Hyperthyroidism is a condition of hyperfunction of the thyroid gland, which is accompanied by excessive production of thyroxine and triiodothyronine. An increase in the level of hormones in the blood accelerates metabolic processes in the body and has a negative effect on almost all organ systems. Symptoms of hyperthyroidism reduce the patient's quality of life. Hyperthyroidism is a condition of hyperfunction of the thyroid gland, which is accompanied by excessive production of thyroxine and triiodothyronine. An increase in the level of hormones in the blood accelerates metabolic processes in the body and has a negative effect on almost all organ systems. Symptoms of hyperthyroidism reduce the patient's quality of life.
Adequate and timely treatment allows you to prevent complications and slow down pathological processes, up to the complete restoration of thyroid function.
Types of hyperthyroidism
There are three forms of the disease:
- Subclinical. There are no obvious symptoms, T4 levels are normal, triiodothyronine levels are low;
- Manifest. Characteristic signs of hyperthyroidism appear. T4 level is normal, triiodothyronine level is low;
- Complicated. Symptoms include heart failure, arrhythmia, psychosis and other severe conditions.
According to the level of occurrence of hyperthyroidism, there are:
- primary – pathology of the thyroid gland;
- secondary – the pituitary gland is affected;
- tertiary – processes develop in the hypothalamus.
Causes of hyperthyroidism
A number of endocrine diseases lead to thyroid dysfunction, such as:
- Graves' disease (Bazedow, Bazedow-Graves) . The syndrome is autoimmune in nature. The body produces antibodies that stimulate the thyroid gland to produce excess amounts of the hormone T4;
- Nodular goiter, toxic adenoma . The listed pathologies are accompanied by the formation of benign nodes in the tissues of the gland. The formations begin to produce hormones and cause hyperthyroidism. Doctors cannot yet say for sure why some adenomas synthesize T4 and others do not;
- Thyroiditis . The inflammatory process destroys thyroid cells. Hormones enter the bloodstream and cause hyperthyroidism. The autoimmune nature of thyroiditis is possible. The body produces antibodies against TSH receptors. The cells cause active growth and inflammation of the thyroid gland.
People with a hereditary predisposition to endocrine pathologies are most susceptible to the disease. Symptoms of hyperthyroidism are more common in women than in men. The development of the disease is also influenced by the environmental situation, chronic iodine deficiency, and stress.
What is Graves' disease?
Graves' disease is the main cause of thyrotoxicosis. According to the Graves' Disease and Thyroid Foundation, about 2-3 percent of the population - about 10 million people - have the disease.
The Virginia Mason Institute states that 70-80 percent of patients with thyrotoxicosis have Graves' disease. This is an autoimmune disease where the immune system attacks the thyroid gland. In response, the thyroid gland produces too much thyroid hormone.
The pituitary gland releases a hormone that helps control thyroid function. Thyrotropin receptor antibodies (Trab) are associated with Graves' disease, and they work as a pituitary hormone regulator. As a result, Trab overrides the normal regulation of the thyroid gland and causes thyrotoxicosis.
Anyone can develop Graves' disease, but there are a number of factors that increase the risk, including:
Women are more likely than men to develop Graves' disease.
- Family history of Graves' disease or other thyroid or autoimmune diseases
- Other autoimmune disorders: People with other immune disorders such as type 1 diabetes or rheumatoid arthritis are at increased risk
- Emotional or physical stress: Stressful life events or illnesses can trigger the onset of Graves' disease
- Pregnancy: Pregnancy or recent childbirth may increase the risk of the disease in some women
- Cigarette smoking may affect the immune system and increase the risk of Graves' disease
Women are also more likely to develop the disorder than men. According to the Office of Women's Health, it affects 10 times more women than men, and often strikes while they are in their 20s and 30s.
Symptoms of hyperthyroidism
The first signs of dysfunction are uncharacteristic, so the disease is often confused with other somatic conditions. Symptoms of hyperthyroidism of the thyroid gland increase as metabolic processes in the body are disrupted.
