Metyrapone
Encyclopedia
Metyrapone is a drug used in the diagnosis of adrenal insufficiency
and occasionally in the treatment of Cushing's syndrome
(hypercortisolism).
synthesis by inhibiting steroid 11β-hydroxylase
. This stimulates ACTH secretion, which in turn increases plasma 11-deoxycortisol levels. When excess ACTH secretion is the cause of hypercortisolism, the metyrapone test helps clarify if the source of the ACTH is pituitary or ectopic (non-pituitary).
. Metyrapone 30mg/kg, maximum dose 3000 mg, is administered at midnight usually with a snack. The plasma cortisol and 11-deoxycortisol are measured the next morning between 8:00 and 9:00 am. A plasma cortisol less than 220nmol/l indicates adequate inhibition of 11β-hydroxylase. In patients with intact Hypothalamo-pituitary-adrenal axis, CRH and ACTH levels rise as a response to the falling cortisol levels. This results in an increase of the steroid precursors in the pathway. Therefore if 11-deoxycortisol levels do not rise and remains less than 7 mcg/dl and ACTH rises, then it is highly suggestive of impaired adrenal insufficiency
, if neither 11-deoxycortisol nor ACTH rise it is highly suggestive of an impaired HPA axis at either the pituitary or hypothalamus
.
Metyrapone test may aid in verifying the cause of Cushing's syndrome. Most patients with pituitary dysfunction and/or pituitary microadenoma will increase ACTH secretion in response to metyrapone, while most ectopic ACTH-producing tumors will not. Pituitary macroadenomas do not always respond to metyrapone.
Adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
and occasionally in the treatment of Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
(hypercortisolism).
Mechanism
Metyrapone blocks cortisolCortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
synthesis by inhibiting steroid 11β-hydroxylase
Steroid 11-beta-hydroxylase
Steroid 11β-hydroxylase is a steroid hydroxylase found in the zona fasciculata. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene....
. This stimulates ACTH secretion, which in turn increases plasma 11-deoxycortisol levels. When excess ACTH secretion is the cause of hypercortisolism, the metyrapone test helps clarify if the source of the ACTH is pituitary or ectopic (non-pituitary).
Uses
Metyrapone can be used in the diagnosis of adrenal insufficiencyAdrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
. Metyrapone 30mg/kg, maximum dose 3000 mg, is administered at midnight usually with a snack. The plasma cortisol and 11-deoxycortisol are measured the next morning between 8:00 and 9:00 am. A plasma cortisol less than 220nmol/l indicates adequate inhibition of 11β-hydroxylase. In patients with intact Hypothalamo-pituitary-adrenal axis, CRH and ACTH levels rise as a response to the falling cortisol levels. This results in an increase of the steroid precursors in the pathway. Therefore if 11-deoxycortisol levels do not rise and remains less than 7 mcg/dl and ACTH rises, then it is highly suggestive of impaired adrenal insufficiency
Adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
, if neither 11-deoxycortisol nor ACTH rise it is highly suggestive of an impaired HPA axis at either the pituitary or hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
.
Metyrapone test may aid in verifying the cause of Cushing's syndrome. Most patients with pituitary dysfunction and/or pituitary microadenoma will increase ACTH secretion in response to metyrapone, while most ectopic ACTH-producing tumors will not. Pituitary macroadenomas do not always respond to metyrapone.