Treatment of ectopic ACTH production syndrome

Treatment of ectopic ACTH production syndrome can be pathogenetic and symptomatic. The first involves removing the tumor - the source of ACTH and normalizing the function of the adrenal cortex. The choice of treatment for ectopic ACTH production syndrome depends on the location of the tumor, the extent of the tumor process and the general condition of the patient. Radical removal of the tumor is the most successful type of treatment for patients, but it often cannot be carried out due to late topical diagnosis of the ectopic tumor and the widespread tumor process or extensive metastasis. In cases of tumor inoperability, radiation therapy, chemotherapy or a combination of both are used. Symptomatic treatment is aimed at compensating for metabolic processes in patients: eliminating electrolyte imbalance, protein dystrophy and normalizing carbohydrate metabolism.

The vast majority of tumors causing ectopic ACTH production syndrome are malignant, so radiation therapy is prescribed after their surgical removal. M. O. Tomer et al. described a 21-year-old patient with rapid clinical development of hypercorticism caused by thymic carcinoma. The examination results allowed to exclude the pituitary source of ACTH hypersecretion. A tumor in the mediastinum was detected using chest computed tomography. Before the operation, metopirone (750 mg every 6 hours) and dexamethasone (0.25 mg every 8 hours) were administered to reduce the function of the adrenal cortex. A 28 g thymic tumor was removed during the operation. After the operation, external irradiation of the mediastinum was prescribed at a dose of 40 Gy for 5 weeks. As a result of the treatment, the patient achieved clinical and biochemical remission. Many authors consider the combination of surgical and radiation methods for mediastinal tumors to be the best method for treating ectopic tumors.

Chemotherapeutic treatment of ectopic ACTH production syndrome is quite limited. There is currently no specific general antitumor treatment for APUD tumors and ACTH-secreting tumors. Treatment can be undertaken individually and depends on the tumor location. FS Marcus et al. described a patient with Itsenko-Cushing syndrome and gastric carcinoid with metastases. Against the background of antitumor chemotherapy, the patient's ACTH levels returned to normal and there was a marked clinical improvement in hypercorticism.

The use of antitumor treatment in patients with ectopic ACTH syndrome can sometimes lead to death. FD Johnson reported on two patients with primary apudoma, small cell liver carcinoma 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 beginning of treatment. In addition, SD Cohbe et al. reported on a patient whose breast cancer proceeded with ectopic ACTH syndrome. Soon after the administration of chemotherapy, the patient also died. It has been suggested that in patients with ectopic tumor and excess corticosteroids, when antitumor drugs are prescribed, the so-called carcinoid crisis occurs. It can be caused by intolerance to chemicals against the background of hypercorticism.

Treatment of patients with ectopic ACTH production syndrome does not only involve direct action on the tumor. The clinical symptoms of the syndrome and the severity of the patients' condition 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, a surgical method of treatment is used - bilateral total adrenalectomy or medications are used - blockers of the biosynthesis of the adrenal cortex.

In patients with ectopic ACTH syndrome, surgical removal of the adrenal glands is a high risk to life due to the severity of the condition. Therefore, most patients undergo drug blockade of hormone biosynthesis in the adrenal cortex. Treatment aimed at normalizing the function of the adrenal cortex is also used in preparation for surgical removal of a tumor or during radiation therapy. When radical methods of treating ectopic ACTH syndrome are impossible, drugs that block the biosynthesis of corticosteroids prolong the lives of patients. These include metopirone, elipten or orimeten and mamomit (glutethimide), chloditan (o'r'DDD) or trilostane. They are used both in Itsenko-Cushing's disease and in patients with ectopic ACTH syndrome. Metopirone is prescribed in a dose of 500-750 mg 4-6 times a day, the daily dose is 2-4.5 g. Orimeten inhibits the conversion of cholesterol into pregnenolone. This drug can have side effects: it has a sedative property, causes loss of appetite and skin rashes. As a result, the dose of the drug is limited to 1-2 g / day.

A more successful treatment is a combination therapy with metopirone and orimeten. A significant reduction in adrenal function is achieved and the toxic effect of the drugs is reduced. Their dose is selected depending on the patient's sensitivity.

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

Hyperglycemia and glucosuria, which are often found in patients, also require the appointment of sugar-lowering therapy. Biguanides, in particular silybin-retard, are considered the most suitable drugs for the treatment of steroid diabetes. The diet should be free of easily digestible carbohydrates.

Patients with hypercorticism develop osteoporosis of the skeleton, most often of the spine. Severe pain syndrome associated with nerve compression and secondary radicular manifestations often confines patients to bed. Calcium preparations and calcitriol (calcitonin) are prescribed to reduce osteoporosis.

Cardiac glycosides and digitalis preparations are used for cardiopulmonary insufficiency. In view of steroid cardiopathy associated with hypokalemia, hypertension and protein dystrophy, it is necessary to prescribe isoptin, panangin, potassium orotate. In cases of persistent tachycardia, cordarone, cordanum, alpha-blockers are indicated.

Septic complications in patients with hypercorticism are severe, so early use of antibiotics and broad-spectrum antibacterial drugs is necessary. Due to the frequent presence of infection in the urinary tract, it is advisable to prescribe sulfanilamide drugs (phthalazole, bactrim) and nitrofuran derivatives (furadonin, furagin).