Main signs of the disease:
- loss of body weight while maintaining appetite, volume and quality of food;
- arrhythmia, tachycardia;
- anxiety, depression;
- increased sweating;
- fine tremor of fingers and hands;
- indigestion;
- the formation of a visible goiter, changing the contours of the neck;
- increased fatigue.
A symptom of hyperthyroidism in men is a decrease in potency and libido. In women, increased levels of thyroid hormones cause menstrual irregularities. Pregnancy may end in spontaneous abortion. A symptom of thyroid hyperthyroidism in women can also be decreased fertility, including infertility. During menopause, the pathology in the initial stages is asymptomatic.
Complications of hyperthyroidism
As the disease progresses, the symptoms of thyroid hyperthyroidism intensify, and complications may arise:
- Disturbances in the functioning of the heart . Atrial fibrillation is added to the general symptoms of hyperthyroidism. The patient does not tolerate physical activity well, and there is a disturbance in heart rhythm. Congestive heart failure may develop. The consequences are reversible. After eliminating hyperthyroidism, the signs of arrhythmia are completely cured.
- Increased bone fragility . In its advanced form, hyperthyroidism causes disturbances in the structure of bone tissue. Osteoporosis develops. The reason bones become brittle is that excess hormones prevent calcium from being incorporated into the bone.
- Eye diseases . Graves' ophthalmopathy adds to the symptoms of hyperthyroidism. The cause of the pathology is the growth and swelling of the tissues located behind the eyeballs. The patient feels pain in the eyes, sensitivity to light, and complains of double vision. Visual acuity gradually decreases. In advanced cases, blindness develops.
- Skin problems . Ocular symptoms in hyperthyroidism often develop in parallel with Graves' dermopathy. The skin becomes swollen and red, especially around the feet and legs.
- Thyrotoxic crisis . An increase in the level of thyroid hormones in the blood can cause a sudden fever and an increase in all the main symptoms. Thyrotoxic crisis is accompanied by tachycardia. In some cases, delirium (mental disorder) occurs. The patient requires emergency medical care.
Diagnosis of hyperthyroidism
Consultation with an endocrinologist
Diagnosis of hyperthyroidism begins with an appointment with an endocrinologist. At the appointment, the doctor asks the patient questions that will help in diagnosis: how long ago did the clinical symptoms appear, what is the dynamics of the disease, are there any other patients with goiter or thyroiditis in the family. A physical examination is required: palpation of the thyroid gland. In case of obvious hyperthyroidism, the doctor will try to palpate the contours of the organ, determine its position, uniformity of structure, and pain. After the examination, the patient receives directions for further examinations to accurately diagnose the cause of the disease.
Laboratory research
Hyperthyroidism is confirmed by blood tests to measure the level of thyroid hormones. Elevated levels of thyroxine in the absence or minimal amount of TSH indicate hyperfunction of the gland. A blood test is especially important in the early diagnosis of the disease in older people. For example, menopausal women may not have symptoms of hyperthyroidism. Pathology is detected only by the results of laboratory tests.
A blood test helps confirm the condition of the endocrine organ, but additional tests will be required to determine the cause of hyperthyroidism.
Instrumental research methods
Ultrasonography. Ultrasound of the thyroid gland allows you to determine the shape and size of the lobes, assess the degree of its enlargement, and detect nodes, cysts, and other neoplasms.
Radioisotope scintigraphy . The patient is given a special solution intravenously. The drug contains radioactive isotopes of iodine, which are actively captured by the thyroid gland. After some time, the doctor assesses the degree of saturation of the tissues and makes a conclusion about their functionality. A large amount of radioiodine indicates excessive production of thyroxine, which develops, in particular, with Graves' disease.
If, with severe symptoms of thyroid hyperthyroidism in a woman or man, a minimal amount of isotopes is observed in the gland, then the probable cause of the pathology is thyroiditis. The radioactive iodine uptake test helps in differential diagnosis.
Fine needle biopsy . Under the control of an ultrasound probe, the doctor takes samples of thyroid tissue for examination. Biopsy materials make it possible to determine the nature of the neoplasm: benign or malignant. The study results also provide information about autoimmune processes that may cause hyperthyroidism.
