Treatment of chronic adrenal insufficiency

Treatment of chronic adrenal insufficiency is aimed, on the one hand, at eliminating the process that caused damage to the adrenal glands and, on the other hand, at replacing the lack of hormones.

If a tuberculous process in the adrenal glands is suspected, it is necessary to prescribe anti-tuberculosis drugs in courses under the supervision of a phthisiatrician. Patients with autoimmune damage to the adrenal glands are treated with levomisol and thymosin, aimed at normalizing the deficiency of T-suppressors. At present, it has not received widespread use.

The recommended diet for hypocorticism should contain an increased amount of calories, proteins, vitamins, and table salt up to 3-10 g/day.

Replacement therapy with synthetic hormones that have glucocorticoid, mineralocorticoid and anabolic effects is vital for patients with chronic adrenal insufficiency and cannot be canceled under any circumstances. Compensation for adrenal insufficiency depends not only on the amount of the drug administered, but also on various conditions associated with the functional state of the body. Synthetic analogs of hormones behave in the body differently than natural ones. For example, it is known that the specific protein transcortin binds about 92% of cortisol and only 70% of its synthetic analogs. It is believed that absorption of hormones in the gastrointestinal tract is almost complete, but with various disorders of the stomach and intestines, these conditions may be violated. Synthetic analogs of glucocorticoid action are used for oral administration: hydrocortisone, cortisone acetate, prednisolone, prednisone, methylprednisolone. Hydrocortisone is the only glucocorticoid that has the qualities of a natural hormone. It is currently registered in Russia under the name Cortef, and is used in tablets of 5, 10, and 20 mg.

Treatment with cortisone began in the 1930s and, despite the emergence of many new analogues, has not lost its significance to this day. Cortisone in the liver is mainly converted into cortisol and becomes physiologically active. The highest concentration of the drug in the blood is determined 1-2 hours after administration, and is almost undetectable after 8-10 hours. 9a-fluorocortisol is more effective than cortisone - already 30 minutes after administration, its level in the blood increases significantly, reaching a maximum after 6-8 hours. Prednisolone remains in the blood for 12-36 hours, and hydrocortisone administered intramuscularly - 4-6 hours. To compensate for chronic adrenal insufficiency, it is necessary to use a combination of prednisolone and cortisone. The dose of drugs depends on the severity of the disease and the degree of compensation.

In mild cases of chronic adrenal insufficiency, it is recommended to treat with cortisone at a dose of 12.5-25 mg/day in one or two doses. If the dose is taken once, then in the morning after breakfast. The treatment can be combined with the prescription of ascorbic acid 1-1.5 g/day during meals.

For moderate severity of the disease, prednisolone is usually prescribed - 5-7.5 mg after breakfast, and in the afternoon - 25 mg of cortisone acetate.

Patients with severe chronic adrenal insufficiency, which is observed both in Addison's disease and after adrenal removal due to Itsenko-Cushing's disease and other diseases, sometimes have to prescribe glucocorticoids in three doses and necessarily combine them with DOXA preparations. For example, prednisolone is recommended in a dose of 5-7.5 mg in combination with 1 DOXA tablet under the tongue after breakfast, cortisone - in doses of 25 mg after lunch and 12.5 mg after dinner. In case of low blood pressure and poor appetite, 1 DOXA tablet can be added to the prescriptions during the day. It is believed that the given doses, although considered schematic, should compensate for adrenal insufficiency, if there are no reasons requiring their increase. Objective indicative effects of glucocorticoids include increased body weight, cessation of nausea and gastrointestinal disorders, decreased pigmentation of the skin and mucous membranes, and improvement or restoration of water tolerance.

Radioimmunoassay of ACTH, cortisol, aldosterone, and renin activity in plasma is considered to be of little use for systematically assessing the effectiveness of replacement therapy for Addison's disease.

