Thyrotoxicosis (hyperthyroidism)- symptoms and treatment

What is thyrotoxicosis (hyperthyroidism)? We will discuss the causes, diagnosis and treatment methods in the article by Dr. O. N. Kurashov, an endocrinologist with 26 years of experience.

Definition of disease. Causes of the disease

Thyrotoxicosis(hyperthyroidism) is a hypermetabolic process caused by an excess of thyroid hormones in the body and their toxic effects on various organs and tissues. Clinically characterized by enlargement of the thyroid gland and damage to other systems and organs.

The first descriptions of this pathology were found in the works of the Persian physician Jurjani, created in 1100.

This syndrome occurs in both women (up to 2%) and men (up to 0.2%). It most often occurs in people aged 20-45 years.

There are many causes of thyrotoxicosis. The main ones include:

• increased production of thyroid hormones due to various diseases (, and others);
• excessive intake of medications containing thyroid hormones (violation of the prescribed treatment regimen).

The provoking factor of the syndrome is the additional amount of iodine entering the body through the independent use of iodine supplements.

The condition of thyrotoxicosis with diffuse toxic goiter is an autoimmune disease. It usually develops as a result of excess production of antibodies to the thyroid-stimulating hormone (TSH) receptor produced by the pituitary gland.

The occurrence of a thyrotoxic state is possible when the functional autonomy of an already existing thyroid nodule occurs - single- and multinodular goiter. This disease develops over a long period of time, mainly in people over 45 years of age. Thus, in the absence of exposure to TSH, the main physiological stimulant, the nodes synthesize an amount of thyroid hormones that exceeds the body’s needs.

If you notice similar symptoms, consult your doctor. Do not self-medicate - it is dangerous for your health!

Symptoms of thyrotoxicosis (hyperthyroidism)

When interviewing patients with suspected increased thyroid function, the following are revealed:

• unpredictable excitability, emotional instability, causeless tearfulness;
• anxiety and difficulty concentrating when being in society;
• daily sleep disturbance;
• fussiness when doing any work;
• weakness when walking;
• increased sweating of a diffuse nature, independent of physical or emotional stress, a feeling of “heat”;
• periodic heartbeats;
• trembling in the body and increasing weight loss (rarely observed).

Emotional disorders are combined with motor-volitional disorders: there is a need for constant movement and choreo-like twitching. Moreover, tremor of the limbs and body is a typical symptom of thyrotoxicosis.

An increased amount of thyroid hormones affects cardiac activity

Effects thyroid hormones			Change cardiac activity
inotropic		+	heart rate amplitude	gain
chronotropic		+	heart rate	increase in frequency
dromotropic		+	conduction of excitation in the heart	improvement
bathmotropic		+	excitability of the heart muscle	promotion

Among the characteristic changes that are detected in people with thyrotoxicosis during an examination by an ophthalmologist are damage to the soft tissues of the orbit. This pathology occurs in 40-50% of patients with involvement of the optic nerve and disease of the auxiliary apparatus of the eye (eyelids, conjunctiva and lacrimal gland). This does not exclude the development of optic neuropathy and corneal lesions with the formation of a cataract.

The main syndromes of thyrotoxicosis in diffuse toxic goiter include:

1. a set of symptoms of the central nervous system: astheno-neurotic and anxiety-depressive syndromes;
2. one of the cardiovascular manifestations: constant sinus tachycardia, paroxysmal or constant atrial fibrillation, absence of tachycardia, thyrotoxic myocardial dystrophy;
3. gastrointestinal syndromes: increased peristalsis and accelerated evacuation, insufficient digestion of food, periodic abdominal pain up to the simulation of an “acute abdomen”, toxic effects on hepatocytes;
4. disorders associated with the endocrine glands: thyroid-induced adrenal insufficiency in women, gynecomastia in men, impaired carbohydrate tolerance, development of osteoporosis.

Pathogenesis of thyrotoxicosis (hyperthyroidism)

The thyroid gland is an organ that produces thyroid hormones such as triiodothyronine (T3) and thyroxine (T4). TSH, a pituitary hormone, has a stimulating effect on them.

With diffuse toxic goiter, thyroid-stimulating antibodies (G) are formed that compete with TSH, a natural stimulator of the thymus gland (an important organ of the immune system).

With the occurrence of TSH deficiency, the immune process begins to progress. Thyroid-stimulating antibodies stimulate the C-cells of the thyroid gland, activating the secretion of thyrocalcitonin (TCT), which acts to enhance immunogenesis and thyrotoxicosis and leads to the progression of the autoimmune process. This effect of antibodies contributes to a decrease in calcium in the blood and increased excitation of thyrocytes (thyroid cells). A decrease in TSH is accompanied by an increase in thyrotropin-releasing hormone and an increase in prolactin.

Emotional stress and “psychotrauma” have a significant impact on the progression of thyrotoxicosis due to the active release of adaptation hormones (adrenaline and norepinephrine), which increase the synthesis and secretion of T3 and T4. This leads to atrophy of the thymus gland, decreased interferon concentrations and increased susceptibility to infectious diseases and cancer.

A separate role in the pathogenesis of thyrotoxicosis is given to the influence of various viruses (triggers of an autoimmune reaction) through thyrocytes.

Classification and stages of development of thyrotoxicosis (hyperthyroidism)

According to ICD 10, there is the following classification of the syndrome:

• E05.0 - thyrotoxicosis with diffuse goiter;
• E05.1 - thyrotoxicosis with toxic uninodular goiter;
• E05.2 - thyrotoxicosis with toxic multinodular goiter;
• E05.3 - thyrotoxicosis with ectopia of thyroid tissue;
• E05.4 - artificial thyrotoxicosis;
• E05.5 - thyroid crisis or coma;
• E05.6 - other forms of thyrotoxicosis;
• E05.7 - thyrotoxicosis, unspecified.

Depending on the influence of TSH, three main types of thyrotoxicosis are distinguished:

Criteria for assessing the severity of thyrotoxicosis

Criteria gravity	Severity
	light	average	heavy
Frequency heart abbreviations (bpm)	80-100	100-120	over 120
Loss body weight (from original)	up to 10-15%	up to 15-30%	more than 30%
Availability complications	No	⠀ temporary disturbances ⠀⠀rhythm ⠀ carbohydrate disorders ⠀⠀exchange ⠀ gastrointestinal ⠀⠀disorders	⠀ temporary disturbances ⠀⠀rhythm ⠀ carbohydrate disorders ⠀⠀exchange ⠀ gastrointestinal ⠀⠀disorders ⠀ osteoporosis ⠀ secondary adrenal ⠀⠀inadequacy

Classification of thyrotoxicosis proposed by professors V.V. Fadeev and G.A. Melnichenko, suggests dividing the syndrome into three types:

Options	manifest type of syndrome	Subclinical type of syndrome
TSH level	short	short
Level T3 and T4	elevated either T3 or T4	normal
Clinical manifestations	characteristic clinic and shifts in level thyroid hormones	absent

The subclinical type of thyrotoxicosis can occur as a result of the formation of functional autonomy of the thyroid nodule, an overdose of thyroid hormones in thyroid cancer or hypothyroidism, or painless thyroiditis.

Complications of thyrotoxicosis (hyperthyroidism)

The long course of the disease affects bone formation: bone density decreases and the risk of bone fractures (primarily tubular bones) increases in awkward situations. In women with increased thyroid function during menopause, the risk of such complications increases.

Cardiovascular disorders also pose a serious danger: paroxysmal atrial fibrillation may occur, turning into a permanent form with the risk of thromboembolic complications.

With an increase in unfavorable environmental factors (for example, stressful situations, various diseases, surgical interventions, etc.), a thyrotoxic crisis may occur. Its characteristic features are:

• sudden excitability;
• increase in body temperature up to 40°C;
• increase in heart rate up to 200 beats/min;
• atrial fibrillation (not always);
• increased nausea (possibly leading to vomiting) and diarrhea;
• increased thirst;
• increase in pulse blood pressure;
• appearance of signs of adrenal insufficiency (occurs later).

The condition worsens after a few hours, so a thyrotoxic crisis requires emergency medical care.

Diagnosis of thyrotoxicosis (hyperthyroidism)

Diagnosis of the syndrome involves interviewing the patient, identifying clinical signs and laboratory tests.

At taking anamnesis in patients with thyrotoxicosis is taken into account

Laboratory research indicated for all patients with thyroid pathology (especially those who have pronounced clinical manifestations of decreased or increased thyroid function), as well as during conservative treatment to monitor the adequacy of therapy and in the presence of concomitant pathology. Determination of total T3 is important for toxicosis, especially in cases of T3 toxicosis. Laboratory diagnostic indicators for thyrotoxicosis are high levels of free T3 and T4, as well as low levels of TSH in the blood.

Due to the fact that most of T3 and T4 are associated with blood proteins, a study of the free fractions of these hormones is carried out in combination with determining the level of TSH. In this case, the free fraction determines the biological effect of thyroid hormones.

⠀Normal concentration of thyroid hormones and TSH⠀
general T3⠀ free T3⠀ general T4⠀ free T4⠀ TTG⠀	⠀1.2 - 2.08 nmol/l ⠀2.5 - 5.8 pg/ml ⠀64 - 146 nmol/l ⠀11-25 pg/ml ⠀0.24-3.4 mEg/ml

Since the content of T3 and T4 is influenced by a number of factors (for example, a low-calorie diet, liver disease, long-term medication use), it is more advisable to conduct studies of the free fractions of thyroid hormones in combination with TSH.

Focus on TSH levels should be paid in the following cases:

• acute mental illnesses requiring hospitalization;
• diseases of the pituitary gland or hypothalamus;
• rapid changes in thyroid status.

In these cases, this test may lead to misdiagnosis.

If thyroid dysfunction is suspected in severely ill patients with intact (“uninvolved”) hypothalamic-pituitary function, a “panel” approach should be used - simultaneous determination of TSH and free T4.

In hyperthyroidism, the synthesis and secretion of TSH is suppressed, so the determination of very low concentrations of TSH is of fundamental importance in the diagnosis of its various forms. The exception is rare cases of TSH-induced thyrotoxicosis (when TSH secretion is increased), which include TSH-producing pituitary adenoma and syndrome of inappropriate TSH secretion, caused by the resistance of this pituitary hormone to the effects of T3 and T4.

Additional diagnostic methods:

The size of the thyroid gland based on palpation results is determined according to the 1994 WHO classification.

Degree increase thyroid gland	Description of the thyroid gland
	Dimensions each beat	State upon palpation
No goiter	less than distal phalanges (tip) patient's thumb	not palpable
I	more distal phalanx	palpated, but not visible to the eye
II	more distal phalanx	palpable and visible to the eye

In the case when the patient palpably detects an increase in size or a suspicion of a nodular formation in the thyroid gland, ultrasound diagnostics (ultrasound) is performed to calculate the volume of the thyroid gland - formula (I. Brunn, 1986):

Volume = [(WxDxL) right + (WxDxL) left] x 0.479;

W, D, L are the width, thickness and length of the thyroid gland, and 0.479 is the correction factor for the ellipsoidal shape of the organ.

