Tumors of the adrenal gland

Adrenal tumors are detected in 1-5% of cases of abdominal CT performed for other indications. However, only 1% of tumors are malignant.

Epidemiology

The incidence of adrenal cancer is 0.6-1.67 per 10 ⁶ people per year. The ratio of women to men is 2.5-3:1. The highest incidence of adrenal cancer is recorded at the age of up to 5 and at 40-50 years.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ]

Causes adrenal tumors

Adrenal tumors are divided into sporadic and those associated with hereditary syndromes [Gardner, Beckwith-Wiedemann, multiple endocrine neoplasia type 1, SBLA (sarcoma, breast cancer, lung and adrenal gland), Li-Fraument syndromes].

Depending on histogenesis, tumors of the adrenal cortex (aldosteroma, corticosteroma, androsteroma, corticoestroma, mixed tumors of the adrenal gland, adenoma, cancer) and adrenal medulla (pheochromocytoma) are distinguished, as well as primary adrenal lymphoma, sarcoma, secondary (metastatic) tumors of the adrenal gland.

Malignant tumors of the adrenal gland are characterized by locally destructive growth with the involvement of neighboring organs (kidney, liver), as well as invasion of the venous system with the formation of tumor venous thrombosis (adrenal and inferior vena cava). Dissemination of tumors occurs through lymphogenous and hematogenous routes. In this case, the retroperitoneal lymph nodes, lungs, liver and bones are affected.

Symptoms adrenal tumors

Symptoms of adrenal tumor consist of manifestations of the primary tumor (palpable mass, pain, fever, weight loss), its metastases (symptoms of adrenal tumor are determined by the localization of tumor metastases) and endocrine symptoms. Hormonally active adrenal cancer accounts for 60% of all cases and can cause the following endocrine syndromes: Cushing's syndrome (30%), virilization and precocious puberty (22%), feminization (10%), primary hyperaldosteronism (2.5%), polycythemia (less than 1%), hyperkalemia (less than 1%), hypoglycemia (less than 1%), adrenal insufficiency (typical of lymphoma), insulin resistance not associated with glucocorticoids, catecholamine crisis (typical of pheochromocytoma), cachexia.

[ 8 ], [ 9 ]

Stages

• Stage 1 - T1N0M0.
• Stage 2 - T2N0M0.
• Stage 3 - T1 or T2. N1M0.
• Stage 4 - any T, any N+M1 or T3, N1 or T4.

[ 10 ], [ 11 ]

Forms

Based on the sign of secretion of hormones of the adrenal cortex (glucocorticoids, mineralocorticoids, androgens, estrogens), functionally active and inactive tumors of the adrenal gland are distinguished. In more than 50% of cases, adrenal cortex cancer is functionally inactive, but malignant tumors of the adrenal gland cause Cushing's syndrome in 5-10% of cases.

TNM classification

T - primary tumor:

• T1 - tumor is 5 cm in diameter or less, no local invasion;
• T2 - tumor more than 5 cm in diameter without local invasion;
• T3 - tumor of any size, there is local invasion, no growth into adjacent organs;
• T4 - a tumor of any size, there is local invasion, there is growth into neighboring organs.

N - regional metastases:

• N0 - no regional metastases;
• N1 - there are regional metastases.

M - distant metastases:

• M0 - no distant metastases;
• Ml - there are distant metastases.

[ 12 ]

Diagnostics adrenal tumors

Examination of patients with adrenal tumors, in addition to routine laboratory tests (general, biochemical blood tests, coagulogram, general urine analysis ), should include tests aimed at identifying increased hormone production. To identify Cushing's syndrome, a dexamethasone test (1 mg) and determination of cortisol excretion in urine (24 hours) are used.

In hyperaldosteronism, the concentration and ratio of aldosterone and renin are assessed; in virilization, the serum level of adrenal androgens (androstenedione, dehydroepiandrosterone sulfate) and testosterone, as well as the excretion of 17-ketosteroids in urine (24 hours) are assessed; in feminization, the concentration of estradiol and estrone in plasma. To exclude pheochromocytoma, it is necessary to assess the daily excretion of catecholamines (epinephrine, norepinephrine, dopamine) and their metabolites in urine (especially metanephrine and normetanephrine), as well as the level of serum metanephrine and catecholamines.

