Multiple endocrinopathies of autoimmune nature

In clinical practice, the greatest diagnostic difficulties are presented by endocrine diseases with symptoms of dysfunction of several endocrine glands. In most cases, clinical features of this kind are manifested in hypothalamic-pituitary disorders. However, endocrine syndromes are known, but little studied, in which the functions of several peripheral endocrine glands are primarily impaired. The most common cause of such pathology is autoimmune lesions or tumors of two or more peripheral endocrine organs.

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Forms

Currently, two main immune-endocrine syndromes are known: types I and II.

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Autoimmune polyglandular syndrome type I

Autoimmune polyglandular syndrome type I (APGSI) is characterized by the classic triad: adrenal insufficiency combined with mucocutaneous candidiasis and hypoparathyroidism. The disease is familial, but usually affects one generation, most siblings. It manifests itself more often in childhood and is known as juvenile familial polyendocrinopathy. The cause of the disease is unclear. Autosomal recessive inheritance is possible.

The first manifestation of autoimmune polyglandular syndrome I is usually chronic mucocutaneous candidiasis, most often in combination with hypoparathyroidism; signs of adrenal insufficiency appear later. Sometimes decades pass between the first and subsequent symptoms of the disease in the same patient. The classic triad of the disease is often accompanied by pathology of other organs and systems. About 2/3 of patients with autoimmune polyglandular syndrome I suffer from alopecia, about 1/3 - from malabsorption syndrome, insufficiency of the sex glands; somewhat less often they have chronic active hepatitis, thyroid disease, pernicious anemia, and about 4% develop insulin-dependent diabetes mellitus.

Patients often have antiadrenal and antiparathyroid antibodies. Many of them have hypersensitivity to any agents, some have selective hypersensitivity to fungi, while candidiasis is rarely observed in patients with autoimmune polyglandular syndrome I that developed in adulthood. In adults, it most often accompanies immunological disorders caused by thymoma. Changes in T-lymphocytes have also been described in patients with autoimmune polyglandular syndrome I.

Treatment of adrenal insufficiency and hypoparathyroidism are described in the relevant chapters. Candidiasis is treated quite successfully with ketoconazole, but rehabilitation requires at least 1 year. However, discontinuing the drug and even reducing the dose of ketoconazole often leads to a relapse of candidiasis.

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Autoimmune polyglandular syndrome type II

Autoimmune polyglandular syndrome type II is the most common variant of autoimmune polyglandular syndrome, characterized by damage to 2 or more endocrine organs with the development of adrenal insufficiency, hyper- or primary hypothyroidism, insulin-dependent diabetes mellitus, primary hypogonadism, myasthenia and steatorrhea. These manifestations are often accompanied by vitiligo, alopecia, pernicious anemia. The causes of autoimmune polyglandular syndrome type II are unknown.

However, these diseases always reveal certain immunogenetic and immunological manifestations related to the pathogenesis of the main components of the disease. Apparently, its trigger is the abnormal expression of antigens of the HLA system on the cell membranes of the endocrine glands. The HLA-induced predisposition to autoimmune polyglandular syndrome is realized under the influence of some external factors.

All diseases that occur in combination in autoimmune polyglandular syndrome type II are associated mainly with the histocompatibility antigen HLA-B8. Heritability of the disease is often associated with the transition from generation to generation of the common haplotype HLA-AI, B8. Even in patients with symptoms of dysfunction of 1-2 endocrine glands, organ-specific antibodies can be detected in the blood, including those to the antigens of those organs that are involved in the pathological process, but its clinical manifestations are not detected.

Microscopic examination of these organs reveals massive lymphoid infiltration with the formation of lymphoid follicles. There is a significant replacement of the organ parenchyma with lymphoid tissue, followed by fibrosis and atrophy of the organ. In approximately 3-5% of cases, not autoimmune thyroiditis but another autoimmune pathology develops in the thyroid gland: Graves' disease with a clinical picture of thyrotoxicosis and characteristic pathology in the thyroid gland with minor lymphoid infiltration. Thyroid-stimulating antibodies are found in the blood of these patients.

The most common variant of autoimmune polyglandular syndrome type II is Schmidt syndrome, in which the adrenal glands and thyroid gland are affected by the autoimmune process; autoimmune thyroiditis develops in it. The main clinical manifestations of the syndrome are symptoms of chronic adrenal cortex insufficiency and hypothyroidism, although in some cases the function of the gland is not impaired, especially in the early stages of the disease.

