Endocrinology / / August 12, 2017
Syndrome Cushing - Cushing - a pathological condition in the pathogenesis of which is a mandatory component of the increased production of the adrenal cortex hydrocortisone caused by various pathological processes - hyperplasia, adenoma or cancer of the adrenal cortex.
term "syndrome" nomenclature introduced in view of the fact that the symptom "Cushing syndrome - Cushing" may be caused by a variety of processes in the adrenal cortex and primary disorders ekstrasuprarenalnoy may be of different locations, such as lung cancer, thymus and other organs.The syndrome is called Cushing - Cushing because the NM Cushing described the first clinical and showed possible involvement in the pathogenesis of certain organic lesions of the central nervous system;Cushing also found frequent presence in this syndrome basophilic adenoma or hyperplasia of basophil cells.
Etiology syndrome Cushing's
Etiology Cushing syndrome - Cushing has not been established.Available individual guidance in the literature for poss
Pathogenesis syndrome Cushing's
compulsory component in the pathogenesis of the syndrome Cushing - Cushing is the overproduction of adrenal cortex hydrocortisone, which determines the basic characteristic manifestations of the syndrome: changes in body weight with disproportionate fat deposits, a change in facial color, hypertension, hypertrichosis, atrophic processes inskin, muscle, and a number of other disorders, including metabolic disorders.
most frequent morphological changes in the adrenal cortex, cause hypersecretion of hydrocortisone is hyperplasia of the zona fasciculata.For more rare morphological changes include adenoma and cancer of the adrenal cortex.
proof of the main values of hyperfunction of the adrenal cortex in the development of the clinical picture of the syndrome is improving incretion hydrocortisone, hydrocortisone frequent increase in blood metabolites and increased release of urine.Another compelling factor in favor of determining the value of hydrocortisone overproduction of adrenal cortex in the pathogenesis of the syndrome is the elimination of the main symptoms after total or subtotal removal of the adrenal glands or the removal of the tumor.Finally, long-term administration of hydrocortisone, cortisone, and their analogues produced for chronic joint and other diseases, develops the typical clinical picture of Cushing syndrome - Cushing.
Some patients at the same time there is an increased androgenic function of the adrenal cortex.
Cushing in 1932 showed 5 of 9 pituitary glands obtained at autopsy of the dead, suffering from Cushing's syndrome - Cushing's presence in the adenohypophysis basophilic adenoma or significant accumulations of basophil cells.These changes, he took a primary role in the pathogenesis, as they observed hypertrophy of the adrenal cortex considered as a secondary change due to the defeat of the pituitary gland.Subsequently, the frequent presence of basophilic adenoma and increasing the number of basophils in the pituitary adenohypophysis with the syndrome - Cushing was confirmed by a number of authors.However, these changes are optional basophilic adenoma of the pituitary gland could not be detected in 40% of patients.They found it in only 49 of 75 patients suffering from Cushing's syndrome - Cushing.
Later basophilic changes in the anterior pituitary gland in the syndrome of Cushing - Cushing came to be regarded as a morphological indicator of increased incretion of ACTH.
In 1935 Srooke using modified Mallory staining found in the cytoplasm of basophils is adenoma, mostly hyaline inclusions, which he regarded as a manifestation of the increased activity of these cells.In other diseases, the changes described Sgooke observed very rarely.In the future, these mostly hyaline changes in the pituitary basophils were installed in the application of cortisone or ACTH therapy, and they are now considered as secondary changes develop as a result of increased incretion of hydrocortisone.But, along with this, the accumulated data, which reinforce the representation of Cushing and others about the presence of hyperfunction basophils, producing excessively AKTT.
At autopsy of deaths from the syndrome Cushing - Cushing's people, except basophil microadenoma repeatedly found malignant tumors of the pituitary.Cushing occurring with malignant tumors of various not endocrine and endocrine organs with simultaneous bilateral adrenal hyperplasia -
cases of Cushing's syndrome have been described.These tumors include bronchogenic carcinoma, thymus, pancreas, thyroid, uterus, ovaries.Brown in 1928 described hypercortisolism in conjunction with bronchopulmonary cancer, a Kepler - a pancreatic tumor.Has been identified in primary bronchial tumors, their metastases in tissues and in plasma, tumors in pancreatic-like activity of ACTH, the pituitary ACTH content was at subnormal levels.Adrenal cortex produced a huge amount of hydrocortisone.Bilateral adrenalectomy removes all the major symptoms of the syndrome and the subsequent course of the disease was determined by a cancerous tumor.
number of authors was in patients with Cushing's syndrome - Cushing shown an increase of ACTH-activity of the blood.All this has led to the view that the increase in ACTH production by the pituitary gland or ACTH-like activity of the tumors that occur with Cushing's syndrome - Cushing, are factors that directly lead to adrenal hyperplasia.
