Primary hypothyroidism

Primary hypothyroidism is hypothyroidism that develops as a result of congenital or acquired dysfunction of the thyroid gland.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ]

Epidemiology of primary hypothyroidism

The most common type of hypothyroidism (occurs in approximately 95% of all cases of hypothyroidism. The prevalence of clinically expressed primary hypothyroidism in the population is 0.2-2%, the frequency of primary subclinical hypothyroidism reaches 10% in women and 3% in men. Congenital primary hypothyroidism occurs with a frequency of 1: 4000-5000 newborns.

[ 7 ], [ 8 ], [ 9 ], [ 10 ]

Causes of Primary Hypothyroidism

Most often, primary hypothyroidism is the outcome of autoimmune thyroiditis, less often - the result of treatment of thyrotoxicosis syndrome, although a spontaneous outcome of diffuse toxic goiter in hypothyroidism is also possible. The most common causes of congenital hypothyroidism are aplasia and dysplasia of the thyroid gland, as well as congenital enzymopathies accompanied by a violation of the biosynthesis of thyroid hormones.

In case of extremely severe iodine deficiency (iodine intake less than 25 mcg/day for a long time) iodine-deficiency hypothyroidism may develop. Many medications and chemicals (propylthiouracil, thiocyanates, potassium perchlorate, lithium carbonate) can impair thyroid function. In this case, hypothyroidism caused by amiodarone is most often transient. In rare cases, primary hypothyroidism is a consequence of the replacement of thyroid tissue by a pathological process in sarcoidosis, cystinosis, amyloidosis, Riedel's thyroiditis). Congenital hypothyroidism may be transient. It develops under the influence of various causes, including prematurity, intrauterine infections, transplacental transfer of antibodies to thyroglobulin and thyroid peroxidase, and intake of antithyroid drugs by the mother.

[ 11 ], [ 12 ], [ 13 ], [ 14 ]

Pathogenesis of primary hypothyroidism

Hypothyroidism is characterized by a decrease in the rate of metabolic processes, which is manifested by a significant decrease in the need for oxygen, a slowdown in oxidation-reduction reactions and a decrease in the basal metabolic rate. There is an inhibition of the processes of synthesis and catabolism. A universal sign of severe hypothyroidism is mucinous edema (myxedema), most pronounced in connective tissue structures. The accumulation of glycosaminoglycans - products of protein breakdown with increased hydrophilicity - causes fluid and sodium retention in the extravascular space. In the pathogenesis of sodium retention, a certain role is assigned to excess vasopressin and a deficiency of natriuretic hormone.

Thyroid hormone deficiency in childhood inhibits physical and mental development and, in severe cases, can lead to hypothyroid dwarfism and cretinism.

[ 15 ], [ 16 ], [ 17 ], [ 18 ], [ 19 ], [ 20 ]

Symptoms of Primary Hypothyroidism

Clinical manifestations of hypothyroidism include:

