cushing's%20syndrome
CUSHING'S SYNDROME
Cushing’s syndrome is a condition which is due to prolonged exposure of the body tissue to excess cortisol (glucocorticoid hormone).
Laboratory tests and radiological findings confirm diagnosis and determine the actual cause of Cushing's syndrome.
Endogenous adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome has adrenal hypersecretion due to adrenal adenoma, adrenal carcinoma, micronodular hyperplasia, and macronodular hyperplasia.
Exogenous ACTH-independent Cushing's syndrome has adrenal hypersecretion due to iatrogenic causes (eg drug-induced, corticosteroid use).

Pharmacotherapy

Replacement Therapy

  • To provide adequate glucocorticoid replacement following surgery until hypothalamic-pituitary-adrenal axis has recovered
  • To ensure life-long glucocorticoid & mineralocorticoid replacement following total bilateral adrenalectomy

Glucocorticoid

  • Hydrocortisone
    • Preferred agent as it is the true replacement of cortisol
    • Potent glucocorticoid with some mineralocorticoid activity

Mineralocorticoid

  • Fludrocortisone is the preferred choice
    • Potent mineralocorticoid with some glucocorticoid activity

Steroid Biosynthesis Inhibitors

  • Actions: Most inhibit steroid biosynthesis by acting on cytochrome P450 enzymes
    • Action is nonspecific & extra-adrenal effects are likely
  • Effects: Use in specific circumstances to decrease effects of hypercortisolism
    • In specific circumstances to decrease the effect of hypercortisolism, eg in preparation for surgery, surgical failure or when surgery cannot be performed, while awaiting the effects of radiotherapy & when patient’s psychiatric or physical state requires immediate control of cortisol levels
  • Adrenocortical insufficiency may occur if not properly monitored
  • Ketoconazole: Effective in hirsutism (in women) as it lowers circulating androgens; monitor liver function due to risk of liver injury
  • Metyrapone: Fast onset; decreases serum cortisol within 2 hours of the 1st dose; advantage in controlling hypercortisolemia
  • Mitotane: Also used for carcinomas not cured by surgery; for non-carcinomas, use lower doses to prepare patient for surgery; used extensively in all forms of hypercortisolism; slow onset; long-term control of cortisol secretion

Glucocorticoid Antagonist

Mifepristone

  • Indicated for patients with Cushing’s syndrome & diabetes who are not surgical candidate & have failed surgery
  • Actions: Blocks peripheral action of cortisol
  • Effects: Use in specific circumstances to decrease effects of hypercortisolism
    • In specific circumstances to decrease the effect of hypercortisolism, eg in preparation for surgery, surgical failure or when surgery cannot be performed, while awaiting the effects of radiotherapy & when patient’s psychiatric or physical state requires immediate control of cortisol levels
    • Clinical improvement has been seen in patients without pituitary-dependent hypercortisolism

Others

  • Some dopamine agonists, gamma-aminobutyric acid (GABA) agonists, serotonin antagonists, have been reported to be occasionally effective in treating Cushing’s disease
    • Cabergoline acts directly on corticotroph tumors to inhibit adrenocorticotropic hormone production
  • Somatostatin analogues are used for unresectable tumors in ectopic adrenocorticotropic hormone (ACTH)/corticotropin-releasing hormone (CRH) syndrome
    • Pasireotide decrease adrenocorticotropic hormone secretion & cell proliferation in cultured human corticotroph tumors

 

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