Clinical protocol for thyrotoxicosis. Diffuse toxic goiter clinical recommendations. Can amiodarone therapy be continued in some cases of AIT?
Diffuse toxic goiter, Graves-Bazedow's disease, Graves' disease, Graves' disease, Perry's disease, Flayani's disease.
Version: MedElement Disease Directory
Thyrotoxicosis with diffuse goiter (E05.0)
Endocrinology
General information
Brief description
Diffuse toxic goiter* (TDD) refers to systemic autoimmune diseases that develop as a result of the production of antibodies to certain antigens, most often to the thyroid-stimulating hormone receptor (TSH), thyroid peroxidase (TPO) and thyroglobulin (TG).
Diffuse toxic goiter is clinically manifested by diffuse damage to the thyroid gland (thyroid gland) with the development of thyrotoxicosis syndrome Thyrotoxicosis is a pathological condition caused by the intake of excessive amounts of thyroid hormones into the body and is characterized by an increase in basal metabolism, dysfunction of the nervous and cardiovascular systems.
and extrathyroidal pathology (endocrine ophthalmopathy Endocrine ophthalmopathy - 1) General name for non-inflammatory pathological processes in the eye caused by dysfunction of the endocrine system; 2) Genetically determined independent autoimmune disease, accompanied by involvement of the eye and all orbital tissues in the pathological process and manifested by exophthalmos and ophthalmoplegia of varying degrees
, pretibial myxedema Cutaneous mucinosis nodular (syn. pretibial myxedema) is a form of cutaneous mucinosis (dermatosis caused by the deposition of mucin in the connective tissue and skin follicles), characterized by dense tumor-like formations on the legs and feet
, acropathy, etc.). The simultaneous combination of all components of a systemic autoimmune process is diagnosed relatively rarely, so their determination is not necessary for making a diagnosis.
In most cases, the greatest clinical significance in DTG is the involvement of the thyroid gland.
* term traditionally used in Russia and Kazakhstan
Classification
Classification of thyrotoxicosis according to the severity of clinical manifestations and hormonal disorders
(Fadeev V.V., Melnichenko G.A., 2007)
|
Subclinical (mild course) |
The clinical picture is absent or blurred. The TSH content is reduced, the content of free T4 and free T3 is within the reference values |
|
manifest (moderate) |
Detailed clinical picture. The TSH content is significantly reduced, the concentrations of free T4 and free T3 are increased. |
| Complicated (severe) | Severe manifestations of thyrotoxicosis and its complications: atrial fibrillation, heart failure, relative adrenal insufficiency, degenerative changes in parenchymal organs, psychosis, severe body weight deficiency. The TSH content is significantly reduced, the concentrations of free T4 and T3 are increased. |
Classification of the degree of enlargement of the thyroid gland
(Nikolaev O.V., 1955)
Note. The disadvantage of the WHO classification (2001) is that only three degrees of enlargement are proposed, and all subsequent increased sizes of the thyroid gland should be classified as 2 degrees. In the classification of goiter according to Nikolaev O.V. six degrees offered. It is clear to clinicians that the treatment tactics for DTG with grade II or III-IV thyroid enlargement are different, and therefore Nikolaev’s classification has advantages and can remain in service with endocrinologist clinicians.
Pathomorphological classification of DTG
Option 1 - hyperplastic changes in combination with lymphoid infiltration (the most common);
- option 2 - without lymphoid infiltration;
- Option 3 - colloidal proliferating goiter with morphological signs of increased function of the thyroid epithelium.
Etiology and pathogenesis
Diffuse toxic goiter (DTG) is a multifactorial disease in which a genetic predisposition is realized against the background of environmental factors (smoking, iodine consumption, viral or bacterial infection, stress).
Along with ethnically associated genetic predisposition (carriage of HLA-B8, -DR3 and -DQA1*0501 haplotypes in Europeans), psycho-emotional stress is of no small importance. A temporal relationship was found between the manifestation of the disease and the loss of a loved one. It was also noted that smoking increases the risk of developing diarrhea by 1.9 times. The importance of infectious and stress factors is discussed. In particular, based on the results of research work, some scientists put forward the theory of “molecular mimicry” between antigens of the thyroid gland, retrobulbar tissue and a number of stress proteins and antigens of bacteria (Yersinia enterocolitica ).
DTG can be combined with other autoimmune endocrine diseases (type 1 diabetes mellitus, primary hypocortisolism); This combination is usually referred to as autoimmune polyglandular syndrome type 2.
Epidemiology
According to the literature, 80-85% of cases of thyrotoxicosis syndrome diagnosed throughout the world are caused by diffuse toxic goiter. In the USA and England, the frequency of new cases of this pathology varies from 30 to 200 cases per 100 thousand population per year, the ratio of sick women to men is 7:1.
The disease can occur at any age, but the peak incidence occurs between 20 and 40 years of age. Diffuse toxic goiter in regions with normal iodine supply is the most common cause of persistent thyrotoxicosis.
Risk factors and groups
At-risk groups:
- carriers of HLA-B8, -DR3 and -DQA1*0501 antigens (in persons of European nationality);
- persons whose immediate relatives have autoimmune diseases of the thyroid gland (diffuse toxic goiter, autoimmune thyroiditis, etc.)
The implementation of a genetic predisposition to diffuse toxic goiter is facilitated by emotional, stress and exogenous (smoking) factors.
Clinical picture
Symptoms, course
The clinical picture of diffuse toxic goiter (DTG) is determined by thyrotoxicosis syndrome.
Characteristic manifestations of thyrotoxicosis:
1. Damage to the central and peripheral nervous system:
- excitability, increased irritability, tearfulness, fussiness, sleep disturbance;
- tremor of the fingers of outstretched arms (Marie’s symptom) and the whole body (telegraph pole symptom);
- increased tendon reflexes;
- muscle weakness that worsens without treatment;
- in severe cases, the development of thyrotoxic psychosis is possible.