VG Baranov in 1955 put forward the idea that hyperplasia, adenoma and cancer of the adrenal cortex are the different stages of the pathological process caused by over-stimulation of the adrenal glands produced by ACTH.For example, development of hyperplasia, adenomas and cancer can be observed in the thyroid gland in excessive its stimulation in the rat thyrotropin, advancing by lowering hormone its function antithyroid drugs, iodine deficiency and other. On the other hand, the off thyroid induces in micepituitary tumors that produce a large amount of thyroid stimulating hormone.Proof of this situation was the discovery of elevated ACTH activity in patients with Cushing's syndrome - Cushing to the presence of hormonally active adenomas in the adrenal cortex.If the adenoma was the primary violation, it should lead not to an increase but to a decrease in blood ACTH activity.Further it found that the clinical picture of Cushing syndrome - Cushing's can be caused by long-term appointment of ACTH.
Cushing's syndrome - Cushing also set increased response of adrenal cortex to ACTH stimulation, and increase response was also demonstrated long-term use of ACTH.
All these data give reason to take ACTH-active pituitary or vnegipofizarnogo origin is essential in the development of hyperplastic processes in the adrenal cortex, is directly determined in the future all of the major manifestations of the syndrome.
development of the doctrine of the hypothalamus neurosecretion would inevitably raise the question of a possible violation of the primary function of the hypothalamic centers that produce factor, corticotropin-releasing (Corticotropin-Releasing-Factor), the second leads to increased production of ACTH anterior pituitary.Most authors link the regulation of anterior pituitary ACTH production from the area median eminence of the hypothalamus.Changes in the midbrain with the syndrome were established in 1924 NM pituitary.However, the hypothalamus involved in the pathogenesis of Cushing syndrome - Cushing in the bulk of the patients has not been proven.
metabolic disorders, changes in tissues and organs, characteristic of the syndrome Cushing - Cushing, determined directly increased incretion of hydrocortisone.
Pathology syndrome Cushing's
most legitimate and pronounced changes in the syndrome of Cushing - Cushing observed in the adrenal cortex.By Jailer adrenal hyperplasia was set at 80-81% of autopsies adenoma - 14% and cancer - 5-6%.Similar data lead Symington et al., Who observed in 70% of hyperplasia and tumor (adenoma or cancer) in 30%.Such data are a number of other researchers.Several different observations Harten-bach, celebrated adrenal hyperplasia and 90% of the tumor in 10%.Children with the syndrome Cushing - Cushing much more frequently than in adults, there are tumors of the adrenal cortex.Thus, filed Soffer et al., In children suffering from this syndrome, cortical tumors were found at autopsy in 75%, and 60% had cancer.
both hyperplastic adrenal weight ranges from 10 to 26 The main changes concern the beam area.It greatly expanded, microscopically is, except for the external departments of the big bright cells with foamy cytoplasm acidophilic loaded with lipids.The nuclei of these cells are large, hyperchromatic.Often there are polynuclear cells and large cells with large nuclei.Cells were observed in a state of amitotic fission.Mostly found adenomatous hyperplasia, which is a microscopically detectable nodosa education, consisting of large light cells with large nuclei.According Soffer et al., This hyperplasia, apparently reflects the response of adrenal cortex to excessive ACTH stimulation.
Glomerular zone is usually narrow, fibrotic changes, in some places is completely absent, and then beam area immediately adjacent to the prostate capsule.
Net zone consists predominantly of compact cells.The net area or on its border with the beam area there are lots of fatty tissue.These fatty inclusions are characteristic feature of the structure during remission of the disease.
often occur mainly in the network area small foci of lymphoid infiltration and small hemorrhages.
in hyperplastic adrenal cells is observed atypia the constant stimulation of the adrenal cortex.
encapsulated adrenal cortex adenomas.their weight is usually between 10 g and above.Microscopically they consist of compact cells arranged in bands, or have the alveolar structure.The opposite adrenal gland undergoes varying degrees of atrophy.Sometimes small adenomas found weighing 5-10 g without wasting a second of the adrenal gland.