Treatment of Basedow's disease
Today, there are three methods of treating diffuse toxic goiter of the thyroid gland: therapy with thyreostatics, radioactive iodine-131 and surgical treatment. They have been used for almost 100 years, and during this time no other effective methods of treating those suffering from Graves' disease have been invented.
1. If Graves' disease was detected for the first time, as well as to achieve a euthyroid state before surgery and radiotherapy, thyreostatic drugs are prescribed. The most commonly used drugs today are thionamides that block the synthesis and release of thyroid hormones—thiamazole and propylthiouracil. Thyreostatics are fairly safe drugs; clinically significant side effects are rarely observed when using them, but we must remember that against their background the development of agranulocytosis is possible.
Indications for the use of thyreostatics are limited. It makes sense to prescribe them for moderately expressed clinical manifestations of newly diagnosed thyrotoxicosis and in the absence of complications [5]. In addition, the course of treatment is one and a half years and not every patient can afford it. During therapy, drug-induced hypothyroidism develops and, as a result, the thyroid gland compensatory enlarges. This makes it necessary to prescribe levothyroxine replacement therapy upon achieving euthyroidism. Along with thyreostatics, beta blockers are often prescribed to relieve manifestations of the cardiovascular system.
It is clear that thyreostatic drugs do not have any effect on the activity of the immune system, in other words, they do not act on the cause of the disease, but only reduce the negative impact of excess thyroid hormones on the body, that is, thyrotoxicosis. After a year and a half course of treatment, approximately half of the patients recover [1, 4]. In addition, there are cases of spontaneous recovery of DTG with virtually no therapy (according to various sources, 2–5% [5]). Thus, the disease either goes away or requires radical treatment.
With DTG, the rate of corticosteroid metabolism always increases: their breakdown and excretion increases, resulting in the development of relative adrenal insufficiency, which intensifies during a crisis.
Sometimes at the very beginning of drug therapy it is possible to make an assumption about its prospects and effectiveness. Experience shows that there is little chance of cure for:
- patients with large goiter;
- men;
- patients with initially high levels of T3 and T4;
- patients with high titers of antibodies to the TSH receptor [6].
2. Surgical treatment of Graves' disease consists of extreme subtotal resection of the thyroid gland or even thyroidectomy. The goal of the operation is to achieve irreversible hypothyroidism, and therefore lifelong replacement therapy with levothyroxine is prescribed.
3. During radioactive iodine therapy, iodine-131 is prescribed with a therapeutic activity of about 10–15 mCi. Indications for treatment with radioiodine do not differ from indications for surgical treatment.
I once had the opportunity to see a patient in whom, as a result of inadequate therapy for moderate clinical thyrotoxicosis, ophthalmopathy led to loss of vision in both eyes and necrotic changes in the cornea. Ophthalmologists sewed up his eyelids, and they did not succeed on the first try - the stitches cut through, the exophthalmos was so pronounced.
The only contraindications to it are pregnancy and lactation. For women of reproductive age, radioactive iodine therapy is given only after a pregnancy test, and contraception is recommended for one year after treatment.
The half-life of radioactive iodine-131 is only 8 days, irradiation is carried out locally. Therefore, due to its non-invasiveness and safety, this method is even preferable to surgical intervention, and in developed countries it has long been the method of choice.
In our country, surgical treatment is still more popular. The use of radioactive iodine is an expensive method, and there is a long waiting list for it, because there is only one radiological center in Russia - in the city of Obninsk, Kaluga region. Domestic radioactive safety standards differ from Western ones and do not allow radioiodine treatment to be performed on an outpatient basis. In addition, patients are often afraid of the word “radioactive” and categorically refuse this method of treatment.
Treatment tactics for patients with Graves' disease in different countries and medical schools can vary significantly. For example, in the USA, in 60% of cases of newly diagnosed DTG, patients are recommended to be treated with radioactive iodine [2].
The patient takes thyreostatics for one and a half years, after which the levels of TSH and thyroid hormones are assessed at certain intervals [5]. If these indicators indicate persistent thyrotoxicosis, the question of radical treatment is raised, which in Europe will most likely be radioactive iodine, and in our country - surgery.
