Long-acting intramuscular ACTH stimulation test for the diagnosis of secondary adrenal insufficiency in children

Abstract

Background The diagnosis of adrenal insufficiency (AI) is based on the basal and stimulated levels of serum cortisol in response to the short Synacthen test (SST). In patients with secondary AI (SAI) due to hypothalamic-pituitary-adrenal (HPA) axis defects, the SST has been validated against the insulin tolerance test (ITT), which is the gold standard. However, injection Synacthen is not easily available in some countries, and endocrinologists often use Acton-Prolongatum (intramuscular [IM] long-acting adrenocorticotropic hormone [ACTH]) in place of Synacthen. There are no studies validating the use of IM-ACTH in children with suspected AI. We evaluated the diagnostic value of the IM-ACTH test against the ITT for the diagnosis of SAI in children. Methods All children with suspected growth hormone deficiency (GHD) undergoing a routine ITT were evaluated using the IM-ACTH test within 1 week. Results Forty-eight patients (36 boys/12 girls, age range: 5–14 years) were evaluated using both the ITT and the IM-ACTH test. Twenty-eight patients had a normal cortisol response (≥18 μg/dL, 500 nmol/L) in the ITT and 20 had low values. In patients with a normal cortisol response on the ITT, the peak value obtained after the IM-ACTH test was higher than that on the ITT (28.7 μg/dL [± 8.8] vs. 23.8 μg/dL [± 4.54], respectively; p=0.0012). Compared to the ITT, the sensitivity and specificity of the IM-ACTH test for the diagnosis of SAI at cortisol cut-offs <18 μg/dL (500 nmol/L) and <22 μg/dL (600 nmol/L) were 57.1% and 92.8%, and 100% and 73.5%, respectively. Conclusions A peak cortisol value <18 μg/dL on the IM-ACTH test is highly suggestive of SAI, whereas a value >22 μg/dL rules out SAI.

Long‐acting porcine ACTH stimulated salivary cortisol in the diagnosis of adrenal insufficiency

“…A previous study from our centre has reported a high diagnostic accuracy (sensitivity100%; specificity88%) for stimulated serum cortisol levels using Acton Prolongatum in subjects with suspected AI in comparison with the SST 22,23 . Other investigators from India have also assessed the performance of Acton prolongatum stimulated serum cortisol measurements in healthy children and adults against SST and ITT 19,35,36 …”

“…22,23 Other investigators from India have also assessed the performance of Acton prolongatum stimulated serum cortisol measurements in healthy children and adults against SST and ITT. 19,35,36 To the best of our knowledge, this is the first study to assess the diagnostic accuracy of salivary cortisol response to long-acting porcine sequence ACTH for diagnosing AI. 24 The reported crossreactivity with cortisone was only 6.58%.…”

Long acting porcine sequence ACTH in the diagnosis of adrenal insufficiency

“…Limitations of our study include absence of dose titration of porcine ACTH and lack of an assay specific cut-off for Synacthen-stimulated serum cortisol in our laboratory. As opposed to previous studies using 25 units of Acton Prolongatum ® for the APST, this study used 30 units considering the ease of dispensing from a 5 mL vial containing 300 units (6,12,13). No adverse events were observed with Synacthen or Acton Prolongatum in the present study.…”

Intramuscular Short-term ACTH Test for the Determination of Adrenal Function in Children: Safe, Effective and Reliable

“…The effectiveness of the im-ACTH test in detecting central AI cases has also been investigated ( 8 ). Cases with short stature and at risk of having multiple hormone deficiencies and tested with ITT were evaluated.…”