Ultrasound of the thyroid gland is usually performed using a high-frequency transducer with a frequency of 7.5 MHz. The use of color Doppler mapping allows you to visualize small vessels in the organ under study and provides information about the direction and average speed of flow.

In some cases, scintigraphy of the thyroid gland can be performed, which shows the organ's ability to take up iodine and other substances (technetium).

Differential diagnosis carried out:

Treatment of thyrotoxicosis (hyperthyroidism)

In the treatment of thyrotoxicosis, the following basic methods are usually used:

The fight against the syndrome involves eliminating the clinical manifestations of thyrotoxicosis with normalization of T3, T4 and TSH values ​​and achieving stable remission of the disease.

Conservative therapy

For the conservative treatment of diffuse toxic goiter in patients with a moderately enlarged thyroid gland (up to 40 ml), propylthiouracil (PTU) or thiamazole (Tirozol or Mercazolil) is prescribed. This helps to achieve normal functioning of the affected organ. In case of diagnosed cases of diffuse toxic goiter in the first trimester of pregnancy and the occurrence of side effects while taking thiamazole, PTU is prescribed. As a result of treatment, after 4-6 weeks there is an improvement - the level of free T4 is normalized. Additionally, beta-blockers are prescribed according to indications (for example, 2.5-5 mg of Concor per day).

In severe cases, it is recommended to take glucocorticoids - up to 10-15 mg of prednisolone per day. Then, over 2-3 weeks, the dose of the thyreostatic agent is reduced to a maintenance dose (no more than 10 mg per day). In parallel, the patient is usually prescribed 50 mcg of levothyroxine per day. This treatment regimen is called “Block and Replace.” Stable maintenance of normal free T4 and TSH levels will indicate the adequacy of the prescribed therapy.

If there are persistent side effects of the prescribed treatment, thyreostatic drugs are canceled, radioactive iodine therapy or surgery is prescribed. In case of relapse of thyrotoxicosis, the question arises about the need for radioiodine therapy or thyroidectomy - complete or partial removal of the thyroid gland.

Treatment with radioactive iodine

Radioiodine therapy for diffuse toxic goiter is carried out in case of persistent relapse of thyrotoxicosis after the end of properly administered conservative therapy (for 12-18 months) and difficulties in taking thyreostatic drugs (decrease in the number of leukocytes in the blood or the occurrence of allergic reactions).

Treatment with radioactive iodine is carried out in specialized centers with radiation and environmental safety for people and nature. The only contraindications for this therapy are pregnancy and breastfeeding.

The goal of radioiodine therapy in destroying hyperfunctioning thyroid tissue is to achieve a stable hypothyroid state.

Surgical treatment

Surgical intervention for diffuse toxic goiter is necessary if the goiter is located behind the sternum, with diffuse and nodular forms of goiter with compression and the patient refuses other methods of therapy. Total and subtotal thyroidectomy are the treatment of choice. If there is a nodular formation in the thyroid gland, it is necessary to perform a puncture biopsy and diagnostic cytological examination. The development of atrial fibrillation and severe manifestations of heart failure in thyrotoxicosis can complicate the course and prognosis of the disease, especially in relation to ability to work and health in general.

When a favorable outcome of the disease occurs, patients with thyrotoxicosis must take preventive measures against relapse in the form of:

• compliance with a gentle lifestyle regime for 3-6 months;
• restrictions on physical activity;
• creation of psychological peace on the part of relatives, and at work - reduction of hours of intense stress, incl. night shifts (if any).

Such prevention of relapse of the disease is extremely important, because the thyroid gland is a fragile and at the same time strong organ, with its own “character”.

Long-term stable remission of thyrotoxicosis is an indication for sanatorium-resort therapy at low altitudes above sea level and periodic country holidays in a comfortable environment. At the same time, it is undesirable to stay in the open sun; at sea you need to use sunscreen.

Treatment and preventive measures include balneotherapy using native radon waters. Their effectiveness and positive effects on the body have been proven by many years of research conducted at mineral water resorts.

Thus, when treating patients with thyrotoxicosis at the Belokurikha resort, the effectiveness of radon procedures together with drug therapy (mercazolyl, microiodine and reserpine) was confirmed. Nitrogen baths that do not contain radon have a preventive effect through thermal and mechanical stimulation of nerve receptors by nitrogen bubbles.

The functioning of the thyroid gland is regulated by the pituitary thyroid-stimulating hormone (TSH). Its concentration varies depending on the content of thyroid hormones in the blood serum.

A reduced level of thyrotropin is observed in diseases of the thyroid gland, accompanied by hyperfunction (hyperthyroidism) or destruction of organ cells and the release of the hormones triiodothyronine and thyroxine into the blood. There are also more rare causes of low TSH.

• Show all

  Causes of low TSH

  Conditions that lead to a decrease in the level of thyroid-stimulating hormone in the body:

  • diffuse toxic goiter (Graves disease);
  • toxic adenoma;
  • decompensated functional autonomy;
  • initial phases of autoimmune and other thyroiditis;
  • physiologically low TSH during pregnancy;
  • gestational thyrotoxicosis;
  • taking medications containing iodine (amiodarone, iodides);
  • overdose of levothyroxine sodium;
  • damage to the pituitary gland and hypothalamus;
  • rarely - thyroid cancer and its metastases, ovarian struma, trophoblastic tumor.

  The most common cause of low thyrotropin is an excess of thyroid hormones in the blood. If there are symptoms associated with their high content, they speak of thyrotoxicosis. It can be clinically pronounced (manifest) and subclinical.

  To clarify the diagnosis, the patient is interviewed and examined, the levels of thyroid-stimulating hormone, free fractions of thyroxine (T4) and (T3), and antibodies are determined. Ultrasound and scintigraphy of the thyroid gland are performed.

  Types of thyrotoxicosis:

  A blood test for TSH is performed in the morning on an empty stomach. The normal range for thyrotropin levels is 0.4–4.0 mU/L.

  

  Symptoms of thyrotoxicosis

  With a high level of thyroid hormones in the blood, patients may present complaints related to disruption of the functioning of most organs and systems. There is general weakness and increased fatigue. Possible irritability, nervousness, emotional instability.

  A number of changes occur in the functioning of the cardiovascular system. Palpitations and irregularities are felt, and blood pressure rises. In severe cases, arrhythmia develops like atrial fibrillation.

  

  The skin of patients is hot to the touch, moist, and often itches. Weight loss despite good appetite. Trembling appears in the hands and body. Excessive sweating is a concern and the temperature rises slightly.

  With thyrotoxicosis, there is a feeling of lack of air, shortness of breath. From the gastrointestinal tract - increased frequency of stools or diarrhea. The functioning of the reproductive system is disrupted - menstruation is irregular or completely absent. Libido increases.

  Characterized by discomfort from the eyes and trembling of the eyelids. With an autoimmune lesion, there may be double vision, swelling of the eyelids, pain when moving the eyeballs.

  In the subclinical course of the syndrome, its symptoms are slightly expressed.

  

  Diffuse toxic goiter (Graves' disease)

  This autoimmune disease is more common among young women. In the blood, for reasons that have not yet been specified, antibodies to TSH receptors appear, which stimulate the thyroid gland. In addition to the pronounced symptoms of thyrotoxicosis, the disease is characterized by the development of endocrine ophthalmopathy. This condition occurs in half of patients and is associated with damage to the fiber of the eyes and extraocular muscles.

  Patients note redness and swelling of the eyelids, protrusion of the eyeball (exophthalmos), increased lacrimation, pain when moving the eyes and at rest, double vision. In severe cases, the optic nerve is compressed, resulting in impaired vision.

  The diagnosis is made on the basis of complaints and examination, laboratory tests. In the blood, thyrotropin is reduced to almost zero values, T4 and T3 are sharply increased. Antibodies to the TSH receptor and to TPO are determined. Ultrasound examination shows that the volume of the thyroid gland is normal or enlarged.

  To treat the pathology, thyreostatics are used - drugs that block the production of thyroid hormones. For women planning a pregnancy and if drug therapy is ineffective, the thyroid gland is removed surgically or radioactive iodine is used.

  

  Autoimmune thyroiditis

  This is an inflammatory disease of the thyroid gland of an immune nature. The prevalence of pathology in women is higher than in men. It occurs in waves with the development of thyrotoxicosis at the beginning of the disease, which gradually turns into hypothyroidism (decreased production of thyroid hormones).

  There is a low TSH content and an increase in the concentration of T3 and T4, which leads to the appearance of symptoms characteristic of hyperfunction of the gland. In contrast to diffuse toxic goiter, during treatment with thyreostatics, the content of thyrotropin increases quickly, sometimes becoming higher than normal. Thyrotoxicosis is temporary and relapses are not typical. There are no signs of eye damage.

  

  According to ultrasound, both a decrease in the thyroid gland and an increase in it are possible. Nodular formations are often identified. When examining blood serum, a high titer of antibodies to TPO is detected, and rarely - antibodies to the TSH receptor.

  Toxic adenoma

  A toxic adenoma is a thyroid nodule that autonomously (independent of TSH) produces large amounts of thyroxine and triiodothyronine. The disease is typical for regions with iodine deficiency. It occurs 4 times more often in patients over 60 years of age than in young people.

  Thyrotoxicosis develops gradually and may be subclinical. The diagnosis is confirmed by palpating the thyroid nodule or identifying it by ultrasound. They also scan the organ with radioactive iodine - in this case, a bright glow of the autonomous formation is observed (a “hot” node).

  To treat the pathology, surgical removal of part of the gland or radioiodine therapy is performed. If there are contraindications to surgery, percutaneous injection of ethyl alcohol into the node is used, which is carried out under ultrasound control.

  Multinodular toxic goiter

  This disease develops against the background of long-existing multinodular goiter. It is more common in women over 50 years of age. For a long time, nothing bothers the patients. There may be complaints related to compression of surrounding organs by the enlarged thyroid gland or neck deformation. Symptoms of thyrotoxicosis increase gradually.

  For diagnosis, ultrasound is used, scintigraphy of the thyroid gland is performed, and sometimes computed tomography of the larynx (if there are signs of compression of the neck organs). In treatment, preference is given to radioactive iodine therapy; surgical intervention is required for large goiters.

  Gestational thyrotoxicosis syndrome

  A large amount of human chorionic gonadotropin enters the blood of a pregnant woman from the placenta. This hormone is able to bind to thyrotropin receptors on the thyroid gland and enhance its function. As a result, in the early stages of pregnancy, a physiological decrease in TSH is observed.

  In some cases, gestational thyrotoxicosis develops with an excessive decrease in thyroid-stimulating hormone and an increase in the synthesis of thyroxine and triiodothyronine in the 1st trimester. To distinguish this condition from Graves' disease that occurs during pregnancy, the level of antibodies to the TSH receptor is determined.

  With the syndrome, a temporary increase in thyroid function is observed. Her hormones gradually return to normal, and TSH rises to acceptable levels. This condition will not cause negative consequences for the fetus and the woman.

  

  Thyroiditis

  Thyroiditis is a large group of pathologies characterized by the development of inflammation and damage to thyroid cells. Depending on the cause, there are different types of diseases:

  • postpartum;
  • painless;
  • subacute;
  • radiation;
  • amiodarone-induced;
  • cytokine-induced;
  • spicy.

