Cushing’s Disease: Causes

Pathogenesis (disease development)

Cushing’s disease is caused by hypercortisolism (overproduction of cortisol). This may be due to:

• Endogenous Cushing’s syndrome – this in turn can be subdivided into:
  • ACTH-dependent
    • Central Cushing’s syndrome (Cushing’s disease) – usually microadenoma of the anterior pituitary [about 65-70% of cases].
    • Ectopic ACTH secretion* (adrenocorticotropic hormone) – paraneoplastic; secretion of ACTH in neoplasms, especially in bronchial carcinoma (lung cancer) [about 15-20% of cases].
    • Ectopic CRH secretion* (corticotropin-releasing hormone).
    • Alcohol-induced
  • ACTH-independent [about 20% of cases].
    • Adrenal Cushing’s syndrome – mainly due to tumors of the adrenal cortex (mostly adenomas; rarely carcinomas) [about 15% of all endogenous Cushing’s syndromes].
    • Primary bilateral NNR hyperplasia (adrenocortical hyperplasia/cell enlargement):
      • Micronodular hyperplasia (PPNAD, primary pigmented nodular adrenocortical diesease); small, pigmented nodules of the NNR.
      • Macronodular dys/hyperplasia (AIMAH, ACTH-independent macronodular adrenal hyperplasia); larger, non-pigmented nodules of the NNR.
• Exogenous Cushing’s syndrome (iatrogenic Cushing’s syndrome) – this form occurs frequently and is triggered by long-term therapy with glucocorticoids (most commonly prednisolone) or precursors of these

* Ca. 15-20% of cases

Etiology (causes)

Biographic causes

• Genetic burden from parents, grandparents.

Behavioral causes

• Chronic alcohol abuse/abuse → hypercortisolism → alcohol-induced pseudo-Cushing’s syndrome.

Disease-related causes

Neoplasms – tumor diseases (C00-D48).

• Pituitary adenomas – benign neoplasms of the pituitary gland (pituitary gland).
• Adrenal adenoma – benign neoplasm of the adrenal gland.
• Adrenocortical carcinoma – malignant neoplasm of the adrenal gland.
• Paraneoplastic in bronchial carcinoma (lung cancer), thymic carcinoid, pancreatic carcinoma (pancreatic cancer), bronchial adenoma (initially benign tumors of the lungs or bronchi, but can degenerate into malignancy).

Psyche – nervous system (F00-F99; G00-G99)

• Pituitary-hypothalamic dysfunction – dysfunction of the pituitary (pituitary gland)/hypothalamus (part of the diencephalon).

Medication

• Long-term use of glucocorticoids – are among the corticosteroids, a class of steroid hormones from the adrenal cortex. The naturally occurring glucocorticoids are derivatives (derivatives) of progesterone (corpus luteum hormone). These include cortisol and corticosterone, with a share of 95% and 5%, respectively. Furthermore, there are derived from the glucocorticoids, artificial corticoids with glucocorticoid effect.
• Long-term use of ACTH (adrenocorticotropic hormone; synonyms: corticotropin, corticotropic hormone, corticotropin, adrenocorticotropin) – a hormone synthesized in the anterior pituitary gland (front lobe of the pituitary gland) that regulates adrenocortical function and stimulates the production of hormones, especially cortisol.