Treatment of Icenko-Cushing's disease

Treatment of Itsenko-Cushing's disease. Pathogenetic and symptomatic methods are used to treat the disease. Pathogenetic methods are aimed at normalizing the pituitary-adrenal relationship, symptomatic methods are aimed at compensating for metabolic disorders.

Normalization of ACTH and cortisol production is achieved by using pituitary irradiation, surgical adenomectomy, or hypothalamic-pituitary system blockers. Some patients have one or both adrenal glands removed and are prescribed inhibitors of hormone biosynthesis in the adrenal cortex. The choice of method depends on the degree of expression and severity of the clinical manifestations of the disease.

Currently, worldwide, in the treatment of Itsenko-Cushing's disease, preference is given to transsphenoidal adenomectomy using microsurgical techniques. This method is considered one of the main methods of pathogenetic therapy of this severe disease, gives a rapid positive clinical result, leads to complete remission of the disease in 90% of patients with restoration of hypothalamic-pituitary-adrenal functions.

In cases of mild to moderate severity of the disease, irradiation of the interpituitary region is used - external beam radiation therapy: gamma therapy (dose 40-50 Gy) and proton beam (dose 80-100 Gy per course).

The use of heavy proton particles for irradiation of the pituitary gland makes it possible to increase the dose, significantly reduce the radiation load on surrounding tissues and conduct one session instead of 20-30 during gamma therapy. The advantage of proton therapy is a faster onset of disease remission and a high percentage of recovery (90%). Irradiation of the interstitial-pituitary region leads to either the disappearance of most clinical manifestations of the disease or some of the symptoms. These changes occur 6-12 months after the end of the course of treatment.

Surgical removal of both adrenal glands in severe cases of the disease is performed in two stages. After removal of one adrenal gland and healing of the surgical wound, the second stage is performed - removal of the second adrenal gland with autotransplantation of sections of the adrenal cortex into the subcutaneous tissue. Autotransplantation of the cortex is performed in order to reduce the dose of hormone replacement therapy, which is lifelong in patients after bilateral total adrenalectomy. Approximately one third of patients develop Nelson's syndrome at different times after removal of the adrenal glands, which is characterized by the growth of a pituitary tumor, severe hyperpigmentation of the skin, and a labile form of adrenal insufficiency. In recent years, due to the development of new treatment methods, the number of patients who underwent adrenal removal has sharply decreased.

In most cases of moderate severity of the disease, combined treatment is used: surgical removal of one adrenal gland and radiation therapy of the intervertebral-pituitary region.

The drug treatment method includes therapy aimed at reducing the function of the pituitary gland and adrenal glands under the influence of drugs that suppress the secretion of ACTH and substances that block the biosynthesis of corticosteroids in the adrenal cortex. The first group includes reserpine, diphenin, cyproheptadine, bromocriptine (parlodel), the second - elipten, chloditan.

Reserpine at a dose of 1 mg/day is prescribed in the subsequent period for 3-6 months to normalize blood pressure and reduce pituitary gland activity. Remission of the disease with such combined therapy occurs earlier. In addition to radiation therapy, cyproheptadine at 80-100 mg or parlodel - 5 mg/day for 6-12 months are also used. Hypothalamic-pituitary system blockers are not recommended for use as monotherapy or before pituitary gland irradiation, since these drugs do not always cause persistent clinical improvement of the disease and reduce the radiosensitivity of pituitary adenomas.

Drugs that inhibit the biosynthesis of hormones in the adrenal glands, elipten and chloditan, are used in addition to other types of treatment. In case of incomplete remission after radiation therapy or in combination with unilateral adrenalectomy, chloditan is prescribed at a dose of 3-5 g/day until the function of the adrenal cortex is normalized, and then a maintenance dose (1-2 g) is left for a long time (6-12 months). Elipten and chloditan are also used for temporary normalization of the function of the adrenal cortex in preparation of seriously ill patients for removal of one or both adrenal glands. Elipten is prescribed at a dose of 1-1.5 g/day.

