Symptoms of diffuse toxic goiter

The pathogenesis of clinical symptoms of diffuse toxic goiter is due to the influence of excess thyroid hormones on various organs and systems of the body. The complexity and multiplicity of factors involved in the development of thyroid pathology also determine the diversity of clinical manifestations of the disease.

In addition to cardinal symptoms such as goiter, exophthalmos, tremor and tachycardia, patients, on the one hand, experience increased nervous excitability, tearfulness, fussiness, excessive sweating, a feeling of heat, slight temperature fluctuations, unstable stool, swelling of the upper eyelids, and increased reflexes. They become quarrelsome, suspicious, overly active, and suffer from sleep disorders. On the other hand, adynamia and sudden attacks of muscle weakness are often observed.

The skin becomes elastic, hot to the touch, hair is dry and brittle. There is a fine tremor of the fingers of outstretched hands, closed eyelids, and sometimes the whole body (the "telegraph pole" symptom). The tremor can be so intense that the patient's handwriting changes, becomes uneven and illegible. An important symptom of the disease is the presence of a goiter. Usually, the thyroid gland is soft and enlarged diffusely and uniformly. The size of the goiter can change: it increases with anxiety, gradually decreases after the start of treatment, and sometimes becomes denser. In some patients, a blowing systolic murmur is palpated and heard above the gland. But the size of the goiter does not determine the severity of the disease. Severe thyrotoxicosis can be observed even with a small goiter.

It is customary to distinguish 5 degrees of thyroid gland enlargement:

1. the gland is not visible to the eye, the isthmus is palpable;
2. the lateral lobes are easily palpated, the gland is visible when swallowing;
3. an enlarged thyroid gland is noticeable upon examination (“thick neck”);
4. the goiter is clearly visible, the configuration of the neck is changed;
5. goiter of enormous size.

Since 1962, the classification of goiter sizes recommended by WHO has been used worldwide. According to the 1994 WHO classification, the following degrees of thyroid gland enlargement are distinguished:

• 0 degree - no goiter,
• 1 - the goiter is palpable but not visible,
• 2 - the goiter is palpable and visible with the neck in a normal position.

The most common symptom of diffuse toxic goiter is progressive weight loss with preserved or even increased appetite. Increased secretion of thyroid hormones leads to increased processes of energy resource consumption in the body, which causes weight loss. In the absence of fatty tissue, the body's energy supply comes from increased catabolism of exogenous and endogenous protein. Diffuse toxic goiter (Graves' disease) is not always accompanied by weight loss. Sometimes an increase in body weight is noted, the so-called "fat Graves' disease", which is associated with the peculiarities of the pathogenesis of the disease and requires the selection of a treatment method.

For many years, it was believed that eye changes in patients with diffuse toxic goiter were one of the symptoms of the disease and were caused by an excess of thyroid hormones. However, it turned out that exophthalmos can occur with both hyperthyroidism and hypothyroidism, with Hashimoto's thyroiditis, and in some cases can precede the appearance of symptoms of thyroid pathology or develop against the background of euthyroidism.

Ophthalmopathy is an autoimmune disease caused by the formation of specific immunoglobulins that cause changes in the retrobulbar tissue and orbital muscles. Ophthalmopathy is often combined with autoimmune diseases of the thyroid gland, namely, diffuse toxic goiter. The pathogenesis of the disease has been consistently associated with excess thyroid hormones, TSH, LATS, LATS-protector, exophthalmic-producing hormones, microsomal antibodies, and the presence of exophthalmic-producing antibodies. Apparently, a genetic defect in the immune control system is associated with the specificity of tissue damage. It has been established that the surface membranes of some orbital muscles have receptors capable of fixing antigen-antibody complexes that occur in autoimmune diseases of the thyroid gland.

