Congenital hypothyroidism: causes, pathogenesis, consequences, prognosis

The disease caused by genetic factors and associated with thyroid insufficiency is congenital hypothyroidism. Consider the features of this pathology, methods of treatment.

The complex of clinical and laboratory signs arising from birth due to the insufficiency of thyroid hormones is a congenital hypothyroidism. According to the international classification of diseases of the 10th revision of the ICD-10, the disease falls into category IV. Diseases of the endocrine system, eating disorders and metabolic disorders (E00-E90).

Diseases of the thyroid gland (E00-E07):

• E02 Subclinical hypothyroidism due to iodine deficiency.
• E03 Other forms of hypothyroidism:
  • E03.0 Congenital hypothyroidism with diffuse goiter. Goiter (non-toxic) congenital: BDI, parenchymal. Excluded: transient congenital goiter with normal function (P72.0).
  • E03.1 Congenital hypothyroidism without goiter. Aplasia of the thyroid gland (with myxedema). Congenital: atrophy of the thyroid gland, hypothyroidism NOS.
  • E03.2 Hypothyroidism caused by drugs and other exogenous substances.
  • E03.3 Post-infectious hypothyroidism.
  • E03.4 Thyroid atrophy (acquired). Excluded: congenital atrophy of the thyroid gland (E03.1).
  • E03.5 Myxedema coma.
  • E03.8 Other specified hypothyroidism.
  • Unspecified E03.9 Hypothyroidism, myxedema BSU.

The thyroid gland is one of the organs of the endocrine system that performs many functions responsible for the full-fledged work and development of the whole organism. It produces hormones that stimulate the pituitary and hypothalamus. The main functions of the gland include:

• Control of exchange processes.
• Metabolism regulation: fats, proteins, carbohydrates, calcium.
• Formation of intellectual abilities.
• Control body temperature.
• Synthesis of retinol in the liver.
• Lower cholesterol.
• Stimulation of growth.

From birth, the organ affects the growth and development of the child’s body, especially the bones and nervous system. The thyroid gland produces the hormone thyroxine T4 and triiodothyronine T3. The deficiency of these substances negatively affects the functioning of the whole organism. Hormonal insufficiency leads to a slowdown in mental and physical development, growth.

With congenital abnormalities, the newborn gains excess weight, has problems with heart rate and blood pressure. Against this background, energy is reduced, intestinal problems and increased bone fragility appear.

[1], [2]

Epidemiology

According to medical statistics, the prevalence of congenital hypothyroidism is 1 case per 5000 babies. The disease is about 2.5 times more common in girls than in boys. As for the secondary form, it is most often diagnosed after 60 years. In 1000 women, about 19 are diagnosed. While among men, only 1 out of 1000 is sick.

At the same time, the total population with thyroid hormone deficiency is about 2%. Danger of a pathological disease in its blurred symptoms complicating the process of diagnosis.

[3], [4], [5], [6], [7],

Causes of the congenital hypothyroidism

Genetic abnormalities are the main factor causing thyroid insufficiency. Possible causes of the disease also include:

• Hereditary predisposition - the violation is closely related to gene mutations, so it can develop in utero.
• Disruptions in the formation of hormones - are due to a decrease in the sensitivity of the thyroid gland to iodine. Against this background, possibly disrupting the transportation of useful substances that are necessary for the synthesis of hormones.
• Pathology of the hypothalamus - the center of the nervous system regulates the functioning of the endocrine glands, including the thyroid gland.
• Decreased sensitivity to thyroid hormones.
• Autoimmune diseases.
• Tumor lesions of the thyroid gland.
• Reduced immunity.
• Overdose drugs. Acceptance of antithyroid drugs during pregnancy.
• Viral and parasitic diseases.
• Treatment with radioactive iodine.
• Iodine deficiency in the body.

In addition to the above, there are many other causes of congenital pathology. In most cases, the cause of the disease remains unknown.

[8]

Risk factors

In 80% of cases, the thyroid gland is impaired due to its developmental defects:

• Gypoplasia.
• Dystopia (displacement) in the retrosternal or sublingual space.

The main risk factors for congenital hypothyroidism include:

• Iodine deficiency in the female body during pregnancy.
• Exposure to ionizing radiation.
• Infectious and autoimmune diseases suffered during gestation.
• The negative impact on the fetus of medicines and chemicals.

In 2% of the pathology caused by mutations of the genes: PAX8, FOXE1, TITF2, TITF1. In this case, the baby has congenital heart defects, the dislocation of the upper lip or hard palate.

About 5% of cases of the disease are associated with hereditary pathologies that cause disruptions in the secretion of thyroid hormones or their interaction with each other. These pathologies include:

• Pendred syndrome.
• Defects of thyroid hormones.
• The organization of iodine.

