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International Medical Scientific Journal        Issue-3 

10.5281/zenodo.5761836 

96 



Art of Medicine           Volume-1 

International Medical Scientific Journal        Issue-3 

10.5281/zenodo.5761836 

97 

 

 

 

Art of Medicine International Medical Scientific journal 

 

Founder and Publisher Pascual Izquierdo-Egea 

Published science may 2021 year. Issued Quarterly. 

Internet address: http://artofmedicineimsj.us 

E-mail: info@artofmedicineimsj.us 

11931 Barlow Pl Philadelphia, PA 19116, USA +1 (929) 266-0862 

 

 
 



Art of Medicine           Volume-1 

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Carbon metal disorders in cushing syndrome 

Kholmatova. Yu.A. 

Ph.D., Narimova G.D. 

Tashkent Pediatric Medical Institute Republic of Uzbekistan 

Abstract: The article analyzes the specificity of carbohydrate metabolism in 

Cushing's syndrome from a scientific point of view. Thus, the article draws 

conclusions about carbohydrate metabolism in Cushing's syndrome. 

Keywords: Cushing's syndrome, steroid diabetes mellitus, hyperglycemia, 

carbohydrate metabolism, hypercortisolism. 

The relevance of studying carbohydrate metabolism in patients with Itsenko-

Cushing's disease is explained by the frequent occurrence of glucose metabolism 

disorders, on the one hand, and difficulties in the selection of antihyperglycemic 

therapy in these categories of patients, on the other. The effectiveness of the 

treatment of hyperglycemia in such patients may be reduced due to the difficulty of 

achieving remission / cure of the underlying disease, as well as due to the use of 

specific therapy that promotes the development of hyperglycemia. Recently, there has 

been growing interest in studies aimed at studying the role of the incretin system in 

the pathogenesis of secondary hyperglycemia associated with neuroendocrine 

diseases[1]. 1 

Itsenko-Cushing's disease (BIK) is a severely symptomatic disease of 

hypothalamic-pituitary genesis, occurring with a clinical picture of hypercortisolism, 

caused by the presence of a pituitary tumor (85%) or pituitary hyperplasia and 

characterized by increased secretion of adrenocorticotropic hormone (ACTH) and an 

increase in adrenocorticotropic hormone (ACTH). 

Epidemiology 

This is the most common cause of endogenous Itsenko-Cushing syndrome (about 

68%). The disease is more common in women than in men. Women are more likely 

to get sick between the ages of 20 and 40, there is an addiction to pregnancy and 

childbirth, as well as from brain injuries and neuroinfections (in particular, herpes 

infection). In adolescents, the disease often begins during puberty [2]. 

 In childhood and old age, Itsenko-Cushing's disease is rarely diagnosed. 

Classification 

There are several degrees of severity of NIK: 

- mild form (moderately severe symptoms of the disease); 

- moderate form (pronounced symptoms in the absence of complications); 

- severe form (severe symptoms in combination with complications, including 

cardiopulmonary failure, steroid diabetes, 

progressive myopathy, pathological fractures, severe mental disorders). 

ticism is distinguished by a rapidly progressive (3-6 months) and torpid course of the 

disease (> one year). There are four main reasons for the state of excess 

glucocorticoids of any origin: 



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1. Exogenous glucocorticoids. Cushing's syndrome develops over time in patients 

who receive glucocorticoids for inflammatory or autoimmune diseases (including 

bronchial asthma, rheumatoid arthritis, systemic lupus erythematosus, skin diseases). 

2. Pituitary Cushing's syndrome. This pathology, called Itsenko-Cushing's disease, 

develops with benign pituitary adenomas, which secrete excess ACTH. 

3. Ectopic ACTH products. Of the two variants of ectopic production, ACTH of the 

first type is caused by malignant tumors, most often of the lungs. Patients have clear 

signs 

metastatic tumor: weight loss, hypertension, hypokalemia, and hyperpigmentation. 