• hypothermic metabolic syndrome: obesity, decreased body temperature, increased triglyceride and LDL levels. Despite moderate excess body weight, appetite is reduced in hypothyroidism, which, combined with depression, prevents significant weight gain. Impaired lipid metabolism is accompanied by a slowdown in both synthesis and degradation of lipids, with a predominance of slower degradation, which ultimately causes accelerated progression of atherosclerosis;
• hypothyroid dermopathy and ectodermal disorder syndrome: myxedematous edema of the face and extremities, periorbital edema, yellowing of the skin (due to hypercarotenemia), brittleness and loss of hair on the lateral parts of the eyebrows, head, possible alopecia areata and alopecia. Due to the coarsening of facial features, such patients sometimes acquire a resemblance to patients with acromegaly;
• sensory organ damage syndrome, difficulty breathing through the nose (due to swelling of the nasal mucosa), hearing impairment (due to swelling of the auditory tube and middle ear), hoarseness (due to swelling and thickening of the vocal cords), impaired night vision;
• syndrome of damage to the central and peripheral nervous system: drowsiness, lethargy, memory loss, bradyphrenia, muscle pain, paresthesia, decreased tendon reflexes, polyneuropathy. Possible development of depression, delirium (myxedema delirium), rarely - typical paroxysms of panic attacks (with attacks of tachycardia);
• cardiovascular damage syndrome ("myxedema heart") signs of heart failure, characteristic changes on the ECG (bradycardia, low voltage of the QRS complex, negative T wave), increased levels of CPK, AST and lactate dehydrogenase (LDH). In addition, arterial hypertension, effusion in the pleural, pericardial, abdominal cavities are characteristic. Atypical variants of cardiovascular damage are possible (with arterial hypertension, without bradycardia, with tachycardia with circulatory failure);
• digestive system damage syndrome: hepatomegaly, biliary dyskinesinia, impaired colon motility, tendency to constipation, decreased appetite, atrophy of the gastric mucosa;
• anemic syndrome: normochromic normocytic, or hypochromic iron deficiency, or macrocytic vitamin B12 deficiency anemia. In addition, the damage to the platelet lineage characteristic of hypothyroidism leads to a decrease in platelet aggregation, which, in combination with a decrease in the plasma levels of factors VIII and IX, as well as increased capillary fragility, aggravates bleeding;
• hyperprolactinemic hypogonadism syndrome: oligopsomenorrhea or amenorrhea, galactorrhea, secondary polycystic ovary disease. This syndrome is based on the hyperproduction of TRH by the hypothalamus during hypothyroxinemia, which promotes an increase in the release of not only TSH but also prolactin by the adenohypophysis;
• obstructive-hypoxemic syndrome: sleep apnea syndrome (due to myxedematous infiltration of the mucous membranes and decreased sensitivity of the respiratory center), myxedematous damage to the respiratory muscles with a decrease in respiratory volume by alveolar hypoventilation (leads to hypercapnia up to the development of hypothyroid coma).

[ 21 ]

Hypothyroid or myxedema coma

This is a dangerous complication of hypothyroidism. Its causes are the absence or insufficient replacement therapy. The development of hypothyroid coma is provoked by cooling, infections, intoxication, blood loss, severe intercurrent diseases and taking tranquilizers.

Manifestations of hypothyroid coma include hypothermia, bradycardia, arterial hypotension, hypercapnia, mucinous edema of the face and extremities, symptoms of CNS damage (confusion, lethargy, stupor, and possible urinary retention or intestinal obstruction). The immediate cause of death may be cardiac tamponade due to hydropericardium.

[ 22 ]

Classification of primary hypothyroidism

Primary hypothyroidism is classified by etiology. There are

Primary hypothyroidism due to destruction or lack of functional activity of thyroid tissue:

• chronic autoimmune thyroiditis;
• surgical removal of the thyroid gland;
• hypothyroidism due to radioactive iodine therapy;
• transient hypothyroidism in subacute, postpartum and painless thyroiditis;
• hypothyroidism in infiltrative and infectious diseases;
• agenesis and dysgenesis of the thyroid gland;

Primary hypothyroidism due to impaired synthesis of thyroid hormones:

• congenital defects of thyroid hormone biosynthesis;
• severe iodine deficiency or excess;
• medicinal and toxic effects (antithyroid drugs, lithium perchlorate, etc.).

[ 23 ], [ 24 ], [ 25 ], [ 26 ], [ 27 ]

Diagnostics

Diagnosis of primary hypothyroidism includes establishing the diagnosis of hypothyroidism, determining the level of damage and clarifying the causes of primary hypothyroidism.

Diagnosis of hypothyroidism and determination of the level of damage: assessment of TSH and free T4 levels _using highly sensitive methods.

Primary hypothyroidism is characterized by an increase in the TSH level and a decrease in the level of free T4 _. Determination of the level of total T4 ₍ i.e. both protein-bound and free biologically active hormone) has less diagnostic value, since the level of total T largely depends on the concentration of the transport proteins that bind it.

Determining the level of T3 _is also inappropriate, since in hypothyroidism, along with an elevated level of TSH and a decrease in T4, _a normal or even slightly elevated level of T3 can be determined _due to compensatory acceleration of the peripheral conversion of T4 _into the more active hormone T3 _.

Clarification of the causes of primary hypothyroidism:

• Thyroid ultrasound;
• thyroid scintigraphy;
• puncture biopsy of the thyroid gland (as indicated);
• determination of antibodies to thyroid peroxidase (if autoimmune thyroiditis is suspected).