  In all thyroiditis, destruction of gland tissue leads to an excessive release of thyroid hormones into the blood and a decrease in TSH. Signs of thyrotoxicosis appear, which can have varying degrees of severity. A complete absence of clinical manifestations is also possible. To correct symptoms, drugs from the adrenergic blocking group (propranolol) are used; thyreostatics are not used.

  The thyroid gland often recovers on its own. As a result of the disease, hypothyroidism may develop, so regular TSH monitoring is required:

  Thyroiditis	Hormonal profile, antibodies	Peculiarities
  Postpartum		Develops 3–6 months after birth. More often in patients with type 1 diabetes mellitus
  Painless	Decrease in TSH with gradual normalization of the indicator. As a result, TSH is elevated. Determined by AT-TPO	Often occurs without developing symptoms
  Subacute	Decrease in TSH initially with gradual normalization of the indicator. In severe cases, TSH is temporarily elevated	It is viral in nature. Develops two weeks after ARVI. Symptoms: pain in the thyroid gland, high temperature (up to 38–39 degrees)
  Spicy	Possible slight decrease in TSH	Most often bacterial in nature. Manifested by fever up to 40 degrees, chills, severe pain in the thyroid gland
  Amiodarone -induced		Taking amiodarone for several months
  Cytokine-induced	Low TSH, can be determined by AT-TPO	Taking medications containing interferon alpha and interleukin-2
  Radiation	A slight decrease in TSH with a further increase and the development of hypothyroidism	Radiation to the head and neck for another disease (such as lymphoma)

Standard approaches to the treatment of thyrotoxicosis and hypothyroidism syndromes

G.A. Melnichenko, S.V. Lesnikova

Department of Endocrinology (Head - Academician of the Russian Academy of Medical Sciences I.I. Dedov) MMA named after. THEM. Sechenov

URL

Thyrotoxicosis syndrome

Thyrotoxicosis syndrome- a clinical syndrome caused by an excess of thyroid hormones.
Thyrotoxicosis syndrome occurs:
I. caused by increased production of thyroid hormones by the thyroid gland:
TSH-independent

• diffuse toxic goiter (DTZ) - Graves' disease - Basedow
• thyrotoxic adenoma
• multinodular toxic goiter
• iodine-induced thyrotoxicosis- (iodine-Bazedov)
• well-differentiated thyroid cancer
• gestational thyrotoxicosis
• chorionic carcinoma, hydatidiform mole
• autosomal dominant non-immunogenic thyrotoxicosis

TSH-dependent

• thyrotropinoma
• syndrome of inadequate secretion of TSH (resistance of thyrotrophs to thyroid hormones)

II. not associated with increased production of thyroid hormones:

• thyrotoxic phase of autoimmune (AIT), subacute viral and postpartum thyroiditis
• artificial
• amiodarone-induced
• iatrogenic

III. caused by the production of thyroid hormones outside the thyroid gland.

• struma ovarii
• functionally active thyroid metastases

Due to the most common occurrence of thyrotoxicosis (90% of all cases of thyrotoxicosis) among all nosoforms, the diagnosis and treatment of thyrotoxicosis syndrome will be considered using the example of this disease with clarification of the characteristics of the course and treatment of the others. DTG is a hereditarily determined organ-specific autoimmune disease (pathogenesis is based on the production of specific thyroid-stimulating antibodies), characterized by prolonged excessive production of thyroid hormones by the thyroid gland, clinically manifested by thyrotoxicosis syndrome and combined in at least 50% of patients with endocrine infiltrative ophthalmopathy.
Clinical criteria

• increased excitability, general weakness, fatigue, tearfulness;
• shortness of breath with little physical exertion;
• tremor of the body and limbs, increased sweating;
• weight loss against the background of increased appetite (but the fat-Bazedov variant may also occur, i.e. a variant of the disease with an increase in body weight);
• low-grade fever;
• fragility and hair loss;
• hyperdefecation;
• heart rhythm disturbances: constant sinus tachycardia, paroxysms and constant atrial fibrillation, paroxysms against the background of normal sinus rhythm;
• there is an increase in systolic pressure with a decrease in diastolic pressure;
• upon examination - ocular symptoms of thyrotoxicosis associated with a violation of the autonomic innervation of the extraocular muscles. Endocrine infiltrative ophthalmopathy occurs in at least 50% of cases;
• on palpation: diffuse enlargement of the thyroid gland (which is not a mandatory criterion - the size of the gland may be normal); “buzzing” (due to abundant vascularization of the gland).

To assess the size of the thyroid gland, the 1994 WHO classification is recommended. This international classification is simplified, accessible to doctors of all specialties and allows you to compare data from different countries.

Grade 0 - no goiter.
Degree 1 - the goiter is not visible, but is palpable, and the size of its lobes is larger than the distal phalanx of the subject’s thumb.
Degree 2 - the goiter is palpable and visible to the eye.

• damage to other internal secretion organs:

1. development of thyroid-induced adrenal insufficiency;
2. ovarian dysfunction with menstrual dysfunction up to amenorrhea, miscarriage;
3. fibrocystic mastopathy in women, gynecomastia in men;
4. impaired carbohydrate tolerance, development of diabetes mellitus;

with DTD often occur associated immunopathies , the most studied are endocrine infiltrative ophthalmopathy and pretibial myxedema, which will be described below.

Long-term results (5 years or more) of treatment for Graves-Bazedow disease :

Outcomes of conservative thyreostatic therapy with thiamazole ( n=80)	Thyroid functions	Outcomes of surgical treatment( n=52)
34.69%(n=34)	Euthyroidism	28.85%(n=16)
2.04%(n=2)	Hypothyroidism	34.54%(n=18)
63.27%(n=62)	Relapse	34.62%(n=19)

Laboratory and instrumental diagnostics as a first order study includes:

• hormonal blood test: decrease in TSH, determined by a highly sensitive method (in TSH-dependent thyrotoxicosis, TSH is increased); increased levels of T3, T4 (during pregnancy, only free fractions of T4, T3 are examined). Determining TSH and free T4 levels is usually sufficient;
• Ultrasound of the thyroid gland with determination of the volume and position of the gland (normal, partially substernal); There is an enlargement of the thyroid gland and a decrease in the echogenicity of the parenchyma.

Using ultrasound according to international standards in adults (over 18 years of age), goiter is diagnosed when the volume of the thyroid gland in women is more than 18 ml, in men more than 25 ml, with the lower limit of normal being 9 ml;
In rare cases, the following studies are performed as a differential diagnosis:

• determination of the level of antibodies to thyroid tissue:
  a) “classical” - there is an increase in antibodies to thyroglobulin (TG) and thyroid peroxidase (TPO) (with AIT, DTG);
  b) “non-classical” - there is an increase in antibodies to the TSH receptor - thyroid-stimulating (in DTG) and blocking TSH binding (in AIT);
• scintigraphy of the thyroid gland (with a retrosternal position of the gland, (multi-)nodular toxic goiter to determine the existence of functional autonomy, or the presence of multiple nodes accumulating radiopharmaceuticals, or the presence of “cold” nodes against the background of increased functioning around the located tissue).

Principles of treatment
Currently, there are three main approaches to the treatment of thyrotoxicosis syndrome (using the example of thyrotoxicosis):
1. conservative therapy;
2. surgical treatment (subtotal resection of the thyroid gland);
3. radiological method - therapy with radioactive iodine - (131I).
For newly diagnosed thyroid disease in Russia, the tactics of long-term conservative therapy with thyreostatics are chosen; in the presence of certain indications, which will be described below, surgical treatment is recommended. Recently, more attention has been paid to radiological treatment.
It should be noted that thyrotoxicosis syndrome is absolutely curable. The means of pathogenetic therapy in this case are thiourea derivatives, which include mercaptoimidazole and propylthiouracil.
Conservative treatment regimen

• The initial dose of thiamazole is 20-40 mg/day, propicil 200-400 mg/day until euthyroidism is achieved (on average, this stage takes 3-8 weeks).
• Gradually reduce the dose of thiamazole by 5 mg (propicil 50 mg) over 5-7 days to a maintenance dose of 5-10 mg thiamazole (propicil 50-100 mg).
• At the stage of euthyroidism - adding levothyroxine 50-100 mcg to therapy ("block and replace" scheme) to prevent the development of drug-induced hypothyroidism and the goitrogenic effect of thyreostatics.
• The duration of treatment is 12-18 months (if there are no indications for surgical treatment and thyreostatics are not used as preoperative preparation).

Among the side effects, special attention should be paid to the state of bone marrow hematopoiesis due to the possibility of developing leukopenic reactions up to agranulocytosis (in 1% of cases), the symptoms of which are the appearance of fever, sore throat, and diarrhea. 1-5% have allergic reactions in the form of a skin rash accompanied by itching and nausea.
Prescribed as symptomatic therapy b - adrenergic blockers until heart rate normalizes, after which the dose is gradually reduced until discontinuation. Besides, b -blockers eliminate tremors, sweating, and anxiety.
Patient monitoring during treatment should be carried out as follows:

• monitoring T4 levels once a month;
• control of TSH determined by a highly sensitive method once every 3 months;
• Ultrasound of the thyroid gland to assess the dynamics of gland volume once every 6 months;
• determination of leukocytes and platelets in the blood:

• 1 time per week in the 1st month of thyreostatic therapy;
• Once a month when switching to maintenance doses.

Typical mistakes encountered in the treatment of thyrotoxicosis are:
a) intermittent courses;
b) inadequate treatment control;
c) re-prescription of long-term thyreostatic therapy in case of relapse of thyrotoxicosis after a full course for 12-18 months.
Currently, the problems of the lack of “ideal” and etiotropic treatment, standard recommendations for monitoring, continuity of inpatient and outpatient treatment, and minimally effective maintenance doses remain unresolved.
The question of necessity surgical treatment for DTG occurs in the following situations:
1. the occurrence or detection of nodes against the background of thyrotoxicosis;

