The neuroendocrine pathology associated with destruction of the hypothalamic centers and pituitary gland, resulting in secondary hypersecretion of adrenal cortical hormones, is called Icenko-Cushing’s disease. Since we are talking about lesions of the hypothalamus, it is necessary to note the affiliation of any pathology associated with the gland’s dysfunction with leptin and other hormones that control eating behavior. You will learn about the symptoms of the disease, its etiology, diagnosis and treatment from the article.
- General information.
- Causes of the disease.
- Prognosis and prevention.
There are two pathological conditions united by the same symptomatology and the name of the authors who described this pathology: syndrome and disease. In fact, it is a single symptomcomplex with different causes of occurrence. The syndrome or primary hypercorticism is based on adrenal cortical tumors with glucocorticoid hypersecretion or hypercorticism due to long-term exoglucocorticoid use.
Sometimes ectopic ACTH syndrome forms with similar symptoms if ovarian or thyroid cancer is underlying, for example. Pathology in the form of disease is a primary lesion of the system at the level of the hypothalamus and pituitary gland, and the periphery (endocrine glands) are involved in the pathological process secondary. The disease affects women 7 times more often than men, and at the same time is of reproductive age.
Causes of the disease
Basophilic or chromophobic adenoma of the pituitary gland producing adrenocorticotropic hormone is considered the main trigger of the disease. In pituitary tumors, patients are diagnosed with microadenoma, macroadenoma, and adenocarcinoma. Sometimes there is a connection between the debut of the pathology and preceding it infectious CNS lesion such as encephalitis, arachnoiditis, meningitis. Other causes of the disease are called craniocerebral trauma, intoxications. In women – hormonal restructuring during pregnancy and childbirth, menopause.
The pathogenesis of the disease is quite complex. It is based on disruption of the hypothalamus, pituitary and adrenal glands with minimization of the inhibition of dopamine mediators on the secretion of releasing hormone, which leads to hypersynthesis of adrenocorticotropic hormone. High levels of bioactive substance (ACTH) provoke a cascade of adrenal and extra-adrenal reactions.
Endocrine organ synthesis of glucocorticoids, androgens, and mineralocorticoids increases. Increased levels of the former have a catabolic effect on protein and carbohydrate metabolism. This in turn is accompanied by muscle and connective tissue atrophy, hyperglycemia, insulin deficiency and resistance to it with the formation of steroid type diabetes mellitus. The affiliation of insulin resistance with leptin resistance explains the development of obesity in Icenko-Cushing’s pathology.
Increased mineralocorticoid activity in pathology stimulates the angiotensin-renin system, helping to develop hypokalemia and hypertension. The catabolic processes in bone tissue are accompanied by calcium leaching and its minimal reabsorption in the digestive tube with the development of osteoporosis. Androgenic qualities of the synthesized hormones provoke ovarian imbalance.
The degree of severity of the disease is divided into mild, moderate, and severe. The first one is accompanied by moderate symptoms: menstruation is preserved, osteoporosis is most often absent. The middle one has bright symptoms, but no complications, and the severe one is characterized by the development of complications: muscle atrophy, hypokalemia, renal hypertension, mental disorders.
According to the rate of pathology formation it is divided into progressive and torpid. The progressive form is a rapid development in six months to a year with increasing complications, and the torpid form is a gradual formation of pathological changes within three to ten years.
The main disturbances that manifest themselves clinically are metabolic disorders on the part of lipids, which are associated with leptin, bone tissue, muscles and nerves, heart and blood vessels. The respiratory system, sexual and digestive systems are altered, and the psyche changes as well. Patients with the disease have a specific appearance, which is associated with localized fat deposits in certain areas: face, neck, shoulders, mammary glands, back, abdomen.
The face becomes moon-shaped, a widow’s hump is formed in the projection zone of the seventh cervical vertebra, and the chest and abdomen increase in volume. However, the arms and legs remain thin, and the skin is dry, flaky, and has a distinct scarlet-marbled pattern. Striae occur in the area of the breasts, on the shoulders and abdomen, and intradermal bruises are clearly visible. Often acne and furunculosis are diagnosed.
Disorders associated with altered hormonal background in women are menstrual disorders, often amenorrhea, hirsutism (hairiness), facial hair and loss of hair on the head. In men – a minimum of facial and body hair, lack of libido, impotence. Debut of the pathology in childhood inhibits sexual development due to the minimum synthesis of gonadotropins.