Differential diagnostics

Primary hypothyroidism is first differentiated from secondary and tertiary. The leading role in differential diagnostics is played by determining the level of TSH and T4 _. In patients with normal or slightly elevated TSH levels, a TRH test can be performed, which allows differentiating primary hypothyroidism (increased TSH levels in response to the introduction of TRH) from secondary and tertiary (reduced or delayed response to TRH).

CT and MRI can detect changes in the pituitary gland and hypothalamus (usually tumors) in patients with secondary or tertiary hypothyroidism.

In patients with severe somatic diseases, primary hypothyroidism should be differentiated from euthyroid sick syndrome, which is characterized by a decrease in the level of T3 _, and sometimes T4 _and TSH. These changes are usually interpreted as adaptive, aimed at preserving energy and preventing protein catabolism in the body in the severe general condition of the patient. Despite the reduced level of TSH and thyroid hormones, replacement therapy with thyroid hormones in euthyroid sick syndrome is not indicated.

[ 28 ], [ 29 ], [ 30 ], [ 31 ], [ 32 ]

Treatment of primary hypothyroidism

The goal of hypothyroidism treatment is complete normalization of the condition: disappearance of disease symptoms and maintenance of TSH levels within the normal range (0.4-4 mIU/l). In most patients with primary hypothyroidism, this is achieved by prescribing T4 _at a dose of 1.6-1.8 mcg/kg of body weight. The need for thyroxine in newborns and children is significantly greater due to increased metabolism of thyroid hormones.

Replacement therapy for primary hypothyroidism is usually carried out for life.

In patients under 55 years of age who do not have cardiovascular diseases, T ₄ is prescribed at a dose of 1.6-1.8 mcg/kg of body weight. In case of obesity, the dose of T ₄ is calculated based on the patient's "ideal" weight. Treatment begins with a full dose of the drug.

Patients over 55 years of age and those with cardiovascular diseases have an increased risk of side effects of T4 _. Therefore, they are prescribed T4 _at a dose of 12.5-25 mcg/day and the dose of the drug is slowly increased until the TSH level is normalized (on average, the required dose is 0.9 mcg/kg of body weight). If hypothyroidism in an elderly patient cannot be perfectly compensated, the TSH level may remain within 10 mIU/L.

Particular attention should be paid to compensating hypothyroidism during pregnancy. During this period, the need for T4 _increases by an average of 45-50%, which requires adequate correction of the drug dose. Immediately after delivery, the dose is reduced to the standard.

Taking into account the high sensitivity of the newborn brain to thyroid hormone deficiency, which subsequently leads to irreversible decline in intelligence, it is necessary to make every possible effort to begin treatment of congenital hypothyroidism T4 _from the first days of life.

In the vast majority of cases, monotherapy with levothyroxine sodium is effective.

Synthetic levorotatory isomer of thyroxine Bagotirox stimulates tissue growth and development, increases tissue oxygen demand, stimulates protein, fat and carbohydrate metabolism, increases the functional activity of the cardiovascular and central nervous systems. The therapeutic effect is observed after 7-12 days, during the same time the effect persists after the drug is discontinued. Diffuse goiter decreases or disappears within 3-6 months. Bagotirox tablets 50, 100 and 150 mcg are produced using the proprietary Flexidose technology, which allows for "dosage steps" of 12.5 mcg.

Patients under 55 years of age who do not have cardiovascular diseases are prescribed:

• Levothyroxine sodium orally 1.6-1.8 mg/kg 1 time per day in the morning on an empty stomach, long-term (in the vast majority of cases - for life).

The approximate starting dose for women is 75-100 mcg/day, for men - 100-150 mcg/day.

Prescribed to patients over 55 years of age and/or with cardiovascular diseases.

• Levothyroxane sodium orally 12.5-25 mcg once a day in the morning on an empty stomach, long-term (every 2 months the dose should be increased by 25 mcg/day until the TSH level in the blood is normalized or the target dose of 0.9 mcg/kg/day is reached).

If symptoms of cardiovascular disease appear or worsen, therapy must be adjusted in conjunction with a cardiologist.

If hypothyroidism in an elderly patient cannot be perfectly compensated, the TTT level may remain within 10 mIU/L.

