A rare but dangerous disease: autoimmune polyglandular syndrome

Endocrinological diseases are rightfully considered one of the most severe in modern medical practice, since patients with such a pathology often require lifelong replacement therapy. An even more serious condition is a combination of pathologies of several endocrine organs. Polyglandular syndrome or polyglandular deficiency syndrome is a multiple organ disease characterized by the presence of a pathological process in several endocrine glands at once,   as a result of their primary autoimmune lesion,   in combination with damage to other organs. The incidence of this disease is low, about  1:10 000 000 in the population, and varies greatly among different ethnic groups.  There is a certain dependence on gender and age,

Etiology and pathogenesis of autoimmune polyglandular syndrome

Several factors play a leading role in the etiology of polyendocrine syndrome. The familial nature of the disease speaks of its genetic determinism.  To date, genes have been identified that determine the predisposition to individual components of the autoimmune polyglandular syndrome. First of all, these are HLA genes. It is also assumed that there are genes whose mutations are the trigger mechanism for this particular autoimmune process as a whole. They can be localized both in the HLA region and in other regions of the genome. According to recent data, the AIRE gene, which regulates autoimmunity, was found on the 21st chromosome. In many patients with autoimmune polyglandular syndrome of the first type, mutations of this particular gene were found.  Today, research in this area continues, since the mechanism of the pathogenesis of the disease is not fully understood. It is known that genetic mutations only cause a predisposition to the occurrence of any of the polyendocrine syndromes. For the appearance of the first manifestations of a characteristic clinical picture, the influence of other, non-genetic factors is now necessary. In the pathogenesis of any autoimmune disease, the leading factor is a decrease in immunological tolerance to cell antigens, which leads to destructive changes  in the tissues of the affected organs.  Therefore,  with autoimmune polyglandular syndrome,  morphologically, fibrosis and tissue atrophy can be seen in the affected glands.

For the appearance of the first manifestations of a characteristic clinical picture, the influence of other, non-genetic factors is now necessary. In the pathogenesis of any autoimmune disease, the leading factor is a decrease in immunological tolerance to cell antigens, which leads to destructive changes  in the tissues of the affected organs.  Therefore,  with autoimmune polyglandular syndrome,  morphologically, fibrosis and tissue atrophy can be seen in the affected glands.

For the appearance of the first manifestations of a characteristic clinical picture, the influence of other, non-genetic factors is now necessary. In the pathogenesis of any autoimmune disease, the leading factor is a decrease in immunological tolerance to cell antigens, which leads to destructive changes  in the tissues of the affected organs.  Therefore,  with autoimmune polyglandular syndrome,  morphologically, fibrosis and tissue atrophy can be seen in the affected glands.

Autoimmune polyglandular syndrome type 1: symptoms of the disease

Whitaker's syndrome or MEDAC syndrome (Multiple Endocrine Deficiency, Autoimmune, Candidiasis, candido polyendocrine syndrome) is characterized by the so-called pathological triad, including manifestations of candidiasis of the skin and mucous membranes, hypoparathyroidism and signs of primary adrenal insufficiency. Other components can be  primary hypothyroidism, chronic active hepatitis, malabsorption syndrome, vitiligo, autoimmune gastritis, alopecia, manifestations of diabetes mellitus (rare).  In many cases  the syndrome manifests itself in an incomplete form, so the diagnosis is established in the presence of two of the three main components.

Autoimmune polyglandular syndrome type 2: symptoms of the disease

Schmidt's syndrome was first described in 1926  M.V. Schmidt,  who described two patients with chronic thyroiditis and primary adrenal insufficiency.  The presence of signs of damage to the thyroid gland and adrenal glands are mandatory  for the diagnosis of polyglandular syndrome type II. Frequent components are also insulin-dependent diabetes mellitus, & nbsp; primary hypogonadism, vitiligo. Type II polyglandular syndrome is the most common form of polyendocrine syndrome. Several generations of the same family are sick, & nbsp; in 75% of cases these are women aged 20-33.  The disease starts with manifestations of adrenal insufficiency and over the next decade other components of the syndrome join.