2. large volume of the gland (more than 45 ml);
3. objective signs of compression of surrounding organs;
4. substernal goiter;
5. relapse of thyrotoxicosis after a full course of thyreostatic therapy;
6. intolerance to thyreostatics, development of agranulocytosis.
Surgical treatment is carried out when euthyroidism is achieved with thyreostatic drugs; subtotal resection of the thyroid gland is more often used.
Currently, indications and age limits for therapy are expanding radioactive iodine, given the comparative safety and effectiveness of this method. According to D. Glinoer, 1987 and B. Solomon, 1990 (questionnaire of the European Thyroid Association), with uncomplicated Graves-Bazedow disease diagnosed for the first time in a 40-year-old woman with children and not planning pregnancy, in Europe and Japan there was the tactics of initial prescription of 131I therapy would be chosen in 20%, in the USA - in 70% of similar cases. In Russia, less than 1% of patients would receive treatment with 131I.
With radioiodine therapy, the incidence of hypothyroidism reaches about 80%, relapse is observed in less than 5% of cases.
Among associated immunopathies The most studied and most common are endocrine infiltrative ophthalmopathy and pretibial myxedema.
At endocrine infiltrative ophthalmopathy (EOP) damage to the periorbital tissues of autoimmune origin occurs, manifested clinically by disorders of the extraocular muscles, trophic disorders and often exophthalmos. Diagnostic criteria are:
-clinically: lacrimation, feeling of “sand”, dryness and pain in the eyes, double vision when looking up, to the sides, limited mobility of the eyeballs, changes in the cornea, exophthalmos, often secondary glaucoma;
-instrumentally: protrusion, signs of thickening of the retrobulbar muscles according to ultrasound, CT, and MR of the orbits.
Treatment endocrine ophthalmopathy presents significant difficulties. A necessary factor is correction of thyroid status. In the presence of double vision when looking up and to the sides, thickening of the retrobulbar muscles and orbital tissues, glucocorticoids are prescribed; there are various treatment regimens. A promising direction in treatment is the use of octreotide, a human immunoglobulin, treatment regimens for which are currently being developed. In case of severe symptoms of ophthalmopathy, lack of effect from steroid therapy and the presence of fibrosis of orbital tissues with the threat of vision loss, surgical correction is performed. In addition, it is necessary to remember such an important provoking factor in the progression of EOP as smoking..
Pretibial myxedema occurs in 1-4% of patients with DTG. The skin of the anterior surface of the leg thickens, becomes swollen, hyperemic, and the disturbances are accompanied by itching. For treatment, bandages with dimethyl sulfoxide are used in combination with steroid therapy, also against the background of correction of the thyroid status.
Second most common cause of thyrotoxicosis - toxic adenoma thyroid gland. The presence of clinical symptoms similar to DTG with more pronounced symptoms of damage to the cardiovascular system and myopathy is noted; endocrine ophthalmopathy is absent. On palpation and ultrasound, a nodular formation is determined (with ultrasound - with a clearly defined capsule and usually increased echogenicity). With scintigraphy, this is a “hot” node with increased accumulation of radiopharmaceuticals (RP) and decreased accumulation in the surrounding tissue. Treatment is surgical or radioiodine therapy.
In case of development of the thyrotoxic phase of autoimmune and postpartum thyroiditis symptomatic therapy possible b - blockers, thyreostatics are not used.
In subacute viral thyroiditis, more often after a viral infection, there are complaints of severe pain in the anterior neck, mostly unilateral, radiating to the ear, and an increase in body temperature up to 390C. Treatment with prednisolone is carried out according to the scheme.
In case of iodine-induced thyrotoxicosis, it is recommended to stop taking iodine-containing drugs.
Surgical treatment is carried out for multinodular toxic goiter, toxic adenoma, thyrotropinoma.
When highly differentiated forms of thyroid cancer are detected, preoperative preparation is carried out with thyreostatics until euthyroidism is achieved, followed by surgical treatment, often in combination with radiation therapy in an oncology hospital.
In autosomal dominant non-immunogenic thyrotoxicosis, extirpation of the thyroid gland is necessary, followed by replacement therapy with levothyroxine.
For the syndrome of inadequate TSH production, a number of authors have proposed using TRIAK for treatment, but there has not yet been a consensus on this issue, and there is no experience in using the drug in our country.

Hypothyroidism syndrome

Hypothyroidism syndrome- a clinical syndrome caused by a long-term, persistent lack of thyroid hormones in the body or a decrease in their biological effect at the tissue level. The prevalence of manifest primary hypothyroidism in the population is 0.2-1%, subclinical primary hypothyroidism - 7-10% among women and 2-3% among men.
According to the level of damage, hypothyroidism can be :

• primary thyroidogenic
• secondary pituitary
• tertiary hypothalamic
• tissue transport peripheral

According to severity they are distinguished:

1. Subclinical (latent)

2. Manifest

• compensated
• decompensated

3. Severe course (complicated) - with the development of heart failure, cretinism, effusion in the serous cavities, secondary pituitary adenoma.
Most common primary hypothyroidism, the reasons for which are:
congenital forms

• abnormalities of the thyroid gland (dysgenesis, ectopia)
• congenital enzymopathies accompanied by impaired biosynthesis of thyroid hormones

acquired forms

• autoimmune thyroiditis (AIT), including within the framework of autoimmune polyglandular syndrome, more often type II (Schmidt syndrome), less often type I.
• thyroid surgery
• thyreostatic therapy (radioactive iodine, thyreostatics, lithium preparations)
• subacute viral, postpartum
• thyroiditis (hypothyroid phase)
• endemic goiter

Reasons secondary hypothyroidism are:

• congenital and acquired panhypopituitarism (Schien-Simmonds syndrome, large pituitary tumors, adenomectomy, pituitary irradiation, lymphocytic hypophysitis)
• isolated TSH deficiency
• within the framework of congenital panhypopituitarism syndromes

Tertiary hypothyroidism:

• disruption of the synthesis and secretion of thyrotropin-releasing hormone

Peripheral hypothyroidism:

• thyroid resistance syndromes
• hypothyroidism with nephrotic syndrome

Clinical criteria

Early symptoms of hypothyroidism are not very specific, so the initial stages of the disease, as a rule, are not recognized and patients are unsuccessfully treated by various specialists.
Patients complain of a feeling of chilliness, an unmotivated increase in body weight against a background of decreased appetite, lethargy, depression, daytime sleepiness, dry skin, yellowness of the skin caused by hypercarotenemia, swelling, hypothermia, a tendency to bradycardia, constipation, progressive memory loss, hair loss head, eyebrows.
Women experience menstrual dysfunction, from menometrorrhagia to amenorrhea; in connection with the hyperproduction of thyrotropin-releasing hormone by the hypothalamus against the background of hypothyroxinemia, the development of hyperprolactinemic hypogonadism in primary hypothyroidism is possible, which is manifested by amenorrhea, galactorrhea and secondary polycystic ovaries.
Laboratory diagnostics Primary hypothyroidism includes:
Hormonal blood test - determination of TSH level. An increase in TSH levels is a very sensitive marker of primary hypothyroidism, and therefore the TSH level is the most important diagnostic criterion for hypothyroidism:

• in the subclinical form - increased TSH (within 4.01< ТТГ < 10 mU/L) при нормальном уровне Т4 и отсутствии клинической симптоматики;
• in the manifest form - increased TSH, decreased T4;
• It should be borne in mind that an increase in TSH levels can occur with uncompensated adrenal insufficiency, taking metoclopramide, sulpiride, which are dopamine antagonists; decrease in TSH when taking dopamine.

Differential diagnosis

In the presence of AIT as the most common cause of primary hypothyroidism, characteristic markers can be determined:

• "classical" antibodies - to TG and TPO;
• "non-classical" antibodies to the TSH receptor - blocking TSH binding. But to make a diagnosis of AIT, it is necessary to additionally carry out:
• Ultrasound of the thyroid gland (presence of linear hyperechoic (fibrous) layers, capsule compaction, heterogeneity of the echostructure with pronounced hypo- and hyperechoic inclusions);

• puncture biopsy (according to indications).

In secondary hypothyroidism, the TSH level is normal or reduced, T4 is reduced. When performing a test with thyrotropin-releasing hormone, the TSH level is examined initially and 30 minutes after intravenous administration of the drug. In primary, TSH increases to more than 25 mIU/l, in secondary, it remains at the same level.
Principles of treatment
Regardless of the level of damage and the cause of hypothyroidism syndrome, replacement therapy with levothyroxine is prescribed (in recent years, combination drugs T3 and T4 have been used much less frequently).
Principles of therapy:

• The older the patient and the longer the duration of hypothyroidism, the lower the initial dose. In the elderly and with severe concomitant pathology, start with 6.25-12.5 mcg with a gradual increase in the dose to a constant maintenance dose. In young people, it is possible to prescribe a full replacement dose immediately.
• A constant maintenance dose is prescribed at the rate of 1.6 mcg of the drug per 1 kg of body weight (75-100 mcg for women, 100-150 mcg for men);
• - for severe concomitant pathology in the manifest form - 0.9 mcg/kg;
• - in case of severe obesity, the calculation is based on 1 kg of “ideal” body weight.
• The dose increase in young patients occurs within 1 month, in older patients - more slowly, over 2-3 months, in the presence of cardiac pathology - over 4-6 months.
• After normalization of TSH levels (which occurs over several months), TSH monitoring is carried out once every 6 months.
• In case of secondary hypothyroidism in combination with secondary hypocortisolism, levothyroxine is prescribed only during corticosteroid therapy. The adequacy of treatment for secondary hypothyroidism is assessed only on the basis of dynamic T4 levels.
• In the treatment of hypothyroid coma - an extremely dangerous, but, fortunately, rare complication at present - a combination of water-soluble preparations of thyroid hormones and glucocorticoids is used.

Pregnancy and thyrotoxicosis syndrome

The incidence of DTZ is 2 cases per 1000 pregnancies. When making a diagnosis, they are based on a decrease in TSH levels, an increase in free fractions of T3, T4, and determination of increased levels of “classical” and “non-classical” antibodies. DTG increases the risk of early miscarriage, stillbirth, premature birth, preeclampsia, and low birth weight. Due to the effect of pregnancy as a factor of immunosuppression, remission of thyrotoxicosis is possible by the 2nd-3rd trimester, which sometimes makes it possible to temporarily cancel thyreostatic therapy. The transfer of thyroid-stimulating antibodies (TSH Ab) from mother to fetus is possible, which is prognostically unfavorable due to the possibility of the child developing craniostenosis, hydrocephalus, and severe neonatal thyrotoxicosis syndrome in the future. Fetal thyrotoxicosis can be suspected after 22 weeks of pregnancy when the fetal heart rate exceeds 160 beats/min.
To treat DTG during pregnancy, small doses of propylthiouracil (200 mg/day) are used. During pregnancy, only the “block” regimen is used (prescribing thyreostatics without adding levothyroxine) and the goal of treatment is to achieve and maintain the FT4 level at the upper limit of normal.
Radioactive iodine therapy is contraindicated during pregnancy, and surgical treatment is indicated in exceptional cases when drug therapy is impossible, severe drug allergies, very large goiter, combination with a malignant process in the thyroid gland, or the need to use large doses of thionamides to support euthyroidism. The safest time to perform subtotal resection of the thyroid gland is the second trimester of pregnancy.
It is necessary to carry out a differential diagnosis of thyrotoxicosis with gestational thyrotoxicosis. The concept of “gestational thyrotoxicosis (GTT)” was introduced by D. Glinoer, according to which GTT is observed in 2-3% of pregnant women and is associated with increased production of human chorionic gonadotropin (CG), which has a structural similarity to TSH and stimulates the thyroid gland. Clinically, this condition is accompanied by severe toxicosis of the first half of pregnancy (nausea, sometimes uncontrollable vomiting - hyperemesis gra v idarum). GTT develops more often in multiple pregnancies.
Laboratory tests during normal pregnancy in the early stages show a decrease in TSH levels, sometimes below standard values, with a normal level of free T4. For differential diagnosis with DTG, a decrease in TSH levels in combination with an increase in free T4 in early pregnancy will indicate in favor of GTT; hCG level more than 100,000 units/l; absence of thyroid-stimulating antibodies; no history of thyroid disease or endocrine ophthalmopathy. Signs of GTT spontaneously regress within 2 months; treatment with thyreostatics is not required; The pregnancy prognosis does not worsen and DTG does not develop in the postpartum period.
The level of hCG may also increase in choriocarcinoma and hydatidiform mole. According to Poertl et al. (1998), out of 85 pregnant women, 28% have a decrease in TSH, and thyrotoxicosis occurs in only 1%, which can be explained either by an increased level of thyroxine-binding globulin or increased excretion of iodine. At the same time, with a decrease in TSH levels in hydatidiform mole (47% of cases) and choriocarcinoma (67% of cases), thyrotoxicosis develops in 1/3 of cases.

