Myxedema in adults and children: pretybial, primary, idiopathic

In endocrinology, myxedema is considered to be the most severe form of thyroid dysfunction and severe hypothyroidism with a critically low level of thyroid hormone synthesis or its complete cessation.

Also called myxedema is the condition associated with thickening and swelling of the skin, which are caused by a metabolic disorder with long-term deficiency of thyroid hormones.

According to ICD-10, this pathology refers to unspecified hypothyroidism and has code E03.9.

[1], [2], [3], [4], [5], [6], [7],

Epidemiology

Subclinical forms of hyperthyroidism are observed in 6-8% of women (including 2.5% of pregnant women) and 3% of men. Moreover, myxedema, as the statistics of the European Thyroid Association shows, is more common in women with  thyroid diseases  (2%) than in men (0.2%).

The incidence of hypothyroidism increases with age and is most common in people older than 50 years. Low level of TSH is observed in 3% of the population over 80 years old.

The most common cause of this pathology worldwide is iodine deficiency. And in regions where there is no problem of its lack, autoimmune and iatrogenic hypothyroidism is more often diagnosed. The first place in the autoimmune lesion of the thyroid gland is in Japan.

Pretybial myxedema is diagnosed in a maximum of 5% of patients with Graves' disease in a fairly old age. A complication of myxedema in the form of myxedema coma in two thirds of cases develops in women whose average age is 70-75 years. In Europe, the incidence of coma due to severe thyroid pathologies does not exceed 0.22 per million inhabitants per year, in Japan this figure is five times higher.

[8], [9], [10],

Causes of the myxedema

This condition is associated with other symptoms of low thyroid functional activity, and the main causes of myxedema are directly related to primary or secondary hypothyroidism, that is, the inadequate production of thyroid hormones - thyroxine (T4) and triiodothyronine (T3).

Primary hypothyroidism, which can develop myxedema, occurs in cases of thyroidectomy (removal of the thyroid gland); irradiation (including during the treatment with iodine radioisotopes); genetically determined  autoimmune thyroiditis  (Hashimoto's thyroiditis). Thyroid deficiency is observed with iodine deficiency or excess, as well as in the presence of inherited fermentopathy (most often, lack of metalloenzyme of peripheral tissues of thyroxine-5-deiodinase, which leads to a decrease in the response of tissue receptors to thyroxin and triiodothyronine).

To inhibit the synthesis and release of thyroid hormones, iatrogenic hypothyroidism, may lead to long-term use of lithium preparations, recombinant alpha interferon, acetylsalicylic acid, systemic corticosteroids, antiarrhythmic agents (Amiodarone or Cordini), and some antitumour cytotoxic drugs (inhibiting kinase enzymes).

In secondary (pituitary) hypothyroidism, the causes of myxedema are associated with partial dysfunction of the pituitary gland and a violation of the process of producing its anterior portion of thyroid-stimulating hormone (thyrotropin or TSH). It can be both congenital forms of pituitary hormone deficiency (with genetic mutations), and the consequences of trauma, surgical interventions, increased radiation doses, postpartum ischemic necrosis of the pituitary ( Shihan syndrome ), brain tumors ( pituitary adenoma ).

Also, the problem may be the inadequate synthesis of the hypothalamus hormone thyreoliberin, a releasing factor stimulating the synthesis of the pituitary thyroid-stimulating hormone.

There is a connection between myxedema and Graves' disease ( diffuse toxic goiter with increased thyroid hormone levels - hyperthyroidism), one of the hallmarks of which is  exophthalmos, as well as a form of thyroid dermopathy, such as pretybial myxedema (myxedema of the lower limbs).

Etiologically, myxedema in children is also associated with oppression or dysfunction of the thyroid gland, see for more details -  Hypothyroidism in children

However, in the presence of severe congenital hypothyroidism developing in cases of prenatal aplasia or hyperplasia of the thyroid gland, as well as due to hypothyroidism of the mother or the intrauterine sensitization of TSH receptors that passed from her, the fetus, the newborn and the child of the first years of life develop cretinism - a state of strong physical and mental development.

The result of idiopathic atrophy of the thyroid gland or sporadic hypothyroidism can be an idiopathic myxedema.

[11], [12], [13], [14], [15], [16], [17]

Risk factors

In fact, the main risk factors for developing myxedema are the patient's presence of hypothyroidism (primary or secondary), as the etiological and pathogenetic correlation of myxedema and hypothyroidism, as well as myxedema and Graves' disease, is evident.

