bubble_chart Overview

Hypothyroidism is a systemic disease caused by insufficient secretion of thyroid hormones by the thyroid gland. Clinically, it is characterized by delayed growth and development, disproportionate short stature, and intellectual disability, hence referred to as cretinism. It is generally classified into two major categories: congenital (sporadic) and acquired (endemic). In recent years, endemic cases have become less common, so this section focuses on sporadic cretinism.

bubble_chart Etiology

Endemic cretinism

occurs in areas with endemic goiter. It is caused by iodine deficiency in the maternal diet during pregnancy or by high levels of calcium or fluorine in local water and food, which interfere with the mother's absorption and utilization of iodine. This leads to insufficient iodine supply to the fetus, resulting in reduced thyroid hormone synthesis and severely affecting the development of the fetal nervous system, particularly the brain.

Sporadic cretinism

is caused by congenital thyroid hypoplasia or functional defects in related enzyme systems.

Known disease causes include the following:

1. Thyroid hypoplasia due to embryonic developmental defects, complete absence of the thyroid, partial remnants, or ectopic thyroid. The developmental abnormalities may result from maternal thyroid diseases, where serum anti-thyroid antibodies destroy fetal thyroid tissue.
2. Impaired thyroid hormone synthesis due to defects in enzyme systems, affecting iodine uptake, organification, or the synthesis of thyroxine (T4) and triiodothyronine (T3), leading to insufficient thyroid hormone secretion and hypothyroidism. Common defects include deficiencies in peroxidase, iodinase, coupling enzyme, deiodinase, or thyroglobulinase.
3. Maternal use of certain medications during pregnancy, such as antithyroid drugs (e.g., thiouracil), iodides, or radioactive iodine therapy. These drugs can cross the placenta and inhibit fetal thyroid hormone synthesis, causing functional deficiency.
4. Pituitary thyroid-stimulating hormone (TSH) secretion deficiency is rare. It may occur due to the thyroid's lack of or reduced response to TSH.

bubble_chart Pathogenesis

The synthesis of thyroid hormones requires iodine and tyrosine as raw materials. After iodine enters the thyroid gland, it is oxidized by oxidase into active iodine. Active iodine combines with tyrosine and, under the action of iodinase, synthesizes monoiodotyrosine and diiodotyrosine. These are then condensed by the action of condensing enzymes to form biologically active triiodothyronine (T3) and thyroxine (T4). Both are attached to thyroglobulin molecules and released into the bloodstream. In terms of quantity, T4 is more abundant than T3, but in physiological activity, T3 is 3–5 times more potent than T4.

The main physiological effects of thyroid hormones are:

1. Promoting metabolism and increasing oxygen consumption.
2. Enhancing protein synthesis and enzyme activity; increasing the absorption and utilization of glucose; accelerating the breakdown and oxidation of fats.
3. Promoting growth and development in children, as well as tissue differentiation and maturation. It also facilitates the synthesis and metabolism of calcium and phosphorus in bones.
4. Supporting the development and function of the central nervous system.
5. Potentiating the effects of Black Catechu phenols.

Therefore, when thyroid function is low, it can lead to slowed metabolism, impaired protein synthesis (resulting in excessive mucoproteins in subcutaneous abdominal masses), and reduced breakdown of fats and sugars (elevated blood cholesterol). The development and function of the central nervous system are suppressed (leading to intellectual impairment), and the effects of Black Catechu phenols are inhibited (causing lowered blood pressure and slowed heart rate), resulting in various physiological dysfunctions and developmental delays.

bubble_chart Clinical Manifestations

This disease is more common in girls, approximately three times as frequent as in boys. The timing of onset and the severity of the condition depend on the amount of thyroid tissue and its function. Infants without a thyroid gland exhibit symptoms within 1 to 3 months after birth, while those with partial glandular tissue often show symptoms after 6 months, and occasionally, symptoms may not become apparent until 4 to 5 years of age.

Prolonged physiological jaundice in the neonatal period is often an initial stage [first stage] symptom, which may include difficulty sucking, less crying and more sleeping, and slow breathing. As age increases, typical signs gradually become more pronounced.

The prominent features of this disease are

1. physiological hypofunction: such as cold intolerance, low body temperature, without sweating, reduced activity, slow respiration and pulse, low blood pressure, bradycardia, prolonged P-R interval on electrocardiogram, flattened T waves, and low voltage. Hypotonia, slow intestinal peristalsis, constipation, and abdominal distension with umbilical hernia.
2. Intellectual developmental delay: manifested as sluggish responses, dullness, and delayed language development.
3. Growth and developmental delay: due to delayed skeletal development, short stature, short limbs with a relatively long trunk, large head, short neck, delayed tooth eruption, and fontanel closure.
4. Special facial features and signs: sallow complexion, sparse and dry hair, widened interocular distance, flattened nasal bridge, enlarged nostrils, thick lips, large and broad tongue, wrinkled forehead, eyelid edema, subcutaneous tissue with mucous edema, and dry, rough skin.

