Causes and pathogenesis of the syndrome of ectopic production of ACTH

Causes of ectopic syndrome of ACTH. Syndrome of hypercorticism caused by ectopic production of ACTH is found in tumors of both non-endocrine organs and endocrine glands. Most often, this syndrome develops with tumors of the chest (lung cancer, carcinoid and bronchial cancer, malignant thymomas, primary carcinoids of the thymus and other mediastinal tumors). Less commonly, the syndrome accompanies tumors of various organs: parotid, salivary glands, urinary and gallbladder, esophagus, stomach, and large intestine. The development of the syndrome in melanoma and lymphosarcoma is described. Ectopic production of ACTH is also found in tumors of the endocrine glands. In cancer cells of the islets of Langerhans, ACTH secretion is often found. Medullary thyroid cancer and pheochromocytoma, neuroblastoma occur with the same frequency. The ectopic production of ACTH in cases of cancer of the cervix, ovaries, testicles and the prostate gland is detected less frequently. It was also found that in many malignant tumors producing ACTH, clinical manifestations of hypercorticism are not observed. At present, the causes of ACTH production in tumor cells have not been found yet. According to the assumption of Pearse in 1966, based on the concept of the APUD-system, the groups of cells formed from nervous tissue are present not only in the central nervous system, but also in many other organs: lungs, thyroid and pancreas, urogenital zone, Cells of tumors of these organs in the conditions of uncontrolled growth begin to synthesize various hormonal substances. These include the releasing hormones that are produced in a healthy person in the hypothalamus; tropic hormones like pituitary: ACTH, STH, TTG, prolactin, gonadotropins, ADH. In addition, secretion of parathyroid hormone, calcitonin, prostaglandins, kinin, erythropoietin, placental lactogen, enteroglucagon, etc. Has been detected in tumors.

The clinical syndromes that develop as a result of the production of hormonal substances are still poorly understood and represent one of the most interesting problems of neuroendocrinology and oncology.

Pathogenesis of the syndrome of ectopic production of ACTH. A characteristic feature of the syndrome of ectopic hormone production is the direct association of the endocrine syndrome with the appearance of a tumor of an organ and a high level of a hormone or hormones in the blood. Regression of clinical manifestations and decrease in hormone levels after tumor removal confirms these provisions. Detection of the corresponding hormones in tumor cells is a sufficiently reliable proof of their ectopic products.

The chemical nature of ACTH in plasma in patients with the syndrome of ectopic production of ACTH in tumors is unusual. Various forms of immunoreactive ACTH, the so-called large, medium and small, have been found. The predominance of "large" ACTH with a relative molecular mass of about 30,000 is found in tumors. It is assumed that its form is passive and only its transformation into ACTH makes the substance active in stimulating the biosynthesis of hormones in the adrenal cortex. Later it was shown that ACTH with a higher relative molecular mass is a common precursor not only for ACTH, but also for endorphins and lipotropins. In addition to these forms of ACTH, in tumors with ectopic production of adrenocorticotropic hormone, the presence of several terminal fragments, C- and its N-molecules, was detected. In ectopic tumors, DN Orth et al. For the first time in 1978 showed the presence of opioid substances. From the cells of the cancer of the pancreas, alpha and beta endorphins, lipotropins, along with corticotropins were isolated. Thus, the tumor secreted many substances from the common precursor. Further studies confirmed that the ectopic tumor (oat cell lung cancer ) is capable of synthesizing all forms of corticotropins, endorphins and lipotropins and that, from the point of view of the ability of simultaneous production, these hormones of tumor cells are almost similar to normal human pituitary corticotrophs. There are some differences in enzymatic processes.

With the development of the study of tumors capable of synthesizing ACTH, it was found that other hormones form in them. In addition, tumors synthesize and hypothalamic hormones - corticotropin-releasing hormone, prolactin-releasing hormone.

For the first time GV Upton has shown that tumors of the pancreas and lungs are capable of synthesizing CRF-like activity. Later, this substance was found in medullary thyroid carcinoma, intestinal cancer and nephroblastoma. In a patient with thyroid cancer, in addition to clinical manifestations of hypercorticism, there was lactorrhea. The tumor secreted, along with corticotropin stimulating activity, and prolactin a stimulating factor, which in turn caused the synthesis of prolactin in the pituitary gland. This was proved by the study of the cell culture of the pituitary gland. After the removal of the thyroid tumor, the patient disappeared manifestations of hypercorticism and lactorrhoea. In addition to two hormones like hypothalamic, the tumor contained a large amount of calcitonin.

With ACTH-ectopic syndrome, tumors also show the synthesis of serotonin and gastrin, luteinizing and follicle-stimulating.

Patanatomy. In the ACTT-ectopic syndrome, the adrenal glands are significantly enlarged due to hyperplasia and hypertrophy, mainly of cells in the beam zone. In electron microscopy, a large number of mitochondria of various sizes, including giant, well-developed lamellar complex, were found in them.

Tumors secreting KRG-ACTH are always malignant and are found in the lungs - ovarian cancer, in the thyroid gland - medullar cancer, in the adrenal medullar layer - solid chromaffinoma, in the mediastinum - chemodectomy, in the pancreas - one of the varieties of carcinoid.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]