Agreement between Acth-low test and Insuline Tolerance Test in Patients with Risk Factors for Central Adrenal Insufficiency
Background: Central adrenal insufficiency(CAI) is a potential life-threatening condition and a prompt diagnosis represents a clinical challenge; indeed, the Insulin Tolerance Test(ITT), gold standard for CAI diagnosis, can be contraindicated in some conditions. Aims were to evaluate the diagnostic value of the ACTH low test(ACTH-LT) compared to the ITT and to identify eventual determinants(primary diagnosis, risk factors, symptoms, baseline cortisol, hypothalamic-pituitary defects) as predictors of a pathological cortisol peak.
Methods: 64 patients(n=41males, n=23females) underwent ITT and ACTH-LT between 2010 and 2021(mean distance 18months) for suspected CAI. According to primary diagnosis, patients were categorized as: tumoral(n=29), multiple-pituitary defects(n=16), idiopathic GHD(n=12), others(n=7). Exclusion criteria were distance between the tests>8years, being on GC therapy, insulin resistance, failure to halve glycemia after ITT. Risk factors considered were brain surgery, brain radiotherapy and prolonged glucorticoids-GC administration. Potential CAI symptoms were defined as asthenia, recurrent headache and/or fatigue. Baseline characteristics are summarized in Table 1.
Results: Thirty-nine patients had pathological cortisol peak values at the ITT(<18µg/dL);ACTH-LT was pathological in 18/39(<16µg/dL), borderline in 14/39(16-22µg/dL) and normal in 7/39. Agreement between ACTH-LT and ITT was 0.83(Cohen’s K 0.51,95% CI:0.26-0.75), with a sensitivity of 88%(44/50), a specificity of 64%(9/14), a positive predictive value of 0.89(44/49) and a negative predictive value of 0.60(9/15). Peak cortisol levels to ACTH-LT were lower in patients with symptoms compared to subjects without them [15.2(IQR 11.3-18.3µg/dL) vs 17.7(IQR 14.5-19.8µg/dL), P=0,017]. No significant differences were found between ITT and ACTH-LT cortisol peak values in pubertal/prepubertal children, subjects with or without risk factors and different primary diagnosis.
|Pre-pubertal at ITT||13(20.3%)|
|Post-pubertal at ITT||51(79.7%)|
|Age at ACTH-LT(years)||13.9[12.8-16.6]|
|BMI-SDS at ACTH-LT||1.0[0.3–2.0]|
|Cortisol peak yes-symptoms(µg/dL)||15.6[13.4-19.1]|
|Cortisol peak no-symptoms(µg/dL)||18.6[15.8-22.1]|
|Age at ITT (years)||14.6[12.2-16.9]|
|BMI-SDS at ITT||0.9[0.2–2.0]|
Conclusion: Preliminary results demonstrate that the ACTH-LT is suitable for screening purposes, but not for final confirmation of CAI in our cohort. Further studies are needed to better define which factors influence the ACTH-LT response and its diagnostic value for clinicians.
15 Sep 2022 - 17 Sep 2022