Corticotropinoma

Corticotropinoma - corticotropic hormone-active (functional) glandular neoplasia - is a benign tumor, its share among all pituitary adenomas is about 15% (data of the American Brain Tumor Association).

Like all adenomas located in the pituitary gland, it is not classified as a brain tumor, but as an endocrine tumor.

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

Epidemiology

Adenomas of the anterior lobe of the pituitary gland, to which corticotropinoma belongs, account for 10-15% of all intracranial neoplasms. Adenomas of this endocrine gland are diagnosed quite often: according to European experts, their prevalence among the population as a whole is about 17%. In women, this pathology is more common than in men.

[7], [8], [9], [10]

Causes of the corticotrophinomas

The mechanism of development of corticotrophinoma of the pituitary gland is the proliferation of adrenocorticotropic hormone (ACTH) synthesizing corticotropic cells of the adenohypophysis (anterior lobe of the pituitary gland).

ACTH is a glucocorticoid, a peptide hormone of the melanocortin family. The polypeptide basis of its production is prohormone proopiomelanocortin. Regulates the synthesis of ACTH glycosylation hormone, corticoliberin, produced by the hypothalamus. And if the role of the hypothalamus in the production of adenohypophyseal hormones is relatively well studied to date, the causes of corticotrophinoma of the pituitary gland, that is, the hyperplasia of corticotropic cells that form this tumor, are the subject of study by specialists in many fields of medicine.

More and more studies support the hypothesis that the pathogenesis of corticotropinoma is associated with gene mutations, although in most cases an explicit hereditary factor is absent (or not yet identified).

This assumption is based on the fact that in the so-called syndrome of multiple endocrine adenomatosis of the first type (genetically determined), point mutations of a number of genes responsible for G-alpha proteins were found, and changes in the sequence of aliphatic amino acids (arginine, glycine, etc.) and nucleotides.

And among the factors that doctors believe contribute to the emergence of corticotropinoma, infectious and traumatic effects on cranial-cerebral structures are noted, including during intrauterine development. In this case, prevention of this pathology is impossible.

[11], [12], [13]

Symptoms of the corticotrophinomas

Ectopic secretion of ACTH-like activity is known for many organs and tissues, including the pancreas. The clinical symptom complex is expressed by glucocorticoid hypercorticism. Here it is necessary to emphasize that ectopic Cushing's syndrome has a number of characteristics, the main ones of which are hyperpigmentation, hypokalemia with edema and alkalosis.

The functioning of the corticotrophinoma of the pituitary causes overproduction of corticotropin (adrenocorticotropic hormone), which in turn leads to hypersecretion of the hormone cortisol with the adrenal cortex, since the pituitary ACTH exerts an adrenal stimulating effect on the cortex. As a result, neuroendocrine pathology develops, known as the Itenko-Cushing's disease.

The first signs of pathology - due to an overabundance of cortisol in the body - are manifested by accumulation of adipose tissue in the characteristic places: in the upper part of the trunk, on the back of the neck, in the abdomen and on the face. At the same time on the limbs fat is not delayed. There is also often nausea and pain in the frontal part of the head.

Symptoms of corticotropin include:

• increased blood pressure (due to a delay in sodium in the body);
• heart rhythm disturbances;
• high blood sugar;
• increased urine (polyuria);
• reduction of strength of bones (osteoporosis);
• atrophy of muscle fibers and muscle weakness;
• thinning and hyperpigmentation of the skin;
• epithelial hemorrhage (ecchymosis);
• excess hair growth (in women, male-type hair growth is hirsutism);
• acne (acne);
• specific striated atrophodermia (striae on the skin have a characteristic intense pink color);
• mental disorders (depression, anxiety, apathy, emotional instability, irritability).

[14], [15], [16], [17], [18]

Complications and consequences

The effects of corticotropin are affected, in the first place, by the state and functioning of the adrenal cortex (up to its hyperplasia).

