Myxedema in adults and children: pretibial, primary, idiopathic

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

Myxedema is also a condition associated with thickening and swelling of the skin, which is caused by metabolic disorders due to a long-term deficiency of thyroid hormones.

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

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Epidemiology

Subclinical forms of hyperthyroidism are observed in 6-8% of women (including 2.5% of pregnant women) and 3% of men. At the same time, myxedema, as statistics from the European Thyroid Association show, 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 over 50. Low TSH levels are seen in 3% of the population over 80.

The most common cause of this pathology worldwide is iodine deficiency. And in regions where there is no problem of its deficiency, autoimmune and iatrogenic hypothyroidism are more often diagnosed. In first place for autoimmune thyroid damage are residents of Japan.

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

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Causes myxedema

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

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

Long-term use of lithium, recombinant alpha interferon, acetylsalicylic acid, systemic corticosteroids, antiarrhythmic drugs (Amiodarone or Cordinil), and some antitumor cytostatic drugs (inhibiting kinase enzymes) can lead to inhibition of the synthesis and release of thyroid hormones – iatrogenic hypothyroidism.

In secondary (pituitary) hypothyroidism, the causes of myxedema development are associated with partial dysfunction of the pituitary gland and disruption of the process of production of thyroid-stimulating hormone (thyrotropin or TSH) by its anterior lobe. These can be both congenital forms of pituitary hormone deficiency (with genetic mutations), and consequences of injuries, surgical interventions, increased doses of radiation, postpartum ischemic necrosis of the pituitary gland ( Sheehan's syndrome ), brain tumors ( pituitary adenomas ).

The problem may also be insufficient synthesis of the hormone thyroliberin by the hypothalamus – a releasing factor that stimulates the synthesis of pituitary thyroid-stimulating hormone.

There is a known connection between myxedema and Graves' disease ( diffuse toxic goiter with increased levels of thyroid hormones - hyperthyroidism), one of the distinctive features of which is exophthalmos, as well as such a form of thyroid dermopathy as pretibial myxedema (myxedema of the lower extremities).

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

However, in the presence of severe congenital hypothyroidism, which develops in cases of prenatal aplasia or hyperplasia of the thyroid gland, as well as due to maternal hypothyroidism or intrauterine sensitization of TSH receptors, the fetus, newborn, and child in the first years of life develop cretinism - a state of severe retardation of physical and mental development.

Idiopathic myxedema may result from idiopathic thyroid atrophy or sporadic hypothyroidism.

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Risk factors

In essence, the main risk factors for the development of myxedema are the presence of hypothyroidism (primary or secondary) in the patient, since the etiological and pathogenetic correlation of myxedema and hypothyroidism, as well as myxedema and Graves' disease, is obvious.

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

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

Women, people over 50, patients with any autoimmune disorders, and those who lack zinc and selenium in their bodies are at risk of hypothyroidism – and, accordingly, myxedema. It is known that zinc and selenium ions are needed to convert thyroxine into active triiodothyronine, and this biochemical reaction is weakly expressed during intrauterine development of the fetus, in infants, and in people over 70 years of age.

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Pathogenesis

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

It is believed that the release of an antigen from the cells of the functionally inactive thyroid gland, which induces the production of antibodies to the receptors of the pituitary thyrotropin, leads to the activation of fibroblasts and increased synthesis of glycosylated proteoglycans. And in Graves' disease, immunocompetent lymphocytes react to the thyroid-stimulating receptors of the thyroid gland and thyroglobulin, infiltrating its tissues - with fibrous changes and accumulation of glycosaminoglycans.

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Symptoms myxedema

In patients with severe hypothyroidism that has reached the stage of myxedema, the first signs appear:

• paleness, dryness and roughness of the skin (especially in the area of the soles of the feet, knees, palms and elbows);
• severe swelling of the tissues around the eyes (swollen eyelids narrow their opening) and in the neck area above the collarbones;
• puffiness of the whole face.

Osmotic edema affects the tongue (causing it to thicken) and the mucous membranes of the larynx, which together leads to hoarseness, difficulty articulating and slurred speech.