The second variety is due to slowly growing 

tumors referred to as carcinoids. Patients with ACTH-producing carcinoid tumors 

may have the same clinical symptoms. 

phenomena and biochemical shifts, as well as patients with pituitary disease Itsenko-

Cushing. Thus, the differential diagnosis between a pituitary tumor and a carcinoid 

tumor in a patient with Cushing's syndrome is difficult [3] 

4. Adrenal causes of Cushing's syndrome. Both benign and malignant adrenal 

tumors can produce excess glucocorticoids and be accompanied by Cushing's 

syndrome. Benign adrenal adenomas are clinically similar to other varieties of this 

syndrome; hirsutism, however, is absent, as the tumor only secretes cocortisol and not 

androgens. Malignant adrenal carcinomas with manifestations of Cushing's syndrome 

are usually large tumors in the abdominal cavity and have poor 

forecast [4]. 

Etiology and pathogenesis 

The reason for the BIK has not been precisely established. Most of the patients 

are diagnosed with a pituitary adenoma, which, according to modern concepts, is the 

cause of the disease. In recent years, using the methods of molecular biology, the 

pathogenesis of pituitary adenomas, and corticotropin in particular, has been clarified. 

It has been shown that most of these adenomas are monoclonal, as evidenced by the 

presence of the same gene mutations in adenoma cells. A potential mechanism for the 

development of corticotropin may be spontaneous mutation of the receptors of the 

corticotropin-releasing hormone (CRH) or vasopressin genes. In the absence of 

obvious signs of a pituitary adenoma, we can talk about damage or dysfunction of 

higher structures, for example, the limbic region [5]. 

Clinical signs and symptoms 

Cortisol and other glucocorticoids have multifaceted effects as physiological 

regulators. They increase glucose production, inhibit protein synthesis and increase 

protein breakdown, stimulate lipolysis and affect immunological and inflammatory 

processes. Glucocorticoids contribute to the maintenance of blood pressure and 

largely determine the body's response to stress. 

The production of cortisol by the adrenal glands is stimulated by ACTH. The 

secretion of ACTH, in turn, depends on the CRH produced in the hypothalamus 



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and vasopressin. Cortisol, acting on the pituitary gland, hypothalamus, 

suppresses the production of ACTH and CRH. In normal (non-stress) conditions, the 

products of cor- 

tizole is carried out in accordance with certain biological rhythms: with a 

higher activity in the morning and a lower activity late in the morning. 

black. Under stressful conditions, the secretion of CRH, ACTH and cortisol 

increases, and biological rhythms are disrupted. Since cortisol levels can vary widely 

throughout the day and increase in a certain way under stress, it can be difficult to 

distinguish between normal and impaired secretion of this hormone.Many 

biochemical tests are used to diagnose pathological hypercortisolemia, but 

none of them is absolutely reliable. Therefore, the examination of a patient 

with suspected NIK is often difficult and can give conflicting results [6]. 

The clinical picture of NIK is caused by excessive secretion of corticosteroids, 

and primarily corticosteroids. Characterized by the defeat of almost all organs and 

systems with the development of a symptom complex inherent in hypercortisolism 

[7]. 

Dysplastic obesity (the earliest and most common symptom). Characterized by 

the redistribution of subcutaneous adipose tissue (cushingoid type of obesity) with the 

deposition of fat in the shoulder girdle, supraclavicular spaces, above the cervical 

vertebrae ("climacteric hump") and on the abdomen with relatively thin limbs. The 

face becomes round (moon-shaped), the cheeks become purple-red (matronism) [8]. 

Trophic changes in the skin. The skin is thinned, dry, with a tendency to 

hyperkeratosis, purple-cyanotic color. Stretch stripes (striae) of red-violet color 

appear on the hips, chest, shoulders, abdomen, due to increased protein catabolism 

and thinning of the skin. Characterized by the formation of hematomas of minor 

injuries due to increased fragility of capillaries and thinning of the skin, 

hyperpigmentation of the skin in places of friction (neck, elbow joints, armpits) due 

to increased secretion of ACTH. Often women have hirsutism (mustache, beard, 

sideburns), breast hypertrichosis. 