Treatment of hyperthyroidism
The approach to therapy depends on the cause of hyperthyroidism, the age and condition of the patient.
Conservative treatment methods:
- Radioactive iodine preparations . Isotopes accumulate in the tissues of the thyroid gland, suppressing compensatory mechanisms. The organ decreases in size, the symptoms of hyperthyroidism gradually weaken. Treatment takes several months. It is important that radioactive iodine suppresses gland function, so over time the patient may develop hypothyroidism, which is corrected by hormone replacement therapy.
- Antithyroid drugs . Medicines suppress the production of thyroid hormones. Symptoms decrease within a few weeks after taking the drugs in the correct dosage. The course of treatment is up to 1 year or longer. In some cases, hyperthyroidism is cured completely, but sometimes relapses occur. It is important that antithyroid drugs can cause allergies, individual intolerance, and can reduce immunity. The effects of this group of drugs cause disturbances in liver function. You can take medications only under the supervision of a doctor.
- Symptomatic treatment . Depending on the severity of the manifestations of hyperthyroidism, the doctor may prescribe medications to lower blood pressure, maintain heart rhythm, etc. Symptomatic treatment is continued until the patient’s general well-being improves.
In cases of severe hyperthyroidism, accompanied by significant enlargement of the thyroid gland, multiple neoplasms in functional tissue, as well as medullary cancer, surgical intervention is indicated. The doctor partially or completely removes the endocrine organ. After the operation, the patient is given a dosage of hormones that are taken for life.
Thyrotoxic crisis (thyroid crisis)
The importance of early treatment of thyrotoxic crisis , the diagnosis of which is based on clinical impression, cannot be overestimated. Before starting treatment, blood should be drawn to test thyroid function and determine cortisol levels, as well as a complete clinical blood count and routine biochemical tests. Cultures are indicated to detect infection. It is advisable to draw up a clear treatment plan to avoid unnecessary delay in specific therapy. The goals of specific treatment are: maintaining the basic functions of the body at the physiological level; inhibition of thyroid hormone synthesis; slowing the release of thyroid hormones; blockade of the effects of thyroid hormones in the periphery; identification and correction of provoking factors. You should strive to achieve all of these goals simultaneously.
Maintaining Basic Body Functions Adequate hydration with intravenous fluids and electrolytes is indicated to replace so-called insensible losses, as well as losses through the gastrointestinal tract. Additional oxygen administration is necessary due to increased oxygen consumption. During a crisis, hyperglycemia and hypercalcemia may occur; they are usually corrected with fluids, but in some cases specific therapy is required to reduce unacceptably high calcium and glucose levels. Fever is controlled with antipyretics and a cooling blanket. Acetylsalicylic acid should be used with caution or not at all, since salicylates increase free T) and T4 levels due to decreased protein binding. This consideration is rather theoretical, since no adverse effects have been noted with the use of acetylsalicylic acid. During thyrotoxic crisis, sedatives should be used with caution. Sedation depresses consciousness, which reduces the value of this parameter as an indicator of clinical improvement in the patient’s condition. In addition, it can cause hypoventilation.
Congestive heart failure is treated with digitalis and diuretics, although failure due to hyperthyroidism may be refractory to digitalis. Cardiac arrhythmias are treated with conventional antiarrhythmic drugs. Atropine should be avoided as its parasympatholytic effect may increase heart rate. In addition, atropine may counteract the effects of propranolol.
Intravenous glucocorticoids are prescribed in a dose equivalent to 300 mg hydrocortisone per day. The role of the adrenal glands in the pathogenesis of thyrotoxic crisis is unclear, but the use of hydrocortisone has been shown to improve survival. Dexamethasone has some advantages over other glucocorticoids, as it reduces the conversion of T4 to T3 in the periphery.