Hypothyroidism and pregnancy

If hypothyroidism is untreated, pregnancy is unlikely.
At the same time, if pregnancy has begun and before the 6-8th week the fetus receives at least sufficient amounts of triiodothyronine, then later the fetal thyroid gland begins to function independently.
Of course, if there is an iodine deficiency and correction is not carried out, then there is a high probability of subsequent severe violations in the intellectual sphere of the unborn child.
In the USA, subclinical hypothyroidism (TSH within 4.01< ТТГ < 10,0 mU/l) регистрируется у 2% беременных. Это состояние встречается и в регионах с йоддефицитом, и в регионах с достаточным поступлением йода, где это, вероятно, связано с аутоиммунным процессом.
Serious complications of decompensated primary hypothyroidism are maternal hypertension, fetal malformations, premature birth, and miscarriage.
Over the past 15 years, mass screening of newborns for neonatal hypothyroidism has been introduced, which includes determination of plasma TSH (from the heel) no earlier than the 4-5th day of life (in premature infants on the 7-14th day): the TSH level is considered to be lower than 20 µU/ml.
Hypothyroidism is treated with levothyroxine, the dose of which is calculated based on the increased need for the drug during pregnancy up to 1.9-2.3 mcg/kg under mandatory TSH monitoring once a month. For subclinical forms of hypothyroidism during pregnancy, levothyroxine is also prescribed.
In addition, in iodine-deficient regions, pregnant women are recommended to prescribe iodine in the form of potassium iodide 200 mcg or as part of special multivitamin preparations, even if present with autoimmune thyroiditis, which does not lead to worsening of AIT during pregnancy, but compensates for iodine deficiency in the fetus. It is extremely dangerous for pregnant women to use any iodine preparations in one form or another that exceed 500 mcg/day, since such doses, through the Wolff-Chaikov effect, cause blockage of the thyroid gland in the fetus.

Literature:
1. Khostalek U. Diseases of the thyroid gland and the possibilities of their effective treatment. - Thyroid Russia. - Collection of lectures. M. 1997; 6-12.
2. Melnichenko G.A. Hypothyroidism. Rus. honey. zhurn., 1999; 7, 7(89 ).
3. Michaud P. Consensus proposal on the use of 131I in the treatment of thyrotoxicosis. Sociedad Chilena de Endocrinologia y Metabolismo, Hospital Dr Sotero del Rio, Santiago, Chile. Rev Med Chil. July 1998; 126(7): 855-65.
4. Glinoer D., Kinthaert J., Lemone M. Risk/benefit of thyroid hormone supplementation during pregnancy. Merck European Thyroid Symposium "The Thyroid and Tissues".- Strasburg. 1994; 194-8.
5. Kimura et al. Gestational thyrotoxicosis and hyperemesis gravidarum: possible role of hCG with higher stimulating activity. Japa Clin. Endocr. 1993; 38: 345-50.

Thyrotoxicosis- a general term used in the presence of elevated levels of triiodothyronine (T 3) and/or thyroxine (T 4) due to various reasons. It is not necessary that the patient should have significant clinical symptoms. Hyperthyroidism refers to the causes of thyrotosicosis, in which the thyroid gland produces hormones in excess quantities. Thyroid autonomy means the spontaneous synthesis and release of thyroid hormones independent of thyroid-stimulating hormone (TSH).

2. What is subclinical thyrotoxicosis?
Subclinical thyrotoxicosis means that the rise in T 3 and/or T 4 levels occurs within the normal range, which nevertheless leads to suppression of TSH secretion by the pituitary gland to subnormal values. Clinical signs and symptoms are often absent or nonspecific.

3. What are the long-term consequences of subclinical thyrotoxicosis?
Some studies have shown an association of subclinical thyrotoxicosis with accelerated bone loss in postmenopausal women and an increased incidence of atrial arrhythmias, including atrial flutter.

4. List the three main causes of hyperthyroidism.
1.Graves' disease- an autoimmune pathology in which antibodies are produced against the TSH receptor, which leads to constant stimulation of the thyroid gland to secrete thyroid hormones. It is often combined with extrathyroid pathology such as ophthalmopathy, pretibial myxedema and thyroid acropachy.
2. Toxic multinodular goiter (TMG) usually occurs in the presence of a long-term multinodular goiter, when individual nodes begin to function autonomously. Patients with mild or overt TMUS are also at increased risk of developing iodine-induced thyrotoxicosis (iodine-Based effect) after intravenous contrast or treatment with iodine-containing drugs, such as amiodarone.
3. Toxic adenoma or autonomously functioning thyroid nodes (AFTN)- benign tumors leading to excessive activation of the TSH receptor or its signal transduction apparatus. These tumors often lead to subclinical thyrotosicosis and are prone to spontaneous hemorrhage. AFTUs must be greater than 3 cm in diameter to achieve sufficient secretory capacity to achieve overt hyperthyroidism.

5. What are other rarer causes of hyperthyroidism?
Rarer causes of hyperthyroidism include TSH-secreting pituitary adenomas; stimulation of the TSH receptor by human chorionic gonadotropin (hCG) in extremely high concentrations, observed in the case of choriocarcinomas in women or germ cell tumors in men; struma ovarii (ectopic production of thyroid hormones by teratomas containing thyroid tissue); resistance of thyroid hormones to TSH. Thyroiditis and the administration of excess amounts of exogenous thyroid hormones (iatrogenic, unintentional, or surreptitious) are causes of thyrotosicosis, but not hyperthyroidism (see question 1).

6. What is the clinical picture of thyrotosicosis?
Main symptoms include palpitations, trembling, insomnia, difficulty concentrating, irritability or emotional lability, weight loss, heat intolerance, shortness of breath on exertion, fatigue, frequent bowel movements, shortened periods, and brittle hair. In rare cases, patients, on the contrary, gain weight, mainly due to polyphagia, which is necessary to cover the accelerated metabolism.

7. What is apathetic (in Russian-language literature - the arrowroot form of thyrotosicosis - Ed.) hyperthyroidism?
Elderly patients may lack typical adrenergic features and, conversely, may experience depression and apathy, weight loss, atrial fibrillation, and congestive heart failure.

8. Describe the signs of thyrotosicosis during physical examination?
Patients with hyperthyroidism may experience tremors, tachycardia, heart murmurs, warm moist skin, hyperreflexia with a rapid relaxation phase, and goiter (in Graves' disease). Clinical ocular symptoms are discussed in question 9.

9. What effect does hyperparathyroidism have on the eyes?
Retraction of the eyelids and an “angry” look are observed with various causes of thyrotosicosis due to increased adrenergic tone. True ophthalmopathy is characteristic only of Graves' disease and occurs in response to a cross-reaction of thyroid antibodies with antigens on fibroblasts, adipocytes and myocytes of the retrobulbar parts of the eye. The most common manifestations of ophthalmopathy include proptosis, diplopia, and inflammatory changes such as conjunctival injection and periorbital edema.

10. What laboratory tests confirm the diagnosis of thyrotoxicosis?
Determination of TSH using second or third generation methods is the most sensitive test for detecting thyrotosicosis. Since low TSH can also be observed in secondary hypothyroidism, it is necessary to measure free T4. If the T4 level is normal, it is necessary to determine the T3 level to exclude T3 thyrotosicosis. Other associated laboratory changes may include mild leukopenia, normocytic anemia, increased liver transaminases and alkaline phosphatase, mild hypercalcemia, and low albumin and cholesterol.

11. In what cases is antithyroid antibody testing performed to diagnose hyperthyroidism?
The cause of hyperthyroidism can usually be identified by history, physical examination, and radionuclide studies. It is advisable to test antibodies to the TSH receptor in pregnant women with Graves' disease to identify the risk of neonatal thyroid dysfunction due to transplacental transfer of stimulating or blocking antibodies. It may also be recommended for euthyroid patients with suspected euthyroid ophthalmopathy and patients with variable periods of hyper- and hypothyroidism due to fluctuations in the levels of TSH receptor blocking and stimulating antibodies.

12. What is the difference between thyroid scintigraphy and iodine uptake testing?
Determination of iodine uptake with isotopes I-131 or 1-123 is used to quantify the functional state of the thyroid gland. Small doses of radioactive iodine are administered orally, followed by assessment of distribution in the thyroid gland after 6-24 hours. High uptake confirms hyperthyroidism. Scintigraphy is a two-dimensional image of the distribution of activity in the thyroid gland. A uniform distribution in patients with hyperthyroidism confirms Graves' disease, a patchy distribution is characteristic of TMUS, and a single-focal distribution of activity corresponding to the position of the node indicates a toxic adenoma.

13. How to treat hyperthyroidism?
The three main treatment options include antithyroid drugs (ATDs) like methimazole and propylthiouracil; radioactive iodine (I-131); surgical intervention. Unless contraindicated, most patients should receive beta blockers for heart rate control and symptomatic treatment. Most thyroidologists prefer prescribing I-131 to surgery or long-term treatment with ATP (In Russia, they prefer conservative treatment; if it is ineffective or tends to relapse of the disease, surgical treatment is used, and in third place is treatment with radioactive iodine. - Ed.). Patients receiving I-131 treatment should avoid pregnancy and should be warned that oral contraceptives may not provide reliable protection in hyperthyroidism due to increased levels of sex hormone-binding globulin and accelerated contraceptive clearance.

14. In what cases is surgery indicated for hyperthyroidism?
Surgery is rarely the treatment of choice for hyperthyroidism. It is most often performed in the presence of a “cold” nodule due to Graves’ disease, in cases where I-131 treatment is contraindicated, as in the case of pregnancy, or in patients with a very large goiter. Before surgery, patients should achieve a euthyroid state in order to reduce the risk of arrhythmias during induction of anesthesia and the risk of postoperative thyroid crisis.

15. Are other treatments used to reduce thyroid hormone levels?
Yes. Inorganic iodine rapidly reduces the synthesis and release of T 4 and T 3 - Suppression of thyroid hormone synthesis by iodine is known as the Wolff-Chaikoff effect. However, since this effect usually “escapes” after 10-14 days, the drug is used only for quick preparation for surgery or as an additional measure in the treatment of thyroid crisis. The usual doses of Lugol's solution are 3-5 drops 3 times a day or a diluted solution of potassium iodide, 1 drop 3 times a day. Ipodate, an oral radiographic contrast agent, has been shown to inhibit T 4 -5" deiodinase activity, thereby reducing T 3 and T 4 levels. Usual doses of ipodate are 1 g per day. Other drugs rarely used to treat hyperthyroidism include: include lithium, which reduces the release of thyroid hormones and potassium perchlorate, which inhibits the uptake of iodine by the thyroid gland.