Changes in bone tissue – the result of osteoporosis, such changes are manifested by pain syndrome, frequent fractures and bone deformities. In children, the skeleton deforms, and growth retardation is observed. Cardiovascular disorders include hypertension, tachycardia, electrolyte steroid cardiopathy, and CHF. Patients with Icenko-Cushing’s disease are often diagnosed with bronchitis, pneumonia, and tuberculosis.
The lesions of the digestive system are manifested by heartburn, pain syndrome in the epigastrium, gastritis of different genesis, diabetes mellitus on steroids, DU and duodenal ulcer, bleeding of the digestive tube. Kidney and urinary tract lesions develop chronic pyelonephritis, IBC, nephrosclerosis, renal failure, uremia.
Neurological disorders are pain and amyotrophic syndrome, which are potentially reversible with adequate treatment. In the absence of it, the processes are irreversible. Nystagmus, ataxia, tendon hyperreflexia, lesion of facial and hyoid nerves are clinically expressed. Mental disorders are neurasthenia, asthenia, epilepsy, depression and hypochondria. Typical are decreased memory, intelligence, lethargy, minimal emotions, suicidal thoughts.
The examination algorithm is quite complex and voluminous:
- Blood biochemistry with hypercholesterolemia, hyperglobulinemia, hyperchloremia, hypernatriemia, and parallel hypokalemia, hypophosphatemia, hypoalbuminemia, decreased activity of alkaline phosphatase. In steroidal diabetes mellitus, glucosuria and hyperglycemia are recorded. Hormonal testing reveals high levels of cortisol, ACTH, renin.
- The OAM reveals erythrocytes, protein, granular and hyaline cylinders, the biochemical analysis of urine has increased content of 17-CS, 17-OX, cortisol.
- For differential diagnosis of the disease and Icenko-Cushing’s syndrome, tests with dexamethasone and metopyron (Liddle’s test) are performed.
- X-ray of the Turkish saddle helps to see macroadenomas of the pituitary gland.
- CT and MRI of the brain with contrast injection – microadenomas.
- Spine radiography reveals osteoporosis.
- Ultrasound and MRI of the adrenal glands, scintigraphy, and CT scans reveal bilateral adrenal hyperplasia.
Differentiate Icenko-Cushing’s disease with the syndrome of the same name, hypothalamic syndrome of the pubertal period, and obesity associated with leptin.
The goal of therapy for Icenko-Cushing’s disease is to eliminate hypothalamic shifts, correct ACTH and corticosteroid synthesis, and restore metabolism. Medications, X-rays, gamma-rays, proton therapy of the hypothalamic and pituitary areas, surgical treatment, and their combination are used for treatment.
Medications are used in the initial stages of Icenko-Cushing’s disease. Rerpin, Bromocriptine, blockers of steroid hormone synthesis in the adrenal glands are recommended for the purpose of blocking the pituitary gland. Correction of protein, mineral, carbohydrate, and electrolyte metabolism is performed.
Radiation therapy is administered to patients who have no radiological signs of a pituitary tumor. One method of such therapy is stereotactic implantation of radioactive isotopes into the pituitary gland. As a rule, a few months after radiation treatment, remission occurs, which is visually accompanied by a decrease in weight, blood pressure, normalization of the monthly cycle, and a minimum of bone and muscle tissue damage. Pituitary irradiation can be combined with unilateral removal of the adrenal gland or targeted destruction of the hyperplasticized substance of the organ.
If the disease is severe, bilateral removal of the adrenal glands with subsequent hormone replacement therapy is recommended. If a pituitary adenoma is detected, endoscopic transnasal or transcranial tumor removal, transsphenoidal cryosurgery are performed. After adenomectomy, remission is recorded in 80%, and relapse in 20%.
Prognosis and prevention
The prognosis of Icenko-Cushing’s disease correlates with the duration and severity of the pathology, as well as the age of the patient. In mild cases in young patients, complete recovery is possible, the long-term existence of the disease, even if the underlying cause is eliminated, causes persistent changes in all body systems. Which significantly complicates the prognosis. Advanced cases with renal failure, sepsis, end fatally. All patients with such pathology require follow-up observation and adherence to all medical recommendations. Prevention consists in the prevention of craniocerebral injuries, infections and intoxications.