2. Damage to the cardiovascular system:
- constant sinus tachycardia Sinus tachycardia is a form of supraventricular tachyarrhythmia characterized by normal sinus rhythm with a heart rate of more than 100 per minute (in adults)
;
- in severe forms of the disease - constant atrial fibrillation Atrial fibrillation is an arrhythmia characterized by fibrillation (rapid contraction) of the atria with complete irregularity of the intervals between heartbeats and the force of contraction of the ventricles of the heart.
or its paroxysms against the background of sinus tachycardia or normal sinus rhythm;
- increased systolic and decreased diastolic blood pressure (increased pulse pressure);
- in the final stage - circulatory failure due to the development of dyshormonal myocardial dystrophy Myocardial dystrophy is the general name for dystrophic lesions of the myocardium of established etiology
.
3. Damage to the gastrointestinal tract:
- intestinal hypermotility, manifested by unstable frequent loose stools;
- increased appetite;
- impaired liver function, in severe cases - the development of thyrotoxic hepatosis Hepatosis is the general name for a number of liver diseases characterized by dystrophic changes in the liver parenchyma in the absence or slight severity of signs of inflammation
.
4. Hypermetabolism:
- progressive weight loss against the background of increased appetite;
- muscle weakness;
- adynamia;
- osteoporosis Osteoporosis is degeneration of bone tissue with a restructuring of its structure, characterized by a decrease in the number of bone crossbars per unit volume of bone, thinning, curvature and complete resorption of some of these elements
;
- low-grade body temperature.
5. Ectodermal disorder syndrome: brittle nails, hair loss, hot, velvety-feeling skin
6.Damage to other endocrine glands:
- ovarian dysfunction with menstrual irregularities;
- decreased libido;
- decreased potency and the appearance of gynecomastia Gynecomastia - enlargement of the mammary glands in men
in men;
- development of relative adrenal insufficiency;
- impaired tolerance to carbohydrates up to the development of secondary diabetes mellitus.
An important sign of DTZ is presence of goiter. Usually the thyroid gland (TG) is soft, diffusely and uniformly enlarged, and may increase in size due to excitement. Sometimes a blowing systolic murmur is heard over the gland. However, the severity of the disease is not determined by the size of the goiter and the development of severe thyrotoxicosis is possible even with its small size.
In some cases, the first place in DTZ may come manifestations endocrine ophthalmopathy(EOP):
- pronounced exophthalmos, often asymmetrical in nature;
- diplopia Diplopia is a visual impairment in which the object being viewed appears doubled
when looking to one side or up;
- lacrimation;
- photophobia;
- feeling of “sand in the eyes”;
- swelling of the eyelids.
Thyrotoxicosis syndrome in 2/3 of cases develops approximately one year earlier than EOP, which in 50% of patients has varying degrees of severity. In the presence of a pronounced EOP, it is possible to establish an almost unmistakable diagnosis. This is due to the fact that, according to the clinical picture, among diseases occurring with thyrotoxicosis, EOP is combined predominantly with thyrotoxicosis.
Main eye symptoms:
- Graefe's symptom - lag of the upper eyelid from the edge of the cornea when the eyeball moves downwards;
- Kocher's symptom - a lag in the movement of the eyeball from the movement of the upper eyelid when looking up, and therefore a section of the sclera is detected between the upper eyelid and the iris;
- Dalrymple's sign - wide opening of the palpebral fissures ("surprised look");
- Krause's symptom - increased shine of the eyes;
- Stellwag's symptom - rare and incomplete blinking movements combined with retraction Retraction is a reduction in the volume of a cell, tissue or other morphological formation (for example, a blood clot) due to reduction (shortening) of some elements of its structure
upper eyelid;
- Rosenbach's symptom - small and rapid trembling of drooping or slightly closed eyelids.
- Moebius symptom - convergence disorder (loss of the ability to focus the eye when an object approaches it).
In 3-4% of patients, DTG develops pretibial myxedema- damage to the skin and subcutaneous fat on the anterior surface of the leg in the form of one- or two-sided clearly defined compaction of a purplish-bluish color. Edema is formed due to a violation of the metabolism of glucoproteins, the carbohydrate components of which are found in the edematous substance - mucin. The development of pretibial myxedema is based on an autoimmune process.
In children DTZ develops mainly acutely.
The first symptoms are increased nervousness and motor activity, trembling, especially choreoid twitching of the head and facial muscles. More typical for children is diffuse enlargement of the thyroid gland; nodes are extremely rare. Exophthalmos is observed more often than in adults Exophthalmos - forward displacement of the eyeball, accompanied by widening of the palpebral fissure
. Children experience progressive weight loss, as well as severe cardiac symptoms without atrial fibrillation and circulatory failure. An ECG reveals a slowing of atrioventricular conduction (prolongation of the P-Q interval).
In elderly patients the phenomena of thyrotoxicosis are asymptomatic or manifest 1-2 symptoms.
The most common manifestations:
- weight loss - in 44% of cases;
- rapid heartbeat or cardiac arrhythmia in the form of paroxysms or a permanent form of atrial fibrillation - 36%;
- weakness.
In older people, cardiac symptoms come to the fore in the absence or minimal manifestation of thyrotoxicosis. If antiarrhythmic treatment is ineffective in elderly patients, the presence of thyrotoxicosis as a cause of cardiac arrhythmia should be excluded.
Goiter is detected in 60% of cases in the elderly and in 14% in the elderly.
Pregnancy occurs rarely against the background of severe thyrotoxicosis. In addition, with uncontrolled thyrotoxicosis, there is a high risk of its spontaneous interruption. In the case when pregnancy has occurred, the clinical course of DTG is characterized by some exacerbation in the first half of pregnancy and a clear clinical improvement in the second half. Presumably this is due to the influence of placental hormones.
In almost 30% of cases, prematurity is observed and, more often, stillbirth.
Diagnostics
Basic examination methods
1. Anamnesis: the presence of autoimmune pathology of the thyroid gland (TG) among relatives, a “short” history of the disease: symptoms develop and progress, as a rule, quickly and in most cases lead the patient to the doctor 6-12 months from the onset of the disease.