The main changes occur in the extraocular muscles and depend on the duration of the disease. In the early stages, interstitial edema and diffuse cellular infiltration are observed, leading to degeneration and disintegration of muscle fiber. The muscles are pale, swollen, and sharply increased in volume. The next phase is the activation of endomysial fibroblasts, which, by producing collagen and mucopolysaccharides, lead to the proliferation of connective tissue and fibrosis; muscle fibers lose their ability to relax, which leads to limited mobility. The contraction process is disrupted. An increase in muscle volume leads to an increase in intraorbital pressure, and the removal of fluid from the interstitial spaces is disrupted. Venous stasis develops, causing edema of the eyelids and orbital tissue. In the late stages, fatty degeneration of the muscles is observed. A. F. Brovkina distinguishes 2 forms of ophthalmopathy - edematous exophthalmos and endocrine myopathy. Foreign researchers speak about the edematous and myopathic stages of ophthalmopathy as stages of a single process with predominant disturbances in the retroorbital tissue or orbital muscles.

Patients are bothered by lacrimation, photophobia, a feeling of pressure, "sand" in the eyes, and swelling of the eyelids. In thyrotoxic exophthalmos, an important diagnostic sign is the absence of double vision. Exophthalmos is usually bilateral, less often unilateral. The degree of exophthalmos can be determined using a Hertel exophthalmometer. In diffuse toxic goiter, the protrusion of the eye sometimes increases significantly. Exophthalmos is accompanied by increased shine of the eyes, develops gradually, sometimes over several days or hours. Its severity usually does not correspond to the severity of thyrotoxicosis.

In addition to exophthalmos, patients also have other eye symptoms: wide opening of the eye slits (Delrymple's symptom), rare blinking (Stellwag's symptom), increased shine of the eyes (Graefe's symptom), lagging of the upper eyelid behind the iris when looking down, so that a white stripe of the sclera appears (Kocher's symptom), weakness of convergence (Moebius's symptom). Sometimes Jellinek's symptom is encountered - darkening of the skin on the eyelids. These signs, especially the protrusion of the eyeballs and wide opening of the eye slits, give the face a characteristic expression of fear. When fixing the gaze - the so-called angry look.

In case of moderate and severe eye damage, visual acuity decrease, double vision as a constant symptom, and scleral vessel injection are observed. Lagophthalmos develops - the inability to fully close the eyelids, ulceration of the cornea and sclera with subsequent secondary infection is possible. The above eye symptoms are aggravated.

In foreign literature, the NOSPECS classification is used, first proposed in 1969 by Werner:

• 0 - no pathological changes in the eyes;
• I - contraction of the upper eyelid - "surprised look", wide palpebral fissure and Graefe's symptom;
• II - changes in the soft tissues of the orbit;
• III - protrusion of the eyeballs (the increase exceeds the norm by 3 mm or more);
• IV - damage to the orbital muscles, limitation of eye movement;
• V - changes in the conjunctiva;
• VI - damage to the optic nerve.

V. G. Baranov considered it appropriate to distinguish 3 degrees of exophthalmos severity:

• I - slight exophthalmos - (15.9±0.2) mm, eyelid edema;
• II - moderate exophthalmos - (17.9±0.2) mm, with significant swelling of the eyelids and pronounced symptoms of damage to the eye muscles;
• III - pronounced exophthalmos - (22.8+1.1) mm, corneal ulceration, diplopia, severe limitation of eyeball mobility.

In 3-4% of patients, a specific lesion of the skin and subcutaneous fat tissue called pretibial myxedema develops on the anterior surface of the shin. Clinically, pretibial myxedema is characterized by a unilateral or bilateral clearly defined compaction of a purple-bluish color on the anteromedial surfaces of the shins. Edema occurs as a result of a violation of the metabolism of glucoproteins, the carbohydrate components of which are found in the edematous substance - mucin. For a long time, the cause of pretibial myxedema was considered to be vascular sclerosis and circulatory stasis leading to trophic disorders. Diencephalic brain lesions, hypersecretion of thyrotropin by the anterior pituitary gland in patients after thyroid removal, changes in the function of the gland and pituitary gland against the background of impaired mechanisms of neurotropic regulation were considered as etiological factors. To date, the most likely mechanism for the development of pretibial myxedema is autoimmune. McKenzie found LATS factor in the blood of most patients with pretibial myxedema.

In men, thickening of the phalanges of the fingers is sometimes observed (thyroid acropathy), caused by swelling of the dense tissues of the phalanges and periosteal bone tissue formation.

