Graves’ disease (diffuse toxic goiter) is a disease caused by hypertrophy and hyperfunction of the thyroid gland, accompanied by the development of thyrotoxicosis. Clinically manifested by increased excitability, irritability, weight loss, palpitations, sweating, shortness of breath, subfebrile temperature. A characteristic symptom is bug–eyed. It leads to changes in the cardiovascular and nervous systems, the development of cardiac or adrenal insufficiency. A thyrotoxic crisis poses a threat to the patient’s life.
Meaning
Graves’ disease is autoimmune in nature and develops due to a defect in the immune system, in which antibodies to TSH receptors are produced, which have a constant stimulating effect on the thyroid gland. This leads to a uniform proliferation of thyroid tissue, hyperfunction and an increase in the level of thyroid hormones produced by the gland: T3 (triiodothyronine) and T4 (thyroxine). An enlarged thyroid gland is called a goiter.
An excess of thyroid hormones enhances the reactions of the basal metabolism, depletes the energy reserves in the body necessary for the normal functioning of cells and tissues of various organs. The most susceptible to thyrotoxicosis are the cardiovascular and central nervous systems.
Graves’ disease develops mainly in women from 20 to 50 years old. In old age and childhood, it occurs quite rarely. So far, endocrinology cannot accurately answer the question of the causes and mechanisms of triggering autoimmune reactions underlying Graves’ disease. The disease is often detected in patients with a hereditary predisposition, which is realized under the influence of many factors of the external and internal environment. The appearance of Graves’ disease is promoted by infectious and inflammatory diseases, mental trauma, organic brain damage (traumatic brain injury, encephalitis), autoimmune and endocrine disorders (functions of the pancreas, pituitary gland, adrenal glands, sex glands) and many others. The risk of goiter development increases almost 2 times if the patient smokes.
Classification
Graves’ disease is manifested by the following forms of thyrotoxicosis, regardless of the size of the thyroid gland:
- mild form – with a predominance of neurotic complaints, without cardiac arrhythmia, tachycardia with a heart rate of no more than 100 beats. in particular, the absence of pathological disorders of the function of other endocrine glands;
- moderate severity – there is a loss of body weight in the range of 8-10 kg per month, tachycardia with a heart rate of more than 100-110 beats. in min.;
- severe form – weight loss at the level of exhaustion, there are signs of functional disorders from the heart, kidneys, liver. It is usually observed with a Graves’ disease that has not been treated for a long time.
Graves’ disease symptoms
Since thyroid hormones are responsible for performing many physiological functions, thyrotoxicosis has a variety of clinical manifestations. Usually, the main complaints of patients are associated with cardiovascular changes, manifestations of catabolic syndrome and endocrine ophthalmopathy. Cardiovascular disorders are manifested by pronounced palpitations (tachycardia). Palpitations in patients occur in the chest, head, abdomen, and hands. Heart rate at rest with thyrotoxicosis can increase to 120-130 beats. in min. With moderate and severe forms of thyrotoxicosis, there is an increase in systolic and a decrease in diastolic blood pressure, an increase in pulse pressure.
In the case of a prolonged course of thyrotoxicosis, especially in elderly patients, severe myocardiodystrophy develops. It is manifested by heart rhythm disturbances (arrhythmia): extrasystole, atrial fibrillation. Subsequently, this leads to changes in the ventricular myocardium, congestion (peripheral edema, ascites), cardiosclerosis. There is an arrhythmia of breathing (increased frequency), a tendency to frequent pneumonia.
The manifestation of the catabolic syndrome is characterized by a sharp weight loss (10-15 kg) against the background of increased appetite, general weakness, hyperhidrosis. Violation of thermoregulation is manifested in the fact that patients with thyrotoxicosis experience a feeling of heat, do not freeze at a sufficiently low ambient temperature. Some elderly patients may experience evening subfebrility.
Thyrotoxicosis is characterized by the development of changes on the part of the eyes (endocrine ophthalmopathy): the expansion of the eye slits due to the lifting of the upper eyelid and the lowering of the lower one, incomplete closing of the eyelids (rare blinking), exophthalmos (bug-eyed), eye shine. In a patient with thyrotoxicosis, the face acquires an expression of fright, surprise, anger. Due to incomplete closing of the eyelids, patients have complaints of “sand in the eyes”, dryness and chronic conjunctivitis. The development of periorbital edema and the proliferation of periorbital tissues squeeze the eyeball and the optic nerve, cause a defect in the field of vision, increased intraocular pressure, pain in the eyes, and sometimes complete loss of vision.