16. What drugs block the conversion of T4 to T3?
Propylthiouracil, propranolol, glucocorticoids, ipodate and amiodarone inhibit the peripheral conversion of T4 to T3

17. How effective are ATPs?
Ninety percent of patients receiving ATP achieve a euthyroid state without significant side effects. About half of patients achieve remission after a full course of treatment for 12-18 months. However, only 30% maintain long-term remission; as experience shows, relapse usually occurs in the first two years after discontinuation of drugs. Usual starting doses of methimazole are 30 mg/day or propylthiouracil 100 mg 3 times a day.

18. What side effects are observed during ATP treatment?
1. Agranulocytosis is a rare but life-threatening complication of ATP therapy, occurring in approximately one case per 200-500 people. Patients should be warned to seek immediate attention in case of fever, mouth ulcers and minor infections that do not resolve quickly.
2. Hepatotoxic effect leading to fulminant hepatitis with necrosis during propylthiouracil therapy and cholestatic jaundice during methimazole therapy. Patients should report pain in the right hypochondrium, lack of appetite, nausea and itching.
3. Skin rash, from localized erythema to exfoliative dermatitis. A reaction to one drug does not resolve when changing to another, although cross-sensitivity occurs in approximately 50% of cases.

19. What laboratory parameters need to be monitored in patients receiving ATP?
It is necessary to study the levels of thyroid hormones when the initial high doses of ATP should be reduced to maintenance (usually 25-50% of the initial one). TSH may remain suppressed for several months; in this situation, the determination of free T4 is of greater importance for assessing thyroid status. Liver enzyme monitoring and a complete blood count with formula should be performed every 1-3 months. Since elevated transaminases and mild granulocytopenia also occur in untreated Graves' disease, it is important to check these parameters before initiating ATP therapy. Many cases of agranulocytosis occur without previous granulocytopenia; thus, a high risk exists even if recent tests were normal. (In Russia, at the initial stages of treatment with a dose of methizol 20-30 mg, a complete blood count with a formula is monitored every 10 days. - Ed.)

20. How does radioactive iodine work?
Thyroid cells capture and concentrate iodine and use it to synthesize thyroid hormones. The organization of I-131 occurs in the same way as natural iodine. Because I-131 produces locally destructive beta particles, cell damage and death are observed for several months after treatment. Doses of I-131 must be high enough to induce permanent hypothyroidism to reduce relapse rates. Usual doses for Graves' disease are 8-15 mCi; with TMUS, higher doses are used - 25-30 mCi. Such doses are effective in 90-95% of patients.

21. In what cases is the use of ATP before treatment with I-131 indicated?
In elderly patients and patients with systemic diseases, ATP is often used to reduce the synthesis of thyroid hormones by the thyroid gland, thereby reducing the risk of I-131-induced thyroid storm. Preparation of ATP is also used in cases of severe thyrotosicosis, the impossibility of permanent treatment or the risk of pregnancy. Preparation may reduce the success rate of radioiodine treatment by inhibiting I-131 organification. When used to prepare ATP, they should be discontinued 4-7 days before using I-131.

22. How long after treatment with I-131 should I avoid pregnancy or breastfeeding?
Pregnancy should be avoided for at least 6 months after treatment with I-131. In addition, it is necessary to achieve stable doses of thyroid hormone replacement therapy and the absence of active ophthalmopathy. The radioactivity of breast milk, as determined in one study after a therapeutic dose of 8.3 mCi of I-131, remained high for 45 days. If 99t technetium is used for diagnostic purposes, feeding can be resumed after 2-3 days.

23. Can I-131 cause or worsen ophthalmopathy in Graves' disease?
This is an area of ​​debate. During the natural course of the disease, 15-20% of patients develop overt ophthalmopathy. In most cases, it occurs in the period from 18 months before the onset of clinical manifestation to 18 months from the onset of thyrotosycosis. Thus, new cases can be expected to coincide with I-131 treatment. Some studies, however, have shown that ophthalmopathy is more likely to worsen with I-131 treatment than with surgery or ATP treatment. As a result, patients with active moderate to severe ophthalmopathy are advised to avoid treatment with I-131.

24. How to manage thyrotosicosis during pregnancy?
It is necessary to interpret the results of laboratory tests during pregnancy with caution, since the first trimester is not characterized by low TSH values, and the total T4 indicator is increased due to an increase in the level of thyroxine-binding globulin (TBG). The best indicator of thyroid function during pregnancy is free T4. Nuclear tests such as iodine uptake determination or scintigraphy are contraindicated during pregnancy due to the effect of isotopes on the fetus. Since the use of I-131 is also contraindicated during pregnancy, treatment options are limited to ATP or surgery in the second trimester. Propylthiouracil is usually preferred because it crosses the placental barrier to a lesser extent than methimazole. Pregnant women with Graves' disease require close monitoring to achieve adequate control and prevention of hypothyroidism, as the disease often improves during pregnancy. It is necessary to determine antibodies to the TSH receptor, which can penetrate the placenta after 26 weeks, in the third trimester to assess the risk of neonatal thyroid dysfunction.

Subclinical thyrotoxicosis

Asim Hasan

Resume:

Thanks to the screening determination of TSH, subclinical thyrotoxicosis is more often detected. Subclinical hyperthyroidism is characterized by decreased concentrations of thyroid-stimulating hormone (TSH) in patients with normal T4 and T3 levels. In this case, minor symptoms and signs of thyrotoxicosis may appear.

Thyrotoxicosis is divided into endogenous in patients with excess production of thyroid hormones associated with thyroid nodules or Graves' disease; and also exogenous with a reduced concentration in the blood serum of thyroid-stimulating hormone as a result of treatment with levothyroxine. Subclinical hyperthyroidism often occurs in older people with autonomous function of a multinodular goiter or a solitary nodule.

Osteoporosis and atrial fibrillation are complications of subclinical hyperthyroidism that may be an indication for treatment. Studies show a possible increase in all-cause mortality in patients with subclinical hyperthyroidism over the age of 60 years, especially in older men.

In many patients with endogenous subclinical thyrotoxicosis who do not have thyroid nodules or complications due to excessive secretion of thyroid hormones, treatment is not necessary, but thyroid function should be monitored every 6 months. In elderly patients with atrial fibrillation or osteoporosis, which may be caused or aggravated by mild excess of thyroid hormones, 131 I therapy is the best option at the beginning of treatment.

In patients with exogenous subclinical thyrotoxicosis, the dose of levothyroxine should be reduced, except in patients with previous thyroid cancer requiring complete TSH suppression. The dose of levothyroxine used to treat hypothyroidism may be reduced if the patient develops episodes of atrial fibrillation, angina, heart failure, or accelerated bone loss.

Introduction

The availability of sensitive tests for thyroid-stimulating hormone (TSH) has led to the diagnosis of patients having low serum TSH concentrations (<0,5 мЕд/л) с нормальным уровнем свободного тироксина (Т4) и трийодтиронина (Т3); эти лабораторные данные описаны как субклинический тиреотоксикоз.

Subclinical thyrotoxicosis is laboratory diagnosed as a low level of thyroid-stimulating hormone (TSH) in the blood serum, with normal values ​​of free thyroxine (T4) and triiodothyronine (T3). Patients with subclinical thyrotoxicosis often have little or no symptoms of the disease.

Subclinical thyrotoxicosis is laboratory characterized by low or undetectable levels of thyroid-stimulating hormone (TSH), with normal concentrations of free thyroxine (T4) and total or free triiodothyronine (T3). Currently, methods are used that can detect TSH less than 0.01-0.02 mIU/L. Subclinical thyrotoxicosis can be divided into two types; detect a reduced TSH level (0.1-0.4 mIU/l), and a suppressed TSH level (less than 0.1 mIU/l). This may occur due to increased endogenous secretion of thyroid hormones, administration of thyroid hormones to treat thyroid cancer, or inadvertent overadministration of thyroid hormones. The manifestation of thyrotoxicosis is higher in individuals with suppressed TSH concentrations, in contrast to those who have low but detectable TSH levels. Subclinical thyrotoxicosis is associated with an increased risk of developing atrial fibrillation in elderly patients, as well as with a decrease in bone mineral density in postmenopausal women.

Subclinical hyperthyroidism is associated with an increased risk of developing atrial fibrillation and, mainly in postmenopausal women, a decrease in bone mineral density.

Reasons

Subclinical thyrotoxicosis may be associated with endogenous hyperproduction of thyroid hormones; or it may be exogenous as a result of deliberate administration of suppressive doses of levothyroxine to suppress thyroid cancer or inadvertent overadministration of hormones in patients with hypothyroidism.

Common causes of endogenous subclinical thyrotoxicosis are Graves' disease, functionally active thyroid adenoma, and toxic multinodular goiter. A transient decrease in TSH may occur during subacute, silent, or postpartum thyroiditis. The relationship between population iodine intake and the prevalence of thyroid dysfunction is inversely related to the higher incidence of iodine deficiency. The differential diagnosis of subclinical thyrotoxicosis is the same as that of manifest thyrotoxicosis. Both subclinical and manifest thyrotoxicosis can be permanent or transient.

Exogenous subclinical thyrotoxicosis

More than 10 million people in the United States and about 200 million people worldwide take thyroid hormones. Most of them are at risk of subclinical thyrotoxicosis, intentionally or unintentionally. Of patients taking levothyroxine, about 25% had low serum thyroid-stimulating hormone (TSH) levels; in one study, 5% had a TSH less than 0.1 mU/L.

Some of these patients have hypothyroidism, and subclinical thyrotoxicosis in them is not the purpose of taking thyroid hormones. However, subclinical thyrotoxicosis is the target of suppressive doses of levothyroxine in patients with thyroid cancer and in some patients with multinodular or diffuse goiter, or a history of head and neck radiation. In these patients, the benefits of TSH suppression outweigh the risks associated with subclinical thyrotoxicosis.

Endogenous subclinical thyrotoxicosis

Thyroid adenomas and multinodular goiter, which independently produce thyroid hormones, are the most common causes of endogenous subclinical thyrotoxicosis. In persons over 55 years of age, subclinical hyperthyroidism due to multinodular goiter was diagnosed in 57% of patients, while due to Graves' disease only 6%.

One imaging study found that 22% of patients with multinodular goiters had subclinical thyrotoxicosis and 28% had an autonomous area of ​​hyperthyroidism.

Subclinical thyrotoxicosis can result from thyroiditis and has also been shown to occur in 63% of cases with euthyroid ophthalmopathies and 4% in patients with Graves' disease in remission. May be observed in patients with Graves' disease before the onset of overt hyperthyroidism. In addition, pregnant women, mainly in the first trimester of pregnancy, with toxicosis or trophoblastic disease, with high serum concentrations of human chorionic gonadotropin, may be diagnosed with subclinical thyrotoxicosis.

