Graves’ disease

Definition

Graves’ disease, or diffuse toxic goiter, is a disease caused by hypertrophy and hyperfunction of the thyroid gland, accompanied by the development of thyrotoxicosis. It is clinically manifested by increased excitability, irritability, weight loss, palpitations, sweating, shortness of breath, and subfebrile temperature. A characteristic symptom is exophthalmos. It leads to changes in the cardiovascular and nervous systems and the development of cardiac or adrenal insufficiency. The thyrotoxic crisis threatens the patient’s life.

General information

Diffuse toxic goiter is an autoimmune disease that develops due to a defect in the immune system. The immune system produces antibodies to TSH receptors, which have a constant stimulating effect on the thyroid gland. It leads to a uniform overgrowth of thyroid tissue, hyperfunction, and increased levels of thyroid hormones produced by the gland: T3 (triiodothyronine) and T4 (thyroxine). An enlarged thyroid gland is called a goiter.

Excess thyroid hormones increase reactions of basic metabolism and deplete energy reserves in the body, which are necessary for the normal vital activity of cells and tissues of various organs. The cardiovascular and central nervous systems are most susceptible to thyrotoxicosis.

Classification

Diffuse toxic goiter is manifested by the following forms of thyrotoxicosis, regardless of the size of the thyroid gland:

• mild form – with predominance of complaints of neurotic character, without heart rhythm disturbance, tachycardia with HR not more than 100 beats per minute, no pathologic disorders of other endocrine glands;
• medium form– weight loss within 8-10 kg per month, tachycardia with HR more than 100-110 beats per minute;
• severe form – weight loss at the level of emaciation, signs of functional disorders of the heart, kidneys, and liver. Usually observed in long-term untreated diffuse toxic goiter.

Symptoms

Since thyroid hormones are responsible for various physiologic functions, thyrotoxicosis has a variety of clinical manifestations. Usually, the main complaints of patients are related to cardiovascular changes, manifestations of catabolic syndrome, and endocrine ophthalmopathy. Cardiovascular disorders are manifested by marked palpitations (tachycardia). Sensations of palpitations in patients occur in the chest, head, abdomen, and arms. HR at rest in thyrotoxicosis can increase to 120-130 beats per minute. In moderate and severe forms of thyrotoxicosis, there is an increase in systolic pressure, a decrease in diastolic blood pressure, and an increase in pulse pressure.

A prolonged course of thyrotoxicosis, especially in elderly patients, can lead to pronounced myocardial dystrophy. This is manifested by heart rhythm disorders (arrhythmias): extrasystole and atrial fibrillation. Subsequently, this leads to changes in the ventricular myocardium, congestion (peripheral edema, ascites), and cardiosclerosis. There is a respiratory arrhythmia (increased frequency) and a tendency to frequent pneumonia.

The manifestation of catabolic syndrome is characterized by sharp weight loss (10-15 kg) against the background of increased appetite, general weakness, and hyperhidrosis. Violation of thermoregulation is manifested in the fact that patients with thyrotoxicosis experience a feeling of heat and do not freeze at a sufficiently low ambient temperature. 

Thyrotoxicosis is characterized by the development of changes in the eyes (endocrine ophthalmopathy): widening of the eye slits by lifting the upper eyelid and lowering the lower one, incomplete closing of the eyelids (rare blinking), exophthalmos (exophthalmos), eye shine. In a patient with thyrotoxicosis, the face acquires an expression of fright, surprise, and anger. Due to incomplete eyelid closure, patients complain of “sand in the eyes,” dryness, and chronic conjunctivitis. The development of periorbital edema and the growth of periorbital tissues compress the eyeball and ocular nerve, causing visual field defects, increased intraocular pressure, eye pain, and sometimes complete loss of vision.

On the part of the nervous system in thyrotoxicosis, mental instability is observed: mild excitability, increased irritability and aggressiveness, restlessness and fidgetiness, mood swings, difficulty in concentrating, and tearfulness. Sleep is disturbed, depression develops, and in severe cases – persistent changes in the patient’s psyche and personality. In thyrotoxicosis, there is often a fine tremor (trembling) of the fingers of outstretched hands. 

In thyrotoxicosis, the skin is soft, moist, and warm to the touch; some patients have vitiligo, darkening of skin folds, especially on the elbows, neck, and lower back, nail damage, and hair loss. In 3 – 5% of patients with thyrotoxicosis, pretibial myxedema develops (edema, thickening, and erythema of the skin in the area of the lower leg and feet, resembling orange peel and accompanied by itching).

