Diffusion toxic craw

Description:

Greyvs's disease (Basedow's disease, diffusion toxic craw)  - the general autoimmune disease which is developing owing to development of antibodies to a receptor of tireotoropny hormone, clinically shown damage of a thyroid gland with development of a syndrome of a thyrotoxicosis in combination with ekstratireoidny pathology: endocrine ophthalmopathy, pretibialny myxedema, acropathy. For the first time the disease was described in 1825 by Caleb Parri, in 1835 - Robert Greyvs, and in 1840 - Karl von Basedow.

Symptoms of the Diffusion toxic craw:

Rather short anamnesis, in most cases, is characteristic of a diffusion toxic craw: the first symptoms usually appear in 4-6 months prior to the address to the doctor and diagnosis. As a rule, key complaints are connected with changes from cardiovascular system, a so-called catabolic syndrome and an endocrine ophthalmopathy.

The main symptom from cardiovascular system is tachycardia and rather expressed feelings of serdtsebiyeniye. Patients can feel heartbeat not only in a thorax, but also the head, hands, a stomach. ChSS at rest at the sinus tachycardia caused by a thyrotoxicosis can reach 120-130 beats per minute.

At it is long the existing thyrotoxicosis, especially at elderly patients, the expressed dystrophic changes in a myocardium which frequent manifestation are supraventricular disturbances of a rhythm, namely fibrillation (blinking) of auricles develop. This complication of a thyrotoxicosis rather seldom develops at patients more young than 50 years. Further progressing of a myocardial dystrophy leads to development of changes of a myocardium of ventricles and congestive heart failure.

As a rule, the catabolic syndrome which is shown the progressing weight loss (sometimes on 10-15 kg and more, especially at persons with initial surplus of weight) against the background of the increasing weakness and the increased appetite is expressed. Skin of patients hot, sometimes is available the expressed hyperhidrosis. The feeling of heat is characteristic, patients do not freeze at rather low temperature indoors. At some patients (especially at advanced age) evening subfebrile condition can be revealed.

Changes from a nervous system are characterized by mental lability: episodes of aggression, excitement, chaotic unproductive activity are replaced by tearfulness, an adynamy (irritable weakness). Many patients are noncritical to the state and try to keep active lifestyle against the background of rather serious somatic condition. It is long the existing thyrotoxicosis is followed by permanent changes of mentality and the identity of the patient. A frequent, but not specific symptom of a thyrotoxicosis is the small tremor: the small shiver of fingers of outstretched arms comes to light at most of patients. At a heavy tiretoksikoz the tremor can be defined in all body and even to complicate the speech of the patient.

Muscular weakness and reduction of volume of muscles, especially proximal muscles of hands and legs are characteristic of a thyrotoxicosis. Sometimes rather expressed myopathy develops. Very rare complication is thyrocardiac gipokaliyemichesky periodic paralysis which is shown by periodically arising sharp attacks of muscular weakness. At a laboratory research the hypopotassemia, increase in the KFK level comes to light. Meets at representatives of Asian race more often.

The intensification of a bone resorption leads to development of a syndrome osteosinging, and the thyrotoxicosis is considered as one of the most important risk factors of osteoporosis. Frequent complaints of patients are the hair loss, fragility of nails.

Changes from digestive tract develop rather seldom. Elderly patients in some cases can have a diarrhea. At it is long the existing heavy thyrotoxicosis dystrophic changes in a liver (a thyrocardiac hepatosis) can develop.

Disturbances of a menstrual cycle meet rather seldom. Unlike a hypothyroidism, the thyrotoxicosis of moderate expressiveness can not be followed by decrease in fertility and does not exclude a possibility of approach of pregnancy. Antibodies to a receptor of TTG get through a placenta in this connection at the children born (1%) of women with a diffusion toxic craw (sometimes years later after the carried-out radical treatment), the tranzitorny neonatal thyrotoxicosis can develop. At men the thyrotoxicosis rather often is followed by erectile dysfunction.

At a heavy thyrotoxicosis of an uryad of patients symptoms of thyrogenic (relative) adrenal insufficiency which needs to be differentiated from true are expressed. The hyperpegmentation of skin, open parts of a body (Ellinek's symptom), arterial hypotension are added to already listed symptoms.

