Autoimmune polyglandular syndrome (APGS) is an autoimmune endocrinopathy that occurs with simultaneous primary multiple lesions of the endocrine glands and other organs. With APGS type 1, there is adrenal insufficiency, candidiasis of the skin and mucous membranes, hypoparathyroidism; APGS type 2 proceeds with the development of adrenal insufficiency, hyper- or hypothyroidism, insulin-dependent diabetes mellitus, primary hypogonadism, myasthenia gravis, steatorrhea, and other disorders. Diagnostics includes the determination of a complex of laboratory parameters (biochemical analysis, blood and urine hormones), ultrasound and CT of the adrenal glands, ultrasound of the thyroid gland. Treatment of disease requires the appointment of hormone replacement therapy (corticosteroids and mineralocorticoids, L-thyroxine).
Meaning
Autoimmune polyglandular syndrome (APGS) is an immunoendocrine disorder characterized by primary functional insufficiency of several endocrine glands, as well as non–endocrine organ-specific diseases. In endocrinology, there are APGS types 1 and 2 (APGS-1, 2), which have their own genetic, immunological and clinical features.
Disease type 1 usually manifests in childhood (10-12 years) and is sometimes referred to in the literature by the term “juvenile familial polyendocrinopathy”. In general, the prevalence of APGS-1 is low, but the disease is somewhat more common in the male population, mainly among residents of Finland, Sardinia, Iran, which is explained by the long-term genetic isolation of these peoples. APGS type 1 includes a triad of signs: adrenal insufficiency, hypoparathyrosis and candidamycosis.
The most common variant of multiple endocrinopathy of an autoimmune nature is APGS type 2, which develops in adults (over 20-30 years old); women predominate among the patients. The components of APGS-2 are adrenal insufficiency, type 1 diabetes mellitus, autoimmune thyroid disease by the type of primary hypothyroidism or thyrotoxicosis. In addition to endocrine disorders, autoimmune polyglandular syndrome types 1 and 2 are accompanied by other organ-specific manifestations.
Causes
Both types of APGS are genetically determined, as indicated by the family-hereditary nature of the disease. At the same time, APGS-1 affects brothers and sisters of the same generation; APGS type 2 – representatives of the same family for several generations.
APGS type 1 is the only known autoimmune disease that has a monogenic nature. A mutation of the autoimmune regulator (AIRE) gene located on the long arm of chromosome 21 (21q22.3) leads to the development of APGS-1. Autoimmune polyglandular syndrome-1 is inherited by autosomal recessive type and is not associated with HLA haplotypes.
APGS type 2 is associated with HLA-haplotype (antigens DR3, DR4, DR5, B8, Dw3). It is likely that the mechanism of APGS-2 development is associated with abnormal expression of HLA-system antigens on the cell membranes of the endocrine glands, which is triggered by any external factors.
Symptoms of APGS type 1
Autoimmune polyglandular syndrome type 1 usually first manifests itself in the first 10 years of life with the development of granulomatous candidiasis (candidamycosis of the skin and mucous membranes) and hypoparathyroidism. In the future (often decades later), chronic adrenal insufficiency (Addison’s disease) joins. The clinical criteria for the diagnosis of the syndrome is a combination of two of the three mentioned endocrine disorders.
Candidiasis in APGS-1 is generalized and affects the mucous membranes of the oral cavity, genitals, respiratory tract and gastrointestinal tract, as well as skin, nail rollers, nails. Hypoparathyroidism is manifested by convulsions of the muscles of the extremities, paresthesia of the skin, laryngospasm, convulsive seizures resembling epilepsy. Adrenal insufficiency in autoimmune polyglandular syndrome increases covertly and may first manifest itself as an addisonic crisis against the background of a stressful state.
The classical triad in autoimmune polyglandular syndrome is often combined with primary hypogonadism (45%), alopecia (30%), malabsorption syndrome (23%), pernicious anemia (14%), chronic autoimmune hepatitis (12%), autoimmune thyroiditis (10%), insulin-dependent diabetes mellitus (4%), vitiligo (4%). Less common are dystrophy of nail plates, hypoplasia of tooth enamel, glomerulonephritis, bronchial asthma, cataracts.