2.Physical examination:
- determination of weight, height;
- examination of the skin, hair, nails;
- determination of blood pressure, pulse rate and rhythm;
- determination of tremor of the fingertips of outstretched arms and body.
3. Examination and palpation of the thyroid gland: determination of the size of the cervix, the presence of palpable nodes.
4. Ophthalmological examination: presence of exophthalmos, eye symptoms, condition of the fundus. According to the recommendations of the thyroidological section of the German Endocrinological Society for the diagnosis of Graves-Basedow disease, in the presence of endocrine ophthalmopathy (EOP), the diagnosis of immunogenic thyrotoxicosis (diffuse toxic goiter) can be considered confirmed, therefore further diagnostic search aimed at determining the cause of thyrotoxicosis is usually inappropriate.
5. Ultrasound of the thyroid gland: diffuse increase in thyroid volume, tissue hypoechogenicity, increased blood flow.
6. (st. T4):
Additional examination methods(used according to indications)
1. Isotope scintigraphy(with 131I or 99mТс) makes it possible to detect a diffuse increase in the uptake of the thyroid isotope. It is used in diagnostically unclear cases, as well as in the presence of nodules in the thyroid gland that are palpable or exceed 1 cm in diameter.
For breastfeeding women (for the differential diagnosis of DTG and postpartum thyroiditis), the study is carried out with the 99mTc isotope; After the usual dose of technetium is administered, breastfeeding is safe for the baby within 12 hours.
2. Electrocardiography:
- increased heart rate;
- tall, pointed P and T waves;
- in complicated cases - atrial fibrillation;
- extrasystole Extrasystole is a form of cardiac arrhythmia, characterized by the appearance of extrasystoles (a contraction of the heart or its parts that occurs earlier than the next contraction should normally occur)
;
- ST segment depression, negative T wave;
- 1/3 of patients are diagnosed with signs of left ventricular hypertrophy, which are functional in nature and disappear after elimination of thyrotoxicosis.
3. Fine needle biopsy(TAB)
6. General blood test
7. Biochemical blood test
Laboratory diagnostics
1. Determination of TSH and free T4 levels(st. T4):
- TSH level is reduced to less than 0.2 IU/l or not detected (suppressed);
- the level of free T4 is increased (in the manifest form);
- if the level of St. T4 is determined within the normal range, then a determination of St. T4 is indicated. T3 for the diagnosis of T3 thyrotoxicosis.
If the content of free fractions of thyroid hormones is within the reference values, then subclinical thyrotoxicosis occurs.
2. Determination of antibody titer to the TSH receptor(AT-rTSH) - is the most informative for diagnosing diffuse toxic goiter. The presence of antibodies confirms the immunogenic nature of hyperthyroidism. This study was recommended by the American Association of Clinical Endocrinologists in 2002. AT-rTSH can be used as a predictor of the outcome of conservative therapy - the higher the titer, the lower the likelihood of stable remission with conservative therapy (Vitti P. et al., 1997).
3. Determination of the titer of “classical” antibodies to the thyroid gland: antibodies to thyroid peroxidase - increased in 90% of cases, antibodies to thyroglobulin - increased in 50% of cases. However, since these antibodies are also found in other autoimmune thyropathies, their increase is not pathognomonic for DTG.
4. General blood test: signs of normocytic or iron deficiency anemia are possible.
5. Biochemical blood test: possible decrease in cholesterol and triglyceride levels as a result of increased clearance, increased liver transaminases, alkaline phosphatase, hyperglycemia, hypercalcemia.
Differential diagnosis
In practice, the most common causes of thyrotoxicosis are diffuse toxic goiter (DTG) and functional autonomy of the thyroid gland (multinodular toxic goiter, toxic adenoma). When carrying out differential diagnosis, it is necessary to find out whether thyrotoxicosis is immunogenic (autoimmune) or whether its cause is the autonomous production of thyroid hormones (not related to the action of thyroid-stimulating antibodies).
DTG must be differentiated from other diseases accompanied by thyrotoxicosis syndrome:
1. Subacute granulomatous thyroiditis - a rare disease of viral etiology. Symptoms: malaise, fever, pain in the thyroid area, which radiates to the ears and intensifies when swallowing or turning the head.
On palpation, the thyroid gland is extremely painful, very dense, nodular. As a rule, the inflammatory process occurs in one of the lobes of the thyroid gland and gradually invades the other lobe.
The ESR is elevated, antithyroid autoantibodies are usually not detected, and the uptake of radioactive iodine by the thyroid gland is sharply reduced.
The duration of the initial (thyrotoxic) stage is several weeks. At this stage, thyrotoxicosis may occur due to damage to the gland tissue. The second (hypothyroid) stage also lasts several weeks, after which recovery occurs.
Due to the short duration of the thyrotoxic stage, antithyroid drugs are usually not used. A positive effect occurs from glucocorticoid therapy.
2. Chronic lymphocytic thyroiditis. With this disease, thyrotoxicosis occurs in less than 5% of cases and, as a rule, is transient. The thyroid gland may not be enlarged at all or very enlarged, but most often there is a small dense goiter.
The thyroid gland is painless on palpation.
There is an increase in total T4, which is associated with damage to the gland tissue.
The main differential diagnostic signs of chronic lymphocytic thyroiditis and DTG:
1. The absorption of radioactive iodine by the thyroid gland in chronic lymphocytic thyroiditis is reduced, and in DTG it is increased.
2. T3/T4 ratio in chronic lymphocytic thyroiditis< 20:1, а при ДТЗ > 20:1.
3. Antibodies to microsomal antigens are detected in 85% of patients with chronic lymphocytic thyroiditis and in no more than 30% of patients with thyroid disease.
4. Thyroid-stimulating autoantibodies are detected mainly in thyroid disease.
3. Subacute lymphocytic thyroiditis with transient thyrotoxicosis(postpartum thyroiditis) - the disease often develops after childbirth. The thyrotoxic (initial) stage lasts from 4 to 12 weeks, followed by a hypothyroid stage lasting several months.