In other cases, factors that can trigger hypothyroidism are:

• Birth injuries.
• Tumor processes in the body.
• Asphyxia of the newborn.
• Disorders of the brain.
• Aplasia of the pituitary gland.

The action of the above factors leads to the development of the syndrome of resistance. That is, the thyroid gland can produce a sufficient amount of thyroid hormones, but the target organs completely lose sensitivity to them, causing symptomatology characteristic of hypothyroidism.

Pathogenesis

The mechanism of development of thyroid anomalies is due to a decrease in biosynthesis and a decrease in the production of iodine-containing hormones (thyroxin, triiodothyronine). The pathogenesis of congenital hypothyroidism due to problems with the production of thyroid hormones is associated with the action of various pathological factors at different stages:

• Defect of iodine accumulation.
• The failure of the process of iodinated thyronines iodinated.
• Transition of mono-iodothyronine and diiodothyronine to triiodothyronine and thyroxin and other hormones.

The development of the secondary form of the disease is associated with such factors:

• Thyrotropic hormone deficiency.
• Decreased concentration of iodides in the thyroid gland.
• The secretory activity of the epithelium of organ follicles, reducing their number and size.

Polyetiological disease provokes a violation of metabolic processes in the body:

1. Lipid metabolism - slowing down the absorption of fat, inhibition of catabolism, increasing the level of cholesterol in the blood, triglycerides and β-lipoproteins.
2. Carbohydrate metabolism - slowing down glucose absorption in the gastrointestinal tract and reducing its utilization.
3. Water metabolism - increased hydration capacity of mucin and violation of hydrophilicity of colloids leads to water retention in the body. Against this background, diuresis and the amount of chlorides output decreases. Potassium levels increase and the amount of sodium in the heart muscle decreases.

The above metabolic pathologies lead to pathologies in the development of the brain and the central nervous system.

[9],

Symptoms of the congenital hypothyroidism

In most cases, the symptoms of congenital dysfunction of the thyroid gland make themselves felt a couple of months after birth. However, in some babies, the first signs of the disease appear immediately.

Symptoms of genetic pathology are:

• The weight of a newborn is more than 4 kg.
• Prolonged jaundice after birth.
• Blue nasolabial triangle.
• Swelling of the face.
• Half open mouth.
• Change voice timbre.

If the above symptoms remain without medical attention, then they begin to progress. After 3-4 months, hypothyroidism is manifested by the following symptoms:

• Disturbance of appetite and swallowing process.
• Peeling and paleness of the skin.
• Dry and brittle hair.
• Tendency to constipation and flatulence.
• Low body temperature, cold limbs.

There are also later, but obvious signs of illness that develop a year after the birth of a child:

• Lag in physical and mental development.
• Late appearance of teeth.
• Low pressure.
• Changing facial expressions.
• Enlarged heart.
• Rare pulse.

The above clinical manifestations make it difficult to diagnose, so early screening is indicated for the detection of the disease. The procedure is carried out for all children during the week after birth.

[10]

Complications and consequences

A decrease in thyroid function is characterized by a partial or complete lack of hormones. A painful condition is a dangerously serious impairment in the development of a newborn. The consequences and complications affect all organs of the infant system, for which the thyroid gland is responsible for the normal operation:

• The formation and growth of the skeleton, teeth.
• Cognitive abilities, memory and attention.
• The assimilation of vital trace elements from breast milk.
• The functioning of the central nervous system.
• Lipid, water and calcium balance.

Congenital hypothyroidism leads to such problems:

• Slow development of the brain and spinal cord, inner ear and other structures.
• Irreversible damage to the nervous system.
• Lag in psychomotor and somatic development.
• Lag in weight and height.
• Hearing impairment and deafness due to tissue swelling.
• Loss of voice
• Delay or complete arrest of sexual development.
• Thyroid gland overgrowth and its malignant degeneration.
• Formation of secondary adenoma and “empty” Turkish saddle.
• Loss of consciousness.

Congenital lack of hormones in combination with developmental disorders leads to cretinism. This disease is one of the most severe forms of delayed psychomotor development. Children with this complication lag behind their peers physically and intellectually. In rare cases, the endocrine system pathology leads to a hypothyroid coma, which in 80% is the risk of death.

[11], [12]

Prevention

Congenital hypothyroidism develops during pregnancy and in most cases for reasons beyond the control of the woman (abnormal development of the fetal organs, gene mutations). But despite this, there are preventive measures to minimize the risk of having a sick child.

Prevention of hypothyroidism consists of a comprehensive diagnosis both during the planning of pregnancy and during gestation.