In Itsenko-Cushing's disease, symptomatic therapy is also necessary, aimed at compensating and correcting protein, electrolyte and carbohydrate metabolism, arterial pressure and cardiovascular insufficiency. It is necessary to treat osteoporosis, purulent complications, pyelonephritis and mental disorders. Anabolic steroids are widely used, most often retabolil is used at 0.5 g intramuscularly once every 10-15 days, depending on the severity of dystrophic disorders. For the treatment of hypokalemic alkalosis, it is advisable to combine potassium and veroshpiron preparations. In steroid diabetes, biguanides are used, sometimes in combination with sulfonamides. Insulin is prescribed before surgery. Cardiovascular insufficiency requires parenteral therapy with cardiac glycosides or digitalis preparations. The use of diuretics should be limited. In case of septic manifestations, broad-spectrum antibiotics are prescribed, taking into account sensitivity.

Symptomatic treatment of osteoporosis is a very important problem, since changes in the bones are subject to reverse development slowly and not in all patients, especially in adolescence and after 50 years. The treatment of steroid osteoporosis should be approached from three positions: to achieve acceleration of the processes of absorption of calcium salts from the intestine, to promote their fixation by the bone matrix, and also to restore the protein component of bone tissue. Increased absorption of calcium is achieved by prescribing derivatives of vitamin D ₃, in particular oxydevita, or the drug alpha-D ₃ -Teva.

To treat steroid osteoporosis, drugs are used that reduce bone resorption and stimulate bone formation.

The first group includes calcitonin preparations and bisphosphonates.

Calcitonins, along with inhibition of bone resorption, also have a pronounced analgesic effect. Currently, the most widely used drug is Miacalcic, which is used in two dosage forms: in ampoules for intramuscular and subcutaneous injections of 100 units and in vials in the form of a nasal spray of 200 units. Courses of treatment with calcitonins are carried out for 2-3 months with the same intervals in treatment, then the drug is prescribed again. During breaks in treatment with calcitonin, bisphosphonates are used, most often the domestic Kydofon, or alendronate (Fosamax). Calcium preparations (500-1000 mg per day) are necessarily added to both types of treatment.

Drugs that stimulate bone formation include compounds containing fluoride salts (ossin, tridine), anabolic steroids.

One of the damaging mechanisms of action of excess glucocorticoids on bone tissue is the suppression of osteoblast function and reduction of bone formation. The use of fluorides, as well as anabolic steroids in steroid osteoporosis, is based on their ability to enhance bone formation.

In case of immunodeficiency developed against the background of Itsenko-Cushing's disease, it is recommended to conduct treatment with thymalin or T-activin, which affect the immune system, accelerating the differentiation and maturation of T-lymphocytes. As a biostimulant, thymalin improves reparative processes, activates hematopoiesis, increases the production of alpha-interferon by segmented leukocytes and y-interferon by T-lymphocytes. Treatment is carried out in courses of 20 days 2 times a year.

The prognosis depends on the duration, severity of the disease and the age of the patient. With a short duration of the disease, a mild form and an age of up to 30 years, the prognosis is favorable. After successful treatment, recovery is observed.

In moderate cases, with a long course after normalization of the function of the adrenal cortex, irreversible disorders of the cardiovascular system, hypertension, renal dysfunction, diabetes mellitus, and osteoporosis often remain.

As a result of bilateral adrenalectomy, chronic adrenal insufficiency develops, therefore constant replacement therapy and dynamic monitoring, prevention of the development of Nelson's syndrome are necessary.

With complete regression of the symptoms of the disease, the ability to work is preserved. Patients are advised to avoid night shifts and heavy physical work. After adrenalectomy, the ability to work is often lost.

Prevention of Itsenko-Cushing's disease

Prevention of the pituitary form of Itsenko-Cushing's disease is problematic, since its cause has not been fully studied. Prevention of functional hypercorticism in obesity and alcoholism consists of prevention of the underlying disease.