The causes and pathogenesis of panhypopituitarism

Hormonal insufficiency of the hypothalamic-adenohypophysial system develops on the basis of infectious, toxic, vascular (for example, systemic collagen diseases), traumatic, tumor and allergic (autoimmune) lesions of the anterior lobe of the pituitary and / or hypothalamus.

A similar clinical syndrome also occurs as a result of radiation and surgical hypophysectomy. Any infection and intoxication can lead to a disruption of the function of the hypothalamic-adenohypophyseal system. Tuberculosis, malaria, syphilis in the recent past often caused destructive processes in the hypothalamus and pituitary gland with the subsequent development of the syndrome Simmonds. Reducing the overall incidence of these chronic infections has reduced their role in the occurrence of hypothalamic-pituitary insufficiency.

The disease can be preceded by influenza, encephalitis, typhus, dysentery, purulent processes in various organs and tissues with thromboembolic complications and necrosis of the pituitary gland, craniocerebral trauma, accompanied by intracerebral hemorrhages in the hypothalamus or pituitary with the formation of cysts as a result of resorption of the hematoma. The development of hypopituitarism can be based on fungal lesions, hemochromatosis, sarcoidosis, primary and metastatic tumors.

One of the most common causes of the disease in women is abortion and especially childbirth, complicated by eclampsia in the last months of pregnancy, sepsis, thromboembolism, massive (700-1000 ml) blood loss, which leads to impaired circulation in the pituitary, angiospasm, hypoxia and necrosis. Repeated and frequent pregnancies and births, as factors of functional pituitary tension, can contribute to the development of hypopituitarism. In recent years, hypothalamic-pituitary insufficiency in women with severe toxicosis of the second half of pregnancy in some cases is associated with the development of autoimmune processes (autoaggression). Proof of this is the detection of autoantibodies to the extract of the anterior lobe of the pituitary gland.

Ischemic changes in it, although rare, but can occur in men after gastrointestinal, nasal bleeding and as a result of systematic, long-term donation.

In a number of patients the causes of hypopituitarism can not be detected (idiopathic hypopituitarism).

Regardless of the nature of the damaging factor and the nature of the destructive process leading ultimately to atrophy, wrinkling and sclerosing of the pituitary gland, the pathogenetic basis of the disease in all clinical variants of the hypothalamic-pituitary insufficiency is a reduction or complete suppression of the production of adenohypophysial tropic hormones. As a result, secondary hypofunction of the adrenal, thyroid and gonadal glands occurs. In rare cases of simultaneous involvement in the pathological process of the posterior lobe or leg of the pituitary gland, the level of vasopressin may decrease with the development of diabetes insipidus. It should be borne in mind that the simultaneous decrease in ACTH and corticosteroids, antagonistic to vasopressin with respect to water metabolism, can level and soften the clinical manifestations of vasopressin deficiency. However, a decrease in its activity in response to osmolar loading is noted in patients with Shiene's syndrome and in the absence of clinical signs of diabetes insipidus. Against the background of substitution therapy with corticosteroids, a manifestation of diabetes insipidus is likely. Depending on the localization, vastness and intensity of the destructive process, uniform, complete (panhypopituitarism) or partial, when the production of one or several hormones is preserved, the loss or reduction of hormone formation in the pituitary gland. Very rarely, in particular with the syndrome of an empty Turkish saddle, there may be an isolated hypofunction of one of the tropic hormones.

Decreased production of growth hormone, and consequently, its universal effect on protein synthesis, leads to progressive atrophy of smooth and skeletal muscles and internal organs (splanchnomycria). There is a perception that it is the involvement of the hypothalamus nuclei in the pathological process that determines the rapidity of development and the severity of depletion.

Defect in the synthesis of prolactin leads to agalactia. In addition, posttraumatic hypothalamic panhypopituitarism with the prolactin-inhibiting factor can be combined with a high level of prolactin. Hyper-pro-tinemia and hypopituitarism are noted in malignant prolactinomas.