As endocrinologists note, the absence of treatment for hypothyroidism often leads to the condition of myxedema, and it is aggravated by infections, extreme hypothermia, other endocrine and hormonal pathologies (especially in women), traumatic brain injury, and the use of certain medications.

The risk factors include the deficiency of amino acids (tyrosine, threonine, tryptophan, phenylalanine), which are necessary for the synthesis of thyroxine and triiodothyronine.

Under the threat of hypothyroidism - and, accordingly, myxedema - are women, people over 50 years old, patients with any autoimmune disorders, as well as those who do not have enough zinc and selenium in their bodies. It is known that for the transformation of thyroxine into active triiodothyronine, zinc and selenium ions are required, and this biochemical reaction is poorly expressed during fetal development in infants and humans after 70 years.

[18], [19], [20], [21], [22], [23]

Pathogenesis

In the context of extirational manifestations of dysfunction of thyroid hormones and their lack of participation in regulation of the general metabolism, the pathogenesis of myxedema, in the form of thyroid dermatological damage, consists in the deposition and accumulation in the skin of the connective tissue produced by the cells of sulfated and non-sulphated glycosaminoglycans (hyaluronic acid, chondroitin sulfate). The complex of these hydrophilic compounds binds the water of the intercellular matrix, causing various localization of swelling in myxedema.

It is believed that the activation of fibroblasts and an increase in the synthesis of glycolized proteoglycans results in the release from the cells of the functionally inactive thyroid gland antigen, which induces the production of antibodies to the receptors of the pituitary tyretropin. And in case of a disease, immunocompetent lymphocytes react to thyroid-stimulating receptors of the thyroid gland and thyroglobulin, infiltrating its tissues with fibrotic changes and accumulation of glycosaminoglycans.

[24], [25]

Symptoms of the myxedema

In patients with severe hypothyroidism, reaching the stage of myxedema, the first signs are manifested:

• pallor and dryness of the skin and its roughness (especially in the soles of the soles of the feet, knees, palms and elbows);
• strong swelling of the tissues around the eyes (swollen eyelids narrow their incision) and in the neck area above the clavicles;
• the puffiness of the whole face.

Osmotic edema seizes the tongue (why it thickens) and the mucous membranes of the larynx, which together leads to hoarseness, difficulties in articulation and slurred speech.

Rare, locally limited form of autoimmune thyroiditis manifestation or Graves' disease - pretybial myxedema (thyroid dermopathy or localized myxedema) - is a dense swelling of the shins. Edema has the appearance of rounded, different in size and towering above the skin formations, located frontal and lateral to the skin and subcutaneous tissues below the knees (closer to the ankles). Damage is usually light, but hyperpigmentation (up to yellow-orange color) and increased keratinization are possible; the damaged skin is compacted and on it are visible hair follicles and a clear picture of the texture of the skin. The area of such edema gradually increases, the legs below the knees thicken, the skin becomes cyanotic. Inflammation of the skin on the swollen areas is possible.

Another type of cutaneous manifestation of hypothyroidism of the thyroid gland (in rare cases, its hyperfunction) is a diffuse tuberous myxedema. It looks like wax-like nodules on the background of swollen skin of the face and neck, upper limbs, chest, back and genitals.

The clinical symptoms of myxedema (defined as the general condition of severe thyroxine, triiodothyronine or titerotropin deficiency) are manifested:

• thinning of hair and their loss (especially noticeable on the eyebrows);
• constipations;
• a decrease in body temperature in the mornings (due to a lack of thyroxine, the rate of thermogenesis slows down) and increased chilliness;
• decreased heart rate;
• shortness of breath, nocturnal apnea;
• accumulation in the abdominal cavity of fluid ( ascites ), in the lungs (pleural effusion) and in the thoracic cavity near the heart (pericardial effusion);
• muscular pain, paresthesia and cramps;
• absence of perspiration;
• increased fatigue, slowing of mental reactions, memory impairment, depressiveness (in elderly patients, these symptoms resemble Alzheimer's ).

Myxedema in children (infantile myxedema) occurs after birth and is manifested during the infancy by slow development and growth. In addition, waxy puffiness of the skin can occur, which causes the baby's lips and nose to swell. This condition is also called infantilism Brissot.

Complications and consequences

Myxedema, which in itself is a complicated form of hypothyroidism, leads to severe complications.