Secondary hypogonadism (early symptom). In women, the menstrual cycle is 

disrupted in the form of opsomenorrhea and amenorrhea, which leads to primary or 

secondary infertility. In men, potency decreases and gynecomastia often develops. At 

puberty, boys have underdevelopment of the testicles and penis, and girls have 

underdevelopment of the mammary glands and primary amenorrhea. These changes 

are accompanied by a decrease in plasma gonadotropins, testosterone and estrogens 

[9]. 

Arterial hypertension (AH). Develops in the majority of patients. Subsequently, 

violations of myocardial metabolism and the appearance of symptoms are possible. 

ptomes of heart failure. Signs of left ventricular hypertrophy can often be seen 

on electrocardiography (ECG). 

Myopathy. Muscle hypotrophy affecting the striated and muscular systems, 

benno of the upper and lower extremities (thinning of the arms and legs), atrophy of 

the muscles of the anterior abdominal wall with an increase in the abdomen [10]. 



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Disorders of carbohydrate metabolism. Manifested by impaired glucose 

tolerance (in 70-80% of patients) or type 2 diabetes mellitus (DM). Diabetes mellitus 

is characterized by hyperinsulinemia, insulin resistance, lack of tendency to 

ketoacidosis, and a favorable course (usually, to compensate for carbohydrate 

metabolism, it is sufficient to prescribe a diet and oral hypoglycemic drugs) [11]. 

Secondary immunodeficiency. Manifested by pustular (acne) or fungal lesions 

of the skin and nail plates, trophic ulcers 

shins, a long period of healing of postoperative wounds, chronic 

pyelonephritis. Characteristic is the inhibition of all links of cellular immunity (a 

decrease in the number of T and B lymphocytes), a decrease in the activity of 

phagocytes and a decrease in humoral immunity. Vegetative changes 

nervous system are pronounced and diverse, they form the syndrome of 

vegetative dystonia, which manifests itself in emotional and personal 

shifts - from mood and sleep disorders to severe psychosis [12]. 

Changes in the skeletal system. In children and adolescents, early symptoms of 

hypercortisolism are growth retardation or complete cessation, as well as a delay in 

skeletal differentiation; there is a difference between passport and bone age of 1–5 

years. Steroid osteoporosis with bone demineralization and suppression of protein 

matrix synthesis at any age is one of the most severe manifestations of 

hypercortisolism. The severity of the process depends on the degree and duration of 

hypercortisolism. Frequent symptoms of osteoporosis are pain in the spine, often a 

decrease in the height of the vertebral bodies and spontaneous fractures of the ribs 

and vertebrae. 

Disorders of carbohydrate metabolism are a frequent symptom of Itsenko-Cushing's 

disease Patients with this pathology may experience en- 

precrinologists, family doctors diagnosed with type 2 diabetes, hypertension, 

dyslipidemia, osteoporosis. At the same time, the secondary genesis of the clinical 

symptoms of the disease often remains unrecognized for a long time, which 

contributes to the progression of the disease and the development of complications. A 

cohort of patients with Itsenko-Cushing's disease has a high risk of atherosclerotic 

cardiovascular disease, which can continue despite remission of the disease and 

normalization of cortisol levels [13]. 

We have presented the patient's case history, which was observed by primary care 

specialists for type 2 diabetes and hypertension. A thorough examination of the 

patient, in which attention was drawn to the rapid weight gain, dysplastic structure, 

matronism, made it possible to suspect the secondary nature of the disorders and 

establish the correct diagnosis of Itsenko-Cushing's disease. The performed surgical 

treatment made it possible to eliminate the clinical manifestations of 

hypercortisolism, namely, secondary diabetes mellitus, dysplastic obesity, 

hypertension. We draw the attention of various specialists to the problem of 

hypercortisolism and the possibility of developing atypical, erased forms of this 

pathology, without characteristic skin symptoms of the disease. Endogenous 

hypercortisolism, in our opinion, should be inappropriate in patients control of 



Art of Medicine           Volume-1 

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diabetes in combination with hypertension, dysplastic obesity or rapid weight gain. 