A mild form of subacute postpartum thyroiditis occurs in 8% of women in labor. As a rule, the disease ends in recovery. In 25% of women who have had subacute postpartum thyroiditis, the disease recurs after repeated births.
In the thyrotoxic stage, propranalol is prescribed to eliminate the symptoms of thyrotoxicosis. Thyrostatics are not used.
The level of thyroid hormones in the blood can be significantly affected by changes in their binding to plasma proteins during pregnancy, under the influence of certain medications, and in severe non-thyroid diseases.
The most common causes of low TSH levels in the blood that are not associated with thyroid diseases:
1. Diseases:
1.1 Severe somatic diseases.
1.2Acute psychosis. Total T4 and free T4 (estimated free T4) are elevated in almost a third of patients hospitalized with acute psychosis. In 50% of patients with elevated T4 levels, T3 levels are also increased. These indicators normalize after 1-2 weeks without treatment with antithyroid drugs.
Presumably the increase in thyroid hormone levels is caused by the release of TSH. However, during the initial examination of hospitalized patients with psychosis, the TSH level is usually reduced or is at the lower limit of normal. It is possible that TSH levels may increase in the early stages of psychosis (before hospitalization). Indeed, in some patients with amphetamine addiction hospitalized with acute psychosis, an insufficient decrease in TSH levels is found against the background of elevated T4 levels.
1.3 High level of human chorionic gonadotropin (first trimester of pregnancy, toxicosis of pregnancy, pregnancy with hydatidiform mole, chorionic carcinoma).
In all women during pregnancy, an increase in the level of total T4 is associated with an increase in the level of TSH (thyroxine-binding globulin) under the influence of excess estrogen. In this regard, free T4 and TSH levels should be used to assess thyroid function during pregnancy.
2. Medicines:
- taking high doses of levothyroxine sodium;
- treatment with GCS;
- taking bromocriptine.
Complications
With thyrotoxicosis, which develops with diffuse toxic goiter, damage to all body systems is observed. In the absence of adequate treatment, the disease ends in severe disability, and in the absence of treatment, the risk of mortality from cardiac arrhythmia (atrial fibrillation, atrial fibrillation) and circulatory failure increases.
With thyrotoxic atrial fibrillation, the risk of developing embolism Embolism - blockage of a blood vessel by an embolus (a substrate circulating in the blood that is not found under normal conditions)
as high as in rheumatic mitral stenosis.
Thyrotoxic crisis- the most severe, life-threatening complication of diffuse toxic goiter. It occurs as a result of untreated or improperly treated severe thyrotoxicosis. It manifests itself as a sudden increase in the severity of symptoms of thyrotoxicosis, caused by a significant increase in the levels of T3 and T4 in the blood plasma.
Thyrotoxic crisis develops in 0.5-19% of cases in patients with severe disease.
Complications after surgical treatment(subtotal resection of the thyroid gland):
- hypothyroidism Hypothyroidism is a thyroid deficiency syndrome characterized by neuropsychiatric disorders, swelling of the face, limbs and trunk, bradycardia
- approximately 25% of cases;
- persistence or relapse of thyrotoxicosis - 10%;
- hypoparathyroidism Hypoparathyroidism is a syndrome of insufficiency of parathyroid gland function, characterized by seizures, nervous and mental disorders, and decreased calcium levels in the blood.
- 1%;
- damage to the recurrent laryngeal nerve - 1%;
- wound suppuration, keloid scars.
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Treatment
Treatment Goals diffuse toxic goiter (DTZ):
1. Relief of manifestations of thyrotoxicosis.
2. Normalization of laboratory parameters of the level of thyroid hormones in the blood.
3. Achieving immunological remission of the disease.
Treatment methods:
- conservative therapy (therapy with thyreostatics in combination with or without thyroid hormones);
- surgical treatment;
- therapy with radioactive iodine (131I).
None of the listed treatment methods is pathogenetic. When choosing a treatment option, it should be adapted to the specific patient, taking into account indications and contraindications.
The first and main stage of treatment for all patients is achieving euthyroidism, that is, normalizing the functional state of the thyroid gland with the help of thyreostatics, iodine preparations or symptomatic therapy with ß-blockers.
Treatment algorithm for DTZ(National Guidelines. Endocrinology, p. 527)
Non-drug treatment:
1. Limiting the intake of iodine-containing drugs (iodine-containing contrast agents, vitamins containing iodine, etc.).
2. Elimination of caffeine, smoking, physical activity.
3. Good nutrition with a sufficient amount of vitamins and microelements.
4. To restore normal sleep and reduce the patient’s increased irritability, sedatives are prescribed.
Conservative therapy
The following drugs have a thyrostatic effect:
1. Derivatives of imidazole (thiamazole) and thiouracil (propylthiouracil) are the main means of conservative therapy. The drugs inhibit the synthesis of thyroid hormones and also have effects that reduce immunological activity in thyroid disease.
2. Potassium perchlorate - currently practically not used in the treatment of DTG.
3. Lithium carbonate - has limited indications in the treatment of DTG. The drug is prescribed only for mild forms of the disease, as well as during the period of preoperative preparation when it is impossible to use imidazole and thiouracil derivatives due to complications (allergies, etc.).
In patients with a slight enlargement of the thyroid gland (volume less than 30 ml), in the absence of clinically significant nodular formations, long-term (12-18 months) conservative therapy is possible, which in 30-40% of cases leads to stable remission of the disease.
It should be borne in mind that if a relapse of the disease develops after one course of therapy with thyreostatics, the appointment of a second course is futile.
In the drug treatment of DTG with thyreostatics, there are two main phases.
First phase- achievement of euthyroidism:
- propylthiouracil orally, regardless of food intake, 100-150 mg 3-4 times. per day, 3-6 weeks or
- thiamazole orally, regardless of food intake, 30-40 mg once a day or in 3 divided doses, 3-6 weeks.
