The causes and pathogenesis of acromegaly and gigantism

The vast majority of cases are sporadic, but cases of familial acromegaly have been described.

At the end of the XIX century, the theory of the pituitary syndrome was put forward. Subsequently, mainly domestic researchers on a large clinical material showed the inconsistency of localistic concepts of the exceptional role of the pituitary gland in the pathogenesis of the disease. It was proved that a primary role in its development is played by primary pathological changes in the interstitial and other parts of the brain.

A characteristic feature of acromegaly is an increased secretion of growth hormone. However, there is not always a direct correlation between its content in the blood and the clinical signs of disease activity. Approximately 5-8% of cases, with a small or even normal level of somatotropic hormone in the blood serum, show pronounced acromegaly in patients, which is explained either by a relative increase in the content of a specific form of growth hormone possessing great biological activity, or by an isolated increase in the level of IGF.

Partial or partial acromegaly, manifested by an increase in individual parts of the skeleton or organs, is generally not associated with excess growth hormone secretion and is an inherent local tissue hypersensitivity.

The literature describes a wide range of pathological and physiological conditions that have a direct or indirect relationship to the development of acromegaly. These include psychoemotional stress, frequent pregnancies, childbirth, abortion, menopausal and post-stroke syndromes, extrhypophysial brain tumors, traumas of the skull with concussion, the influence of specific and nonspecific infectious processes on the central nervous system.

Thus, the causes of acromegaly as a syndrome may be the primary pathology of the hypothalamus or overlying sections of the central nervous system, leading to stimulation of somatotropic function and hyperplasia of pituitary cells; primary development of the tumor process in the pituitary gland with autonomous hypersecretion of the somatotropic hormone or its active forms; increase in the blood content or activity of the IGF, directly affecting the growth of the osteoarticular apparatus; increased sensitivity to the action of growth hormone or IRP of peripheral tissues; tumors secreting somatotropic hormone or STG-releasing factor and ectopic to other organs and tissues of the body - lungs, stomach, intestines, ovaries.

Pathanatomy

The main cause of acromegaly and gigantism are pituitary adenomas from somatotrophs and somatotropin- and prolactin-secreting cells, the ratio of which varies from case to case. There are two types of adenomas of the pituitary gland, which produce somatotropic hormone: acidophilic-cellular adenomas (abundantly granulated and slightly granulated) and chromophobic adenomas. Very rarely somatotropinomas are oncocyte-cell tumors.

Acidophilic-cellular adenoma is an encapsulated or bivalent benign tumor, usually consisting of acidophilic, less often with an admixture of large chromophobic cells or transitional forms. Tumor cells form strands and fields separated by a richly vascularized stroma. They are identified at the level of light microscopy, ultrastructurally and immunocytochemically as somatotrophs with numerous secretory granules 300-400 nm in diameter. Some cells contain large nucleoli, an intensively developed endoplasmic reticulum, and a small number of secretory granules, which reflects their high secretory activity.

Chromophobic pituitary adenomas cause the development of acromegaly or gigantism on average in 5% of patients. They refer to weakly granulated tumors. The cells that form them are less acidophilic, the cytoplasm is scant, with a small number of electronically dense granules 80-200 nm in diameter with an electronically dense shell and perigranular areola. The cell nucleus is compact, contains nucleoli. The largest cells include a large number of secretory granules, although less than in acidophilic adenomas. Chromophobic adenomas of a solid or trabecular structure occupy the lower-lateral part of the pituitary gland. Cases when chromophobic adenomas with ultrastructural features of TTG-producing cells, but secreting and growth hormone, are at the basis of the development of acromegaly.

A part of patients with acromegaly and gigantism due to hypersecretion of STG-RH with hypothalamus in the pituitary gland produces diffuse or multifocal hyperplasia of acidophilic cells. Acromegaly can develop in patients with apodomas of different locations, with islet-cell tumors that produce either growth hormone or STH-RH, which stimulates the adenohypophysis somatotrophs. Sometimes it has a paracrine effect, stimulating the formation of somatotropic hormone by the tumor cells themselves. STG-RG is also produced by the ganglionocytes of the hypothalamus, ovate-cell and squamous cell lung cancers, bronchial carcinoid.

About 50% of patients with acromegaly have an enlarged nodular thyroid gland, which may be due to the hyperproduction of TSH by tumor cells.

Patients with acromegaly and gigantism exhibit splanchnomegaly due to hypertrophy of the parenchymal structures and excessive growth of fibrous tissue. Hypertrophy of the adrenal glands in a number of patients is associated with the overproduction of ACTH by both tumor cells and para-adenomatous pituitary tissue. The growth of bones and pathological changes in them are due to the high functional activity of osteoblasts. In the late stage of the disease, they resemble changes in Paget's disease.

Patients with acromegaly belong to the risk group for polyps and bowel cancer. They are found in more than 50% of patients and are combined with skin stigmata (papillomatosis), which are external markers of polyps of the large intestine.