This development of coronary heart disease and cardiovascular insufficiency, psychosis, osteoporosis, as well as increased vulnerability to infections. In women, myxedema is fraught with infertility, miscarriages, stillbirths or the birth of a child with congenital defects.

The rare, but the most serious and life-threatening consequence of this condition in adults is myxedematous or hypothyroid coma (code E03.5 for ICD-10) - with complete loss of consciousness, hypoxia, hypercapnia, hypoventilation, falling BP and hypothermia. The death rate due to cardiac arrest with myxedema coma is at least 20%.

[26], [27], [28], [29], [30]

Diagnostics of the myxedema

Diagnosis of myxedema carried out by endocrinologists is based on a comprehensive examination, including examination of the patient and laboratory blood tests for:

• level of hormones T4, T3 and TTG;
• thyroglobulin;
• antibodies to the TSH receptor;
• level of glucose, creatine kinase and prolactin.

Applied instrumental diagnostics: ultrasound, scintigraphy and MRI of the thyroid gland, chest X-ray (for visualization of pleural and pericardial effusions). If you suspect a secondary hypothyroidism, you need an MRI of the brain.

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Differential diagnosis

Differential diagnosis of this condition is extremely important - in order to distinguish it from other disorders: insufficiency of the adrenal glands, liver or kidneys; stroke, sepsis or syndrome of inadequate secretion of antidiuretic hormone (ADH).

Treatment of the myxedema

As in the case of hypothyroidism, treatment of myxedema is performed with hormone replacement therapy (for most patients - lifelong).

Used with myxedema medicines:

• Levothyroxine sodium (other trade names - L-thyroxine, Levoxil, Eutirox, Eferox) - the dosage is determined by the doctor based on the results of tests on the level of thyroid hormones;
• Thyroidin (Thiroid, Tyrant, Tyrothan) - daily dose of 50 to 200 mg (the dosage is calculated by body weight);
• Thibon (Triiodothyronine, Lyotyronin, Cytomel).

These drugs are taken inside - in appropriate doses, which helps stop the progression of pathology.

To alleviate the symptoms of the disease, in particular, thyroid dermopathy (pretybial myxedema), local corticosteroids are used in the form of ointments, creams and gels - for occlusive dressing (for several weeks). Also in the lesions are introduced hyaluronidase, which cleaves the deposits of glycosaminoglycans in the skin and subcutaneous tissue. It is recommended to wear compression knitwear to reduce swelling of the legs.

Alternative treatment

Endocrinologists consider folk treatment of hypothyroidism and myxedema problematic. Indeed, the condition with miksedem is not suitable for experiments with self-medication.

But some patients are treated with herbs, such as gentian yellow (infusion from the roots); marena heart-shaped (decoction of the rhizome reduces swelling); Echinacea (recommended for Graves' disease and Hashimoto's thyroiditis); Lycopus (zyuznik) is European; White bloodroot. Eleuterococcus, which has an adaptogenic effect on the body, is advised to take with all pathologies of the thyroid gland, although it does not provide a specific therapeutic effect.

Before using these herbs, you should consult an endocrinologist, because their use is not useful to everyone and can only exacerbate the condition. So, brown algae ( Ascophyllum  nodosum ) containing iodine does not replace the reception of thyroid hormones, but in cases of minor thyroid dysfunction (to which the myxedema does not apply) they can stimulate the synthesis of endogenous thyroid hormones. Remember that algae are contraindicated in persons with hyperthyroidism, pregnant women and lactating women.

More information in the material -  Treatment of thyroid diseases by alternative means

Homeopathy offers a drug Lymphomyosot - a multicomponent alcohol-containing drops, which are recommended to take (10 drops three times a day) to improve the outflow of lymph in the legs.

[36], [37], [38], [39], [40], [41]

Prevention

The best way to cope with any disorder is to prevent it from occurring, but the problem is that there are no definite ways to prevent the transition of hypothyroidism to the state of myxedema. Therefore, patients with hypothyroidism should regularly visit their doctor to take a blood test and make sure that the dose of substitute drug is suitable and the disease does not progress.

[42], [43], [44], [45], [46], [47]

Forecast

If hypothyroidism is not treated, the prognosis of endocrinologists is disappointing: in the late stages of this disease a myxedema develops, which can cause acute symptoms and have fatal consequences.

However - if the thyroid hormone levels are correctly regulated - the intensity of all the symptoms of myxedema can be reduced, and some symptoms are completely cured.

[48], [49], [50], [51], [52]