Second phase- maintaining a euthyroid state (after achieving clinical euthyroidism and normalizing the level of thyroid hormones in the blood). The dose of thiamazole is gradually reduced over 3-4 weeks to maintenance (usually 5-10 mg/day), and propylthiouracil to 50-100 mg/day.
To prevent relapses of thyrotoxicosis, maintenance doses of thyreostatic drugs are recommended to be used for a long time (12-18 months) without interruption, under the control of a general blood test (leukocytes and platelets) once a month.
Starting from the moment of normalization of T4 concentration or slightly later, in parallel the patient is prescribed sodium levothyroxine at a dose of 50-100 mcg/day. This scheme is called “block and replace”: one drug blocks the gland, the other replaces the emerging deficiency of thyroid hormones. Maintenance therapy according to this regimen (10-15 mg of thiamazole and 50-100 mcg of levothyroxine sodium) should be carried out for 12 to 24 months.
Patients with a high risk of thyrotoxicosis (large goiter, high titer of antithyroid antibodies and thyroid hormones when diagnosing the disease) may be recommended combination therapy if for some reason they cannot undergo more radical treatment (surgical or radioactive iodine).
If the patient cannot regularly monitor thyroid function, he can also be offered this treatment regimen.
After completing the course of treatment, the drugs are discontinued. Relapse of the disease most often develops during the first year after discontinuation of drugs.
When treating thyrotoxicosis, if possible, you should limit yourself to the minimum dose to maintain a euthyroid state, since high doses of thyreostatics do not reduce the frequency of relapses, but may increase the frequency of adverse reactions (allergic reactions, hepatitis, arthritis, agranulocytosis).
When pregnancy occurs against the background of thyroid disease, thyreostatic drugs are prescribed in the minimum dose necessary to maintain the T4 concentration at the upper limit of normal or slightly above normal. The use of the “block and replace” regimen is not indicated due to the fact that the thyreostatic agent must be prescribed in a larger dose, and this is undesirable due to the risk of goiter formation and hypothyroidism in the fetus.
The drug of choice in this case is propylthiouracil, which penetrates the hemoplacental barrier less well and binds to proteins to a slightly greater extent.
Iodine preparations(at a dose of more than 0.1 mg/kg body weight) inhibit intrathyroidal iodine transport and thyronine biosynthesis according to the ultrashort feedback principle, and also reduce the rate of release of thyroid hormones into the blood.
Currently, their use is limited due to their short-term thyreostatic effect (no more than 14-16 days).
Iodides, as a rule, are used for preoperative preparation of patients with thyrostatic disease in combination with thyreostatics, as well as in combination with other drugs for the treatment of thyrostatic crisis. Iodine/potassium iodide is used in a dose of 3-5 drops 3 times a day, 10-14 days.
Therapy with ß-blockers
It is used as a symptomatic treatment, which is aimed at reducing the symptoms of thyrotoxicosis caused by the action of catecholamines:
- non-selective ß-blockers: propranalol;
Selective ß-blockers: atenolol, metoprolol.
These drugs have the ability to quickly alleviate the symptoms of thyrotoxicosis and provide a quick positive effect from the start of treatment, which makes them vital in the treatment of thyrotoxicosis.
Selective beta blockers are preferred because they also reduce peripheral conversion of T4 to T3.
Once euthyroidism is achieved, ß-blockers are discontinued.
Dosage:
- atenolol orally 50 mg 1-2 times a day, until clinical manifestations are eliminated or
- metoprolol orally 50 mg 2-3 times a day, until clinical manifestations are eliminated or
- propranolol orally 20-40 mg 3-4 times/day, until clinical manifestations are eliminated.
Surgical method
Surgical treatment is optimal in the following situations:
- ineffectiveness of conservative treatment (presence of relapses, severe course of DTZ);
- impossibility of conservative treatment (allergy to antithyroid drugs, agranulocytosis, etc.);
- pregnancy;
- children's age;
- large goiter with signs of compression of nearby organs or its nodular form, including thyrotoxic adenoma and multinodular toxic goiter;
- retrosternal location of the goiter.
Purpose of surgical treatment- removal of as much of the thyroid gland as possible to eliminate any possibility of relapse of thyrotoxicosis.
It is recommended to perform an extremely subtotal resection of the thyroid gland, leaving no more than 2-3 ml of thyroid residue. With a smaller volume of surgery, there is a certain risk of persisting thyrotoxicosis or distant relapse.
Radioactive iodine therapy is used in the following cases:
- relapse of thyrotoxicosis after surgical treatment of thyrotoxicosis during drug treatment;
- impossibility of conservative treatment;
- the presence of pronounced cardiovascular disorders in patients with small thyroid glands.
Comparative characteristics of surgical treatment and radioactive iodine therapy
| Surgical treatment | Radioactive iodine therapy |
| Extremely subtotal resection of the thyroid gland | Dose 150-200 g. with calculation of activity per volume of the entire thyroid gland |
| Rapid elimination of thyrotoxicosis (several hours) | Elimination of thyrotoxicosis within a few weeks |
| Carried out against the background of euthyroidism achieved by thyreostatics | Does not require preparation; cheaper method |
| Extremely undesirable for postoperative relapse of thyrotoxicosis | Method of choice for postoperative relapse of thyrotoxicosis |
| Specific complications: laryngeal paresis and hypoparathyroidism | Absolute contraindication: pregnancy and lactation |
| Preferable for large goiters | If the goiter is large (more than 60 ml), the method is less preferable |
In both surgical treatment and radioactive iodine therapy, the resulting hypothyroidism is considered not as a complication, but as a goal of these treatment methods. As a result, levothyroxine sodium in an individual dose for replacement purposes is prescribed for life.
After conservative therapy In the future, a clinical examination and monitoring of TSH and St. are indicated. T4: in the first six months - once every 3 months, then over the next 2 years - every 6 months, then annually.