In most cases at a diffusion toxic craw there is an increase in the sizes of a thyroid gland which, as a rule, has diffusion character. Quite often gland is increased considerably. In some cases over a thyroid gland it is possible to listen to systolic noise. Nevertheless the craw is not an obligate symptom of a diffusion toxic craw as it is absent not less than at 25-30% of patients.

In diagnosis of a diffusion toxic craw changes from eyes which are peculiar "business card" of a diffusion toxic craw have key value, i.e. their detection at the patient with a thyrotoxicosis almost unambiguously testifies to a diffusion toxic craw, but not to other disease. Very often thanks to existence of the expressed ophthalmopathy in combination with thyrotoxicosis symptoms the diagnosis the diffusion toxic craw is obvious already at survey of the patient.

Another rare (less than 1% of cases), associated with a diffusion toxic craw, a disease is the pretibialny myxedema. Skin of a front surface of a shin becomes edematous, condensed, purple-red color ("orange-peel"), often is followed by an erythema and an itch.
The clinical picture of a thyrotoxicosis can have deviations from classical option. So, if at young people a diffusion toxic craw it is characterized by the developed clinical picture, elderly patients have its current often oligo-or even monosimptomny (disturbance of a heart rhythm, subfebrile condition). At "apathetic" option of a course of a diffusion toxic craw which occurs at elderly patients clinical manifestations include appetite loss, a depression, a hypodynamia.

Very rare complication of a diffusion toxic craw is thyrocardiac crisis which pathogeny is not quite clear as crisis can develop also without ultraboundary increase in level of thyroid hormones in blood. The acute infectious diseases accompanying a diffusion toxic craw, performing surgery or therapy a radioiodine against the background of the expressed thyrotoxicosis, cancellation of thyreostatic therapy, introduction to the patient of contrast iodinated agent can appear the reason of thyrocardiac crisis.

Clinical displays of thyrocardiac crisis include sharp weighting of symptoms of a thyrotoxicosis, a hyperthermia, confusion of consciousness, nausea, vomiting, sometimes diarrhea. Sinus tachycardia over 120 beats/min is registered. The ciliary arrhythmia, high pulse pressure with the subsequent expressed hypotonia is quite often noted. In a clinical picture heart failure, a respiratory distress syndrome can dominate. Manifestations of relative adrenal insufficiency are quite often expressed as a skin hyperpegmentation. Integuments can be zheltushna owing to development of a toxic hepatosis. At a laboratory research the leukocytosis (even in the absence of the accompanying infection), a moderate hypercalcemia, increase in level of an alkaline phosphatase can come to light. Mortality at thyrocardiac crisis reaches 30-50%.

Reasons of the Diffusion toxic craw:

The diffusion toxic craw is a multifactor disease at which genetic features of immune reaction are implemented against the background of action of factors of the environment. Along with ethnically associated genetic predisposition (a carriage of haplotypes of HLA-B8, - DR3 and - DQA1*0501 at Europeans), in a pathogeny of a diffusion toxic craw a certain significance is attached to psychosocial advanced factors. Emotional stressorny and exogenous factors, such as smoking, can promote implementation of genetic predisposition to a diffusion toxic craw. Smoking increases risk of development of a diffusion toxic craw by 1,9 times. The diffusion toxic craw in some cases is combined with other autoimmune endocrine diseases (a diabetes mellitus of 1 type, primary hypocorticoidism).

As a result of unresponsiveness disturbance, desease-producing lymphocytes (CD4+ and CD8 + T lymphocytes, V-lymphocytes) with the participation of adhesive molecules (ICAM-1, ICAM-2, E-selectin, VCAM-1, LFA-1, LFA-3, CD44) infiltrirut a parenchyma of a thyroid gland where distinguish a number of antigens which prezentirutsya by dendritic cells, macrophages and V-lymphocytes. Further cytokines and alarm molecules initiate antigenspetsifichesky stimulation of V-lymphocytes therefore products of specific immunoglobulins against various components of tirotsit begin. In a pathogeny of a diffusion toxic craw major importance is attached to formation of the stimulating antibodies to a receptor of TTG (AT-RTTG).