Transient or persistent hypopituitarism, partial or complete, may complicate operative or radiation treatment of pituitary and hypothalamic tumors. The operation of hypophysectomy is also undertaken sometimes with the purpose of suppressing the contrinulsory hormones in patients with severe, progressive diabetic retinopathy with the threat of vision loss.

Pathanatomy

Pangipopituitarism develops when the damage is not less than 90-95% of the pituitary tissue. Rarely, it is due to aplasia of the pituitary gland due to the congenital absence of the organ or the defect in the formation of Ratka's pocket. Sometimes there is only anterior lobe of the gland. Congenital atrophy usually occurs on the basis of compression of the pituitary gland from the pocket of Ratka.

Acute pituitary inflammation (purulent hypophysitis) as a cause of panhypopituitarism is due to septicemia or infection from neighboring areas. In these cases, abscesses that destroy the pituitary gland can begin. One of the rare causes of panhypopituitarism is lymphoid hypophysitis with massive lymphoid infiltration of the gland and the replacement of pituitary lymphoid tissue, which can be combined with autoimmune diseases of other endocrine organs.

Granulomatous lesions of the pituitary gland of various etiologies are often accompanied by hypopituitarism due to destruction of the pituitary tissue. Tuberculosis of this endocrine organ occurs when the process is disseminated, and pathological changes in it are typical for tuberculosis of any localization. Syphilis of the pituitary gland develops either as a process of diffuse scarring, or as a gummy process that destroys the glandular tissue.

Hypothalamic insufficiency due to syphilitic damage, sarcoidosis, giant cell granulomas, suprasellar metastases (pineal germinoma and other tumors) are possible causes of panhypopituitarism.

With generalized hemochromatosis and hemosiderosis, iron deposits in the parenchymal cells of the hypothalamus and pituitary gland occur, followed by the destruction of these cells and the development of fibrosis most often in the anterior lobe of the pituitary gland. In histiocytosis, X-xantomal deposits and histiocytic cell infiltrates are often found in both parts of the pituitary gland. They cause the destruction of glandular cells.

Chronic hypophysial insufficiency can be caused by the functionally inactive chromophobic adenoma of the pituitary gland, intrasellar and extrasellular cysts, tumors: craniopharyngioma, glioma of the hypothalamus or visual intersection, suprasellar meningioma, angioma of the pituitary foot, etc. In all these cases, thrombosis of portal vessels may be the main cause of pituitary tissue. Destruction of the funnel leads to complete death of the anterior lobe of the pituitary gland. The cause of necrosis of adenohypophysis in the syndrome of Shien is an occlusive spasm of arterioles at the place of their entry into the anterior lobe; it lasts 2-3 hours, during which necrosis of the pituitary gland occurs. The resumption of blood flow through the vessels of the funnel does not restore circulation through the portal vessels affected by ischemia. Often accompanying postpartum haemorrhage, the syndrome of intravascular coagulation leads to a thrombosis of passively dilated vessels and to necrosis of a significant part of the pituitary gland, mainly the central one. At this place a scar appears, calcifying and even ossifying.

The family hypopituitarism syndrome, combined with an enlarged Turkish saddle and the "empty Turkish saddle" syndrome, arises from the pituitary tumor present in childhood, spontaneously reversed over time, but caused irreversible compression and atrophy of the adenohypophysis.

People who died from pituitary insufficiency, found from 1-2 to 10-12% of the preserved pituitary tissue. In the neurohypophysis, marked subcapsular atrophy and scar changes are noted. In the hypothalamus (in the posterior, supraoptic and paraventricular nuclei), atrophic changes develop with time, and in subventricular nuclei, hypertrophy of neurons. In the internal organs (in the heart, liver, spleen, kidneys, thyroid gland, gonads and adrenal glands) there are atrophic changes, sometimes with severe fibrosis.