1. First of all, it is necessary to determine the level of thyroid hormones and the concentration of specific antibodies to thyroglobulin and thyroperoxidase. Normally, antibodies are absent or circulate on average up to 18 U / ml for AT-TG and 5.6 U / ml for AT-TPO. Elevated values indicate the development of autoimmune inflammatory processes in the thyroid gland. Elevated antibodies to thyroglobulin increase the risk of cancer of organ tissue.

• If the disease was diagnosed before pregnancy, then treatment is provided. Therapy begins with the intake of synthetic hormones and other drugs to restore normal synthesis of hormones and restore the functioning of the thyroid gland.
• If the pathology is detected after conception, then the patient is prescribed the maximum dose of thyroid hormone drugs. The treatment lasts until the thyroid hormone is replenished.

1. Hypothyroidism can develop due to iodine deficiency. For the normalization of iodine balance and the prevention of deficiency of this substance in the body, the following remedies are recommended:

• Yodomarin

The preparation of iodine with the active substance is potassium iodide 131 mg (pure iodine 100/200 mg). Used to treat and prevent diseases of the thyroid gland. The trace element is indispensable for the normal functioning of the body. Replenishes iodine deficiency in the body.

• Indications for use: prevention of thyroid diseases caused by iodine deficiency in the body. Prevention of iodine deficiency in people who need increased consumption of this substance: pregnant, lactating women, children and adolescents. Prevention of the formation of goiter in the postoperative period or after drug therapy. Treatment of diffuse non-toxic goiter, diffuse euthyroid goiter.
• Method of application: the dosage depends on the patient's age and indications for use. On average, patients are prescribed from 50 to 500 mg per day. Long-term preventive treatment - 1-2 years of courses or continuously. In severe cases, the prevention of iodine deficiency is carried out throughout life.
• Side effects: develop with improperly selected dosage. Transition of latent hyperkeratosis into manifest form, iodine-induced hyperkeratosis, various allergic reactions are possible. Overdose has similar symptoms.
• Contraindications: hyperthyroidism, intolerance to iodine preparations, toxic thyroid adenoma, herpetiform dermatitis Dühring. The use of the drug during pregnancy and lactation is not prohibited.

Iodomarin is available in tablet form in bottles of 50, 100 and 200 capsules.

• Iodineactivity

It compensates for the lack of iodine in the body. With a deficiency of this trace element is actively absorbed, and with an excess - is excreted from the body and does not enter the gland. The drug is prescribed for the treatment and prevention of diseases associated with iodine deficiency in the body.

IodActiv is contraindicated for patients with hypersensitivity to its components. The drug is taken 1-2 capsules 1 time per day, regardless of the meal. The duration of treatment is determined by the attending physician.

• Jodbalans

Inorganic compound of iodine, replenishing iodine deficiency in the body. Normalizes the synthesis of the main thyroid hormones. Reduces the formation of inactive forms of thyroid hormones. 1 capsule of the drug contains the active substance potassium iodide 130.8 mg or 261.6 mg, equal to 100 or 200 mg iodine, respectively.

The active component restores and stimulates metabolic processes in the central nervous system, musculoskeletal, cardiovascular and reproductive systems. It contributes to the normalization of intellectual-mnestic processes, maintains homeostasis.

• Indications for use: prevention of iodine deficiency states during gestation and lactation. The postoperative period after thyroid surgery. Goiter prevention, comprehensive treatment of euthyroid syndrome in newborns and adult patients.
• Method of application: the daily dosage is determined by the attending physician, individually for each patient. Most often, patients are prescribed 50-200 mg per day. If the medicine is prescribed to the newborn, then for the convenience of its use, the tablets are dissolved in 5-10 ml of boiled warm water.
• Side effects: allergic reactions, tachycardia, arrhythmia, sleep and wakefulness, increased irritability, emotional lability, increased sweating, disorders of the gastrointestinal tract.
• Contraindications: hyperthyroidism, Dürring dermatitis, solitary thyroid cysts, nodose toxic goiter. Hyperthyroidism of non-iodine deficiency etiology, thyroid cancer. Not prescribed for patients with congenital lactase and galactase deficiency.

Jodbalans is available in tablets for oral use.

3. Another important preventive point is nutrition with a sufficient amount of iodine. During pregnancy in the female body the level of thyroid hormones sharply decreases. Without additional supply of the body with this microcell, there is a risk of hypothyroidism.