Cancerous tumors of the adrenal glands can reach a weight of 1800 sometimes observed invasion of tumor cells in v.cava inferior.Permanently marked areas of hemorrhage and necrosis.Tumor consists mainly of compact cells with oval nuclei.There may be mitotic figures and giant cells.Malignant tumors rapidly metastasize to the adrenal glands, lungs, brain, bones and liver.
The adenohypophysis in the majority of deaths observed hyperplasia cells or basophil basophilic microadenoma.It rarely seen changes in the pituitary include basophil adenocarcinoma, chromophobe adenoma, eosinophilic adenoma.
Similar changes have also been established and eosinophilic cells.
neurohypophysis in the syndrome of Cushing - Cushing's almost no neurosecretion.
Rare pathological changes include cancers of the bronchi, thymus, ovary, pancreas, etc.., Arenoblastomy.
Clinic syndrome Cushing's syndrome
Cushing - Cushing's disease is a rare, relatively more common in women.Most often ill persons aged 20-40 years, but the presence of the syndrome described in infants aged 3-5 months and older persons aged 70 years.
are frequent complaints of fatigue, headaches, weight build-up, change in appearance, hypertrichosis, menstrual disorders in women and impotence in men, pain in the back, legs, and other phenomena associated with the defeat of a number of tissues and organs.
thin skin, atrophic and dry.Pronounced purple-cyanotic color of the face, chest, back;marble pattern leather limbs and trunk.Clearly emerges venous pattern on the chest and limbs.There akrotsianoz.In 2/3 of the patients on the skin of the abdomen, the internal parts of the shoulders, hips, in the breast skin atrophy observed in bands of red and purple (striae cutis distensae purpura-viollette).They can reach a length of 10 cm or more in diameter and be up to 2-3 cm.
Stretch marks are a common, but not mandatory manifestation of the syndrome.They may appear in the dynamics have already developed symptoms.A characteristic hallmark of stretch marks is to preserve the typical color for the entire period of the active stage of the disease.By eliminating the syndrome Cushing - Cushing stretch marks fade.Development
atrophic striae is the result of changes in the skin until its deep layers, associated with an increased catabolism and anabolism down proteins.Purplish-red skin atrophy of the bands is due to candling vascular beds.This factor leads to a sharp protrusion vein pattern.
Histological examination of the skin epidermis with flattening of the lack of papillae, the corium edema, changes in elastic fibers, a reduction of collagen fibers and fibrous tissue.
The skin often have petechiae and ecchymosis, the occurrence of which is due to small changes in the vessel walls.Capillaries and venules of the skin expanded, walls are thin, sometimes observed their aneurysmal expansion.The gaps between the endothelial cells of small vessels increased, which probably leads to stepping erythrocytes per diapedesis.
often marked hyperpigmentation of the skin, due to the increased production of the hormone melanophore (intermedin) having a close relation to the production of ACTH.
on the skin of the back, chest, face women often observed of acne, the development of which has a value of increased incretion of androgens.
This factor underlies common in Cushing syndrome - Cushing hypertrichosis in women in the area of the face, extremities, abdomen.However, hypertrichosis does not reach usually largely observed in the androgen hormone-active tumors of the adrenal cortex.
Hair often fall, and hair loss in women is male pattern - at the temples, crown and nape.
has an increased tendency to furunculosis and to the development of erysipelas.
- subcutaneous tissue. noted excessive deposition of fat mostly in the torso, neck and face.A person takes the form of "full moon", which together with the purple-cyanotic coloration of the skin gives the characteristic appearance of the patient and allows a distance often diagnose the syndrome.
Figure: Patient 29 years with a syndrome of Cushing - Cushing.The disproportionate distribution of fat, stretch marks on the abdomen, thighs, in the underarm area.
In the upper thoracic vertebrae often have fatty deposits in the form of a hump.At the extremities of excess fat deposits is not observed.In some patients, there is less than a typical distribution of body fat.
- Muscles. The most permanent changes are atrophic processes striated muscle of different intensity, especially noticeable in the muscles of the upper and lower extremities.This leads to a thinning and loss of limbs their normal shape.The absence of excess fat deposits in the extremities and atrophy of the muscles of the body contribute to the formation of a typical configuration of the patients.Muscle atrophy that develops as a result of increased catabolism and anabolism of proteins and low presence of hypokalemia, causes the appearance of muscle weakness - one of the most constant symptoms of Cushing's syndrome - Cushing.
Histologically marked atrophy of the muscle fibers, many of which are heavily infiltrated with fat.Involved mainly the proximal muscles of the lower extremities.Art.Art.