Endemic cretinism is clinically characterized by goiter and symptoms of hypothyroidism, with early symptom onset and high sensitivity to iodine treatment.

bubble_chart Auxiliary Examination

1. Bone X-ray examination shows bone age lagging behind chronological age. In newborns, knee radiography can be performed because the ossification centers of the distal femur and proximal tibia are normally present at birth, but absent in affected children, indicating delayed bone age, which has diagnostic significance. For children over 1 year old, wrist radiography can be done, revealing delayed appearance of ossification centers with uneven calcification and a spotted appearance.
2. Serum T3 and T4 measurement: The normal reference range for serum T3 is 1.23–3.07 nmol/L (80–200 μg/dL). In mild cases, T3 may be normal, while in severe cases it decreases. In endemic cretinism, T3 may increase. The normal range for serum T4 is 64.4–167.3 nmol/L (5–13 μg/100 mL). In this disease, T4 often decreases below 64.4 nmol/L, and a neonatal level <77.2 nmol/L can confirm the diagnosis.
3. Thyroid ¹³¹I uptake measurement: The normal 24-hour uptake is 31.8±8.0%. In children with thyroid hypoplasia, the ¹³¹I <吸附率往往在20%以下。甲狀腺缺如者¹³¹I uptake is below 10%.
4. Serum thyroid-stimulating hormone (TSH) measurement: The normal value is <100 μU/L. Due to the lack of negative feedback from thyroid hormones, TSH secretion increases in this disease, often exceeding 200 μU/L.
5. Serum thyroglobulin measurement: A negative result suggests the absence of thyroid tissue or abnormal thyroglobulin synthesis. A positive result with decreased T4 and T3 and elevated TSH indicates residual thyroid tissue.
6. Serum cholesterol measurement: Often elevated, it may exceed 4 g/L.

bubble_chart Diagnosis

Based on medical history, intellectual disability, delayed growth and development, distinctive facial features, X-ray, and laboratory tests, a diagnosis can be made. For cases where clinical diagnosis is difficult and testing facilities are unavailable, administering thyroid tablets for 2-3 weeks may help. If the condition is present, improvements such as increased responsiveness, greater appetite, reduced constipation, and disappearance of mucous edema may be observed.

bubble_chart Treatment Measures

After diagnosis is confirmed, thyroid preparations should be administered as early as possible in sufficient and long-term doses. During treatment, adjust the {|###|}dose{|###|} based on the child's response to avoid adverse effects.

1. Thyroid tablets: Initial {|###|}dose{|###|} for infants is 5-10mg/d, for children 10-20mg/d. Increase by 5-10mg/d every 2-4 weeks until the child becomes lively, appetite improves, {|###|}constipation{|###|} disappears, {|###|}abdominal distension and fullness{|###|} alleviates, and no hyperthyroidism symptoms such as {|###|}dysphoria{|###|} or weight loss appear. Then the maintenance dose can be used. For children under 1 year: 20-40mg/d; 1-3 years: 40-60mg/d; 3-6 years: 60-80mg/d; 6-10 years: 80-120mg/d; over 10 years: 120-160mg/d, taken once daily or divided into two doses. The dose may be appropriately reduced after adolescence. If symptoms such as {|###|}dysphoria{|###|}, restlessness, {|###|}profuse sweating{|###|}, significant weight loss, {|###|}abdominal pain{|###|}, or {|###|}diarrhea{|###|} occur during treatment, it indicates excessive dose, and the dose should be appropriately reduced.
2. Sodium-L-thyroxine: 100μg is equivalent to 40mg of thyroid tablets. The initial dose for infants is 50μg/d, increased to 100μg/d after 2-4 weeks. For older children, the initial dose is 100-150μg/d.

After treatment with thyroid tablets, supplement with multivitamins, trace elements, and sufficient protein to meet the needs of physical growth and development.

bubble_chart Prevention

Strengthen maternal healthcare, and pregnant women should avoid infections and the use of antithyroid drugs as much as possible. Improve nutrition and avoid excessive fatigue. In areas where goiter is prevalent, the widespread consumption of iodized salt (containing 0.01% potassium iodide) has shown significant effects in preventing endemic cretinism. Women with goiter should receive active treatment. Pregnant women should appropriately increase their intake of iodine-rich foods such as kelp.

bubble_chart Differentiation

1. Down syndrome: Intellectual disability, characteristic facial features, tongue not significantly protruding, delicate skin, simian crease, karyotype showing trisomy 21, normal serum T3 and T4 levels.
2. Rickets: Normal intelligence, presenting with symptoms and signs of rickets, abnormal blood calcium, phosphorus, and alkaline phosphatase levels, X-ray findings indicating rickets changes in long bones.
3. Achondroplasia: Short limbs, large head, normal intelligence, skeletal X-rays showing short and thick long bones, widened metaphyses, and occasionally ossification centers embedded within the widened metaphyses.
4. Pituitary dwarfism: Short stature but with normal facial features, intelligence, and body proportions, agile and nimble movements.