Treatment of the syndrome of ectopic production of ACTH

Treatment of the syndrome of ectopic production ACTH can be pathogenetic and symptomatic. The first is to remove the tumor - the source of ACTH and in the normalization of the function of the adrenal cortex. The choice of a method of treatment in the syndrome of ectopic production of ACTH depends on the location of the tumor, the vastness of the tumor process and the general condition of the patient. Radical tumor removal is the most successful type of treatment for patients, but often can not be done because of late topical diagnosis of the ectopic tumor and the widespread tumor process or extensive metastasis. In cases of inoperability of the tumor, radiotherapy, chemotherapeutic treatment, or a combination thereof is used. Symptomatic treatment is aimed at compensating metabolic processes in patients: elimination of electrolyte imbalance, protein dystrophy and normalization of carbohydrate metabolism.

The vast majority of tumors that cause the syndrome of ectopic AKTH production are malignant, therefore, after their prompt removal, radiation treatment is prescribed. M.O. Tomer et al. Described a patient at the age of 21 with a rapid clinical development of hypercorticism caused by thymus carcinoma. The results of the examination made it possible to exclude the pituitary source of hypersecretion of ACTH. Using a computed tomography of the chest, a tumor in the mediastinum was found. Before the operation to reduce the function of the adrenal cortex, methopyron (750 mg every 6 hours), dexamethasone (0.25 mg after 8 hours) was treated. The operation removed the thymus tumor with a mass of 28 g. After the operation, an external irradiation of the mediastinum in a dose of 40 Gy for 5 weeks was prescribed. As a result of the treatment, the patient underwent clinical and biochemical remission. Combination of surgical and radiation methods in mediastinal tumors is considered by many authors to be the best method for treating ectopic tumors.

Chemotherapy treatment of the syndrome of ectopic products of ACTH is rather limited. Specific general antitumor treatment for APUD tumors and tumors secreting ACTH is not currently developed. Treatment can be undertaken individually and depends on the location of the tumor. FS Marcus et al. Described a patient with Isenko-Cushing's syndrome and gastric carcinoid with metastases. Against the background of the use of antitumor chemotherapy, the patient normalized the ACTH content and there was a marked clinical improvement in hypercorticism.

The use of antitumor treatment in patients with the syndrome of ectopic ACTH production can sometimes lead to death. FD Johnson reported two patients with a primary aphidoma, small cell carcinoma of the liver, and clinical manifestations of hypercorticism. During his course of antitumor chemotherapy (intravenous cyclophosphamide and vincristine), they died on the 7th and 10th days from the start of treatment. In addition, SD Cohbe et al. Informed about the patient, whose breast cancer was with the syndrome of ectopic AKTH production. Soon after the appointment of chemotherapy, the patient also died. There was an opinion that in patients with an ectopic tumor and an excess of corticosteroids in the appointment of antitumor drugs, the so-called carcinoid crisis occurs. Its possible cause may serve as intolerance to chemicals on the background of hypercorticism.

The treatment of patients with the syndrome of ectopic production of ACTH is not only the effect directly on the tumor. The clinical symptoms of the syndrome and the severity of the condition of patients depend on the degree of hypercorticism. Therefore, an important point for treatment is the normalization of the function of the adrenal cortex. For these purposes, the surgical method of treatment is used - two-sided total adrenalectomy or medications are used - blockers of biosynthesis of the adrenal cortex.

In patients with the syndrome of ectopic production of ACTH because of the severity of the condition, the surgical removal of the adrenal glands is a great risk to life. Therefore, most patients resort to a drug blockade of hormone biosynthesis in the adrenal cortex. Treatment aimed at normalizing the function of the adrenal cortex is also used to prepare for the prompt removal of a tumor or for radiation therapy. When the implementation of radical methods of treatment of the syndrome of ectopic production of ACTH is impossible, drugs that block the biosynthesis of corticosteroids prolong the life of patients. These include metopirone, elliptan or oriteen and mamomite (glutetimide), chloridan (o'r'DDD) or trilostane. They are used both in the case of the Itenko-Cushing disease and in patients with the syndrome of ectopic production of ACTH. Metopyrone is prescribed in a dose of 500-750 mg 4-6 times a day, a daily dose of 2-4.5 g. Orimeten inhibits the conversion of cholesterol to pregnenolone. This drug may have side effects: it has a sedative effect, causes an eating disorder and skin rashes. As a result, the dose of the drug is limited to 1-2 g / day.

A more successful treatment is combined therapy with metopyron and orimethene. A significant decrease in the function of the adrenal gland is achieved and the toxic effect of the drugs is reduced. Their dose is selected depending on the sensitivity of the patient.

Along with the effect on the tumor and the function of the adrenal cortex, patients with the syndrome of ectopic ACTH production show symptomatic treatment. It is aimed at normalizing electrolyte disorders, protein catabolism, steroid diabetes and other manifestations of hypercorticism. To normalize hypokalemia and hypokalemic alkalosis, veroshpiron is used, which helps delay the excretion of potassium by the kidneys. It is prescribed in a dose of 150-200 mg / day. Along with veroshpiron the patient is administered various potassium preparations and restricts salt. With the manifestations of edematous syndrome with caution appoint diuretics - furosemide, brinaldix and others in combination with veroshpiron and potassium preparation. Products containing potassium are shown, as well as in order to reduce proteinaceous dystrophy - retabolil in a dose of 50-100 mg every 10-14 days.

Often occurring in patients with hyperglycemia and glucosuria also require the appointment of hypoglycemic therapy. The most suitable drugs for the treatment of steroid diabetes are biguanides, in particular silubin-retard. The diet should be devoid of digestible carbohydrates.

In patients as a result of hypercorticism, there is osteoporosis of the skeleton, more often the spine. Severe pain syndrome, associated with squeezing nerves and secondary radicular manifestations, often rivet the patients to bed. To reduce osteoporosis, calcium and calcitrine preparations (calcitonin) are prescribed.

In occasion of cardiopulmonary insufficiency, cardiac glycosides and digitalis preparations are used. In view of steroid cardiopathy associated with hypokalemia, hypertension and protein dystrophy, isoptin, panangin, potassium orotate is needed. In cases of persistent tachycardia, cordarone, cordanum, alpha-blockers are shown.

Septic complications in patients with hypercortisy are difficult, therefore early use of antibiotics and antibacterials of a wide spectrum of action is necessary. Due to the frequent presence of infection in the urinary tract, it is advisable to prescribe sulfanilamide preparations (phthalazole, bactrim) and derivatives of nitrofuran (furadonin, furagin).