The low dose ACTH stimulation test is less sensitive than the overnight metyrapone test for the diagnosis of secondary hypoadrenalism

Abstract

The normal cortisol response to low dose ACTH stimulation in 50% of the patients with ACTH deficiency proven on metyrapone testing suggests that the 1 microgram ACTH stimulation test, like the 250 microgram-test, lacks sensitivity for the diagnosis of ACTH deficiency.

Relationship between Cortisol Increment and Basal Cortisol: Implications for the Low-Dose Short Adrenocorticotropic Hormone Stimulation Test

“…At this cutoff Clinical Chemistry 52, No. 4,2006 point, however, false-positive rates are high, leading to low specificity (19 ).…”

“…The LDST has also been advocated as a more sensitive test for ACTH deficiency than the HDST (18 ), but use of the same cutoff points for the LDST and HDST would serve to increase the apparent sensitivity of the LDST because peak cortisol responses are less after 1 g than 250 g of ACTH (19 ). At this cutoff Clinical Chemistry 52, No.…”

“…Any value Ͻ400 nmol/L (14.5 g/dL) after LDST will therefore be abnormal. Any value above this and up to 600 nmol/L (21.7 g/dL), our mean value at zero increment, needs a confirmatory test such as IIH or overnight metyrapone testing because the false-negative rate could be as high as 50% (19 ). Above 600 nmol/L (21.7 g/dL), the test result is highly specific and need not be confirmed.…”

“…The composition of the cocoa power was determined as described by Andrés-Lacueva et al (18 ); the flavonoid concentrations for the cocoa powder portion used in this study were 56.4 mg of (Ϫ)-epicatechin, 51 mg of procyanidin B 2 , 16.8 mg of catechin, and 4 mg of flavonols, including isoquercitrin, quercetin, quercetin-glucoside, and quercetin-arabinoside. Synthetic urine was prepared as described by Miró-Casas et al (19 ) to avoid any possible interference generated by the matrices with F-C reagent. A series of (ϩ)-catechin calibrators with concentrations of 1, 2, 4, 6, 8, 10, and 12 mg/L was prepared in this synthetic urine.…”

Adrenal Insufficiency

“…This test is simple, relatively inexpensive, very sensitive, and requires a single blood drawing. 24 The administration of metyrapone (30 mg/kg; maximal dose, 3000 mg) occurs at midnight, and blood is drawn the following morning at 8 AM for cortisol and 11-deoxycortisol. 25 In response to metyrapone, serum cortisol level should decrease to less than 5 µg/dL, and 11-deoxycortisol should increase to more than 7 µg/dL.…”