In diffuse toxic goiter, the thyroid gland is uniformly enlarged. Sometimes, the gland is significantly enlarged, and sometimes, the goiter may be absent (in 25-30% of cases). The severity of the disease is not determined by the size of the goiter since a severe form of thyrotoxicosis is possible with a small thyroid gland size.

Diagnosis

The patient’s objective status (appearance, body weight, skin, hair, nails, manner of speaking, pulse, and blood pressure measurement) allows the doctor to assume the presence of hyperfunction of the thyroid gland. The diagnosis of thyrotoxicosis is almost apparent in the presence of apparent symptoms of endocrine ophthalmopathy.

If thyrotoxicosis is suspected, it is mandatory to determine the level of thyroid hormones in the thyroid gland (T3, T4), thyroid stimulating hormone (TSH), and free fractions of hormones in the serum. Diffuse toxic goiter should be distinguished from other diseases accompanied by thyrotoxicosis. Using enzyme-linked immunosorbent assay (ELISA) of blood determines the presence of circulating antibodies to TSH receptors, thyroglobulin (AB-TG), and thyroid peroxidase (AB-TPO). Ultrasound of the thyroid gland determines its diffuse enlargement and changes in echogenicity.

Thyroid scintigraphy allows the detection of functionally active gland tissue, the determination of the shape and volume of the gland, and the presence of nodular formations in it. In the presence of symptoms of thyrotoxicosis and endocrine ophthalmopathy, scintigraphy is not mandatory; it is performed only in cases when it is necessary to differentiate diffuse toxic goiter from other thyroid pathologies. In diffuse toxic goiter, an image of the thyroid gland with increased isotope uptake is obtained.

Treatment

Conservative treatment of thyrotoxicosis consists of taking antithyroid drugs. These drugs can accumulate in the thyroid gland and inhibit the production of thyroid hormones. The dose of drugs is reduced strictly individually, depending on the disappearance of signs of thyrotoxicosis: normalization of the pulse (up to 70-80 beats per minute) and pulse pressure, increase in body weight, absence of tremors, 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 excludes relapses of thyrotoxicosis. Indications for surgery are allergic reactions to prescribed drugs, persistent decrease in the level of blood leukocytes in conservative treatment, goiter of large size (above III degree), and cardiovascular disorders. Surgery for thyrotoxicosis is possible only after medication compensation of the patient’s condition to prevent the development of thyrotoxic crises in the early postoperative period.

Radioactive iodine therapy is one of the main methods of treating diffuse toxic goiter and thyrotoxicosis. This method is noninvasive, considered effective, and relatively inexpensive, and does not cause complications that can develop during thyroid surgery. Contraindications to radioactive iodine therapy are pregnancy and breastfeeding. Radioactive iodine isotope (I 131) accumulates in thyroid cells, where it begins to decay, providing local irradiation and destruction of thyroid cells. Radioactive iodine therapy is carried out with mandatory hospitalization in specialized departments. Hypothyroidism usually develops within 4-6 months after iodine treatment.

In the presence of diffuse toxic goiter in a pregnant woman, the management of pregnancy should be carried out not only by a gynecologist but also by an endocrinologist. 

All these treatment options are available in more than 820 hospitals worldwide (https://doctor.global/results/diseases/graves-disease). For example, Total thyroidectomy can be performed in these countries at following approximate prices:

Turkey$4.7 K in 14 clinics

Israel$4.8 K – 15.7 K in 10 clinics

China$13.5 K K in 8 clinics

Germany$14.0 K in 28 clinics

United States$20.6 K in 10 clinics.

Prognosis

Prognosis In the absence of treatment, the outlook is unfavorable, as thyrotoxicosis gradually causes cardiovascular failure, atrial fibrillation, and exhaustion. With the normalization of thyroid function after treatment of thyrotoxicosis, the prognosis of the disease is favorable—in most patients, cardiomegaly regresses, and sinus rhythm is restored.

After surgical treatment of thyrotoxicosis, hypothyroidism may develop. Patients with thyrotoxicosis should avoid insolation, iodine-containing drugs, and foods.

Prevention

The development of severe thyrotoxicosis should be prevented by dispensary monitoring of patients with an enlarged thyroid gland without changes in its function. If the anamnesis indicates a familial nature of the pathology, children should also be under observation. It is essential to conduct general strengthening therapy and sanitation of chronic foci of infection as preventive measures.