Diagnosis of chronic adrenal insufficiency

The diagnosis of chronic adrenal insufficiency is made on the basis of anamnestic data, the clinical picture of the disease, the results of a study of the function of the adrenal cortex, and also taking into account the state of other organs of the endocrine system.

The anamnesis of the disease is characterized by a long course, deterioration of health in the autumn-spring season, increased sensitivity to sunburn, decreased body weight, decreased appetite, rapid fatigue after physical exertion, dizziness, and 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 combinations of asthenia and adynamia with weight loss, hypotension, melasma, and mental disorders. The presence of hyperpigmentation always indicates primary adrenal insufficiency.

Tuberculosis of the adrenal glands is determined based on active or inactive foci of tuberculous lesions in other organs or the detection of calcifications in the adrenal glands. The tuberculous process in the adrenal glands is often combined with lesions of the genitourinary system. In the absence of a tuberculous process in other organs, tuberculin tests allow one to exclude or confirm a chronic infectious process in the adrenal glands. Due to the slow development of tuberculous infection in the adrenal glands, the symptoms of adrenal insufficiency develop gradually, slowly, over several years and become clinically detectable with almost complete destruction of the adrenal cortex.

Computed tomography and echography can diagnose tuberculosis, intra-adrenal calcifications, tumors, metastases, and fungal diseases. Percutaneous aspiration biopsy of the adrenal glands allows for a more precise characterization of the adrenal gland lesion, such as primary T-cell lymphoma of the adrenal glands accompanied by adrenal insufficiency or parasitic infections (echinococcus).

The diagnosis of autoimmune Addison's disease is based on the determination of adrenal autoantibodies. To determine them in the blood of patients, complement fixation reactions, passive hemagglutination, precipitation, and the indirect immunofluorescence method, which has the highest sensitivity, are used. It is based on the interaction of an antigen (adrenal tissue) with an antibody (patient serum) to form an antigen-antibody complex, which, upon further interaction with antigammaglobulin (labeled with a fluorescent dye), produces a specific glow on adrenal sections. If it is detected, the reaction is considered positive.

Using the indirect immunofluorescence method, autoantibodies to adrenal cortex cells were detected in patients with insulin-dependent diabetes mellitus and their relatives. At the same time, their cortisol and aldosterone levels were normal, and ACTH was elevated. The results obtained indicate the presence of latent adrenal insufficiency in patients with other autoimmune disorders. Timely detection of autoantibodies facilitates early diagnosis of adrenal cortex dysfunction.

To diagnose primary adrenal insufficiency, both indirect and direct methods of studying the functional state of the adrenal cortex can be used. Indirect indicators of adrenal cortex function include a water load test, a glycemic curve after a glucose load, a study of the potassium and sodium content in blood plasma, and the Thorne test. Direct methods include determining the content of ACTH and corticosteroids - cortisol, aldosterone - in the blood and urine.

The Robinson-Power-Kepler water test is based on the retention of water in the body of patients with Addison's disease after its introduction into the body. This is associated with an increase in the secretion of antidiuretic hormone. A positive water load test can be sufficiently conclusive 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 preliminary administration of cortisone orally or hydrocortisone intramuscularly at a dose of 50 mg.

Low fasting blood glucose, spontaneous hypoglycemia after carbohydrate-rich meals and glucose loads are characteristic of most patients with adrenal cortex insufficiency. Frequent hypoglycemia with loss of consciousness during insulin treatment of type I diabetes patients is suspicious for the presence of symptoms of Addison's disease. Antibodies to the adrenal cortex are often found in their blood serum.

Patients with insufficient secretion of corticosteroids are characterized by a decrease in the potassium level and an increase in the sodium content in the blood serum, as well as a decrease in the sodium/potassium ratio, but even in untreated patients these indicators are clearly detected only in the pre-crisis state. The Thorne eosinopenic test, described in detail by L. Soffer and G. A. Zefirova, is considered an indirect method for determining the function of the adrenal cortex.