On the part of the nervous system with thyrotoxicosis, mental instability is observed: mild excitability, increased irritability and aggressiveness, restlessness and fussiness, mood variability, difficulty concentrating, tearfulness. Sleep is disturbed, depression develops, and in severe cases – persistent changes in the psyche and personality of the patient. Often, with thyrotoxicosis, a small tremor (trembling) of the fingers of outstretched hands appears. With a severe course of thyrotoxicosis, tremor can be felt throughout the body and make it difficult to speak, write, perform movements. It is characterized by proximal myopathy (muscle weakness), a decrease in the musculature of the upper and lower extremities, it is difficult for the patient to get up from a chair, from squatting. In some cases, increased tendon reflexes are noted.
With prolonged thyrotoxicosis, under the influence of an excess of thyroxine, calcium and phosphorus are washed out of bone tissue, bone resorption (the process of destruction of bone tissue) is observed and osteopenia syndrome develops (a decrease in bone mass and bone density). There are pains in the bones, fingers can take the form of “drumsticks”.
From the gastrointestinal tract, patients are concerned about abdominal pain, diarrhea, unstable stools, rarely nausea and vomiting. With a severe form of the disease, thyrotoxic hepatosis gradually develops – fatty liver dystrophy and cirrhosis. Severe thyrotoxicosis in some patients is accompanied by the development of thyrogenic (relative) adrenal insufficiency, manifested by hyperpigmentation of the skin and open areas of the body, hypotension.
Ovarian dysfunction and menstrual cycle disorders with thyrotoxicosis are rare. Premenopausal women may experience a decrease in the frequency and intensity of menstruation, the development of fibrocystic mastopathy. Moderate thyrotoxicosis may not reduce the ability to conceive and the possibility of pregnancy. Antibodies to TSH receptors that stimulate the thyroid gland can be transmitted transplacentally from a pregnant woman with Graves’ disease to the fetus. As a result, a newborn may develop transient neonatal thyrotoxicosis. Thyrotoxicosis in men is often accompanied by erectile dysfunction, gynecomastia.
With thyrotoxicosis, the skin is soft, moist and warm to the touch, some patients have vitiligo, darkening of skin folds, especially on the elbows, neck, lower back, nail damage (thyroid acropachia, onycholysis), hair loss. 3-5% of patients with thyrotoxicosis develop pretibial myxedema (swelling, thickening and erythema of the skin in the lower leg and feet, resembling orange peel and accompanied by itching).
With Graves’ disease, there is a uniform increase in the thyroid gland. Sometimes the gland is significantly enlarged, and sometimes the goiter may be absent (in 25-30% of cases of the disease). The severity of the disease is not determined by the size of the goiter, since with a small size of the thyroid gland, a severe form of thyrotoxicosis is possible.
Complications
Thyrotoxicosis is dangerous with its complications: serious lesions of the central nervous system, the cardiovascular system (the development of a thyrotoxic heart), the gastrointestinal tract (the development of thyrotoxic hepatosis). Sometimes thyrotoxic hypokalemic transient paralysis may develop with sudden, intermittent attacks of muscle weakness.
The course of thyrotoxicosis of goiter may be complicated by the development of a thyrotoxic crisis. The main causes of thyrotoxic crisis are improper therapy with thyrostatics, treatment with radioactive iodine or surgical intervention, cancellation of treatment, as well as infectious and other diseases. Thyrotoxic crisis combines the symptoms of severe thyrotoxicosis and thyrogenic adrenal insufficiency. Patients with a crisis have pronounced nervous excitability up to psychosis; strong motor anxiety, which is replaced by apathy and disorientation; fever (up to 400C); pain in the heart, sinus tachycardia with a heart rate of more than 120 beats. in min.; respiratory failure; nausea and vomiting. Atrial fibrillation, an increase in pulse pressure, an increase in symptoms of heart failure may develop. Relative adrenal insufficiency is manifested by hyperpigmentation of the skin.
With the development of toxic hepatosis, the skin becomes jaundiced. The lethal outcome in thyrotoxic crisis is 30-50%.
Diagnostics
The objective status of the patient (appearance, body weight, condition of the skin, hair, nails, manner of conversation, measurement of pulse and blood pressure) allows the doctor to assume the existing hyperfunction of the thyroid gland. In the presence of obvious symptoms of endocrine ophthalmopathy, the diagnosis of thyrotoxicosis is almost obvious.
