Agreement between Acth-low test and Insuline Tolerance Test in Patients with Risk Factors for Central Adrenal Insufficiency

Marta Panciroli; Alessia Angelelli; Daniela Fava; Giuseppa Patti; Flavia Napoli; Iorgi Natascia Di; Mohamad Maghnie

P1-407

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ESPE Abstracts (2022) 95 P1-407

ESPE2022 Poster Category 1 Adrenals and HPA Axis (52 abstracts)

Agreement between Acth-low test and Insuline Tolerance Test in Patients with Risk Factors for Central Adrenal Insufficiency

Marta Panciroli ^1,2 , Alessia Angelelli ^1,2 , Daniela Fava ^1,2 , Giuseppa Patti ^1,2 , Flavia Napoli ² , Natascia Di Iorgi ^1,2 & Mohamad Maghnie ^1,2

Author affiliations

¹Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (D.I.N.O.G.M.I.), University of Genova, Genova, Italy; ²Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genova, Italy

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.


Characteristics	n.(%)	Median[1st–3rd quartile]
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]
Baseline cortisol(µg/dL)		9.9[8.0–13.0]
Cortisol peak(µg/dL)		18.2[15.2-21.3]
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]
Baseline cortisol(µg/dL)		9.3[6.9-13.5]
Cortisol peak(µg/dL)		16.9[13.8-19.4]
Risk Factors	45(70.3%)
Symptoms	17(26.6%)

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.