Syndromes of polyglandular insufficiency

Polyglandular deficiency syndromes (autoimmune polyglandular syndromes; polyendocrine deficiency syndromes) are characterized by concurrent dysfunction of several endocrine glands. Etiology in most cases. Symptoms are determined by a combination of endocrine deficiencies, which may constitute one of three known types of pathology. Diagnosis is based on the results of hormonal studies and determination of antibody levels against the endocrine glands involved in the pathological process. Treatment includes replacement of the lost or deficient hormone.

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Causes of polyglandular insufficiency syndrome.

The development of endocrine deficiencies can be caused by infections, infarctions or tumors that cause partial or complete destruction of the endocrine gland. However, the trigger for polyglandular insufficiency is an autoimmune reaction that leads to the development of autoimmune inflammation, lymphocytic infiltration and partial or complete destruction of the endocrine gland. The involvement of one endocrine gland in the pathological autoimmune process is almost always followed by the involvement of other glands, leading to the development of multiple endocrine deficiencies. Three models of emerging autoimmune disorders are described.

Type I

Onset is usually in childhood (especially between 3 and 5 years of age) or in adults up to 35 years of age. Hypoparathyroidism is the most common endocrine abnormality (79%), followed by adrenal insufficiency (72%). Development of gonadal insufficiency occurs after puberty in 60% of women and about 15% of men. Chronic mucocutaneous candidiasis is a characteristic pathology. Malabsorption associated with cholecystokinin deficiency may occur; other etiologic factors include interstitial lymphangiectasia, IgA deficiency, and bacterial overgrowth. Although two-thirds of patients have antibodies to pancreatic glutamic acid decarboxylase, development of type 1 diabetes mellitus is uncommon. Ectodermal diseases (e.g. enamel hypoplasia, tympanic membrane sclerosis, tubulointerstitial pathology, keratoconjunctivitis) may also occur. Type I may develop as a hereditary syndrome, usually transmitted in an autosomal recessive manner.

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Type II (Schmidt syndrome)

Multiple endocrine deficiencies usually develop in adulthood, with a peak at age 30. This pathology is twice as common in women. The adrenal cortex and often the thyroid gland and pancreatic islet cells are always involved in the pathological process, the pathology of which is the cause of type 1 diabetes. Antibodies against target organs are often detected, especially against adrenocorticotropic hormones cytochrome P450. There may be a deficiency of both mineralocorticoid and glucocorticoid functions. Destruction of the endocrine glands mostly develops as a result of cell-mediated autoimmune reactions, or as a result of a decrease in the suppressor function of T cells, or as a result of the development of other types of T-cell-mediated damage. A characteristic sign is a decrease in systemic T-cell-mediated immunity, manifested by negative results of intradermal tests for standard antigens. In first-degree relatives, reactivity is also reduced by approximately 30%, with normal endocrine function.

Some patients are found to have thyroid-stimulating antibodies and initially present with clinical symptoms of hyperthyroidism.

Theoretically, specific HLA types may have increased sensitivity to certain viruses, which may induce an autoimmune reaction. The pathology is usually inherited in an autosomal dominant manner, with variable expressivity.

Ill type

Type Ill is characterized by endocrine disorders that develop in adults, especially in middle-aged women. In this case, the adrenal cortex is not involved in the pathology, but at least 2 of the following pathologies develop: thyroid dysfunction, type 1 diabetes, pernicious anemia, vitiligo, and alopecia. Heritability may be autosomal dominant, with partial penetrance.

Symptoms of polyglandular insufficiency syndrome.

Clinical manifestations of polyendocrine deficiency syndrome in patients consist of the sum of symptoms of individual endocrine diseases. In these syndromes, there are no such specific clinical signs as in a single endocrine pathology. Therefore, in patients with a diagnosed endocrine disease, after a certain period of time, screening (clinical examination and laboratory diagnostics) should be carried out for the presence of additional endocrine deficiencies. Relatives of patients with this pathology should be aware of the diagnosis, and they are strongly recommended to undergo a screening medical examination as prescribed by a doctor. Measuring the levels of antibodies to glutamic acid decarboxylase can help in establishing the degree of risk of developing pathology.

Diagnostics of polyglandular insufficiency syndrome.

The diagnosis is made clinically and confirmed by laboratory detection of hormone deficiency. Measurement of autoantibody levels to the endocrine gland tissue involved in the pathological process can help differentiate autoimmune endocrine syndrome from other causes of intraorgan pathology (e.g., adrenal hypofunction of tuberculous etiology, non-autoimmune hypothyroidism).

Polyendocrine deficiency syndrome may indicate pathology of the hypothalamic-pituitary zone. In almost all cases, elevated plasma levels of triple pituitary hormones indicate a peripheral nature of the developing defect; however, hypothalamic-pituitary insufficiency sometimes develops as part of type II polyendocrine deficiency syndrome.

Patients at risk without clinical manifestations of the syndrome should be tested for the presence of autoantibodies, since these antibodies can circulate in the blood for a long time without causing any endocrine pathology.

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Treatment of polyglandular insufficiency syndrome.

Treatment of various endocrine pathologies developing in specific endocrine organs has been discussed in the relevant chapters of this Guide. The presence of signs of multiple organ endocrine pathology in the clinical picture may complicate treatment.

Chronic candidiasis of the skin and mucous membranes usually requires long-term antifungal therapy. If the patient is given immunosuppressive doses of cyclosporine at the early stages of endocrine disorders (within the first few weeks or months), then successful treatment can be achieved.

IPEX syndrome

IPEX (immune disorders, polyendocrinopathy, enteropathy, syndrome, X-linked) is a syndrome inherited in an autosomal recessive manner and characterized by pronounced immune autoaggression.

Without treatment, IPEX syndrome is usually fatal within the first year of life after diagnosis. Enteropathy leads to diarrhea. Immunosuppressive therapy and bone marrow transplantation can prolong life, but the syndrome is incurable.

POEMS syndrome

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes, Crowe-Fukase syndrome) is a non-autoimmune polyendocrine deficiency syndrome.

POEMS syndrome probably results from circulating immunoglobulins produced by abnormal plasma cell aggregates. Patients may develop hepatomegaly, lymphadenopathy, hypogonadism, type 2 diabetes mellitus, primary hypothyroidism, hyperparathyroidism, adrenal insufficiency, and increased monoclonal IgA and IgG in myeloma and skin abnormalities (eg, skin hyperpigmentation, skin thickening, hirsutism, angiomas, hypertrichosis). Patients may present with edema, ascites, pleural effusion, papilledema, and fever. Patients with this syndrome may also have elevated circulating cytokines (IL1p, IL6), vascular endothelial growth factor, and tumor necrosis factor-a.

Treatment involves autologous hematopoietic stem cell transplantation followed by chemotherapy and radiation therapy. Five-year survival for this pathology is about 60%.