Cardiovascular disorders are also characteristic of the clinical picture of thyrotoxicosis. "Patients with Graves' disease suffer from the heart and die from the heart" (Moebius). Cardiovascular disorders in diffuse toxic goiter are caused, on the one hand, by the pathological sensitivity of the cardiovascular system to catecholamines, and on the other hand, by the direct effect of excess thyroxine on the myocardium. The summation of the effect of excessive secretion of thyroid hormones and the effect of increased sympathetic activity on the heart and peripheral circulation is noted. The resulting hemodynamic disorders, the discrepancy between the level of delivery, consumption and utilization of oxygen by the heart muscle lead to severe metabolic-dystrophic damage and the development of thyrotoxic cardiomyopathy, the clinical manifestations of which are rhythm disturbances ( tachycardia, extrasystole, atrial fibrillation and flutter) and heart failure. The processes underlying thyrotoxic cardiomyopathy are reversible. An almost constant symptom of thyrotoxicosis is tachycardia, against which attacks of atrial fibrillation may occur. Tachycardia is characterized by the fact that it does not change when the patient changes position and does not disappear during sleep. Another feature is a weak response to therapy with cardiac glycosides. The pulse rate can reach 120-140 beats per minute, and with movement, physical exertion and excitement - 160 or more. Patients feel a pulse beating in the neck, head, and abdomen.

The heart is enlarged to the left, systolic murmur is heard. High pulse pressure is characteristic due to excessive increase in systolic and low diastolic. No characteristic features are found on the electrocardiogram. High pointed P and T waves are often found, atrial fibrillation and extrasystole are observed. Sometimes depression of the ST segment and a negative T wave can be seen on the electrocardiogram. Changes in the terminal part of the ventricular complex can be observed both in the absence of anginal pain and in the presence of angina; they are usually reversible. As compensation for thyrotoxicosis is achieved, positive dynamics of ECG changes are noted.

Patients with diffuse toxic goiter (Graves' disease) often have gastrointestinal disorders. Patients complain of changes in appetite, bowel disorder, attacks of abdominal pain, and vomiting. Sometimes spastic constipation is observed. In severe cases of the disease, the liver is affected. An increase in its size, pain in the right hypochondrium, and sometimes jaundice are noted. With adequate therapy for thyrotoxicosis, liver dysfunction is reversible. With diffuse toxic goiter,pancreatic function also suffers. Patients often have elevated glycemia levels, and a glucose tolerance test is impaired. When the symptoms of thyrotoxicosis are eliminated, carbohydrate metabolism indicators return to normal.

Women experience menstrual irregularities, including amenorrhea. Men suffering from thyrotoxicosis experience decreased libido and potency, and sometimesgynecomastia disorders. Under the influence of thyroid hormones, cortisol is rapidly destroyed, resulting in hypocorticism developing in severe thyrotoxicosis. With long-standing diffuse toxic goiter, adrenal cortex depletion also occurs, causing relative adrenal insufficiency.

A study of the clinical picture of thyrotoxicosis shows that patients do not always have clear signs of the disease. Often there is no significant enlargement of the thyroid gland, constant tachycardia, characteristic facial expressions, or eye symptoms. Patients are bothered by periodically occurring attacks of palpitations, accompanied by unpleasant sensations in the heart area, shortness of breath. Outside of attacks, the heart rate may be within normal limits, the ECG is normal, and the level of thyroid hormones in the blood is unchanged. During an attack, the content of triiodothyronine and thyroxine in the blood is sharply increased.

Triiodothyronine toxicosis, occurring against the background of normal thyroxine levels in the blood, but an elevated level of triiodothyronine, occurs in 5% of cases of diffuse toxic goiter, and in autonomous adenomas - up to 50%. One of the reasons for the violation of the thyroxine and triiodothyronine ratio in the thyroid gland may be a lack of iodine, leading to compensatory synthesis of the most active hormone.

Another reason for an isolated increase in the T3 level may be an accelerated peripheral transition of T4 _to T3 _. The symptoms of this form of thyrotoxicosis do not have any special features.