- pp. 91-114
- pp.110-128
- pp.351-360
- 124-144
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RCHR (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical protocols of the Ministry of Health of the Republic of Kazakhstan - 2013
Thyrotoxicosis, unspecified (E05.9)
Endocrinology
General information
Brief description
Approved by the Minutes of the meeting
Expert Commission on Health Development of the Ministry of Health of the Republic of Kazakhstan
No. 23 dated December 12, 2013
Thyrotoxicosis is a clinical syndrome caused by an excess of thyroid hormones in the body. There are three options:
1. Hyperthyroidism - hyperproduction of thyroid hormones of the thyroid gland (thyroid gland) (Graves disease (GD), multinodular toxic goiter (MTZ)).
2. Destructive thyrotoxicosis - a syndrome caused by the destruction of thyroid follicles with the release of their contents (thyroid hormones) into the blood (subacute thyroiditis, postpartum thyroiditis).
3. Drug-induced thyrotoxicosis - associated with an overdose of thyroid hormones.
I. INTRODUCTORY PART
Protocol name: Thyrotoxicosis in adults
Protocol code
ICD 10 codes:
E 05.
E 05.0 Thyrotoxicosis with diffuse goiter
E 05.1 Thyrotoxicosis with toxic uninodular goiter
E 05.2 Thyrotoxicosis with toxic multinodular goiter
E 05.3 Thyrotoxicosis with ectopia of thyroid tissue
E 05.4 Artificial thyretoxicosis
E 05.5 Thyroid crisis or coma
E 05.8 Other forms of thyrotoxicosis
E 05.9 Thyrotoxicosis, unspecified
E 06.2 Chronic thyroiditis with transient thyrotoxicosis
Abbreviations used in the protocol:
AIT - autoimmune thyroiditis
GD - Graves' disease
TSH - thyroid stimulating hormone
MUTZ - multinodular toxic goiter
TA - thyrotoxic adenoma
T3 - triiodothyronine
T4 - thyroxine
thyroid gland - thyroid gland
FNA - fine-angle aspiration biopsy of the thyroid gland
I 131 - radioactive iodine
AT to TPO - antibodies to thyroperoxidase
AT to TG - antibodies to thyroglobulin
AT to rTSH - antibodies to the TSH receptor
Date of protocol development: 2013
Protocol users: endocrinologists in hospitals and clinics, GPs, therapists.
Classification
Clinical classification
1. Thyrotoxicosis caused by increased production of thyroid hormones:
1.1. Graves' disease
1.2. Multinodular toxic goiter, toxic adenoma (TA)
1.3. Iodine-induced hyperthyroidism
1.4. Hyperthyroid phase of autoimmune thyroiditis
1.5. TSH - conditioned hyperthyroidism
1.5.1. TSH-producing pituitary adenoma
1.5.2. Syndrome of inappropriate TSH secretion (resistance of thyrotrophs to thyroid hormones)
1.6. trophoblastic hyperthyroidism
2. Hyperthyroidism caused by the production of thyroid hormones outside the thyroid gland:
2.1. struma ovarii
2.2. Metastasis of thyroid cancer producing thyroid hormones
2.3. Chorinonepithelioma
3. Thyrotoxicosis not associated with overproduction of thyroid hormones:
3.1. Drug-induced thyrotoxicosis (overdose of thyroid hormone drugs)
3.2 Thyrotoxicosis as a stage of subacute de Quervain’s thyroiditis, postpartum thyroiditis
4. By severity: light, medium, heavy. The severity of thyrotoxicosis in adults is determined by the symptoms of damage to the cardiovascular system (“thyrotoxic heart”): the presence of atrial fibrillation, fibrillation, chronic heart failure (CHF).
5. Subclinical
6. Manifest
7. Complicated
Diagnostics
II. METHODS, APPROACHES AND PROCEDURES FOR DIAGNOSIS AND TREATMENT
List of basic and additional diagnostic measures
Before planned hospitalization: blood glucose test, CBC, TAM, biochemical blood test (AST, ALT).
Basic diagnostic measures:
- General blood test (6 parameters)
- General urine analysis
- Blood glucose test
- Biochemical blood test (creatinine, ALT, AST, bilirubin, sodium, potassium)
- Ultrasound of the thyroid gland to determine the volume and early detection of nodules
- Determination of thyroid-stimulating hormone (TSH) in the blood
- Determination of free T4 and T3 in the blood
- Determination of AT to TPO, AT to TG, AT to r TSH
Additional diagnostic measures:
- Fine-needle aspiration biopsy (FNA) - cytological examination to exclude thyroid cancer (if indicated)
- ECG
- Thyroid scintigraphy (according to indications)
Diagnostic criteria
Complaints and anamnesis
Complaints to:
- nervousness,
- sweating,
- heartbeat,
- increased fatigue,
- increased appetite and, despite this, weight loss,
- general weakness,
- emotional lability,
- shortness of breath,
- sleep disturbance, sometimes insomnia,
- poor tolerance to elevated ambient temperatures,
- diarrhea,
- discomfort from the eyes - unpleasant sensations in the area of the eyeballs, trembling of the eyelids,
- menstrual cycle disorders.
History:
- presence of relatives suffering from thyroid diseases,
- frequent acute respiratory diseases,
- local infectious processes (chronic tonsillitis).
Physical examination:
- Increase in the size of the thyroid gland,
- cardiac dysfunction (tachycardia, loud heart sounds, sometimes systolic murmur at the apex, increased systolic and decreased diastolic blood pressure, attacks of atrial fibrillation),
- disorders of the central and sympathetic nervous system (tremor of the fingers, tongue, entire body, sweating, irritability, feelings of anxiety and fear, hyperreflexia),
- metabolic disorders (heat intolerance, weight loss, increased appetite, thirst, accelerated growth),
- disorders of the gastrointestinal tract (diarrhea, abdominal pain, increased peristalsis),
- eye symptoms (wide opening of the palpebral fissures, exophthalmos, frightened or wary gaze, blurred vision, double vision, lag of the upper eyelid when looking down and the lower eyelid when looking up),
- muscular system (muscle weakness, atrophy, myasthenia gravis, periodic paralysis).
