Triple serum draw improves low-dose ACTH stimulation test sensitivity

medwireNews: The risk of a false–positive result on a low-dose adrenocorticotropic hormone (ACTH) stimulation test (LDST) can be reduced in children by measuring cortisol levels at three consecutive time points instead of just one, researchers say.

The LDST is a validated assay for the diagnosis of paediatric central (pituitary-dependent) adrenal insufficiency (AI) but the optimal timings of cortisol level measurement have not been defined, explain Alexandra Ahmet and colleagues from the Children’s Hospital of Eastern Ontario in Ottawa, Canada.

The researchers reviewed LDST results for 221 patients aged between 3 months and 20 years (mean age 9.7 years, 32% female) who underwent the test at their institution between 2014 and 2017. The majority (77.8%) of individuals had suspected adrenal suppression secondary to glucocorticoid use, while other indications included septo-optic dysplasia, pituitary tumours and genetic syndromes, such as Kabuki and Prader Willi.

AI was defined as a cortisol value of less than 18 µg/dL (500 nmol/L) and 55.6% of the patients passed the LDST with a peak value on or above this threshold.

The patients had cortisol levels measured at baseline and 15, 30 and 60 minutes after receiving 1 µg cosyntropin, with peak concentrations reported in 0%, 19%, 67% and 14% of the patients at these intervals, respectively.

When measuring cortisol at 15 minutes, 8.1% of the patients had a peak level on or above 18 µg/dL (500 nmol/L) who would otherwise have failed the test on the basis of the 30-minute measurement, while testing after 60 minutes allowed a further 3.6% of the group to pass the LDST.

Thus, for every 24 patients who underwent testing after 15 minutes as well as the standard 30-minute interval, one false–positive LDST result would be avoided. And measuring cortisol after 30 and 60 minutes would avoid one false–positive result for every 55 patients tested.

“Of the 123 patients who passed the LDST, discontinuing the 15 and 60 minute samples would have misdiagnosed 11 patients (9.9%)”, emphasize Ahmet and co-authors in The Journal of Clinical Endocrinology & Metabolism.

Analysis revealed that peak cortisol timing was affected by multiple factors. For example, peak cortisol occurred at a later time in younger than older patients, with children aged 9 years or less significantly more likely to have peak cortisol at 60 minutes than their older counterparts.

In addition, each BMI z-score standard deviation increase was associated with a significant 1.34-minute reduction in the time to peak cortisol, while individuals who were referred for LDST after glucocorticoid use had peak cortisol an average of 7.18 minutes faster than individuals with other indications for testing.

“Of note, all eight patients who would have failed the LDST without a 15-minute sample were being evaluated for adrenal suppression due to glucocorticoid exposure”, the team remarks.

The researchers admit that their study is limited by its retrospective design and the absence of a gold standard diagnostic test for AI but strengthened by the “relatively robust sample size” and “homogenous testing practices” at their institution.

They conclude: “As AI is a burdensome diagnosis, we recommend that practitioners consider testing cortisol levels at 15, 30 and 60 minutes to reduce the risk of misdiagnosing adrenally sufficient patients with AI.”

By Lynda Williams

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

J Clin Endocrinol Metab 2019; doi:10.1210/jc.2019-00295
Martin Savage
Programme Director

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