In moderate to severe chronic adrenal insufficiency, most patients with Addison's disease and all patients after adrenalectomy should be given drugs with mineralocorticoid effect in addition to glucocorticoid drugs. The daily requirement for deoxycorticosterone acetate is 5-10 mg. DOXA preparations are available in various forms for oral and intramuscular administration. DOXA tablets of 5 mg are used sublingually. 0.5% oil solution of DOXA is used 1 ml intramuscularly. The prolonged-release drug trimethyl acetate of deoxycorticosterone is prescribed intramuscularly at 1 ml once every 10-12 days. The most active synthetic mineralocorticoid is fludrocortisone acetate. In Poland it is produced under the name Cortinef, and in the UK - Florinef. The drug in a dose of 0.05-0.1 mg is used as a maintenance drug. During the period of decompensation of the disease, its dose is increased by 2-3 times. Objective indicators of the action of mineralocorticoids include an increase in blood pressure, normalization of the sodium/potassium ratio, an increase in the sodium level in plasma and a decrease in the potassium content.

There are several important conditions for replacement therapy in chronic adrenal insufficiency. The dose and time of administration of drugs should be prescribed taking into account the production and daily rhythm of excretion of corticosteroids in a healthy person: 2/3 of the daily dose is administered from 7-9 am and % - in the afternoon; drugs are always prescribed after meals. The use of corticosteroids for years can lead to gastrointestinal tract disorders; in stress, infections, operations, injuries, the dose of gluco- and mineralocorticoids increases 2-3 times compared to the maintenance dose.

In the event of gastrointestinal disorders in patients with chronic adrenal insufficiency, oral medications are replaced by parenteral administration of hydrocortisone at 50-100 mg 4-6 times a day and DOXA at 5-15 mg until the condition is compensated.

It is necessary to dwell on the peculiarities of patient management after adrenal gland removal due to Itsenko-Cushing's disease. After removal of one adrenal gland, hormonal therapy is not prescribed, since the remaining adrenal gland compensates for the body's need for hormones. After removal of the second adrenal gland (stage II), immediately on the 1st day, patients receive 75-100 mg of water-soluble hydrocortisone intravenously by drip. At the same time, intramuscular injections of hydrocortisone are prescribed according to the following scheme: 1-2 days - 50-75 mg every 3 hours, 3rd day - 50 mg every 4-5 hours, 4-5th - 50 mg every 5 hours, 6-7th days - 50 mg every 8 hours, 9-10th - 50 mg 2 times a day. As a rule, from the 8th-9th day, patients are gradually transferred to oral corticosteroids, and a fixed dose of drugs is established during observation. Prednisolone is prescribed at 5-15 mg / day or 5 mg of the drug in the morning with 1 tablet of DOXA, or 1 tablet of Cortinef and 25 mg of cortisone in the afternoon. If hypertension persists in patients after removal of the adrenal glands, the dose of replacement therapy is prescribed the same as without hypertension, and DOXA drugs are also used. Hormone replacement therapy is combined with antihypertensive drugs, preference is given to rauwolfia drugs. It should be noted that Addisonian crisis in patients with adrenal insufficiency and hypertension can occur against the background of high blood pressure. Under these conditions, patients need therapy aimed at eliminating the Addisonian crisis.

After minor surgical interventions, patients with chronic adrenal insufficiency (abscess opening, biopsy, tooth extraction) are given 50 mg of hydrocortisone intramuscularly 3 times on the 1st day, 50 mg 2 times on the 2nd-3rd day, and from the 3rd-4th day the patient is transferred to the usual dose of corticosteroid drugs in tablets.

