 hours, decreasing or withdrawing after waking up.
5.Actively control the infection.
6.Boosting drugs. If the blood pressure does not rise after the above treatment, a small amount of antihypertensive drugs can be used, but the combination of antihypertensive drugs and thyroid hormone is prone to heart rate disorders.
7.Replenish glucose solution and vitamin B complex, but the amount of rehydration should not be too much, so as not to induce heart failure.
After the above treatment, if the condition improves in about 24 hours, it can gradually recover after a week. If it cannot be reversed after 24 hours, most of them cannot be saved.
Prognosis prevention
It is extremely important, for endemic cretinism embryonic iodine deficiency in pregnant women is the key to the pathogenesis. Therefore, in endemic goiter areas, pregnant women should be supplied with adequate iodide, and potassium iodide 20-30 mg daily can be added in the last 3-4 months of pregnancy; those with Graves’ disease treated with thioureas should try to avoid excessive doses and add small doses of dry thyroid preparations at the same time. Radioactive 131 iodine therapy is prohibited for hyperthyroidism in pregnancy, and oral administration of diagnostic tracers should be avoided, but in vitro testing is possible.
In endemic areas of China, due to the vigorous prevention and treatment of iodized salt and iodized oil, cretinism has become very rare.
Many hypothyroidism in adults is caused by surgical removal or treatment of hyperthyroidism with radioactive 131 iodine. It is important to control the amount of thyroid function removed and the dose of radioactive 131 iodine to avoid too much removal and too high a dose, which can lead to this disease.