Cushing's Syndrome

Causes and forms of hypercorticism

The development of the pathology is always based on an excess of glucocorticoids, but the mechanisms of its occurrence may vary. Several main variants are distinguished:

1. Central forms (Cushing's disease). Occur when the hypothalamopituitary system is affected. A decrease in the inhibitory effect of hypothalamic dopamine leads to an excess of corticotropin-releasing hormone. This forces the anterior pituitary to secrete a huge amount of ACTH, which causes hyperplasia and hyperfunction of both adrenal glands. A similar effect is produced by an ACTH-secreting basophilic or chromophobe pituitary adenoma.
2. Iatrogenic syndrome. Develops against the background of long-term use of glucocorticoid medications for therapeutic purposes. Due to the artificial excess of hormones, the secretion of own ACTH is suppressed, which leads to bilateral hypotrophy of the adrenal cortex.
3. Functional hypercorticism. Not associated with primary adrenal damage, but accompanied by a similar clinical picture. It occurs in hypothalamic syndrome, pubertal-adolescent dyspituitarism, severe obesity, diabetes mellitus, and certain liver diseases.

Impact on metabolism

Excess glucocorticoids radically alter all types of metabolism, which forms the classic appearance and complaints of the patient:

• Protein metabolism. There is a potentiation of catabolism. Proteins break down, leading to hypotrophy of skeletal muscles and myocardium, skin thinning, and the appearance of specific crimson striae (stretch marks) on the chest, abdomen, and thighs.
• Carbohydrate metabolism. Glycogen breakdown in the liver (glycogenolysis) and the formation of new glucose (gluconeogenesis) are activated. Hyperglycemia occurs. One in five patients develops steroid diabetes mellitus due to the pronounced counter-regulatory effect of cortisol.
• Lipid metabolism. Lipogenesis is stimulated, leading to the deposition of adipose tissue. Obesity has a dysplastic character and is detected in 85–90% of patients.
• Water-electrolyte balance. Glucocorticoids exhibit mineralocorticoid activity, triggering the renin-angiotensin-aldosterone system (RAAS). Sodium is retained in the blood (hypernatremia) and potassium is lost (hypokalemia).

Pathogenesis of main clinical syndromes

Arterial hypertension (occurs in 75% of cases) Blood pressure elevation is caused by the combined action of cortisol and aldosterone. They increase circulating blood volume, cardiac output, and arteriolar tone. In addition, glucocorticoids potentiate the action of vasoconstrictors — catecholamines and serotonin.

Muscle weakness and hypodynamia (observed in 80%) Associated with profound dystrophic changes and ion balance disorders. Sodium accumulates inside muscle cells, and potassium levels drop critically. Additionally, myocytes suffer from glucose deficiency.

Osteoporosis (affects 75% of patients) Cortisol inhibits collagen synthesis in the bone matrix and triggers the mobilization of calcium from bones. The situation is aggravated by the fact that the hormone suppresses vitamin D hydroxylation, causing calcium ion absorption in the intestine to drop sharply.

Damage to other systems The immunobiological surveillance system suffers — severe secondary immunodeficiency develops. Disorders of the reproductive system are observed, caused by an excess of adrenal androgens (e.g., testosterone) and a secondary decrease in pituitary gonadotropin production.

Briefly: answers to topical questions

What else to study on this topic

• Pathogenesis of primary hyperaldosteronism (aldosteronoma)
• Electrolyte disorders in adrenal pathology: mechanisms of alkalosis development
• The role of the renin-angiotensin-aldosterone system (RAAS) in blood pressure regulation
• Mechanisms of polyuria formation when renal receptor sensitivity to ADH decreases

Other topics in "Chapter 27. Typical Forms of Endocrine System Pathology"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.