Corticotropinoma

Corticotropinoma – corticotropic hormonally active (functional) glandular neoplasia – is a benign tumor, its share among all pituitary adenomas is approximately 15% (data from the American Brain Tumor Association).

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

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Epidemiology

Adenomas of the anterior pituitary gland, which include corticotropinoma, account for 10 to 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%. This pathology is more common in women than in men.

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Causes corticotropinomas

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

ACTH is a glucocorticoid, a peptide hormone of the melanocortin family. The polypeptide basis of its production is the prohormone proopiomelanocortin. The synthesis of ACTH is regulated by the releasing hormone corticoliberin, produced by the hypothalamus. And if the role of the hypothalamus in the production of adenohypophyseal hormones is relatively well studied today, then the causes of pituitary corticotropinoma, that is, hyperplasia of corticotropic cells that form this tumor, are the subject of study by specialists in many areas of medicine.

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

This assumption is based on the fact that in the so-called multiple endocrine adenomatosis syndrome type 1 (genetically determined), point mutations have been discovered in a number of genes responsible for G-alpha proteins, and changes in the sequence of aliphatic amino acids (arginine, glycine, etc.) and nucleotides have also been recorded.

And among the factors that, as doctors believe, contribute to the development of corticotropinoma, infectious and traumatic effects on craniocerebral structures are noted, including during the period of intrauterine development. At the same time, prevention of this pathology is impossible.

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Symptoms corticotropinomas

Ectopic secretion of ACTH-like activity is known for many organs and tissues, including the pancreas. Clinically, the symptom complex is expressed by glucocorticoid hypercorticism. It should be emphasized that ectopic Cushing's syndrome has a number of features, the main ones being hyperpigmentation, hypokalemia with edema, and alkalosis.

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

The first signs of pathology - due to excess cortisol in the body - are manifested by accumulations of fatty tissue in characteristic places: in the upper part of the body, on the back of the neck, in the abdominal area and on the face. At the same time, fat is not deposited on the extremities. Nausea and pain in the frontal part of the head are also common.

Symptoms of corticotropinoma also include:

• increased blood pressure (due to sodium retention in the body);
• heart rhythm disturbances;
• high blood sugar;
• increased urine production (polyuria);
• decreased bone strength (osteoporosis);
• muscle fiber atrophy and muscle weakness;
• thinning and hyperpigmentation of the skin;
• epithelial hemorrhages (ecchymosis);
• excessive hair growth (in women, male-pattern hair growth – hirsutism);
• acne;
• specific stripe atrophoderma (striae on the skin have a characteristic intense pink color);
• mental disorders (depression, anxiety, apathy, emotional instability, irritability).

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Complications and consequences

The consequences of corticotropinoma primarily affect the condition and functioning of the adrenal cortex (up to its hyperplasia).

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

In addition, as the corticotropic adenoma grows, it can penetrate into adjacent structures of the skull. In particular, compression of the optic nerve by the tumor, passing in the sphenoid bone area, can lead to loss of peripheral vision (bitemporal hemianopsia). And when the corticotropinoma grows to the sides, compression of the abducens nerve with lateral (side) paralysis often occurs. With larger sizes (over 1 cm in diameter), the neoplasm can cause a persistent increase in intracranial pressure.

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Diagnostics corticotropinomas

Diagnosis of corticotropinoma is based on a comprehensive examination of patients, 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-hydroxycorticosteroids).

Stimulation pharmacological tests performed by endocrinologists to assess the production of ACTH and the functioning of the entire hypothalamus-pituitary-adrenal system help to determine the diagnosis.

Instrumental diagnostics using CT (computer tomography) and MRI (magnetic resonance imaging) of the skull in the sella turcica area (depression in the sphenoid bone) allows visualization of the smallest corticotropinomas of the pituitary gland.

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Differential diagnosis

Differential diagnostics are designed to exclude the presence of obesity, diabetes, hypertension, etc. in the patient that are not associated with pituitary corticotropinoma.

It is also necessary to differentiate corticotropinoma from Addison's disease, ectopic adrenocorticotropic hormone syndrome, virilism (adrenogenital) syndrome in women, and craniopharyngioma.

Treatment corticotropinomas

Corticotropinoma is detected already at the metastasis stage, therefore surgical treatment of the disease consists of a palliative measure - bilateral adrenalectomy, which eliminates the manifestations of hypercorticism. It is also possible to medicinally influence the function of the adrenal cortex with the help of chloditan and elypten.

It is generally recognized that drug treatment of corticotropinoma is ineffective, and specific drugs for this pathology do not yet exist.

However, in drug therapy for Cushing's disease, drugs belonging to the group of inhibitors of the biosynthesis of hormones of the adrenal cortex are used - Chloditan (Lysodren, Mitotane) or Aminoglutethimide (Orimeten, Elipten).

The drug Chloditan (in tablets of 500 mg) inhibits the production of cortisol. It is recommended to take it, calculating the daily dose of 100 mg per kilogram of body weight (the dose is divided into three doses during the day, after meals). When prescribing this drug, the doctor monitors the hormone levels (urine or blood tests are taken once every two weeks) and determines the duration of its use. Vitamins A, B1, C and PP are also prescribed at the same time.

Chloditan has side effects such as nausea, loss of appetite, dizziness, increased sleepiness and tremor. The drug is contraindicated in infectious diseases and pregnancy.

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

It should be borne in mind that only surgical treatment can cure corticotropinoma, i.e. tumor removal either through tissue dissection in the nasal cavity (transsphenoidal) or using an endoscopic method (also through the nasal cavity). Corticotropinoma can also be removed using stereotactic radiation therapy (radiosurgery).

Forecast

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

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