Unlike other autoimmune diseases at a diffusion toxic craw there is not a destruction, but stimulation of a target organ. In this case autoantibodies are developed to a fragment of a receptor of TTG which is on a membrane of tirotsit. As a result of interaction with an antibody this receptor comes to an active state, starting the post-receptor cascade of synthesis of thyroid hormones (thyrotoxicosis) and, besides, stimulating a hypertrophy of tirotsit (enlargement of the thyroid gland). For not quite obvious reasons T lymphocytes, sensibilized to antigens of a thyroid gland, infiltrirut and cause an immune inflammation in some other structures, such as retrobulbar cellulose (an endocrine ophthalmopathy), cellulose of a front surface of a shin (a pretibialny myxedema).

Treatment of the Diffusion toxic craw:

There are three methods of treatment of a diffusion toxic craw (conservative treatment by thyreostatic drugs, surgical treatment and therapy 131I), at the same time any of them is not etiotropic. In the different countries the specific weight of use of the specified treatment methods traditionally differs. So, in the European countries as primary method of treatment conservative therapy of a tireostatikama is most accepted, in the USA the vast majority of patients receives therapy 131I.

Conservative therapy is performed by means of thiourea drugs to which Thiamazolum belongs (mercazolil, тирозол, метизол) and propylthiouracil (technical training college, propitsit). The mechanism of effect of both drugs is that they actively collect in a thyroid gland and block synthesis of thyroid hormones thanks to inhibition of thyroid peroxidase which carries out accession of iodine to the tyrosine remains in thyreoglobulin.

The purpose of operational treatment, as well as therapy 131I is removal practically of all thyroid gland, on the one hand the providing development of a postoperative hypothyroidism (which is rather easily compensated), and with another - excluding any possibility of a recurrence of a thyrotoxicosis.

In the majority of the countries of the world the main part of patients with a diffuzny toxic craw, as well as with other forms of a toxic craw, as the main method of radical treatment receives therapy radioactive 131I. It is connected with the fact that the method is effective, noninvasive, rather inexpensive, deprived of those complications which can develop in time of operation on a thyroid gland. The only contraindications to treatment 131I are pregnancy and breastfeeding. In significant quantities 131I collects only in a thyroid gland; after hit in it it begins to break up with allocation of beta particles which have run length about 1-1,5 mm that provides local beam destruction of tirotsit. Essential advantage is that treatment 131I can be carried out without preliminary preparation of a tireostatikama. At a diffusion toxic craw when the purpose of treatment is destruction of a thyroid gland, therapeutic activity taking into account the volume of a thyroid gland, the maximum capture and time of semi-removal 131I of a thyroid gland is calculated proceeding from an estimated absorbed dose in 200-300 Gray. At empirical approach to the patient without preliminary dosimetric researches at a craw of the small size about 10 mCi are appointed, at a craw of the bigger size - 15-30 mCi. The hypothyroidism usually develops within 4-6 months after introduction 131I.

Feature of treatment of a diffusion toxic craw during pregnancy is in what тиреостатик (preference is given to technical training college which gets through a placenta worse) is appointed in minimum necessary dose (only according to the scheme "block), which is necessary for maintenance of level of free T4 on the upper bound of norm or slightly above it. Usually in process of increase in durations of gestation requirement to a vtireostatika decreases also most of women after 25-30 weeks drug does not accept at all. Nevertheless at most of them after the delivery (usually in 3-6 months) the disease recurrence develops.

Treatment of thyrocardiac crisis means intensive actions about purpose of high doses of tireostatik. Preference is given to technical training college in a dose of 200-300 mg each 6 hours, at impossibility of independent reception by the patient - via the nazogastralny probe. Besides, are appointed ß adrenoblockers (propranolol: 160-480 mg pass per os or in in/in at the rate of 2-5 m of g/hour), glucocorticoids (a hydrocortisone: To 50-100 mg there are each 4 hours or Prednisolonum (60 mg/days), disintoxication therapy (normal saline solution, 10% glucose solution) under control of a hemodynamics. An effective method of treatment of thyrocardiac crisis is the plasma exchange.