Autoimmune polyglandular syndrome type 3: symptoms of the disease

This type of polyglandular syndrome is characterized by a combination of autoimmune & nbsp; thyroid lesions with another autoimmune disease (not necessarily endocrinopathy), but without the addition of chronic adrenal insufficiency.  Most often, women aged 30-40 get sick. It is customary to distinguish three types of autoimmune polyglandular syndrome type 3, depending on what the thyroid disease is combined with.

APS 3А – combination of autoimmune thyroid disease with type 1 diabetes mellitus;
APS 3B – autoimmune damage to the thyroid gland and autoimmune damage to the stomach (pernicious anemia, atrophic gastritis);
APS 3С – autoimmune thyroid disease and other autoimmune disease (alopecia, vitiligo, myasthenia gravis, etc.)

Other components of autoimmune polyglandular syndrome type 3 may include diseases such as hypogonadism, neurohypophysitis, celiac disease, autoimmune hepatitis, primary biliary cirrhosis,  sclerosing cholangitis, autoimmune thrombocytopenia, autoimmune hemolytic anemia, multiple sclerosis,  some vasculitis and collagenosis.

Criteria for the diagnosis of autoimmune polyglandular syndrome

The primary link in establishing the diagnosis of autoimmune polyglandular syndrome is a well-collected anamnesis, since the presence of similar manifestations in other family members, the frequency and nature of the addition of new symptoms can not only help in establishing a diagnosis, but also indicate a probable & nbsp; character  course of the disease in a particular patient.

At physical examination  it is important, first of all, to pay attention to the skin, nails, hair, teeth, mucous membranes, to identify signs of hypoparathyroidism and candidiasis.

Laboratory and instrumental studies are a very important component in the diagnosis of polyendocrine syndrome, since  directly confirm the presence of hormonal changes. Assessment of the level of calcium, phosphorus and parathyroid hormone in the blood plasma is carried out to diagnose hypoparathyroidism. The level of potassium and sodium, cortisol and ACTH in the blood helps in the diagnosis of adrenal insufficiency.  Blood sugar, glycosylated hemoglobin and results  glucose tolerance test confirm the addition of diabetes mellitus.

To confirm the autoimmune nature of the disease, the presence of autoantibodies is determined  to target organs. For example,  u  50 & mdash; 70% of patients with autoimmune polyglandular syndrome of the second type are determined & nbsp; antithyroid autoantibodies, 10—20% — autoantibodies to islet cells, in 8 —15% — autoantibodies to antigens of the adrenal cortex.

Molecular genetic diagnostics, which can identify a mutated gene, can help in making a diagnosis, & nbsp; both at the stage of clinical manifestations and in the detection of the disease before the manifestation of its symptoms, for example, in relatives of the diseased.

Treatment of patients with polyglandular syndrome: pharmacological and non-pharmacological treatment

Because the disease is autoimmune and multi-organ, treatment is aimed primarily at eliminating the symptoms of the disease and preventing the occurrence of emergency conditions.

Hormone replacement therapy with glucocorticoids and mineralocorticoids is being performed to correct adrenal insufficiency and hypothyroidism. Calcium and vitamin D preparations are used to correct the condition in case of hypoparathyroidism. All drugs are administered in strictly individual dosages. Immunosuppressants such as cyclosporine are used to correct blood sugar levels. In most cases,   insulin therapy.  To eliminate manifestations & nbsp; candidiasis, antifungal drugs such as fluconazole are used.

Patients must be on an individually tailored diet,  compiled on the basis of the results of biochemical blood tests. The diet strictly forbids the intake of alcoholic beverages.

Surgical treatment may be necessary in some cases, such as thymoma. To date, studies are underway to explore the possibility of radical surgical treatment of polyglandular syndrome through transplantation of endocrine organs and tissues.

The treatment of polyendocrine syndrome is aimed primarily at preventing the occurrence of acute conditions requiring emergency medical care, & nbsp; as well as to prevent the addition of other components of the syndrome.