Inhibition of thyroid hormone synthesis Antithyroid drugs propylthiouracil (PTU) and methylmazole block the synthesis of thyroid hormones by inhibiting the organification of tyrosine residues. This action begins within an hour after administration, but the full therapeutic effect is not achieved even after several weeks. Initially, a loading dose of PTC is prescribed (900-1200 mg, and then 300-600 mg per day for 3-6 weeks or until a therapeutic effect is obtained (control of thyrotoxicosis). An acceptable alternative is the administration of methylmazole at an initial dose of 90-120 mg followed by 30-60 mg per day. Both drugs are administered orally or through a nasogastric tube, since their parenteral forms are not available. PTU has an advantage over methyl mazole: it inhibits the peripheral conversion of T4 to T3 and produces a therapeutic effect more quickly. Although these drugs inhibit synthesis again formed thyroid hormones, they do not affect the release of already accumulated hormones.
Slowing down the release of thyroid hormones The introduction of iodine preparations immediately slows down the release of thyroid hormones from the sites of their accumulation. Iodides can be given as strong iodine solutions (30 drops orally every day) or as sodium iodide (1 g every 8 to 12 hours as a slow intravenous infusion). Iodide should be administered an hour after a loading dose of an antithyroid drug to prevent the thyroid gland from using iodine during the synthesis of new hormone.
Blockade of the peripheral effects of thyroid hormones Adrenergic blockade is the mainstay of treatment for thyrotoxic crisis. In an extensive series of observations, Waldstein et al. (1960) noted an increase in patient survival when using reserpine. Guanethidine was subsequently demonstrated to be effective in alleviating the symptoms and signs of thyrotoxicosis due to sympathetic hyperactivity. Currently, the beta-blocker propranolol is the drug of choice. In addition to reducing sympathetic hyperactivity, propranolol partially blocks the conversion of T4 to T3 in the periphery.
Propranolol can be administered intravenously at a rate of 1 mg/minute, with careful increases in the dose of 1 mg every 10 to 15 minutes until a total dose of 10 mg is reached. The positive effects of the drug (control of cardiac and psychomotor manifestations of thyrotoxic crisis) are observed within 10 minutes. The lowest dose sufficient to control thyrotoxic symptoms should be used; if necessary, this dose can be repeated every 3-4 hours. The oral dose of propranolol is 20-120 mg every 4-6 hours. When administered orally, propranolol is effective for approximately 1 hour. Propranolol has been successfully used in the treatment of thyrotoxic crisis in children. Young children may require high doses of the drug (240-320 mg/day orally).
Usual precautions should be taken when prescribing propranolol to patients with bronchospastic syndrome and heart block. If it is used, a preliminary ECG study is carried out to assess conduction disorders. In patients with congestive heart failure, the beneficial effects of the drug (reduction in heart rate and some arrhythmias) should be compared with the risk of its use (inhibition of myocardial contractile function with beta-adrenergic blockade). Urbanic believes that the benefits of propranolol treatment outweigh the risks in this situation, but the author recommends pre-administration of digitalis.
When treating thyrotoxicosis or thyrotoxic crisis, propranolol should not be relied upon alone. Two cases of thyrotoxicosis occurring in patients who received seemingly adequate propranolol therapy for thyrotoxicosis are described. It is known that with a single or repeated oral dose of propranolol, its plasma level is very variable in controls and in patients with thyrotoxicosis. Treatment of thyrotoxic crisis should be quite flexible and individualized.
One of the authors recommends a gradual reduction in the dose of propranolol as the thyrotoxic crisis resolves. He believes that an objective assessment of the patient's condition may be difficult because propranolol masks the symptoms of hypermetabolism. In patients who have already received beta blockers, the symptoms of thyroid crisis may be masked, which carries the risk of late diagnosis of thyrotoxic crisis.
Alternative drugs to propranolol are guanethidine and reserpine, which also provide effective autonomic blockade. Guanethidine reduces catecholamine stores and blocks their release. When administered orally at 1-2 mg/kg per day (50-150 mg), it is effective within 24 hours, but its maximum effect may take several days. Toxic reactions are cumulative and include postural hypotension, myocardial decompensation and diarrhea. The advantage of guanethidine over reserpine is the absence of the pronounced sedative effect characteristic of reserpine.