Against the background of autoimmune polyglandular syndrome type 1, women have ovarian hypoplasia (autoimmune oophoritis), accompanied by primary or secondary amenorrhea. Male hypogonadism is manifested by a decrease in libido, impotence, infertility.
Symptoms of APGS type 2
The manifestation of autoimmune polyglandular syndrome type 2 occurs at a mature age (about 30 years). The first manifestation of endocrinopathy is usually chronic adrenal insufficiency. Other autoimmune components (type 1 diabetes mellitus, autoimmune thyroiditis), as a rule, are attached after 7-10 or more years.
Patients with APGS type 2 often develop primary hypogonadism, myasthenia gravis, vitiligo, dermatitis, alopecia, autoimmune gastritis, celiac disease, steatorrhea, polyserositis (pleurisy, pericarditis, ascites), thymoma. With autoimmune polyglandular syndrome, optic nerve atrophy, pituitary tumors, autoimmune thrombocytopenic purpura, etc. can be observed.
Most often in clinical practice there is a variant of autoimmune polyglandular syndrome type 2, combining primary chronic adrenal insufficiency with autoimmune thyroid disease: autoimmune thyroiditis, less often – diffuse toxic goiter (Schmidt syndrome). Multiple endocrinopathies mutually burden each other and aggravate the course of the disease.
Diagnostics
The criteria for making a clinical diagnosis are laboratory and instrumentally confirmed isolated components of autoimmune polyglandular syndrome (cutaneous mucosal candidiasis, hypoparathyroidism and CNN in APGS-1; CNN, autoimmune thyroiditis and diabetes mellitus in APGS-2). In case of type 1 APGS, the most significant is the molecular genetic analysis, which allows to identify a characteristic gene mutation.
Laboratory examination in autoimmune polyglandular syndrome includes the determination of biochemical blood parameters (the level of total and ionized calcium, phosphorus, potassium, sodium, bilirubin, transaminases, alkaline phosphatase, total protein, urea, creatinine, glucose), blood CBS, etc. Important diagnostic information is provided by the results of hormone studies: TSH, free thyroxine, parathyroid hormone, ACTH, insulin, C-peptide, cortisol, renin, aldosterone, somatomedin C, AT-TPO, AT to pancreatic beta cells and GAD, testosterone, LH, FSH, etc.
Instrumental studies include ultrasound of the abdominal cavity, thyroid gland, pelvic organs (in women) and scrotum in men, EchoCG, CT of the adrenal glands. If there are indications, consultations of narrow specialists are held – diabetologist, gastroenterologist, hepatologist, dermatologist, mycologist, neurologist, hematologist, ophthalmologist, gynecologist-endocrinologist, andrologist, rheumatologist.
Treatment
Therapy of autoimmune polyglandular syndrome is a complex task and consists of the treatment of its individual components. The basis of pathogenetic therapy is constant hormone replacement therapy for functional insufficiency of the affected endocrine glands. With adrenal insufficiency, glucocorticoids (hydrocortisone, dexamethasone, prednisone, triamcinolone), mineralocorticoids (DOXA, trimethyl acetate of deoxycorticosterone, etc.) are prescribed, with hypothyroidism – L-thyroxine.
When candidamycosis accompanies autoimmune polyglandular syndrome type 1, antifungal drugs are used. In diabetes mellitus on the background of autoimmune polyglandular syndrome type 2, immunosuppressive therapy with cyclosporine may be required. Patients are recommended to use an increased amount of ascorbic acid and salt. It is forbidden to take alcohol, certain medications.
Forecast
Early detection of autoimmune polyglandular syndrome and adequate replacement therapy make it possible to control the course of the disease. However, the ability to work, as a rule, decreases – patients are assigned group II-III disability.
Patients with APGS are subject to dispensary observation by an endocrinologist and other specialists. With stressful conditions, intercurrent infections, physical or mental overstrain, patients need to increase the dose of hormones. It is necessary to immediately consult a doctor in case of any deterioration in health. Fatal outcome in autoimmune polyglandular syndrome can occur from laryngospasm, visceral candidiasis, acute adrenal insufficiency.