When patients with chronic adrenal insufficiency undergo planned surgical interventions, hydrocortisone is administered intramuscularly at 50 mg every 8 hours the day before the operation. On the day of the operation, 75 mg of hydrocortisone is administered intramuscularly, and during the operation, 75-100 mg of water-soluble hydrocortisone in saline or 5% glucose solution is administered intravenously by drip. On the 1st-2nd day after the operation, hydrocortisone is administered intramuscularly at 50-75 mg every 6 hours. On the 3rd-4th day - 50 mg every 8 hours, and on the 5th-6th day - 50 mg 2 times a day, and prednisolone is used orally at 5-10 mg per day. On the 7th day, 50 mg of hydrocortisone is administered intramuscularly and 5 mg of prednisolone 2-3 times a day. From the 8th day, patients are transferred to the usual replacement oral therapy with corticosteroids according to a fixed dose, individual for each patient. In addition, during the first 3-4 days, patients receive 5-10 mg of DOXA as a single intramuscular injection. In the postoperative period, careful monitoring of the patient's condition is necessary. For this purpose, blood pressure should be measured every hour. In case of signs of adrenal insufficiency, urgently begin additional intravenous administration of water-soluble hydrocortisone at the rate of 75 mg per 1-1.5 hours. The amount of hormones administered should be large, and the duration of their use may vary depending on the patient's condition, the severity of the surgical intervention, and complications.

In case of emergency surgery, 75-100 ml of hydrocortisone is administered intramuscularly immediately before the operation, and then according to the given scheme.

Symptoms of overdose of both glucocorticoid and mineralocorticoid drugs may occur during the treatment of chronic adrenal insufficiency. This is evidenced by rapid weight gain, headaches, muscle weakness, increased blood pressure, fluid retention, facial swelling, decreased plasma potassium levels, and increased sodium levels. The dose of the administered drugs should be reduced by at least half. Overdose symptoms resolve slowly over 4-8 weeks. The maintenance dose should be reduced after drug-induced hypercorticism has been eliminated.

This phenomenon often occurs when glucocorticosteroids are prescribed in increased doses. Adding DOXA to the therapy allows for a reduction in the dose of glucocorticoid hormones and compensation for adrenal insufficiency.

In conclusion, it is necessary to consider the features of replacement therapy in patients with chronic adrenal insufficiency during pregnancy, in combination with diabetes mellitus, diseases of the thyroid and parathyroid glands. The dose of replacement therapy during pregnancy remains the same, a slight increase is required after the 3rd month. All patients are hospitalized before delivery. During delivery, hormones are administered under the same conditions as during planned operations. With a combination of chronic adrenal insufficiency and diabetes mellitus, it is recommended to first compensate for the adrenal insufficiency, and then increase the insulin dose. In patients with a combination of chronic adrenal insufficiency and hypothyroidism or thyrotoxicosis, full compensation of the adrenal insufficiency is first achieved, and then either thyroxine or antithyroid therapy is added. The same conditions are met in the presence of hypoparathyroidism. Patients with chronic adrenal insufficiency should be monitored and provided with corticosteroids free of charge.

Forecast

The use of synthetic hormones for replacement therapy in chronic adrenal insufficiency has opened up wide possibilities for treating this disease and prolonging the lives of patients.

The prognosis of the disease depends on the presence of active tuberculosis in other organs (miliary, renal, pulmonary) and the patient's sensitivity to antibacterial therapy.

In case of autoimmune damage to the adrenal glands, the patient's future depends on the combined damage to other endocrine glands, for example, in the development of diabetes mellitus.

The patient's condition and life are determined by the correct selection of drug dosages, their combination, careful administration and self-control.

Concomitant diseases complicating the course of chronic adrenal insufficiency pose a great danger. Correct tactics in intercurrent diseases and surgical interventions, as well as in labor management, can prevent the development of a crisis and its consequences.

[ 1 ]

Working capacity

Transferring the patient to light work, devoid of heavy physical exertion, night shifts, and a standardized work day helps maintain the ability to work.

Prevention of chronic adrenal insufficiency comes down to measures taken to reduce the incidence of tuberculosis and autoimmune diseases. These issues are related to social and environmental problems.

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