The action of reserpine is aimed at reducing catecholamine reserves. After the initial dose (1-5 mg intramuscularly), the drug is administered every 4-6 hours at 1-2.5 mg. Improvement in the patient's condition can be observed after 4-8 hours. Side effects of reserpine include drowsiness, mental depression (this can be severe), cramping abdominal pain and diarrhea.
Identification and elimination of provoking factors A thorough assessment of the provoking factors of thyrotoxic crisis is carried out. Treatment of thyrotoxic crisis should not be delayed until these factors are identified; appropriate examination can be carried out as the patient’s condition stabilizes. The provoking factor is identified in 50-75% of cases.
Recovery After starting treatment, symptomatic improvement is observed within a few hours, primarily due to adrenergic blockade. Elimination of a thyrotoxic crisis requires the destruction of circulating thyroid hormones, the biological half-life of which is 6 days for T4 and 22 hours for T3. Thyrotoxic crisis can last from 1 to 8 days (average duration - 3 days). If standard methods of crisis control are unsuccessful, alternative therapeutic options may be considered, including peritoneal dialysis, plasmapheresis, and charcoal hemoperfusion to remove circulating thyroid hormones. After recovery from the thyrotoxic crisis, radioactive iodine therapy is the treatment of choice for hyperthyroidism.
Mortality If thyrotoxic crisis is untreated, the mortality rate approaches 100%. There is a reduction in mortality with the use of antithyroid drugs. The lowest mortality rate for thyrotoxic crisis over a 10-year period is reported to be 7%; its usual figure is 10-20%. In many cases, the cause of death is a preexisting disease. The main means of reducing mortality, of course, is to prevent the development of thyrotoxic crisis. Early recognition and timely treatment of this complication of hylerthyroidism gives the patient a better chance of survival.
Prevention of hyperthyroidism
People with a family history, women during menopause and older men need to be examined annually by an endocrinologist and take a blood test to check the level of thyroid hormones.
It is recommended to balance the diet according to the BZHU and introduce foods rich in vitamins A, B, C and minerals into the diet. Diet and hydrotherapy help not only in the prevention of hyperthyroidism, but also in the rehabilitation of patients after treatment. Regular visits to specialized sanatoriums help maintain and improve the health of the endocrine system.
Forecast
The prognosis is favorable in most cases. In the case of long-term drug treatment, and sometimes in its absence (this is also possible), patients develop extrathyroidal complications, most often from the cardiovascular system. But thyrotoxicosis sooner or later gives way to hypothyroidism: the thyroid gland, which has been functioning intensively for a long time, is eventually depleted, and the amount of hormones it produces drops below normal.
Thus, patients, both those who received radical treatment and those who did not receive it at all, come to the same result - hypothyroidism. True, the quality of life of the latter in all the years of the existence of DTZ is low, and the former, subject to continued lifelong use of levothyroxine, live a full life.
There is a certain difference in domestic and Western terminology.
In Western literature, the concept of “hyperthyroidism” is used along with the term “thyrotoxicosis” and in a synonymous meaning. Russian endocrinologists call hyperthyroidism any increase in the functional activity of the thyroid gland, which can be not only pathological, but also physiological, for example, during pregnancy. This fact should be taken into account when reading English-language literature. 1. Fadeev V.V. Thyroidologist's Handbook, 2002 2. 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. 3. Muller AF, Berghout A., Wiersinga WM, Kooy A., Smit JWA, Hermus A., working group Thyroid Function Disorders of the Netherlands Association of Internal Medicine. Thyroid function disorders — Guidelines of the Netherlands Association of Internal Medicine// Neth. J. Med. 2008. V. 66. P. 134–142. Translation and comments by V.V. Fadeeva “Clinical and experimental thyroidology” 2008, volume 4, No. 2, (https://medi.ru) 4. Balabolkin M.I. Endocrinology, 1998 https://med-lib.ru 5. Petunina N.A. Conservative treatment of diffuse toxic goiter: opportunities, problems, solutions (2009) medi.ru 6. Olovyanishnikova I.V. The effectiveness of various drug therapy regimens for diffuse toxic goiter. Prognostic aspects (2005) https://www.dissercat.com