Radiological diagnostics of adrenal tumors includes CT or MRI of the abdomen (assessment of the size and syntopy of the primary tumor, detection of metastases), as well as X-ray or CT of the chest (detection of metastases). Radiological signs of adrenal cancer are irregular shape of the adrenal tumor, its size is more than 4 cm, high density on CT exceeding 20 HU, heterogeneous structure caused by hemorrhages, necrosis and calcifications, as well as invasion of surrounding structures.

Routine biopsy to verify the diagnosis before starting treatment for adrenal tumors is not recommended.

[ 13 ], [ 14 ], [ 15 ]

Differential diagnosis

Differential diagnosis of adrenal tumors is carried out with neuroblastoma and nephroblastoma in children and hamartomas, teratomas, neurofibromatosis, amyloidosis and granulomas of the adrenal glands in adults.

Treatment adrenal tumors

Treatment of adrenal tumors, especially hormonally active tumors, involves their removal. It is difficult to exclude the malignant nature of a hormonally inactive localized neoplasm before treatment. In adults, the probability of a malignant nature of tumors less than 6 cm is low. In such cases, careful dynamic observation is possible. For neoplasms of a larger diameter, as well as small adrenal tumors in children, surgical treatment is indicated. The standard volume of surgery is adrenalectomy; for small hormonally inactive tumors, adrenal resection can be performed. Laparotomy access is routinely used, but for small neoplasms without signs of local invasion, laparoscopic adrenalectomy can be performed without compromising oncological results.

Adrenal cancer is a radioresistant tumor, its sensitivity to chemotherapy is low. The only effective treatment for this category of patients is surgery. The frequency of local relapses after surgery is high (80%). The optimal approach to the treatment of local recurrent tumors in patients without distant metastases is surgery. The use of adjuvant chemotherapy and radiation in radically operated patients does not improve the treatment results.

In disseminated adrenal cancer, moderate efficacy of mitotane at a dose of 10-20 g/day, long-term (objective response rate of 20-25%, control of hormone hypersecretion - 75%) has been demonstrated. Data have been published indicating a possible increase in relapse-free survival when using the mitotane regimen (10-20 g/day, long-term). Cisplatin-based regimens (cisplatin, cyclophosphamide, 5-fluorouracil) are used as the second line of chemotherapy in patients who have not responded to mitotane treatment. Symptomatic therapy aimed at eliminating the endocrine symptoms of hormonally active tumors plays an important role in the treatment of adrenal tumors. Mitotane, ketoconazole, mifepristone and etomidate are used in monotherapy or various combinations in Cushing's syndrome.

Hyperaldosteronism is an indication for the use of spironolactone, amiloride, triamterene and antihypertensive drugs (calcium channel blockers). In case of hyperandrogenism, steroidal (cyproterone) and non-steroidal (flutamide) antiandrogens are used. ketoconazole, spironolactone and cimetidine; in case of hyperestrogenism - antiestrogens (clomiphene, tamoxifen, danazol). Adrenal insufficiency requires hormone replacement therapy. In case of mixed carcinomas with a pheochromocytoma component, it is possible to use radioactive metaiodobenzylguanidine preparations. Increased blood pressure, including in case of pheochromocytoma, is an indication for the use of alpha-blockers followed by the use of beta-blockers (propranolol).

Forecast

Benign tumors of the adrenal gland have a favorable prognosis. The overall 5-year survival rate for adrenal cancer is 20-35%. The prognosis for patients with hormonally active tumors is better than for endocrine-inactive forms of the disease, which is associated with early detection and timely treatment of tumors that produce hormones. The overall 5-year survival rate for radically operated patients reaches 32-47%, for non-operated patients with locally advanced tumors - 10-30%; among patients with disseminated adrenal cancer, no one survives 12 months.

[ 16 ], [ 17 ], [ 18 ]