Cushing Syndrome

Causes and Forms of Hypercortisolism

The underlying mechanism of the pathology is always an excess of glucocorticoids, though the exact etiology varies. The main variants include:

1. Central Forms (Cushing Disease). Caused by hypothalamic-pituitary axis pathology. A reduction in the inhibitory tone of hypothalamic dopamine leads to excess corticotropin-releasing hormone (CRH). This stimulates the anterior pituitary to secrete massive amounts of ACTH, resulting in bilateral adrenal hyperplasia and hyperfunction. A similar effect is produced by an ACTH-secreting basophilic or chromophobe pituitary adenoma.
2. Iatrogenic Syndrome. Develops secondary to long-term therapeutic glucocorticoid administration. The artificial hormone excess suppresses endogenous ACTH secretion, leading to bilateral atrophy of the adrenal cortex.
3. Functional Hypercortisolism. Not caused by primary adrenal pathology, but presents with a similar clinical picture. It is observed in hypothalamic syndrome, pubertal-adolescent dyspituitarism, severe obesity, diabetes mellitus, and certain liver diseases.

Effects on Metabolism

Glucocorticoid excess profoundly alters all metabolic pathways, driving the classic patient presentation and clinical complaints:

• Protein Metabolism. Potentiation of catabolism occurs. Proteins are broken down, leading to skeletal muscle and myocardial atrophy, skin thinning, and the appearance of characteristic purplish striae on the chest, abdomen, and thighs.
• Carbohydrate Metabolism. Hepatic glycogenolysis and gluconeogenesis are activated, resulting in hyperglycemia. Approximately 1 in 5 patients develops steroid-induced diabetes mellitus due to the pronounced counter-regulatory (anti-insulin) effect of cortisol.
• Lipid Metabolism. Lipogenesis is stimulated, leading to fat redistribution. Dysplastic obesity develops in 85–90% of patients.
• Water-Electrolyte Balance. Glucocorticoids exhibit mineralocorticoid activity, activating the renin-angiotensin-aldosterone system (RAAS). This leads to renal sodium retention (hypernatremia) and potassium wasting (hypokalemia).

Pathogenesis of Main Clinical Syndromes

Hypertension (occurs in 75% of cases) Elevated blood pressure is driven by the combined effects of cortisol and aldosterone, which increase circulating blood volume, cardiac output, and arteriolar tone. Additionally, glucocorticoids potentiate the vasoconstrictive effects of catecholamines and serotonin.

Muscle Weakness and Decreased Stamina (observed in 80%) Caused by profound dystrophic changes and ion imbalances. Sodium accumulates intracellularly within myocytes, while potassium levels drop critically. Additionally, myocytes suffer from impaired glucose uptake.

Osteoporosis (affects 75% of patients) Cortisol inhibits collagen synthesis in the bone matrix and mobilizes calcium from bones. The situation is compounded because the hormone inhibits the 1-alpha-hydroxylation of vitamin D, drastically reducing intestinal calcium absorption.

Multisystem Involvement Immune surveillance is impaired, leading to severe secondary immunodeficiency. Reproductive system disorders develop due to excess adrenal androgens (such as testosterone) and secondary suppression of pituitary gonadotropin release.