Schmidt syndrome is a multiple endocrinopathy with a hereditary predisposition, including primary chronic adrenal insufficiency (CAI), autoimmune thyroid disease (more often in the form of lymphocytic thyroiditis, less often – diffuse toxic goiter). The clinic consists of symptoms of hypocorticism (hyperpigmentation of the skin, signs of hypoglycemia, hypotension), hypothyroidism (swelling, lethargy, hair loss) or thyrotoxicosis (irritability, tremor). The diagnosis is made based on the level of hormones of the adrenal cortex, thyroid gland. Lifelong hormone replacement therapy is prescribed for treatment.
ICD 10
E31.0 Autoimmune polyglandular insufficiency
Meaning
Schmidt syndrome (autoimmune polyglandular syndrome type 2, thyroadrenocortical insufficiency) is a symptom complex consisting of primary hypocorticism and hypothyroidism (rarely hyperthyroidism). It was first described in 1926 by the German endocrinologist M. Schmidt. This syndrome is the most common variant of polyendocrine disorders of autoimmune genesis (it occurs in 1.4-4.5 people per 100,000 population). The ratio of women to men is 3:1. The average age of manifestation of the disease is 30-35 years. In isolated cases, the syndrome is observed in children.
Causes
The exact etiology of Schmidt syndrome is unknown. Many researchers classify it as a group of hereditary diseases with an autosomal recessive type of inheritance. Certain antigens of the main histocompatibility complex – HLA-B8, HLA-DW3 – are considered to be a genetic marker of predisposition to Schmidt syndrome.
Also, as evidence of the connection of some haplotypes with the occurrence of pathology, the fact that cases of Schmidt syndrome are more common among close relatives than among strangers is considered. The risk of developing this syndrome increases if a person has other autoimmune diseases, such as Sjogren’s syndrome, dermatomyositis, rheumatoid arthritis, etc.
Pathogenesis
Due to unknown reasons, a genetically predisposed organism has a violation of the regulation of T-cell immunity, namely, excessive activation of T-killers and T-helpers, suppression of T-suppressors. This leads to an autoimmune lesion of the endocrine target organs (thyroid gland and adrenal cortex) – their destruction, atrophy, and a decrease in hormone production develop.
Aldosterone deficiency causes a water-electrolyte imbalance, a decrease in vascular tone, cortisol deficiency reduces resistance to various stressors (mainly infections), increases the threshold of sensitivity of cardiomyocytes and vascular smooth muscle cells to catecholamines, disrupts gluconeogenesis and glycogenolysis in the liver.
Due to the low level of cortisol, the concentration of adrenocorticotropic and melanocytostimulating hormone increases according to the feedback principle, which causes excessive deposition of melanin in the skin. Deficiency of triiodothyronine and thyroxine slows down all metabolic processes in the body (redox reactions, synthesis and catabolism), which disrupts the functioning of all organs and systems, primarily the central nervous, cardiovascular.
Symptoms
Manifestations of CAI
In the vast majority of cases, Schmidt syndrome manifests with adrenal insufficiency. The clinical picture develops gradually, over several months or even years. There is general and muscle weakness, loss of appetite, weight loss. In almost all cases, there are signs of hypoglycemia – a feeling of fear, trembling throughout the body, sweating, tachycardia. Hyperpigmentation of the skin is considered a characteristic feature, it acquires a brown-bronze hue.
Changes are especially pronounced in open areas of the body (face, neck, hands), areas subject to friction (axillary, inguinal, palmar folds, elbow and knee bends), nipples of the mammary glands. The mucous membrane of the oral cavity is also pigmented – the gums, soft, hard palate are covered with gray-black spots. An enlarged thyroid gland in many patients causes discomfort in the neck.
Due to weak vascular tone, symptoms of low blood pressure are observed – dizziness, orthostatic hypotension, loss of consciousness (fainting). Dyspeptic phenomena are not uncommon – abdominal pain (may be paroxysmal), nausea, vomiting, diarrhea. Due to reduced resistance to infections, patients with Schmidt syndrome are prone to frequent respiratory viral diseases.
Symptoms of hypothyroidism
Approximately 7-10 years after the manifestation of Schmidt syndrome, autoimmune thyroiditis occurs, which is asymptomatic in the first months (phases of euthyroidism and subclinical hypothyroidism). After a while, manifest hypothyroidism occurs. Patients become drowsy, inhibited, their cognitive functions (memory, attention) deteriorate. There is swelling, especially pronounced on the face, neck, hands, brittleness, hair loss, nails. The tongue thickens, teeth marks remain on its surface.
Due to the weakening of the motor function of the intestine, constipation occurs. Sometimes pain develops in the extremities according to the type of radiculopathy due to swelling and compression of nerve roots and fibers. Carpal tunnel syndrome is the most typical. Possible mental changes in the form of depressive disorders, psychoses. Due to metabolic shifts in the myocardium, patients often experience aching pains in the heart area. Menstrual disorders are common in women.
Symptoms of thyrotoxicosis
Diffuse toxic goiter (DTG) in Schmidt syndrome is extremely rare and is considered, rather, its atypical variant. Patients become irritable, their mood often changes, sleep worsens, up to insomnia. Characterized by constant subfebrility, tremor of the whole body, arterial hypertension. Another typical sign of hyperthyroidism is ophthalmopathy, manifested by exophthalmos, double vision.
Complications
The most threatening complication of Schmidt syndrome, which often leads to death, is considered an adrenal crisis – acute adrenal insufficiency, in which high fever, severe abdominal pain, a sharp drop in blood pressure (vascular collapse) occurs. Due to low infection resistance, patients have a high risk of pneumonia, meningitis, tuberculosis.
