Diagnosis of chronic adrenal insufficiency

Diagnosis of chronic adrenal insufficiency is based on anamnestic data, clinical picture of the disease, the results of the study of the function of the adrenal cortex, as well as taking into account the state of other organs of the endocrine system.

Anamnesis of the disease is characterized by the duration of the course, deterioration of well-being in the autumn-spring season, increased sensitivity to sunburn, decreased body weight, decreased appetite, rapid fatigue after physical exertion, dizziness, fainting.

Based on the analysis of the frequency of clinical symptoms of Addison's disease, it has been shown that the most informative signs are the combination of asthenia and adynamia with a decrease in body weight, hypotension, melanoderma, and mental abnormalities. The presence of hyperpigmentation always indicates a primary adrenal insufficiency.

Adrenal tuberculosis is determined on the basis of active or inactive foci of tuberculous lesion of other organs or the detection of calcifications in the adrenal gland. The tuberculosis process in the adrenal glands is often combined with damage to the genitourinary system. In the absence of a tuberculosis process in other organs, tuberculin tests allow the elimination or confirmation of a chronic infectious process in the adrenal glands. Because of the slow development of tuberculosis infection in the adrenal glands, the symptoms of adrenal insufficiency develop gradually, slowly, for several years and become clinically detectable with almost complete destruction of the adrenal cortex.

With the help of computed tomography and ultrasound, it is possible to diagnose the tuberculosis process, intranasal calcifications, tumors, metastases and fungal diseases. Percutaneous aspiration biopsy of the adrenal glands allows us to clarify the nature of adrenal damage, for example, primary T-cell adrenal lymphoma, accompanied by adrenal insufficiency, or parasitic infections (echinococcus).

The diagnosis of Addison's autoimmune disease is based on the definition of adrenal autoantibodies. To determine them in the blood of patients, the reactions of complement fixation, passive hemagglutination, precipitation are used; indirect immunofluorescent method, which has the greatest sensitivity. It is based on the interaction of the antigen (adrenal tissue) with the antibody (serum of the patient) to form an antigen-antibody complex, which, upon further interaction with the anti-gammaglobulin (labeled with a fluorescent dye), gives specific luminescence on the adrenal glands. If it is found, the reaction is considered positive.

Using the method of indirect immunofluorescence, auto-antibodies to adrenal cortex cells were detected in patients with insulin-dependent diabetes mellitus and their relatives. At the same time the level of cortisol and aldosterone in them was normal, ACTH - increased. The results indicate a hidden adrenal insufficiency in patients with other autoimmune disorders. Timely detection of autoantibodies contributes to early diagnosis of adrenocortical dysfunction.

For the diagnosis of primary adrenal insufficiency, both indirect and direct methods for studying the functional state of the adrenal cortex can be used. Indirect parameters of the function of the adrenal cortex include a sample with a water load, a glycemic curve after loading with glucose, an examination of the content of potassium and sodium in the blood plasma, a Thorn test. Direct methods are the determination of blood and urine levels of ACTH and corticosteroids - cortisol, aldosterone.

The Robinson-Powers-Kepler water test is based on water retention in patients with addison disease after oral administration. This is due to the increased secretion of antidiuretic hormone. A positive test with a water load can be sufficient evidence for the diagnosis of chronic adrenal insufficiency in the absence of kidney disease, heart failure, liver cirrhosis in patients and if fluid retention can be prevented by the prescription of cortisone orally or hydrocortisone intramuscularly at a dose of 50 mg.

Low fasting glucose in the blood, spontaneous hypoglycemia after carbohydrate-rich food and glucose load are typical for most patients with adrenal cortex deficiency. Frequent hypoglycemia with loss of consciousness in the treatment of patients with type I diabetes insulin are suspicious for the presence of symptoms of Addison's disease. In the serum, antibodies to the adrenal cortex are often detected.

For patients with insufficient secretion of corticosteroids, a decrease in the level of potassium and an increase in the sodium content in the blood serum, as well as a decrease in the sodium / potassium ratio, are typical, but even in untreated patients, these indices are clearly detected only in the pre-cri- sis state. Thorne's eosinopenic test, described in detail by L. Soffer and GA Zefirova, is considered as an indirect method for determining the function of the adrenal cortex.

More accurate for the diagnosis of Addison's disease are direct methods for studying the functional state of the pituitary-adrenal system. These include the determination of the content of ACTH, cortisol, aldosterone in blood plasma in patients during the day; study of excretion in the urine of 17-ACS, 17-CS before and after the appointment of ACTH. An increase in the level of ACTH in plasma is an important diagnostic sign of primary adrenal insufficiency. Violated the rhythm of ACTH secretion: the level of ACTH increases both in the morning and at night. But further stimulation of ACTH by prolonged administration of corticoliberin does not cause an increase in hormone production.