The literature describes patients whose course of thyrotoxicosis was complicated by attacks of partial or complete paralysis of the proximal skeletal muscles in combination with vegetative disorders: sweating, thirst, tachycardia, increased blood pressure, increased excitability. Sometimes, mild manifestations of periodic paralysis in the form of transient weakness in the legs were noted.

Thyrotoxicosis in the elderly is not uncommon. According to Geffrys, its incidence among them is 2.3%. The disease develops gradually, against the background of somatic pathology. Weight loss, loss of appetite, and muscle weakness come to the fore. Patients are calm rather than excited. A characteristic feature of the clinical picture is the rapid development of heart failure, heart rhythm disturbances in the form of atrial fibrillation, refractory to conventional therapeutic doses of cardiac glycosides. With thyrotoxic atrial fibrillation, the risk of embolism is as high as with rheumatic mitral stenosis. Thyrotoxic atrial fibrillation develops with subclinical hyperthyroidism. Latent forms of ischemic or hypertensive cardiopathy, common with hyperthyroidism, in the elderly turn into overt forms (heart failure, atrial fibrillation, angina pectoris ). Elderly patients with thyrotoxicosis rarely have exophthalmos, and they often have no goiter. Sometimes there is a so-called apathetic form of thyrotoxicosis. Clinical manifestations include apathy, depression, significant weight loss, heart failure, atrial fibrillation, and proximal myopathy. Patients have an apathetic face, wrinkled skin, blepharoptosis, and temporal muscle atrophy, which can be explained by a relative deficiency of catecholamines or a decrease in the response to them. The level of thyroid hormones in the elderly may be at the upper limit of normal or slightly elevated. It is believed that hyperthyroidism in them develops due to increased sensitivity of peripheral tissues to the action of hormones. A thyroliberin test can help in diagnosis. A normal response to the introduction of TRH excludes the diagnosis of thyrotoxicosis, with the exception of forms caused by selective pituitary resistance to thyroid hormones.

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Severity of thyrotoxicosis

Depending on the severity of thyrotoxicosis, mild, moderate and severe forms of the disease are distinguished.

In mild cases, the pulse is no more than 100 beats/min, body weight loss is 3~5 kg, eye symptoms are absent or slightly expressed, and the absorption of ¹³¹ I increases after 24 hours.

Moderate severity is characterized by increased tachycardia up to 100-120 beats/min, pronounced tremor, weight loss up to 8-10 kg, increased systolic and decreased diastolic pressure, and increased uptake of isotopes by the thyroid gland from the first hours.

The severe form (marantic, visceropathic) develops with a relatively long history of the disease, without treatment. Weight loss reaches the degree of cachexia, the pulse rate exceeds 120-140 beats/min. The listed symptoms are accompanied by liver dysfunction, cardiovascular system. Atrial fibrillation and myopathy, adrenal insufficiency are observed.

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Thyrotoxic crisis

Thyrotoxic crisis is the most severe, life-threatening complication of diffuse toxic goiter. It develops when all symptoms of hyperthyroidism suddenly worsen, often several hours after a non-radical operation against the background of insufficiently compensated thyrotoxicosis. Stressful situations, physical overexertion, infections, surgical interventions, and tooth extraction can play the role of provoking factors. In the pathogenesis of thyrotoxic crisis, the main role is played by the sudden release of large quantities of thyroid hormones into the blood, increased adrenal insufficiency, activity of the higher parts of the nervous system, and the sympathetic-adrenal system. Functional and morphological disorders in various organs and tissues that develop during a thyrotoxic crisis are caused, on the one hand, by a sharp increase in the blood level of thyroid hormones, excessive production of catecholamines or increased sensitivity of peripheral tissues to them, and on the other hand, by a deficiency of adrenal cortex hormones. With further depletion of their reserve capacity, the crisis can be fatal. Patients become restless, blood pressure increases significantly. Significant agitation, tremor of the limbs, and severe muscle weakness develop. Gastrointestinal disorders are observed: diarrhea, nausea, vomiting, abdominal pain, jaundice. Renal function is impaired, diuresis decreases to anuria. Heart failure may develop. Sometimes acute liver atrophy joins in. Further agitation is replaced by a stuporous state and loss of consciousness, the development of a clinical picture of coma.

The prognosis is determined by the timeliness of diagnosis and treatment.