Immediately after detection of primary hypothyroidism, newborns are prescribed:

• Levothyroxine sodium orally 10-15 mcg/kg once a day in the morning on an empty stomach for a long time.

Children are prescribed:

• Levothyroxine sodium orally 2 mcg/kg (or more if necessary) once a day in the morning on an empty stomach, for life.

With age, the dose of levothyroxine per kg of body weight decreases.

Age	Daily dose, T4, mcg	Thyroxine dose based on weight, mcg/kg
1-6 months	25-50	10-15
6-12 months	50-75	6-8
1-5 years	75-100	5-6
6-12 years	100-150	4-5
More than 12 years	100-200	2-3

Hypothyroid coma

The success of treatment of hypothyroid coma depends primarily on its timeliness. The patient should be hospitalized immediately.

Complex treatment includes:

• administration of an adequate dose of thyroid hormones,
• use of glucocorticosteroids
• combating hypoventilation and hypercapnia;
• treatment of diseases that led to the development of coma

Treatment of coma begins with the introduction of glucocorticosteroids; in a patient in a coma, it is difficult to rule out the presence of Schmidt syndrome, as well as to conduct differential diagnostics between primary and secondary hypothyroidism. When hypothyroidism is combined with adrenal insufficiency, the use of thyroid hormones alone can provoke the development of an adrenal insufficiency crisis.

Hydrocortisone intravenously by jet stream 50-100 mg 1-3 times a day (up to a maximum dose of 200 mg/day), until stabilization.

Levothyroxine sodium 100-500 mcg (within 1 hour), then 100 mcg/day, until the condition improves and the patient can be transferred to long-term/lifelong oral administration of the drug in the usual dosage (in the absence of injectable drugs, levothyroxine sodium tablets can be administered in crushed form through a gastric tube).

+

• Dextrose, 5% solution, intravenously by drip 1000 ml/day, until the condition stabilizes or
• Sodium chloride. 0.9% solution intravenously by drip up to 1000 ml/day, until the condition stabilizes.

[ 33 ], [ 34 ], [ 35 ], [ 36 ]

Evaluation of the effectiveness of treatment for primary hypothyroidism

The treatment effectiveness is assessed by monitoring the TSH level, which should be in the normal range (0.4- -4). Recently, there have been reports that the optimal TSH level is 0.5-1.5 mIU/L, which is observed in most healthy people. After the full replacement dose of levothyroxine sodium is prescribed, the adequacy of therapy is assessed after 2-3 months. With a normal TSH level, a repeat check is recommended after 4-6 months due to the possibility of increasing the clearance of levothyroxine sodium after achieving a euthyroid state, which will require an increase in the dose of the drug. Thereafter, the TIT level is determined annually.

[ 37 ], [ 38 ], [ 39 ], [ 40 ]

Complications and side effects of primary hypothyroidism treatment

An overdose of sodium levothyroxine, leading to the development of subclinical thyrotoxicosis, is dangerous mainly due to two complications - myocardial dystrophy with the development of atrial fibrillation and osteopenia syndrome.

[ 41 ], [ 42 ], [ 43 ], [ 44 ]

Errors and unjustified appointments

Late diagnosis of hypothyroidism and inadequate therapy are fraught with serious complications; insufficient dose of levothyroxine sodium leads to an increased risk of development and progression of coronary heart disease due to dyslipidemia, as well as to reproductive dysfunction in young women and depression.

The use of sodium levothyroxine in Wilson's syndrome (the presence of clinical signs of hypothyroidism with normal laboratory parameters of thyroid function) is unjustified. Symptoms of hypothyroidism are nonspecific and can often be a consequence of other causes, in particular, decreased activity of the sex glands in women during menopause. In the vast majority of patients in this case, sodium levothyroxine therapy is ineffective, and the sometimes observed improvement in the condition is short-lived and is explained by the "placebo effect".

[ 45 ], [ 46 ], [ 47 ]

Forecast

In the vast majority of cases of hypothyroidism, the prognosis is favorable. It depends on the duration of hypothyroidism (with long-term hypothyroidism, cardiovascular diseases become important for the prognosis of patients due to the accelerated development of atherosclerosis), the adequacy of therapy and the development of complications (primarily hypothyroid coma). Even with early treatment, the mortality rate for hypothyroid coma is 50%.