The results of the study of the initial content in plasma of cortisol, aldosterone and the daily amount of 17-ORS in urine do not always correctly reflect the function of the adrenal cortex, since in patients with partial damage these parameters can be normal. Therefore, more reliable study of the function of the adrenal cortex in conditions of stimulating tests.

To identify the nature and extent of hormone secretion disorders, the adrenal cortex uses short-term and long-term samples with ACTH. The drug is administered intramuscularly and intravenously. For a short-term trial, the drug ACTH-synakten (firm "Sandos", Switzerland) is used, intravenously. With a view to prolonged stimulation of the adrenal cortex, intramuscularly prescribe a suspension of zinc-corticotropin or synaktene-depot. A short-term sample with intravenous injection allows one to determine the reaction of the adrenal cortex to stress and differentiate the gluco- and mineralocorticoid deficiency according to the level of cortisol and aldosterone in plasma, determined 30 and 60 minutes after rapid intravenous injection of 25 units (0.25 mg) of synactin dissolved in 5 ml of physiological saline. It is believed that with a normal function of the adrenal cortex, a minimum increase in the concentration of cortisol and aldosterone in the plasma under the influence of the drug should be at least 200%. If the level of hormones does not increase with this sample, this indicates that there are no available reserves of the adrenal cortex. A normal increase in the content of cortisol and aldosterone as a result of the sample does not exclude adrenal insufficiency, since this test does not reveal potential reserves.

To determine the potential reserves of the adrenal cortex, a trial is used with prolonged stimulation of the adrenal glands with the use of prolonged ACTH drugs administered intramuscularly: suspensions of zinc-corticotropin and synaktena-depot. In a sample with a suspension of zinc-corticotropin, the drug is administered at 30-40 units intramuscularly daily for 3-5 days. In a sample with synakton, the injection is performed once and also intramuscularly. Determination of 17-ACS in urine is carried out both before the administration of drugs, and during the 1-, 3-, and 5-day stimulation of the adrenal cortex. In healthy people, the excretion of 17-OC in the urine increases to 300-700% of the baseline level. With complete primary adrenal insufficiency, the level of 17-ACS in blood and in urine will be low and the same before and after stimulation. With relative adrenal insufficiency, the initial content of 17-ACS can be normal or decreased, on the 1st day of stimulation it increases to the level of healthy people, however on day 3 the content of 17-ACS remains at the same level. Thus, while maintaining the reserves of hormone secretion by the adrenal cortex, there is a lack of potential reserves. In contrast, with secondary adrenal insufficiency in the first days of ACTH stimulation, hormone secretion may not increase, and in the next 3-5 days their content can reach normal values. An important point for diagnosing chronic adrenal insufficiency is the correct evaluation of the data obtained during the ACTH tests. It is necessary to take into account the initial level of hormones and the degree of their increase after the loading test in percent.

The physician should be aware of the full measure of responsibility when diagnosing hypocorticism, since corticosteroid replacement therapy is prescribed for life and, in case of an erroneous diagnosis, can not be canceled due to suppression of ACTH secretion and development of secondary adrenal insufficiency observed in patients receiving corticosteroids for other diseases.

Differential diagnosis should be conducted between primary and secondary adrenal insufficiency, with diseases occurring with hyperpigmentation, hypotension and gastrointestinal disorders.

Secondary adrenal insufficiency of the pituitary origin is characterized by pallor of the skin, signs of insufficiency of other endocrine glands due to a decrease in the secretion of tropic hormones in the pituitary gland. Hypothyroidism, hypogonadism and insufficient growth are more common. With secondary adrenal insufficiency, unlike the primary one, a reduced level of ACTH and potential reserves of the adrenal cortex are detected with prolonged stimulation.

It is much more difficult to make a differential diagnosis between polyglandular insufficiency of autoimmune origin and pituitary insufficiency. In these cases, in the diagnosis of the autoimmune process, it is important to determine in the blood of patients the organ specific autoantibodies.

Hyperpigmentation of the skin is seen in patients with pellagra, dermatomyositis, scleroderma, melanoma metastasis, liver cirrhosis, hepatochromatosis, with drugs containing arsenic, silver, gold, bismuth. Anamnestic data and results of the study of the function of the adrenal cortex make it possible to exclude all these diseases. It is necessary to remember about hereditary, national pigmentation and individual sensitivity to sunlight. Differential diagnostics with hypotonic disease is simple and carried out with the help of laboratory tests.

Anorexia and gastrointestinal disorders occur in patients with stomach diseases, pregnancy, nephritis, anorexia nervosa, neurasthenia. This group of patients does not have hyperpigmentation. Studies of the functional state of the adrenal cortex help to exclude from them Addison's disease.

With frequent hypoglycemia, a differential diagnosis should be performed with functional and organic hyperinsulinism.

[1], [2], [3], [4], [5], [6], [7]