Tumors of the adrenal gland

Tumors of the adrenal gland are revealed in 1-5% of cases with CT of the abdomen performed on other indications. However, only 1% of tumors have a malignant character. 

Epidemiology

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

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

Causes of the adrenal gland tumors

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

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

For malignant tumors of the adrenal gland is characterized by local-destroying 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 lymphogenous and hematogenous pathways. In this case, retroperitoneal lymph nodes, lungs, liver and bones are affected.

Symptoms of the adrenal gland tumors

Symptoms of an adrenal tumor are made up of manifestations of the primary tumor (palpable formation, pain, fever, weight loss), its metastases (adrenal tumor symptoms are determined by localization of tumor screenings) and endocrine symptoms. Hormonal cancer of the adrenal glands is 60% of all observations and can cause the following endocrine syndromes: Cushing's syndrome (30%), virilization and premature puberty (22%), feminization (10%), primary hyperaldosteronism (2.5%), polycythemia less than 1%), hyperkalemia (less than 1%),  hypoglycemia  (less than 1%), adrenal insufficiency (typical for lymphoma), insulin resistance not associated with glucocorticoids, catecholamine crisis (characteristic 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, the adrenal cortex (glucocorticoids, mineralocorticoids, androgens, estrogens) secrete functionally active and inactive adrenal tumors. In more than 50% of cases, adrenocortical cancer is not functionally functional, but malignant adrenal tumors cause Cushing's syndrome in 5-10% of cases.

Classification of TNM

T - primary tumor:

• T1 - a tumor of 5 cm in diameter and less, there is no local invasion;
• T2 - tumor more than 5 cm in diameter without local invasion;
• T3 - a tumor of any size, there is a local invasion, there is no germination of neighboring organs;
• T4 is a tumor of any size, there is a local invasion, there is a germination of 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 of the adrenal gland tumors

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

With hyperaldosteronism, the concentration and ratio of aldosterone and renin are evaluated; when virilization - serum level of adrenal androgens (androstenedione, dihydroepiandrosterone sulfate) and testosterone, as well as excretion of 17-ketosteroids in urine (24 hours); when feminization - the concentration of estradiol and estrone in plasma. To exclude pheochromocytoma, an estimate of 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, is necessary.

Radiological diagnosis of adrenal gland tumors includes CT or MRI of the abdomen (evaluation of the size and sintopy of the primary tumor, detection of metastases), as well as radiography or chest CT (detection of metastases). Radiological signs of adrenal cancer - an irregular form of the adrenal tumor, its size is more than 4 cm, high density with CT, exceeding 20 HU, a heterogeneous structure due to hemorrhages, necrosis and calcifications, and the invasion of surrounding structures.

Routine biopsy for the purpose of verifying the diagnosis before starting treatment for adrenal tumors is not recommended.

[13], [14], [15]

Differential diagnosis

Differential diagnosis of adrenal gland tumors is performed with neuroblastoma and nephroblastoma in children and with hamartomas, teratomas, neurofibromatosis, amyloidosis and adrenal granulomas in adults.

Treatment of the adrenal gland tumors

Treatment of tumors of the adrenal gland, and especially of hormonally active tumors, consists in their removal. Eliminate the malignant nature of hormonal inactive localized neoplasm before the start of treatment is difficult. In adults, the probability of malignant tumors less than 6 cm is low. In such cases, careful dynamic observation is possible. With neoplasms of larger diameter. As well as small tumors of the adrenal gland in children showed surgical treatment. The standard volume of surgery is adrenalectomy, with small hormonal inactive tumors can be performed adrenal resection. Laparotomic access is routinely used, however, with small tumors without signs of local invasion, laparoscopic adrenalectomy can be performed without compromising oncological outcomes.

Adrenal cancer is a radioresistant tumor, its sensitivity to  chemotherapy  is low. The only effective treatment for this category of patients is operative. The frequency of local recurrences after surgery is high (80%). The optimal approach to the treatment of local recurrent tumors in patients who do not have distant metastases is operative. The appointment of adjuvant chemotherapy and irradiation of radically operated patients does not improve the results of treatment.

With disseminated adrenal cancer, moderate mitotane has been shown to be effective at a dose of 10-20 g / day, for a long time (the frequency of objective responses is 20-25%, control of hypersecretion of hormones - 75%). The data indicating a possible increase in relapse-free survival with the use of mitotane (10-20 g / day, for a long time) has been published. Regimens based on cisplatin (cisplatin, cyclophosphamide, 5-fluorouracil) are used as the second line of chemotherapy in patients who did not respond to treatment with mitotane. An important role in the treatment of adrenal tumors is symptomatic therapy aimed at eliminating the endocrine symptoms of hormone-active tumors. Cushing's syndrome uses mitotane, ketoconazole, mifepristone, and etomidate in monotherapy or various combinations.

Hyperaldosteronism serves as an indication for the administration of spironolactone, amiloride, triamterene and antihypertensive drugs (calcium channel blockers). In hyperandrogenia, steroid (cyproterone) and non-steroidal (flutamide) antiandrogens are used. Ketoconazole, spironolactone and cimetidine; when hyperestrogenia - anti-estrogens (clomiphene, tamoxifen, danazol). Adrenal insufficiency requires hormone replacement therapy. With mixed carcinomas with pheochromocytoma component, it is possible to use preparations of radioactive metahedobenzylguanidine. Increase in blood pressure, including with pheochromocytoma, serves as an indication for the appointment of alpha-adrenoblockers with subsequent 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 of patients with hormone-active tumors is better than with endocrine-inactive forms of the disease, which is associated with early detection and timely treatment of hormone-producing tumors. The general 5-year survival of radically operated patients reaches 32-47%, of unoperated patients with locally advanced tumors - 10-30%; among patients with disseminated adrenal cancer, none survive 12 months.

[16], [17], [18]