Such patients require a comprehensive endocrinological examination, including a 

study of cortisol, a small dexamethasone test, an assessment of the content of thyroid-

stimulating hormone, lipid profile, as well as the state of bone tissue [14]. 

Steroid diabetes mellitus is an endocrine pathology that develops as a result of a high 

content of adrenal cortex hormones in the blood plasma and a violation of 

carbohydrate metabolism. It is manifested by symptoms of hyperglycemia: rapid 

fatigue, increased thirst, increased profuse urination, dehydration, increased appetite. 

Specific diagnosis is based on laboratory detection of hyperglycemia, assessment of 

the level of steroids and their metabolites (urine, blood). Treatment for steroidal 

diabetes includes withdrawal or reduction of glucocorticoid dosage, surgery to reduce 

the production of corticosteroid hormones, and antidiabetic therapy. 

Steroid diabetes mellitus (SD) can be triggered by a prolonged increase in the 

secretion of corticosteroids or by taking them in the form of drugs. In the second 

case, the disease has a synonymous name - drug diabetes. Initially, it is not associated 

with the functional state of the pancreas, develops against the background of 

hormonal treatment and can go away on its own after drug withdrawal. SJS, provoked 

by an increase in natural hormones, is most often observed in Itsenko-Cushing's 

disease. In this group of patients, epidemiological indicators reach 10-12%. There is 

no exact information on the prevalence of SJS in the general population. 

Causes 
Etiologically, steroidal diabetes mellitus is subdivided into endogenous and 

exogenous. In the endogenous form, pancreatic dysfunction is caused by primary or 

secondary hypercortisolism. The reasons for this group include: 

Secondary hypercortisolism. Cushing's syndrome occurs when the level of 

ACTH, a hormone produced by the pituitary gland and regulating the activity of the 

adrenal glands, rises. The secretion of corticoids increases, there is a high risk of 

dysfunction of the pancreas. 

Adrenal neoplasms. In primary hypercortisolism, corticosteroid production is 

stimulated by the growing tumor of the adrenal gland. SJS is often diagnosed with 

corticosteroma, aldosteroma, corticoestroma, androsteroma. 

The second variant of the origin of steroidal diabetes is exogenous. The high-

risk group includes patients with autoimmune pathologies, chronic renal failure, and 

arterial hypertension. Diabetes develops with prolonged therapy with drugs that 

inhibit the secretion of insulin by beta cells in the pancreas. These drugs are 

glucocorticoids, thiazide diuretics, hormonal contraceptives [15]. 

 The level of incretins can act as a possible marker of specific disorders of 

carbohydrate metabolism in patients with Itsenko-Cushing's disease and, presumably, 

can help in the differential diagnosis of steroidal diabetes and type 2 diabetes 

mellitus. Further research is needed to confirm these assumptions. 

Itsenko-Cushing's disease and type 2 diabetes sometimes have a similar clinical 

picture, which complicates the timely diagnosis of endogenous hypercortisolism. The 

presence of disorders of carbohydrate metabolism, especially in combination with 



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other manifestations of this neuroendocrine disease, such as dysplastic obesity, 

poorly controlled arterial hypertension, etc., dictates the need to exclude its secondary 

nature. In turn, the achievement of a satisfactory postoperative result in relation to 

corticotropinoma does not always lead to a regression of the formed complications. 

The lack of normalization of glycemic parameters, lipid metabolism, and blood 

pressure puts patients at high risk for the development of cardiovascular 

complications in the future and dictates the need for careful dynamic monitoring by 

specialists. To achieve compensation for DM in comorbid patients, it is worth 

considering therapy with new generation drugs (inhibitors of dipeptidyl peptidase-4, 

inhibitors of sodium glucose transporter type 2), if necessary, in combination with 

other drugs. 

 

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