More accurate methods for diagnosing Addison's disease are direct methods of studying the functional state of the pituitary-adrenal system. These include determining the content of ACTH, cortisol, aldosterone in the blood plasma of patients during the day; studying the excretion of 17-OCS, 17-KS with urine before and after the administration of ACTH. An increase in the level of ACTH in the plasma is an important diagnostic sign of primary adrenal insufficiency. The rhythm of ACTH secretion is disrupted: the level of ACTH increases both in the morning and at night. However, 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 plasma cortisol, aldosterone content and the daily amount of 17-OCS in urine do not always correctly reflect the function of the adrenal cortex, since in patients with partial damage to them, these indicators may be normal. Therefore, a more reliable study of the function of the adrenal cortex is under stimulating tests.

Short-term and long-term ACTH tests are used to identify the nature and degree of hormone secretion disorders by the adrenal cortex. The drug is administered intramuscularly and intravenously. For a short-term test, the ACTH drug synacthen (Sandos, Switzerland) is administered intravenously. For long-term stimulation of the adrenal cortex, a zinc-corticotropin suspension or synacthen-depot is administered intramuscularly. A short-term test with intravenous administration allows one to determine the adrenal cortex's response to stress and differentiate gluco- and mineralocorticoid insufficiency by the level of cortisol and aldosterone in the plasma, determined 30 and 60 minutes after rapid intravenous administration of 25 U (0.25 mg) of synacthen dissolved in 5 ml of saline. It is believed that with normal adrenal cortex function, the minimum increase in plasma cortisol and aldosterone concentrations under the influence of the drug should be at least 200%. If the hormone level does not increase with this test, this indicates the absence of available reserves of the adrenal cortex. A normal increase in cortisol and aldosterone levels as a result of the test does not exclude adrenal insufficiency, since this test does not reveal potential reserves.

To determine the potential reserves of the adrenal cortex, a test with prolonged stimulation of the adrenal glands is used using prolonged ACTH preparations administered intramuscularly: zinc-corticotropin suspension and synacthen-depot. In the test with zinc-corticotropin suspension, the drug is administered intramuscularly at 30-40 U daily for 3-5 days. In the test with synacthen, the injection is administered once and also intramuscularly. Determination of the content of 17-OCS in urine is carried out both before the administration of the drugs and during the 1st, 3rd, 5th day of stimulation of the adrenal cortex. In healthy people, the excretion of 17-OCS in urine increases to 300-700% of the initial level. In complete primary adrenal insufficiency, the level of 17-OCS in the blood and urine will be low and the same before and after stimulation. In relative adrenal insufficiency, the initial content of 17-OCS may be normal or decreased, on the 1st day of stimulation it increases to the level of healthy people, but on the 3rd day the content of 17-OCS remains at the same level. Thus, while the available reserves of hormone secretion by the adrenal cortex are preserved, there is a lack of potential reserves. On the contrary, in secondary adrenal insufficiency, there may be no increase in hormone secretion in the first days of ACTH stimulation, and in the following 3-5 days their content may reach normal values. An important point for diagnosing chronic adrenal insufficiency is the correct assessment of the data obtained during 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 must be aware of the full extent of responsibility when diagnosing hypocorticism, since replacement therapy with corticosteroids is prescribed for life and in the case of an erroneous diagnosis cannot be canceled due to the suppression of ACTH secretion and the development of secondary adrenal insufficiency observed in patients receiving corticosteroids for other diseases.

Differential diagnosis should be made between primary and secondary adrenal insufficiency, with diseases that occur with hyperpigmentation, hypotension and gastrointestinal disorders.

Secondary adrenal insufficiency of pituitary origin is characterized by pale skin, signs of insufficiency of other endocrine glands due to decreased secretion of pituitary tropic hormones. Hypothyroidism, hypogonadism and insufficient growth are most often observed. In secondary adrenal insufficiency, in contrast to primary, a reduced level of ACTH and potential reserves of the adrenal cortex are detected during their 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 organ-specific autoantibodies in the blood of patients.

Hyperpigmentation of the skin occurs in patients with pellagra, dermatomyositis, scleroderma, melanoma metastases, liver cirrhosis, hepatochromatosis, and treatment with drugs containing arsenic, silver, gold, and bismuth. Anamnestic data and the results of the study of the function of the adrenal cortex allow us to exclude all these diseases. It is necessary to remember about hereditary, national pigmentation, and individual sensitivity to sunlight. Differential diagnostics with hypotension is simple and is carried out using laboratory tests.

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

In case of frequent hypoglycemia, differential diagnosis should be made with functional and organic hyperinsulinism.

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