Hypothyroidism in these patients may be latent. In 30% of patients, the syndrome is combined with insulin-dependent diabetes mellitus, in 38%, antibodies to thyroid microsomes are detected, in 11% - to thyroglobulin, in 7% - to islet cells, and in 17% - to steroid-producing cells. The listed antibodies can be detected in relatives of patients even in the absence of clinical manifestations of the disease. They can also have antiparietal antibodies.

Autoimmune polyglandular syndrome II is often accompanied by optic nerve atrophy, lipodystrophy, autoimmune thrombocytopenic purpura, idiopathic diabetes insipidus with autoantibodies to vasopressin-producing cells, multiple endocrine tumor syndrome, hypophysitis, pseudolymphoma, isolated ACTH deficiency, pituitary tumors, scleredema.

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Diagnostics multiple endocrinopathies of an autoimmune nature.

To diagnose the disease, especially in individuals with damage to only one endocrine organ, such as the adrenal glands, it is necessary to determine the content of T4 _and TSH in the blood, the level of glucose on an empty stomach; pay attention to the presence of signs of pernicious anemia, gonadal insufficiency and other endocrine symptoms.

Screening of families with patients with autoimmune polyglandular syndrome type II is performed among its members aged 20 to 60 years every 3-5 years; they are examined for signs of the disease. In addition, they determine fasting glucose, antibodies to islet cell cytoplasm, T4 and TSH levels _in the blood, and the level of urinary excretion of 17-keto- and 17-oxycorticosteroids under basal conditions and under ACTH test conditions.

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Treatment multiple endocrinopathies of an autoimmune nature.

Treatment of the syndrome is complex and comes down to the treatment of its constituent diseases. Its methods are described in the relevant chapters. It should be noted that therapy of adrenal insufficiency with corticosteroids can be accompanied by an improvement in functional disorders caused by autoimmune thyroiditis. These features of the course of combined autoimmune diseases of endocrine organs allow differentiating, for example, Schmidt syndrome from Addison's disease with secondary decrease in thyroid function. It is interesting to note that in some cases of Addison's disease of tuberculous etiology, lymphomatous thyroiditis develops in the thyroid gland, and, on the contrary, with Hashimoto's goiter, the adrenal glands are affected by the autoimmune process quite rarely.

It is also necessary to remember that a decrease in the need for insulin in patients with insulin-dependent diabetes mellitus may be the first manifestation of adrenal insufficiency even before the manifestation of electrolyte disturbances and the appearance of hyperpigmentation. Diabetes mellitus in autoimmune polyglandular syndrome II often requires immunotherapy. However, side effects are also possible. Thus, cyclosporine causes nephrotoxicosis, hepatotoxicosis, decreased hemoglobin levels, hirsutism, gingival hypertrophy, and the development of lymphomas. Antilymphocyte globulin causes anaphylaxis, increased body temperature, skin rashes, transient, mild thrombocytopenia, etc. Cytotoxic agents and azathiaprine contribute to the inhibition of myelopoiesis and the development of malignant neoplasms.

Polyglandular deficiency syndromes include such a combination as pseudohypoparathyroidism and isolated THT deficiency, the cause of which is unclear; this association is obviously of genetic origin. Another combination of diseases (diabetes mellitus and diabetes insipidus, optic nerve atrophy) is considered a genetic anomaly with autosomal recessive inheritance. Polyglandular deficiency can develop in hemochromatosis, when iron deposition is observed not only in the pancreas, liver, skin, as in the classic version of hemochromatosis, but also in the parenchymatous cells of the thyroid and parathyroid glands, pituitary gland and adrenal glands.

"Bronze" diabetes, often observed in hemochromatosis, is caused not only by iron deposition in the skin, but also by concomitant hypocorticism. Loss of function of many endocrine glands can result from lesions of the pituitary gland, adrenal glands, thyroid gland and other endocrine organs by giant cell granulomatosis of unknown etiology (non-tuberculous, non-sarcoidosis, non-philitic). It most often develops in women aged 45-60. The autoimmune nature of the process cannot be ruled out, since lymphoid elements are a constant component of granulomas.