Another complication associated with a high mortality rate is hypothyroid coma. With hypothyroidism, a large amount of fluid may accumulate in the serous cavities (pericardium, pleural, abdominal cavity). Pronounced swelling of the soft tissues of the pharynx can lead to obstructive sleep apnea syndrome. With thyrotoxicosis, atrial fibrillation often occurs, which increases the risk of blood clots and cardioembolic stroke.
Diagnostics
Patients with Schmidt syndrome are supervised by an endocrinologist. In the diagnosis of pathology, physical examination is important. During the examination, attention is drawn to the thickening and dryness of the skin, cold limbs, a decrease or absence of tendon reflexes. With auscultation of the heart, you can often hear muffled heart tones, slowing heart rate. To verify the diagnosis , the following are assigned:
- Routine laboratory tests. In the general blood test, hypochromic anemia, eosinophilia, lymphocytosis are detected. In the biochemical analysis of blood, low glucose, sodium, high cholesterol, triglycerides, potassium are noted.
- The study of thyroid hormones. With hypothyroidism, a high concentration of thyroid–stimulating hormone, antibodies to thyroperoxidase, thyroglobulin, a decrease in free thyroxine (T4) is detected, with thyrotoxicosis – a decrease in TSH, high T4, antibodies to TSH receptors.
- The study of adrenal hormones. A decrease in the content of aldosterone, cortisol and an increase in adrenocorticotropic hormone (ACTH), a high titer of antibodies to steroid 21-hydroxylase are determined. The stimulation test with ACTH is negative.
- Instrumental research. During CT or MRI of the adrenal glands, their atrophy is visualized. Ultrasound of the thyroid gland shows its diffuse increase, decrease in echogenicity. The ECG shows atrial fibrillation, signs of hyperkalemia (bradycardia, high pointed T teeth, expansion of QRS complexes). During ophthalmoscopy, it is possible to detect disc edema or optic atrophy in patients with DTG.
Differential diagnosis of Schmidt syndrome should be carried out according to the symptoms prevailing in the clinical picture. Hyperpigmentation of the skin and mucous membranes should be distinguished from Cushing’s disease, hemochromatosis. Signs of hypoglycemia can be observed with insulinoma, nezidioblastosis. Muscle weakness must be differentiated from muscular dystrophies.
Treatment
Conservative therapy
The beginning of therapy of patients is always carried out in a hospital (department of endocrinology). The basis of treatment is constant hormone therapy. When an improvement in the general condition of the patient is achieved, regression of clinical symptoms and normalization of laboratory parameters, the dose of the drug can be reduced to maintenance, but the intake remains lifelong. In the conservative therapy of Schmidt syndrome , the following means are used:
- Corticosteroids. Glucocorticoids (hydrocortisone) and mineralocorticoids (fludrocortisone) are prescribed taking into account the physiological rhythm of hormone secretion (2/3 of the daily dose in the morning, 1/3 in the evening). In stressful situations (surgery, infectious disease accompanied by fever), it is necessary to increase the dose of medications 2-3 times.
- Thyroid hormones. The drug L-thyroxine is used. The dose is selected individually under the control of TSH. In the elderly and in people suffering from coronary heart disease, in order to avoid aggravation of angina episodes, treatment should begin with small doses.
- Thyrostatic agents. To suppress the hormone-producing function of the thyroid gland, thyrostatic agents (propylthiouracil, thiamazole) are used either in monotherapy mode or in combination with levothyroxine (the “block and replace” scheme).
- Radioactive iodine. If the drug treatment of thyrotoxicosis is ineffective, radioactive iodine therapy is used.
- Beta-blockers. These drugs are prescribed to reduce the adrenergic manifestations of thyrotoxicosis. Propranolol, which suppresses the peripheral conversion of T4 to T3, is considered to be the means of choice.
With a combination of chronic adrenal insufficiency and hypothyroidism, treatment should always begin with the correction of hypocorticism. This is due to the fact that levothyroxine accelerates the clearance of glucocorticoids in the liver, and its administration to a patient with uncompensated CAI can provoke the development of acute adrenal insufficiency.
Surgical treatment
If conservative therapy of hyperthyroidism is unsuccessful (frequent relapses) or drug intolerance, surgical removal of the thyroid gland is resorted to – total thyroidectomy. Prior to surgery, it is necessary to achieve a state of euthyroidism (normalization of thyroid hormone indicators) with thyrostatics or large doses of potassium iodide. After removal of the gland, levothyroxine is prescribed in a replacement dose.
Prognosis and prevention
With timely diagnosis and well-conducted therapy, Schmidt syndrome has a favorable prognosis. The patient’s life expectancy may not differ in any way from that in the general population. The main causes of death in decompensated hormonal deficiency are severe generalized infections, adrenal crisis, myxedematous coma.
Since the exact causes of the disease are unknown, there are no methods of primary prevention. Secondary prevention (prevention of complications) consists in regular monitoring of clinical (general well-being of the patient, blood pressure) and laboratory parameters (concentration of TSH, glucose, potassium).
Literature
- Update on autoimmune polyendocrine syndrome (APS)/ C. Betterle, R. Zanchetta// Acta. Biomed. Ateneo. Parmense. — 2003. — Vol. 74, № 1.
- Autoimmune polyglandular syndrome type 2. Typical difficulties of diagnosis and treatment/ N.Y. Sviridenko, M.V. Brizhan, G.F. Alexandrova// Clinical thyroidology. – 2003. — Vol. 1, No. 4.