Hypercorticism

Classification and etiology

The pathology is divided into several main forms depending on the level of the lesion and the causes of occurrence.

1. Cushing's disease (central form). The primary defect is located in the hypothalamo-pituitary system (most commonly an adenoma of the anterior pituitary). The tumor excessively secretes ACTH, leading to bilateral adrenal cortex hyperplasia and the release of huge amounts of gluco- and mineralocorticoids.
2. Cushing's syndrome. Combines peripheral disorders. Includes the adrenal form (adenoma or carcinoma of the adrenal cortex itself) and the ectopic form (extra-adrenal tumors, such as bronchogenic carcinoma, which independently begin to secrete ACTH-like substances).
3. Iatrogenic hypercortisolism. Develops as a side effect of long-term glucocorticoid therapy in patients with autoimmune diseases, dermatoses, or blood disorders.
4. Cerebral origin. Develops as a consequence of trauma (traumatic brain injury) or neuroinfections. Hypothalamic damage causes excessive synthesis of corticoliberin, which entails an increase in ACTH levels.

Metabolic manifestations

The key symptoms of hypercortisolism are directly related to the effect of cortisol on various types of metabolism.

• Lipid metabolism. Dysplastic obesity develops with uneven distribution of subcutaneous fat. Fat is deposited on the face (forming a "moon face"), in the posterior and lower neck ("buffalo hump"), and above the clavicles.
• Protein metabolism. A severe catabolic syndrome is triggered. Muscles atrophy (limbs become thin), and the skin thins. Due to the destruction of collagen fibers against the background of a growing abdomen, striae appear — wide pinkish-purple stretch marks. The vascular wall becomes fragile, leading to frequent hemorrhages.
• Carbohydrate metabolism. A spectrum of disorders is observed: from impaired glucose tolerance to the manifestation of steroid diabetes with hyperglycemia and glucosuria. Notably, ketoacidosis rarely occurs in this condition.
• Bone matrix. Steroids have a pronounced catabolic effect on bone tissue. Patients are bothered by bone and joint pain, osteoporosis develops early (may be one of the first symptoms), and the risk of spontaneous fractures is high.

Systemic disturbances

The impact of hypercortisolism is not limited to metabolism — internal organs and the patient's mental state are also under attack.

Cardiovascularly, arterial hypertension is registered in 3/4 of patients. Dystrophic changes occur in the myocardium, accompanied by cardialgia and ECG repolarization abnormalities. Water-electrolyte balance shifts: sodium and water are retained in the body, provoking edema syndrome, while potassium levels drop critically (hypokalemia).

The gastrointestinal tract reacts with abdominal pain and a high risk of ulcerogenesis — the formation of "steroid" gastric ulcers. In the reproductive sphere, menstrual irregularities and hirsutism (male-pattern hair growth) are observed. The psycho-emotional background is extremely unstable: complaints of general weakness, fatigue, headaches, irritability, emotional lability, and deep depressive states are typical.

Diagnostics and treatment principles

The laboratory picture includes neutrophilic leukocytosis and possible erythrocytosis in the complete blood count. Hypokalemia and metabolic alkalosis are biochemically confirmed. The hormonal profile demonstrates high blood cortisol and an elevated level of free cortisol in 24-hour urine. A specific sign of Cushing's disease is an elevated plasma ACTH level.

CT or MRI is used to visualize pituitary or adrenal tumors. The main tool for differential diagnosis between pituitary origin (disease) and adrenal origin (syndrome) is the low-dose and high-dose dexamethasone suppression tests.

Treatment tactics depend on the etiology:

• In pituitary lesions, radiation therapy, cryosurgery, or hypophysectomy are used.
• In adrenal lesions, surgery is indicated — unilateral or bilateral adrenalectomy.
• Pharmacologically, drugs blocking ACTH secretion (bromocriptine) or steroidogenesis blockers (aminoglutethimide) are used.

A combined approach is often required, combining adrenalectomy with radiation therapy or pharmacological correction.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Methodology and interpretation of results of the low-dose and high-dose dexamethasone suppression tests.
• ECG signs of myocardial dystrophic changes and repolarization disorders in hypercortisolism.
• Pathogenesis of metabolic alkalosis and hypokalemia against the background of mineralocorticoid excess.
• Mechanisms of ectopic ACTH syndrome formation using bronchogenic carcinoma as an example.
• Tactics of gradual drug tapering for the prevention of withdrawal syndrome in iatrogenic hypercortisolism.

Other topics in the section "Endocrine System and Metabolism"

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