If thyrotoxicosis is suspected, it is necessary to determine the level of thyroid hormones of the thyroid gland (T3, T4), thyroid-stimulating hormone of the pituitary gland (TSH), free fractions of hormones in the blood serum. Graves’ disease should be distinguished from other diseases accompanied by thyrotoxicosis. Using enzyme immunoassay (ELISA) of blood, the presence of circulating antibodies to TSH receptors, thyroglobulin (AT-TG) and thyroid peroxidase (AT-TPO) is determined. The method of ultrasound of the thyroid gland determines its diffuse increase and change in echogenicity (hypoechogenicity, characteristic of autoimmune pathology).
To detect functionally active gland tissue, to determine the shape and volume of the gland, the presence of nodular formations in it allows scintigraphy of the thyroid gland. In the presence of symptoms of thyrotoxicosis and endocrine ophthalmopathy, scintigraphy is not required, it is performed only in cases where it is necessary to differentiate Graves’ disease from other thyroid pathologies. With Graves’ disease, an image of the thyroid gland with increased isotope absorption is obtained. Reflexometry is an indirect method of determining the function of the thyroid gland, measuring the time of the Achilles tendon reflex (it characterizes the peripheral action of thyroid hormones – with thyrotoxicosis it is shortened).
Graves’ disease treatment
Conservative treatment of thyrotoxicosis consists in taking antithyroid drugs – thiamazole (mercazolil, metisol, tyrosol) and propylthiouracil (propicil). They can accumulate in the thyroid gland and suppress the production of thyroid hormones. Reducing the dose of drugs is carried out strictly individually, depending on the disappearance of signs of thyrotoxicosis: normalization of the pulse (up to 70-80 beats. in min.) and pulse pressure, increased body weight, absence of tremor and sweating.
Surgical treatment involves almost total removal of the thyroid gland (thyroidectomy), which leads to a state of postoperative hypothyroidism, which is compensated by medication and eliminates recurrence of thyrotoxicosis. Indications for surgery are allergic reactions to prescribed drugs, a persistent decrease in the level of white blood cells during conservative treatment, a large goiter (above grade III), cardiovascular disorders, the presence of a pronounced goiter effect from mercazolil. Surgery for thyrotoxicosis is possible only after medical compensation of the patient’s condition to prevent the development of a thyrotoxic crisis in the early postoperative period.
Radioactive iodine therapy is one of the main methods of treatment of Graves’ disease and thyrotoxicosis. This method is non-invasive, is considered effective and relatively inexpensive, does not cause complications that may develop during thyroid surgery. Contraindications to radiotherapy are pregnancy and breastfeeding. The isotope of radioactive iodine (I 131) accumulates in the cells of the thyroid gland, where it begins to disintegrate, providing local irradiation and destruction of thyrocytes. Radioiodotherapy is carried out with mandatory hospitalization in specialized departments. The condition of hypothyroidism usually develops within 4-6 months after treatment with iodine.
In the presence of Graves’ disease in a pregnant woman, pregnancy management should be carried out not only by a gynecologist, but also by an endocrinologist. Treatment of Graves’ disease during pregnancy is carried out with propylthiouracil (it does not penetrate the placenta well) at the minimum dose necessary to maintain the amount of free thyroxine (T4) at the upper limit of the norm or slightly above it. With increasing gestation, the need for thyrostatics decreases, and most women after 25-30 weeks. pregnancy drug is no longer accepted. After childbirth (after 3-6 months) they usually develop a recurrence of thyrotoxicosis.
Treatment of thyrotoxic crisis includes intensive therapy with large doses of thyrostatics (preferably propylthiouracil). If it is impossible for the patient to take the drug independently, it is administered through a nasogastric probe. Additionally, glucocorticoids, b-blockers, detoxification therapy (under the control of hemodynamics), plasmapheresis are prescribed.
Forecast
The prognosis in the absence of treatment is unfavorable, since thyrotoxicosis gradually causes cardiovascular insufficiency, atrial fibrillation, exhaustion of the body. With the normalization of thyroid function after treatment of thyrotoxicosis – the prognosis of the disease is favorable – cardiomegaly regresses in most patients and the sinus rhythm is restored.
After surgical treatment of thyrotoxicosis, hypothyroidism may develop. Patients with thyrotoxicosis should avoid insolation, the use of iodine-containing drugs and food products.
Prevention
The development of severe forms of thyrotoxicosis should be prevented by conducting dispensary monitoring of patients with an enlarged thyroid gland without changing its function. If the anamnesis indicates the familial nature of the pathology, children should also be monitored. As preventive measures, it is important to carry out general restorative therapy and rehabilitation of chronic foci of infection.