Laboratory research
| Test | Indications |
| TSH | Reduced to less than 0.5 mIU/l |
| Free T4 | Promoted |
| Free T3 | Promoted |
| AT to TPO, AT to TG | Promoted |
| AT to TSH receptor | Promoted |
| ESR | Increased in subacute de Quervain's thyroiditis |
| Human chorionic gonadotropin | Increased in choriocarcinoma |
Instrumental studies:
- ECG - tachycardia, arrhythmia, fibrillation
- Ultrasound of the thyroid gland (increased volume, heterogeneity in AIT, nodular formations in MUTZ and TA). Thyroid cancer is characterized by hypoechoic formations with uneven contours of the node, growth of the node beyond the capsule and calcification
- Scintigraphy of the thyroid gland (uptake of radiopharmaceuticals is reduced in destructive thyroiditis (subacute, postpartum), and in diseases of the thyroid gland with hyperproduction of thyroid hormones - increased (GD, MUTZ). For TA and MUTZ, “hot nodes” are characteristic, for cancer - “cold nodes”.
- TAB - cancer cells in thyroid neoplasms, lymphocytic infiltration in AIT.
Indications for specialist consultations:
- ENT, dentist, gynecologist - for the treatment of infections of the nasopharynx, oral cavity and external genitalia;
- ophthalmologist - to assess the function of the optic nerve, assess the degree of exophthalmos, identify disturbances in the work of the extraocular muscles;
- neurologist - to assess the state of the central and sympathetic nervous system;
- cardiologist - in the presence of arrhythmia, development of heart failure;
- infectious disease specialist - in the presence of viral hepatitis, zoonotic, intrauterine and other infections;
- phthisiatrician - if tuberculosis is suspected;
- dermatologist - in the presence of pretibial myxedema.
Differential diagnosis
| Diagnosis | In favor of diagnosis |
| Graves' disease | Diffuse changes on the scintigram, increased levels of antibodies to peroxidase, the presence of endocrine ophthalmopathy and pretibial myxedema |
| Multinodular toxic goiter | Heterogeneity of the scintigraphic picture. |
| Autonomous hot nodes | “Hot” lesion on the scanogram |
| Subacute de Quervain's thyroiditis | The thyroid gland is not visualized on the scanogram, elevated levels of ESR and thyroglobulin, pain syndrome |
| Iatrogenic thyrotoxicosis, Amiodarone-induced thyrotoxicosis | History of taking interferon, lithium, or drugs containing large amounts of iodine (amiodarone) |
| Struma ovarii | increased radiotracer uptake in the pelvic area during whole body scanning |
| TSH-producing pituitary adenoma | Increased TSH level, lack of TSH response to stimulation with thyrotropin-releasing hormone |
| Choriocarcinoma | strong increase in human chorionic gonadotropin levels |
| Thyroid cancer metastases | In most cases there was a previous thyroidectomy |
| Subclinical thyrotoxicosis | Iodine uptake by the thyroid gland may be normal |
| Relapse of thyrotoxicosis | After treatment of diffuse toxic goiter |
In addition, differential diagnosis is carried out with conditions similar in clinical picture to thyrotoxicosis and cases of suppression of TSH levels without thyrotoxicosis:
- Anxiety states
- Pheochromocytoma
- Euthyroid pathology syndrome (suppression of TSH levels in severe somatic non-thyroid pathology). Does not lead to the development of thyrotoxicosis
Treatment abroad
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Treatment
Treatment goals:
Achieving persistent euthyroidism
Treatment tactics
Non-drug treatment:
- the regimen depends on the severity of the condition and the presence of complications. Avoid physical activity, because with thyrotoxicosis, muscle weakness and fatigue increase, thermoregulation is disrupted, and the load on the heart increases.
- until euthyroidism is established, it is necessary to limit the intake of iodine into the body with contrast agents, because iodine in most cases contributes to the development of thyrotoxicosis
- exclude caffeine, because caffeine may increase symptoms of thyrotoxicosis
Drug treatment:
Conservative thyreostatic therapy.
To suppress the production of thyroid hormones of the thyroid gland, thyreostatic drugs are used - tyrosol 20-45 mg/day or mercazolil 30-40 mg/day, propylthiouracil 300-400 mg/day.
Therapy with thyreostatics during pregnancy should be carried out for hyperthyroidism caused by GD. In the first trimester, it is recommended to prescribe propylthiouracil (no more than 150-200 mg), in the second and third - thiamazole (no more than 15-20 mg). The block-and-replace regimen is contraindicated in pregnant women.
Possible side effects of thyreostatic therapy: allergic reactions, liver pathology (1.3%), agranulocytosis (0.2 - 0.4%). Therefore, it is necessary to conduct a general blood test once every 14 days.
The duration of conservative treatment with thyreostatics is 12-18 months.
* TSH remains suppressed for a long time (up to 6 months) during the treatment of thyrotoxicosis. Therefore, determining the TSH level is not used to adjust the dose of thyreostatic. The first TSH control is carried out no earlier than 3 months after achieving euthyroidism.
The dose of the thyreostatic agent should be adjusted depending on the level of free T4. The first control of free T4 is prescribed 3-4 weeks after the start of treatment. The dose of the thyreostatic agent is reduced to a maintenance dose (7.5-10 mg) after reaching a normal level of free T4. Then free T4 is monitored once every 4-6 weeks using the “Block” regimen and once every 2-3 months using the “block and replace” regimen (levothyroxine 25-50 mcg) in adequate doses.
Before discontinuing thyreostatic therapy, it is advisable to determine the level antibodies to TSH receptor, as this helps in predicting the outcome of treatment: patients with low levels of AT-rTSH have a greater chance of stable remission.
Drug treatment also includes prescription beta blockers(anaprilin 40-120 mg/day, atenolol 100 mg/day, bisoprolol 2.5-10 mg/day). For subclinical and asymptomatic thyrotoxicosis, β-blockers should be prescribed to elderly patients, as well as most patients with a resting heart rate exceeding 90 beats per minute or with concomitant cardiovascular diseases.