Dietary advice:

• Use iodized salt regularly.
• Products that contribute to the formation of goiter should be subjected to heat treatment: broccoli, cauliflower and Brussels sprouts, millet, mustard, soy, turnip, spinach.
• Eat foods rich in vitamin B and E: nuts and olive oil, dairy products, eggs, meat, seafood.
• Include in the diet foods with beta-carotene: pumpkin, carrots, juice of fresh potatoes.
• Replace coffee with green or black tea. The drink contains fluorides that regulate thyroid function.

All of the above recommendations are very important, and every woman who plans to become a mother in the near future should be aware of them. The thyroid gland of the child is laid on the 10th-12th week of intrauterine development, therefore the maternal organism must contain a sufficient amount of useful substances and be ready for their replenishment.

[13], [14],

Forecast

The outcome of the congenital form of hypothyroidism depends on the timely diagnosis of the pathology and the time of onset of hormone replacement therapy. If the treatment was started in the first months of life, then the child’s intellectual abilities and psychophysical development are not impaired. Treatment of babies older than 3-6 months allows you to stop developmental delays, but the existing intellectual disabilities will remain forever.

• If the pathology is caused by Hashimoto's disease, radiation therapy, or lack of thyroid, then the patient will receive lifelong therapy.
• If hypothyroidism is caused by other diseases and disorders of the body, then after the removal of the causal factors, the patient’s condition returns to normal.
• In case of a disease caused by medical preparations, the synthesis of hormones is restored after discontinuation of the medication.
• If the pathology proceeds in a latent, that is, subclinical form, then treatment may not be carried out. But the patient needs regular visits to the doctor to monitor the general condition and identify signs of disease progression.

If the disease was late diagnosed, the time of onset of replacement therapy is missed, or medication does not start, the prognosis of congenital hypothyroidism worsens. There is a risk of severe complications of the disease: oligophrenia, cretinism and disability.

[15], [16], [17], [18], [19]

Disability

According to medical statistics, the disability in congenital hypothyroidism is 3-4%. Partial or complete loss of performance is observed in the advanced stages of the disease and in severe forms of pathology, which interfere with a full life.

A patient with impaired functioning of the thyroid gland becomes hormone-dependent, which leaves a negative mark not only on health, but also on lifestyle. In addition, certain stages of the disease are complicated by comorbidities, which further aggravates the patient's condition.

To establish the disability of the patient is sent to the medical social examination and medical consultation commission. The main indications for passing the medical board are:

• Hypothyroidism 2 or 3 severity.
• Endocrine cardiomyopathy.
• Parathyroid failure.
• Pronounced mental changes and disorders.
• Pericardial effusion.
• Decreased performance.
• The need to change working conditions.

To confirm the disability, the patient must undergo a series of diagnostic procedures:

• Hormonal blood tests for TSH, TG.
• The analysis on electrolytes and triglytsida.
• Ultrasound and electromyography.
• The study of antibodies to thyroglobulin.
• The level of sugar and cholesterol in the blood.

According to the results of the tests, the patient receives a certificate of disability.

Disability has several categories, each of which has its own characteristics:

Power	Features of violations	Restrictions	Disability group	Prohibited work
I	Light somatic disorders. Increased fatigue and drowsiness. Slight decrease in psychomotor development. Growth retardation Hormone levels are normal or slightly elevated.	There are no disabilities	IAC restriction	In the night shift. Associated with nervous and mental overload. Associated with exposure to toxic substances and chemicals. High-altitude work. In extreme conditions. With frequent crossings.
II	Moderate somatic disorders. Fatigue and sleepiness. Puffiness Lability of blood pressure. Neurosis-like symptom complex. Neuropathy, growth retardation. Mild dementia. Hormone levels are moderately reduced.	I degree of restrictions: Self catering Movement. Communication Work. Orientation. Training. Behavior control.	III group	Driving a car. Physical exercise. Strenuous mental activity. Work on the conveyor.
III	Severe somatic disorders. Bradycardia and myopathy. Growth delay and memory loss. Violation of sexual function. Long constipation. Hypothyroid polyserositis. Mental retardation. Pronounced hormonal disorders.	II degree of restrictions: Self catering Movement. Communication Labor - III degree Orientation. Training. Behavior control.	Group II	Incapacity
IV	Severe somatic disorders. Pronounced pathology of the cardiovascular system. Gastrointestinal disturbance. Violations of the urinary system. Neuropsychic pathologies. Growth retardation Mental retardation severe or moderate. Significant hormonal disorders.	III degree of restrictions: Self catering Movement. Communication Work. Orientation. Training. Behavior control.	I group	Incapacity

Congenital hypothyroidism is a serious pathology of the endocrine system, which without timely medical care threatens with numerous complications and deterioration of the quality of life. In severe forms of the disease, disability is a necessary measure to alleviate the patient’s condition and improve the quality of his life.