A rather rare, locally limited form of autoimmune thyroiditis or Graves' disease - pretibial myxedema (thyroid dermopathy or localized myxedema) - is a dense swelling of the shins. The swellings look like rounded, various in size and raised above the skin formations, located frontally and laterally on the skin and in the subcutaneous tissues below the knees (closer to the ankles). The lesions are usually light, but their hyperpigmentation (up to a yellow-orange color) and increased keratinization are possible; the damaged skin is compacted and hair follicles and a clear pattern of skin texture are visible on it. The area of such swellings gradually increases, the legs below the knees thicken, the skin becomes cyanotic. Inflammation of the skin in the swollen areas is possible.

Another type of skin manifestation of hypothyroidism (in rare cases of hyperthyroidism) is diffuse tuberous myxedema. It has the appearance of wax-like nodules on the background of swollen skin of the face and neck, upper limbs, chest, back and genital area.

Clinical symptoms of myxedema (defined as a general condition of severe deficiency of thyroxine, triiodothyronine, or thyrotropin) include:

• thinning hair and hair loss (especially noticeable on the eyebrows);
• constipation;
• a decrease in body temperature in the morning (due to a lack of thyroxine, the rate of thermogenesis slows down) and increased chilliness;
• decrease in heart rate;
• difficulty breathing, sleep apnea;
• accumulation of fluid in the abdominal cavity ( ascites ), in the lungs (pleural effusion) and in the chest cavity near the heart (pericardial effusion);
• muscle pain, paresthesia and cramps;
• absence of sweating;
• increased fatigue, slowed mental reactions, memory impairment, depression (in elderly patients, these symptoms resemble Alzheimer's disease ).

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

Complications and consequences

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

This is the development of ischemic heart disease and cardiovascular failure, 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.

A rare, but most serious and life-threatening consequence of this condition in adults is myxedema or hypothyroid coma (code E03.5 according to ICD-10) – with complete loss of consciousness, hypoxia, hypercapnia, hypoventilation, drop in blood pressure and hypothermia. The mortality rate due to cardiac arrest in myxedema coma is at least 20%.

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Diagnostics myxedema

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

• levels of hormones T4, T3 and TSH;
• thyroglobulin;
• TSH receptor antibodies;
• glucose, creatine kinase and prolactin levels.

Instrumental diagnostics are used: ultrasound, scintigraphy and MRI of the thyroid gland, chest X-ray (to visualize pleural and pericardial effusions). If secondary hypothyroidism is suspected, MRI of the brain is necessary.

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Differential diagnosis

Differential diagnosis of this condition is extremely important to distinguish it from other disorders: adrenal, liver or kidney insufficiency; stroke, sepsis or syndrome of inappropriate secretion of antidiuretic hormone (ADH).

Treatment myxedema

As with hypothyroidism, myxedema is treated with hormone replacement therapy (lifelong for most patients).

Medicines used for myxedema:

• Levothyroxine sodium (other trade names: L-thyroxine, Levoxyl, Euthyrox, Eferox) - the dosage is determined by the doctor based on the results of tests for thyroid hormone levels;
• Thyroidin (Thyroid, Tiranoy, Tirotan) – daily dose from 50 to 200 mg (dosage is calculated based on body weight);
• Tibon (Triiodothyronine, Liothyronine, Cytomel).

The listed drugs are taken orally in appropriate doses, which helps stop the progression of the pathology.

To relieve symptoms of the disease, in particular, thyroid dermopathy (pretibial myxedema), local corticosteroids are used in the form of ointments, creams and gels - under an occlusive dressing (for several weeks). Hyaluronidase is also injected into the affected areas, breaking down glycosaminoglycan deposits in the skin and subcutaneous tissue. Wearing compression hosiery to reduce leg swelling is recommended.

Folk remedies

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

But some patients benefit from herbal treatments such as yellow gentian (root infusion); heart-leaved madder (rhizome decoction reduces swelling); echinacea (recommended for Graves' disease and Hashimoto's thyroiditis); European lycopus; white cinquefoil. Eleutherococcus, which has an adaptogenic effect on the body, is recommended for all thyroid pathologies, although it does not provide a specific therapeutic effect.

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

More information in the material - Treatment of thyroid diseases with folk remedies

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

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Prevention

The best way to manage any disorder is to prevent it from occurring, but the problem is that there are no specific ways to prevent hypothyroidism from progressing to myxedema. Therefore, patients with hypothyroidism should visit their doctor regularly to have blood tests and make sure that the dosage of replacement medication is appropriate and the disease is not progressing.

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Forecast

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

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

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