Epidemiology and etiology

Numerous large studies have been conducted on the prevalence of subclinical thyrotoxicosis. Data from these studies, mainly in individuals over 55-60 years of age, are presented as follows:

The incidence of subclinical thyrotoxicosis varies among studies due to variability in the determination of TSH levels, the age of the patient population studied, and the administration of thyroid hormones. The occurrence of subclinical hyperthyroidism in the population ranges from 0.7 to 12.4%.

In a US medical study (NHANES III), which did not include people with diagnosed thyroid disease, 0.7% of 16,533 individuals with subclinical hyperthyroidism (TSH) were reported<0,1 мЕд/л). Субклинический тиреотоксикоз более распространен в районах с легким и умеренным дефицитом йода.

It has been shown that the prevalence of subclinical thyrotoxicosis can be as high as 15% in patients over 70 years of age in iodine-deficient areas. It is most common in people receiving thyroid hormone treatment, where the prevalence can be up to 20%. In addition, subclinical thyroid dysfunction is more common in women, smokers and older people.

The most common condition is thyroid hormone use, in which the prevalence can be up to 20%. In addition, subclinical thyroid dysfunction is more common in women, smokers and the elderly.

Typically, subclinical thyrotoxicosis does not progress to manifest thyrotoxicosis. Risk factors affecting the underlying process include the level of TSH suppression. One prospective study evaluated 102 women over 60 years of age with subclinical thyrotoxicosis with TSH concentrations between 0.1 and 0.4 mIU/L over a 41-month period.

Among these women, 2.9% developed overt hyperthyroidism; in 3.9%, the TSH level decreased to less than 0.1 mIU/l, with normal T3 and T4 values; in 23.5% TSH returned to normal; and in 69.5% the TSH level remained in the range of 0.1 - 0.4 mIU/l. This is equivalent to the development of 1% of manifest thyrotoxicosis per year.

The only significant factor for progression was a preliminary TSH value of less than 0.2 mIU/l. Women over 65 years of age with subclinical thyrotoxicosis and a TSH less than 0.1 mIU/L had a 27% rate of developing overt hyperthyroidism over the next 2 years, showing that the chances of progression are greater in patients with TSH levels less than 0.1 mIU/L.

The chances of progression are higher in patients with TSH levels less than 0.1 mIU/L.

Retrospective studies of the natural history of subclinical hyperthyroidism have shown that the course of thyrotoxicosis is more unpredictable in patients with Graves' disease than in patients with diffuse toxic multinodular goiter. In Graves' disease, patients may go into remission, progress, or remain unchanged until 3 years of follow-up, whereas most patients with multinodular goiter have stable thyroid function during the same follow-up period. More commonly, multinodular goiter in iodine-deficient areas, as well as iodine administration, including iodine-containing drugs such as amiodarone, can precipitate subclinical thyrotoxicosis.

In a prospective study, 40-60% of patients with subclinical hyperthyroidism had normal results. This is most likely to occur in individuals with a slight decrease in TSH levels (eg, 0.1 to 0.5 mU/L) early in the study. In a primary care study that included 422,242 subjects without overt thyroid dysfunction, 52% had serum TSH levels<0,35 мМЕ/л исходно, после этого имели нормальный уровень ТТГ без какого-либо лечения.

There are conflicting data regarding the incidence of progression from subclinical to overt thyrotoxicosis. Progression to overt hyperthyroidism appears to be related to the TSH level underlying the diagnosis.

Based on a society report from Scotland, 2024 people with subnormal TSH levels were studied over a 4-month period (<0,4 мЕд/л) отдельно с нормальным свободным или общим тироксином (Т4) и общим трийодтиронином (T3). В течение первого года исследования, общее развитие от субклинического до явного гипертиреоза составило 6,1%. У пациентов с постоянным состоянием субклинического гипертиреоза, который не прогрессировал в следующем году, дальнейшие скорости прогрессирования на 2, 5 и 7 лет были 0,6, 0,7 и 0,5%, соответственно. Отмечено, что число пациентов, у которых состояние прогрессировало до явного гипертиреоза, было мало, прогрессия примерно в два раза чаще встречается у пациентов с ТТГ в сыворотке крови <0,1 мЕд/л по сравнению с ТСГ 0,1-0,4 мЕд/л.

In a study conducted in New Zealand, 96 patients with endogenous subclinical thyrotoxicosis (TSH)<0,25 мМЕ/л), развитие гипертиреоза произошло в 8% в течение 1 года, и увеличилось до 26% в течение 5 лет. Через 5 лет прогрессирование субклинического гипертиреоза до явного, вследствие болезни Грейвса, узлового зоба и автономных узлов наблюдалось у 9, 21 и 61% больных соответственно.

In a study conducted in Brazil, of 48 women over 65 years of age who had twice confirmed TSH<0,1 мЕд/л, 20% с узловыми образованиями щитовидной железы и 40% с болезнью Грейвса, уровень ТТГ прогрессировал до явного гипертиреоза в течение 2 лет. В другом исследовании женщин старше 60 лет с легким тиреотоксикозом (ТТГ 0,1-0,4 мЕд/л), прогрессирование явного гипертиреоза было нечастым (примерно 1% в год).

The UK conducted a study that showed that 20.3% of patients with subclinical thyrotoxicosis with TSH<0,1 мЕд/л развивается явный гипертиреоз в среднем за 32 месяцев на 6,8% больше, чем при исходном уровне ТТГ 0.1-0.39 мЕд/л.

In patients over 60 years of age in the Framingay TSH study<0,1 мЕд/л, только у 4,3% уровень ТТГ прогрессировал до манифестного тиреотоксикоза в течение после последующих 4-х лет.

Clinical results

The main target organs affected in subclinical thyrotoxicosis are the bones and the cardiovascular system, although abnormalities in other systems may also develop (see Table 10.1).

Table 10.1 Clinical manifestations of subclinical thyrotoxicosis

Cardiac manifestations:

Sinus tachycardia and atrial fibrillation

Increased myocardial contractility

Hypertrophy of the left ventricle, interventricular septum and posterior wall of the myocardium

Increased atrial fibrillation

Manifestations from bone tissue:

Decreased bone density, especially in postmenopausal women

Increased biochemical markers of increased bone resorption

Increased urinary excretion of pyridinoline and deoxypyridinoline

Increased hydroxyproline excretion

Other:

Anxious dream

Mood disorders

Laboratory changes:

Increased serum concentrations of sex-binding globulin

Elevated serum concentrations of liver enzymes and creatine kinase

Decrease in serum concentrations of total cholesterol and LDL

Atrial fibrillation

A prospective cohort study of approximately 2000 patients over 60 years of age (without atrial fibrillation) over 10 years reported an increase in atrial fibrillation in individuals with subclinical thyrotoxicosis.

For patients with TSH values ​​less than 0.1 mU/L, or 0.1–0.4 mU/L, or within the normal range, the overall incidence of atrial fibrillation was 28%, 16%, and 11%, respectively. In laboratory-confirmed euthyroid individuals, TSH and free T4 concentrations may also be associated with the risk of atrial fibrillation. In a study of a population of 1426 patients, those with low TSH levels had a higher risk of developing atrial fibrillation than patients with euthyroidism. Comparable results were seen in another population-based study of 5519 euthyroid (normal TSH and free T4) older adults. Higher serum concentrations of free T4 (but within the normal range) were independently associated with atrial fibrillation.

Mineral metabolism

Subclinical thyrotoxicosis may reduce bone mineral density (BMD), predominantly in the cortex, although this may be influenced by the duration of the disease, other associated risk factors for bone loss, and the level of TSH inhibition. Loss of bone density in hyperthyroidism is a consequence of increased bone destruction due to an imbalance between bone resorption and bone formation, resulting in decreased BMD and increased markers of bone turnover. Although overt thyrotoxicosis is associated with an increased risk of fractures, the findings are not consistent with subclinical hyperthyroidism.

Subclinical thyrotoxicosis significantly affects BMD in postmenopausal women. In a cross-sectional analysis of women with endogenous subclinical thyrotoxicosis (TSH 0.01-0.1 mU/L), postmenopausal women had a marked decrease in BMD at the femoral and lumbar regions, whereas premenopausal women had only a moderate decrease in BMD at the femur compared to the euthyroid control group. A meta-analysis of 12 studies found an association between a significant decrease in BMD in postmenopausal women compared with premenopausal women or men.

There is evidence that subnormal TSH leads to increased markers of bone destruction, especially in postmenopausal women with exogenous subclinical thyrotoxicosis. Data support bone remodeling in postmenopausal women with subclinical thyrotoxicosis. Postmenopausal women with subclinical thyrotoxicosis (TSH less than 0.2 mU/L) due to multinodular goiter, with or without radioactive iodine therapy, were observed for 2 years. Patients treated with radioactive iodine had normal TSH levels and no significant changes in lumbar and hip BMD, while patients with low TSH levels had persistent bone loss of approximately 1-2% per year. One study noted a significant increase in BMD in patients with overt or subclinical thyrotoxicosis (2.8 and 1.5%, respectively) after 6 months of euthyroidism.

Quality of life

In persons with subclinical thyrotoxicosis, especially in persons under 50 years of age, sympathoadrenal activity may be increased. Quality of life and thyroid hormone overactivity were analyzed in 23 patients aged 43 years whose TSH levels were below 0.3 mU/L.

Individuals with low TSH levels had higher rates of irritability, tremors, heat intolerance, palpitations, and sweating, and poorer health and well-being, compared with euthyroid controls. However, other studies have found no relationship between TSH concentrations and health-related quality of life measures in patients who were treated for hyperthyroidism or in a population-based study of women that included participants with subclinical thyrotoxicosis.

Patients with exogenous subclinical hyperthyroidism have been reported to have sleep disturbances and decreased physical activity, with or without effects on temperament or psychological status. In a study of patients with hypothyroidism, on a standard dose of levothyroxine, compared with a higher dose of the drug, physical and global health scores were worse in the group with subclinical thyrotoxicosis. While mental health, temperament and physical learning were better.

In another six-month randomized study of increased T4, and continued TSH suppression versus normal TSH, in 24 patients with a history of thyroid carcinoma, there were no significant changes in any of the quality of life components in either group.

In another open-label study in which subjects were given a dose of thyroxine 50 mcg above or below the normal dose, subjects with the higher dose had improved "feelings of well-being" using a visual analogue scale compared to baseline.

Patients with endogenous subclinical thyrotoxicosis appear to have lower scores on both physical and psychological health than euthyroid controls. The low effectiveness was due to clinical symptoms associated with excess thyroid hormones.

Thus, quality of life may be improved in some patients with subclinical thyrotoxicosis, mainly the endogenous form. The discrepancy in results may be due to differences in the duration of subclinical hyperthyroidism, the degree of TSH suppression, and the patient population.

Grade

Patients with subclinical thyrotoxicosis should be asked about symptoms of hyperthyroidism (eg, tremor, palpitations, heat intolerance), as well as history of thyroid disease, exposure to iodinated contrast agents or iodine in herbal products, and therapies that may stimulate the thyroid gland ( high doses of glucocorticoids, thyroxine). Women of childbearing age should be asked about the possibility of pregnancy. In addition, all patients should be evaluated for thyroid enlargement and nodules.