When combined with endocrine ophthalmopathy, they resort to corticosteroid therapy. If there are symptoms of adrenal insufficiency, treatment with corticosteroids is also indicated: prednisolone 10-15 mg or hydrocortisone 50-75 mg intramuscularly.
Other treatments
Worldwide, most patients with HD, MUTZ, and TA receive therapyI 131
(radioactive iodine therapy). In HD, the appropriate activity of I 131 should be administered once (usually 10-15 mCi) in order to achieve hypothyroidism in the patient.
The choice of treatment method is determined by the patient’s age, the presence of concomitant pathology, the severity of thyrotoxicosis, the size of the goiter, and the presence of endocrine ophthalmopathy.
Surgical treatment(thyroidectomy).
Indications:
- Relapse of HD after ineffective conservative therapy for 12-18 months
- Large goiter (more than 40 ml)
- Presence of nodules (functional autonomy of the thyroid gland, TA)
- Intolerance to thyreostatics
- Lack of patient compliance
- Severe endocrine ophthalmopathy
- Presence of antibodies to rTSH after 12-18 months of conservative treatment
Before undergoing thyroidectomy, the patient must achieve a euthyroid state while receiving thiamazole therapy. Potassium iodide can be prescribed directly in the preoperative period. Extreme subtotal or total thyroidectomy is the surgical treatment of choice for Graves' disease.
If there is a need for thyroidectomy during pregnancy, the operation is optimally performed in the second trimester.
After thyroidectomy for Graves' disease, it is recommended to determine the level of calcium and intact parathyroid hormone, and, if necessary, prescribe additional calcium and vitamin D supplements.
Preventive measures
There is no primary prevention for thyrotoxicosis. Secondary prevention includes sanitation of foci of infection, prevention of increased insolation, stress, liberation from heavy physical labor, night shifts, and overtime work.
Further management:
- Dynamic monitoring of patients receiving thyreostatic therapy for early detection of side effects, such as rash, liver pathology, agranulocytosis. It is necessary to study the levels of free T4 and TSH every 4 weeks for early detection of hypothyroidism and initiation of replacement therapy. Within a year after achieving euthyroidism, laboratory assessment of thyroid function is performed once every 3-6 months, then every 6-12 months.
After therapy with radioactive iodine I 131, thyroid function progressively decreases. Monitor TSH levels every 3-6 months
After therapy with I 131 or surgical treatment, the patient should be monitored throughout his life in connection with the development of hypothyroidism.
In case of Graves' disease during pregnancy, it is necessary to use the lowest possible doses of thyroid hormones to maintain thyroid hormone levels slightly above the reference range, with suppressed TSH.
Free T4 levels should be slightly above the upper limit of reference values.
Thyroid function during pregnancy should be assessed monthly and the dose of thyreostatic agent adjusted as necessary.
Indicators of treatment effectiveness
Reduction or elimination of symptoms of thyrotoxicosis, allowing the patient to be transferred to outpatient treatment. Remission develops in 21-75% of cases. Favorable prognostic signs during treatment are a decrease in the size of the goiter, a decrease in the dose of thyreostatics required to maintain euthyroidism, and the disappearance or decrease in the content of antibodies to TSH receptors.
Hospitalization
Indications for hospitalization
Planned:
- Newly diagnosed thyrotoxicosis
- Decompensation of thyrotoxicosis
Emergency:
- Thyrotoxic crisis
Information
Sources and literature
- Minutes of meetings of the Expert Commission on Health Development of the Ministry of Health of the Republic of Kazakhstan, 2013
- 1. I.I. Dedov, G.A. Melnichenko, V.V. Fadeev. Endocrinology, "GEOTAR", Moscow 2008, p. 87-104 2. Clinical recommendations of the Russian Association of Endocrinologists. "GEOTAR", Moscow, 2009, pp. 36-51 3. Clinical recommendations of the American Thyroid Association and the American Association of Clinical Endocrinologists for the treatment of thyrotoxicosis. Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN. Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. // Thyroid – 2011 - Vol. 21.
Information
III. ORGANIZATIONAL ASPECTS OF PROTOCOL IMPLEMENTATION
List of protocol developers
Professor of the Department of Endocrinology of KazNMU named after. S.D. Asfendiyarova, Doctor of Medical Sciences Nurbekova Akmaral Asylovna.
Reviewers: Associate Professor, Department of Endocrinology, KazNMU, Ph.D. Zhaparkhanova Z.S.
Disclosure of no conflict of interest: absent.
Indication of the conditions for reviewing the protocol: after 3 years from the date of publication
Attached files
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RUSSIAN ASSOCIATION OF ENDOCRINOLOGISTS
FSBI "ENDOCRINOLOGICAL RESEARCH CENTER" OF THE RUSSIAN MINISTRY OF HEALTH
THYROTOXICOSIS WITH DIFFUSE GOITTER (diffuse toxic goiter, Graves-Bazedov's disease), NODUAL/MULTINODULAR GOITTER
Troshina E.A., Sviridenko N.Yu., Vanushko V.E., Rumyantsev P.O., Fadeev V.V., Petunina N.A.
Reviewers: Melnichenko G.A. Grineva E.N.
Moscow 2014
Approved at the II All-Russian Congress with the participation of CIS countries “Innovative technologies in endocrinology” (May 25-28, 2014)
LIST OF ABBREVIATIONS
Autoimmune thyroiditis |
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Computed tomography |
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Diffuse toxic goiter |
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Multislice computed tomography |
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Radioiodine therapy |
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Thyroid-stimulating hormone receptor |
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Radiopharmaceutical |
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Free triiodothyronine |
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Free thyroxine |
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Thyroglobulin |
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Thyroid peroxidase |
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Thyroid-stimulating hormone of the pituitary gland |
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Ultrasound examination |
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Thyroid gland |
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Endocrine ophthalmopathy |
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Endocrine ophthalmopathy clinical activity scale) 
Certificate of registration of mass media EL No. FS 77 - 57771 dated 04/18/2014.
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