Generic name: METYRAPONE 250mg
Dosage form: capsule, gelatin coated
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Single-Dose Short Test
This test, usually given on an outpatient basis, determines plasma 11-desoxycortisol and/or ACTH levels after a single dose of Metopirone. The patient is given 30 mg/kg (maximum 3 g Metopirone) at midnight with yogurt or milk. The same dose is recommended in children. The blood sample for the assay is taken early the following morning (7:30-8:00 a.m.). The plasma should be frozen as soon as possible. The patient is then given a prophylactic dose of 50 mg cortisone acetate.
Normal values will depend on the method used to determine ACTH and 11-desoxycortisol levels. An intact ACTH reserve is generally indicated by an increase in plasma ACTH to at least 44 pmol/L (200 ng/L) or by an increase in 11-desoxycortisol to over 0.2 µmol/L (70 µg/L). Patients with suspected adrenocortical insufficiency should be hospitalized overnight as a precautionary measure.
Day 1: Control period - Collect 24-hour urine for measurement of 17-OHCS or 17-KGS.
Day 2: ACTH test to determine the ability of adrenals to respond - Standard ACTH test such as infusion of 50 units ACTH over 8 hours and measurement of 24-hour urinary steroids. If results indicate adequate response, the Metopirone test may proceed.
Day 3-4: Rest period.
Day 5: Administration of Metopirone: Recommended with milk or snack.
Adults: 750 mg orally, every 4 hours for 6 doses. A single dose is approximately equivalent to 15 mg/kg.
Children: 15 mg/kg orally every 4 hours for 6 doses. A minimal single dose of 250 mg is recommended.
Day 6: After administration of Metopirone - Determination of 24-hour urinary steroids for effect.
The normal 24-hour urinary excretion of 17-OHCS ranges from 3 to 12 mg. Following continuous intravenous infusion of 50 units ACTH over a period of 8 hours, 17-OHCS excretion increases to 15 to 45 mg per 24 hours.
Normal response: In patients with a normally functioning pituitary, administration of Metopirone is followed by a two- to four-fold increase of 17-OHCS excretion or doubling of 17-KGS excretion.
Subnormal response: Subnormal response in patients without adrenal insufficiency is indicative of some degree of impairment of pituitary function, either panhypopituitarism or partial hypopituitarism (limited pituitary reserve).
1. Panhypopituitarism is readily diagnosed by the classical clinical and chemical evidences of hypogonadism, hypothyroidism, and hypoadrenocorticism. These patients usually have subnormal basal urinary steroid levels. Depending upon the duration of the disease and degree of adrenal atrophy, they may fail to respond to exogenous ACTH in the normal manner. Administration of Metopirone is not essential in the diagnosis, but if given, it will not induce an appreciable increase in urinary steroids.
2. Partial hypopituitarism or limited pituitary reserve is the more difficult diagnosis as these patients do not present the classical signs and symptoms of hypopituitarism. Measurements of target organ functions often are normal under basal conditions. The response to exogenous ACTH is usually normal, producing the expected rise of urinary steroids (17-OHCS or 17-KGS).
The response, however, to Metopirone is subnormal; that is, no significant increase in 17-OHCS or 17-KGS excretion occurs.
This failure to respond to metyrapone may be interpreted as evidence of impaired pituitary-adrenal reserve. In view of the normal response to exogenous ACTH, the failure to respond to metyrapone is inferred to be related to a defect in the CNS-pituitary mechanisms which normally regulate ACTH secretions. Presumably the ACTH secreting mechanisms of these individuals are already working at their maximal rates to meet everyday conditions and possess limited “reserve” capacities to secrete additional ACTH either in response to stress or to decreased cortisol levels occurring as a result of metyrapone administration.
Subnormal response in patients with Cushing’s syndrome is suggestive of either autonomous adrenal tumors that suppress the ACTH-releasing capacity of the pituitary or nonendocrine ACTH-secreting tumors.
Excessive response: An excessive excretion of 17-OHCS or 17-KGS after administration of Metopirone is suggestive of Cushing’s syndrome associated with adrenal hyperplasia. These patients have an elevated excretion of urinary corticosteroids under basal conditions and will often, but not invariably, show a “supernormal” response to ACTH and also to Metopirone, excreting more than 35 mg per 24 hours of either 17-OHCS or 17-KGS.