Common complications of this pathology: arterial hypertension, heart failure, diabetes, obesity, menstrual cycle disorders in women. In the presence of corticotropinoma in children, their growth and development slow down.

In addition, with an increase in corticotropic adenoma, it can penetrate into the adjacent structures of the skull. In particular, the compression of the optic nerve by the tumor passing in the region of the sphenoid bone can lead to the loss of peripheral vision (bitemporal hemianopsia). And when the corticotrophinoma grows to the sides, the retractive nerve often contracts with lateral (lateral) paralysis. With larger dimensions (more than 1 cm in diameter), neoplasm can cause a persistent increase in intracranial pressure.

[19], [20], [21], [22]

Diagnostics of the corticotrophinomas

Diagnosis of corticotropinoma based on a comprehensive examination of patients is carried out, which includes:

• blood tests for ACTH, cortisol, glucose, sodium and potassium levels;
• daily urine analysis for the amount of excreted cortisol and its derivatives (17-oxycorticosteroids).

Help to determine the diagnosis of stimulatory pharmacological tests conducted by endocrinologists to evaluate the production of ACTH and the functioning of the entire system of the hypothalamus-pituitary-adrenal glands.

Instrumental diagnosis using CT (CT) and MRI (magnetic resonance imaging) of the skull in the area of the Turkish saddle (deepening in the sphenoid bone) allows visualizing the smallest corticotrophinomas of the pituitary gland.

[23], [24], [25], [26]

Differential diagnosis

Differential diagnosis is designed to exclude the presence of the patient is not associated with pituitary corticotrophic obesity, diabetes, hypertension, etc.

It should also be differentiated corticotropin with Addison's disease, ectopic adrenocorticotropic hormone production syndrome, viral (adrenogenital) syndrome in women, craniopharyngioma.

Treatment of the corticotrophinomas

Corticotropinoma is detected already in the stage of metastasis, therefore surgical treatment of the disease consists in a palliative measure - bilateral adrenalectomy, which eliminates manifestations of hypercorticism. It is also possible to medicate the effect on the function of the adrenal cortex with the help of chloriditan and elliptan.

It is generally accepted that the drug treatment of corticotropin has no effect, and there are no specific drugs for this pathology yet.

However, medicines related to the group of inhibitors of biosynthesis of hormones of the adrenal cortex - Chloditane (Lizodren, Mitotan) or Aminoglutethimide (Orimeten, Elipten) are used in drug therapy of Cushing's disease.

The drug Chloditan (in tablets of 500 mg) inhibits the production of cortisol. It is recommended to take it, calculating a daily dose of 100 mg per kilogram of body weight (the dose is divided into three doses during the day, after meals). With the appointment of this drug, the doctor monitors the level of hormones (urine or blood tests are surrendered every two weeks) and determines the duration of its use. At the same time, vitamins A, B1, C and PP are prescribed.

Chloditan has side effects in the form of nausea, decreased appetite, dizziness, increased drowsiness and tremor. In infectious diseases and pregnancy, the drug is contraindicated.

Aminoglutethimide (250 mg tablets) is prescribed for one tablet 2-3 times a day (with a possible increase in dosage, the expediency of which is determined by the endocrinologist who monitors the cortisone content in the blood). The manifestation of side effects of the drug has the form of movement disorders, decreased reaction, skin allergy, nausea, diarrhea and congestion in the bile ducts also occur.

It should be borne in mind that only surgical treatment can remove corticotropinoma, that is, removal of the tumor either through tissue dissection in the nasal cavity (transsphenoidal) or through the endoscopic method (also through the nasal cavity). Also, corticotropinoma can be removed using stereotaxic radiation therapy (radiosurgery).

Forecast

The prognosis of this pathology has a direct dependence on the size of the neoplasm and the rate of its increase. In any case, the removal of a small tumor (0.5-1 cm in size) in almost ninety cases out of a hundred leads to a cure. Although the likelihood that corticotropinoma from benign will degenerate into malignant neoplasia, there is.

[27], [28]