Diagnostics

The negative feedback between the level of thyroxine, triiodothyronine and the level of thyroid-stimulating hormone is directly proportional. Thus, even a slight increase in the concentration of T4 and T3 in the blood serum (caused by exogenous or endogenous excess of thyroid hormones) suppresses TSH secretion. There is general agreement that serum TSH measurement is the most sensitive indicator of thyroid hormone activity without pituitary or hypothalamic pathology. The primary initial screening test for thyroid disease is serum TSH.

If the serum TSH concentration is subnormal (<0,5 мЕд/л), анализ крови на ТТГ следует повторить вместе со свободными Т4 и Т3 для подтверждения диагноза субклинического тиреотоксикоза. Диагноз субклинического тиреотоксикоза зависит от сочетания низкого уровня ТТГ в сыворотке и нормального уровня Т4 и Т3. Данные изменения могут протекать с клиникой гипертиреоза или иметь бессимптомное течение. Поскольку концентрация ТТГ в сыворотке может быть снижена временно, уровень ТТГ вместе со свободными Т4 и Т3 должен быть переоценен через 1-3 месяца для подтверждения диагноза.

Subclinical thyrotoxicosis should be distinguished from other diagnoses with reduced TSH concentrations that are not associated with the functional activity of the thyroid gland, for example, central hypothyroidism. Some patients with central hypothyroidism have low serum TSH levels and normal (but usually low or subnormal) free T4 and T3 concentrations. Thyroid disease patients with euthyroid nonthyroid disease, especially those receiving high doses of glucocorticoids or dopamine, may have low serum TSH levels and low normal free concentrations of T4 and T3. TSH concentrations may remain low for several months, which may alter normal T4 and T3 concentrations in patients treated for hyperthyroidism or hyperthyroidism caused by thyroiditis and mental illness, especially emotional disorders. T4 and T3 levels tend to be lower in patients with these disorders, whereas in patients with subclinical thyrotoxicosis, T4 and T3 concentrations may be in the mid-to-high normal range.

When the diagnosis of subclinical thyrotoxicosis is uncertain, assessment of 24-hour radioiodine uptake and thyroid scan may be helpful. A low serum TSH level in combination with a high or relatively high 24-hour 131I uptake, or a focal area of ​​increased radiopharmaceutical uptake, will confirm the diagnosis of subclinical hyperthyroidism.

In patients not taking levothyroxine who have persistent subnormal TSH values ​​and are being considered for treatment, radionuclide scanning is used to help establish the etiology of subclinical thyrotoxicosis (Table 10.2). Women of childbearing age must have a negative pregnancy test before undergoing a radioactive iodine scan.

A low serum TSH level may be explained if the scan reveals one or more areas of increased radiotracer uptake. If there are focal areas of increased uptake, thyroid ultrasound will be helpful to identify individual nodules. In patients with low or no radioiodine uptake, thyroiditis or recent iodine exposure may be the cause.

In postmenopausal women or other patients at risk of developing osteoporosis, bone densitometry testing may be useful in deciding whether treatment for subclinical hyperthyroidism or further monitoring is necessary.

Table 10.2. Causes of subclinical thyrotoxicosis

I. Thyrotoxicosis with normal or high uptake of radioactive iodine:

1. Functional autonomy of the thyroid gland (absorption may be low if recent iodine loading leads to iodine-induced thyrotoxicosis):

Toxic adenoma

Toxic multinodular goiter

2. Autoimmune pathology of the thyroid gland:

Graves' disease

Hashitoxicosis

3. Thyrotoxicosis mediated by human chorionic gonadotropin: Trophoblastic disease

Hydatidiform mole

4. TSH-mediated thyrotoxicosis:

TSH-secreting pituitary adenoma

Nonneoplastic TSH-mediated hyperthyroidism

II. Thyrotoxicosis with minimal uptake of radioactive iodine:

1. Exogenous consumption of thyroid hormones:

Excessive replacement therapy

Intentional suppressive therapy

Food thyrotoxicosis

Amiodarone-induced thyrotoxicosis

2. Thyroiditis:

Subacute granulomatous (de Quervain) thyroiditis

Painless thyroiditis (“silent”, lymphocytic thyroiditis)

Postpartum thyroiditis

Palpable thyroiditis

Radiation thyroiditis

3. Ectopic hyperthyroidism

Struma ovarii

Metastases of follicular thyroid cancer

Pregnancy

The diagnosis of subclinical or overt thyrotoxicosis during pregnancy can be difficult due to changes in thyroid function that occur during normal pregnancy. Transient subclinical thyrotoxicosis in the first trimester is considered a normal physiological state. True subclinical thyrotoxicosis may occur, but is not associated with negative outcomes during pregnancy and does not require therapy. Additionally, in pregnant women with overt hyperthyroidism, the goal of treatment is to maintain serum T4 concentrations in the normal range and serum TSH concentrations in the low-normal or suppressed range (ie, to maintain persistent but minimal mild hyperthyroidism).

There is no consensus regarding population screening for subclinical thyrotoxicosis. The criterion for approval of a screening test must be that diagnosing and treating the condition in asymptomatic patients will lead to significantly improved health outcomes compared with people who are not screened. In 2004, the US Preventive Services Task Force determined that there is sufficient evidence that suppressed TSH concentrations are a risk factor for the future development of atrial fibrillation, but there is no data to show whether any treatment can prevent this complication. Similarly, a group consisting of members of the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrinology Society published their consensus findings proposing population-based thyroid function screening. However, it is emphasized that evidence-based recommendations are population-based and that clinicians should use their best clinical judgment in the screening situation of individual patients.

Treatment Options

Treatment options for patients with subclinical thyrotoxicosis are similar to those for overt thyrotoxicosis and depend on the underlying cause. Beta blockers are useful for symptomatic control of sympathoadrenal overactivity (eg, palpitations, tremor).

For people with Graves' disease or nodular goiter with functional autonomy, treatment options include medication, surgery, and radioactive iodine treatment.

In patients with low or absent uptake of radiotracer by the thyroid gland, subclinical thyrotoxicosis may be caused by thyroiditis or exogenous administration of thyroid hormones (Table 10.2). Most patients with thyroiditis do not require treatment, since thyroid dysfunction is rarely severe and temporary. However, thyroid function assessment should be repeated from the beginning every 4-8 weeks until normalization. Patients may receive beta blockers symptomatically.

Subclinical thyrotoxicosis is laboratory diagnosed by low levels of thyroid-stimulating hormone (TSH) but normal levels of free thyroxine (T4) and triiodothyronine (T3). Patients with subclinical thyrotoxicosis often have few or no symptoms of hyperthyroidism.

The most common causes of subclinical thyrotoxicosis are levothyroxine therapy, autonomously functioning thyroid adenomas, and multinodular goiter.

Subclinical thyrotoxicosis is associated with an increased risk of atrial fibrillation and, mainly in postmenopausal women, reduces bone mineral density.

Patients receiving thyroid hormone replacement therapy for hypothyroidism and having TSH values ​​below normal should have their dose titrated to maintain normal serum TSH levels (approximately 0.5 to 5.0 mU/L).

For patients with thyroid malignancies and some patients with benign thyroid nodules, subclinical thyrotoxicosis is the goal of treatment with thyroid hormones. In these patients, the benefits of TSH inhibition are considered to outweigh the risks of subclinical thyrotoxicosis.

In individuals with endogenous subclinical thyrotoxicosis at high risk of cardiac or bone complications (ie, the elderly) and whose TSH level is less than 0.1 mU/L, treatment of the underlying cause of subclinical hyperthyroidism is recommended.

For patients whose TSH concentration is between 0.1 and 0.5 mU/L, treatment is recommended if bone density is low and/or if thyroid scintigraphy reveals one or more focal areas of high uptake. If bone density is normal and the thyroid scan does not show a focal area of ​​increased uptake, patients are usually kept under close observation. In these patients, TSH, free T4 and T3 are monitored every 6 months.

For patients with endogenous subclinical thyrotoxicosis at low risk of cardiac or bone complications (young adults, premenopausal women) and TSH less than 0.1 mU/L, treatment is recommended if scintigraphy shows one or more focal areas of high uptake. For low-risk patients with TSH values ​​between 0.1 and 0.5 mU/L, observation only is recommended. Monitor TSH, free T4 and T3 every 6 months.

Treatment options for patients with subclinical thyrotoxicosis are similar to those for overt hyperthyroidism and depend on the underlying cause.

Conclusion

Subclinical thyrotoxicosis is defined by low or undetectable serum levels of thyroid-stimulating hormone, with normal levels of free thyroxine and triiodothyronine. This may be caused by endogenous overproduction of thyroid hormones, the administration of suppressive doses of thyroid hormones to treat thyroid malignancies, or an overdose of thyroid hormones. The rate of development of overt hyperthyroidism is increased in patients with suppressed thyroid-stimulating hormone levels compared with those with low but detectable levels. Subclinical thyrotoxicosis is associated with an increased risk of atrial fibrillation in older adults and with decreased bone mineralization in postmenopausal women. Possible relationships between subclinical thyrotoxicosis and quality of life factors, cognition, and increased mortality are controversial. Prospective randomized controlled trials are needed to review the results of early treatment of potential pathologies to help determine whether screening should be advocated in the asymptomatic general population.

Subclinical hypothyroidism

Asim Hasan

Resume

Subclinical hypothyroidism is characterized by normal levels of free T4 and T3, and slightly elevated TSH (no more than 10 mU/l) in the blood serum. Which is a mild form of hypothyroidism and is a consequence of a very sensitive feedback loop between the thyroid gland and the pituitary gland. In this situation, a slight decrease in the production of thyroid hormones by the thyroid gland, in which the serum T4 level is still within the normal range, leads to an increase in the TSH level (usually up to 10 mU/L).

Whether subclinical hypothyroidism is a serious health problem that requires treatment remains a matter of debate. Some patients may have mild symptoms of hypothyroidism as well as elevated lipid levels and other risk factors for atherosclerotic cardiovascular disease. Progression to overt hypothyroidism may occur over time, especially if serum levels of antithyroid antibodies are high. On the other hand, most patients are asymptomatic, especially when TSH levels are less than 10 mU/L, and the relationship between atherosclerosis is still not fully understood.

Subclinical hypothyroidism most often results from Hashimoto's autoimmune thyroiditis. The main complication of Hashimoto's thyroiditis is progressive hypothyroidism. Most patients with autoimmune thyroiditis initially have a small goiter and subclinical hypothyroidism. This contrasts with overt hypothyroidism, in which free T4 levels are subnormal. The clinical picture of severe myxedema is usually clear, but with subclinical hypothyroidism the symptoms are mild or may be completely absent. This has led to recommendations from some professional organizations to screen for hypothyroidism, especially in high-risk groups such as older women, where the prevalence is high (up to 20% in women over 65 years of age) and in pregnant women, in whom untreated hypothyroidism can cause adverse outcomes in a child.

Treatment of subclinical hypothyroidism is a matter of debate, but is often prescribed based on the presence of symptoms; dyslipidemia, which can be corrected by levothyroxine therapy; and positive antithyroid antibody titers, which predict a higher likelihood of progression to overt hypothyroidism over time. It is enough to give levothyroxine to normalize TSH and regression of goiter.