Evaluation of adrenal function using the human corticotrophin-releasing hormone test, low dose Synacthen test and 9am cortisol level in children and adolescents with central adrenal insufficiency

Context The low-dose short synacthen test (LDSST) is recommended for patients with suspected central adrenal insufficiency (AI) if their basal serum cortisol (F) levels are not indicative of an intact hypothalamic–pituitary–adrenal (HPA) axis. Objective To evaluate diagnostic threshold for salivary F before and 30 min after administering 1 μg of synacthen, performed before 09:30 h. Design A cross-sectional study from 2014 to 2020. Setting A tertiary referral university hospital. Patients In this study, 174 patients with suspected AI, 37 with central AI and 137 adrenal sufficient (AS), were included. Main outcome measure The diagnostic accuracy (sensitivity (SE), specificity (SP)) of serum and salivary F levels measured, respectively, by chemiluminescence immunoassay and liquid chromatography-tandem mass spectrometry. Results Low basal serum or salivary F levels could predict AI. For the LDSST, the best ROC-calculated threshold for serum F to differentiate AI from AS was 427 nmol/L (SE 79%, SP 89%), serum F > 500 nmol/L reached SP 100%. A salivary F peak > 12.1 nmol/L after administering synacthen reached SE 95% and SP 84% for diagnosing central AI, indicating a conclusive reduction in the likelihood of AI. This ROC-calculated threshold for salivary F was similar to the 2.5th percentile of patients with a normal HPA axis, so it was considered sufficient to exclude AI. Considering AS those patients with salivary F > 12.1 nmol/L after LDSST, we could avoid unnecessary glucocorticoid treatment: 99/150 subjects (66%) had an inadequate serum F peak after synacthen, but salivary F was >12.1 nmol/L in 79 cases, who could, therefore, be considered AS. Conclusions Salivary F levels > 12.1 nmol/L after synacthen administration can indicate an intact HPA axis in patients with an incomplete serum F response, avoiding the need to start glucocorticoid replacement treatment.

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Adrenal insufficiency is seen in more than one-third of patients during ongoing low-dose prednisolone treatment for rheumatoid arthritis

Acta Endocrinologica ◽

10.1530/eje-17-0251 ◽

2017 ◽

Vol 177 (4) ◽

pp. 287-295 ◽

Cited By ~ 15

Author(s):

Stina Willemoes Borresen ◽

Marianne Klose ◽

Bo Baslund ◽

Åse Krogh Rasmussen ◽

Linda Hilsted ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adrenal Insufficiency ◽

Low Dose ◽

Adrenal Function ◽

Function Evaluation ◽

Concomitant Treatment ◽

Glucocorticoid Treatment ◽

Cross Sectional ◽

Prednisolone Treatment ◽

Synacthen Test

Objective Patients receiving long-term glucocorticoid treatment are at risk of developing adrenal insufficiency during treatment. We investigated the prevalence of prednisolone-induced adrenal insufficiency in the particular clinical situation where patients receive ongoing low-dose (5 mg/day) prednisolone treatment, a dose by itself too low to cover glucocorticoid needs during stress. Design and methods Cross-sectional study in 42 patients with rheumatoid arthritis (29 women, aged 36–86 years) treated with 5 mg prednisolone/day, who had received prednisolone for ≥6 months (median: 66, range: 6–444 months). Adrenal function was evaluated by a 250 μg Synacthen test performed after mean 48.7 h prednisolone pause. Local assay-specific cut-off for normal adrenal function was P-cortisol ≥420 nmol/L 30 min after Synacthen injection. Results Overall, 20 of the 42 patients (48%, 95% CI: 33–62%) had an insufficient adrenal response to the Synacthen test. Including only patients who had not received concomitant treatment with any other glucocorticoid formulas within the last 3 months, 13 of 33 patients (39%, 95% CI: 25–56%) had an insufficient response. Adrenocorticotrophic hormone (ACTH) concentrations were generally low and anti-adrenal antibodies were negative indicating secondary adrenal insufficiency as the most likely diagnosis. There was no correlation between duration of treatment and 30 min P-cortisol (P = 0.62). Adrenal function did not depend on sex or seropositivity of rheumatoid arthritis. Conclusion We demonstrate a high prevalence of adrenal insufficiency during ongoing low-dose prednisolone treatment. The results urge to increase focus on the condition to ensure identification and correct management of insufficient patients during stress and withdrawal. Strategies for adrenal function evaluation during ongoing low-dose glucocorticoid treatment need to be established.

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The Short Synacthen Test and Its Utility in Assessing Recovery of Adrenal Function in Patients With Central Adrenal Insufficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-01317 ◽

2018 ◽

Vol 104 (1) ◽

pp. 17-20 ◽

Cited By ~ 3

Author(s):

Mark Sherlock ◽

Paul M Stewart

Keyword(s):

Adrenal Insufficiency ◽

Adrenal Function ◽

Synacthen Test ◽

Central Adrenal Insufficiency ◽

Short Synacthen Test

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Is Low Dose Synacthen Test Reliable in Detecting Adrenal Insufficiency in Cirrhosis

Journal of Clinical and Experimental Hepatology ◽

10.1016/j.jceh.2016.06.097 ◽

2016 ◽

Vol 6 ◽

pp. S50

Author(s):

Deni Joseph ◽

D. Krishnadas ◽

A. Shanid ◽

S. Sreejaya ◽

K.S. Prasanth ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Low Dose ◽

Synacthen Test

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Adrenal insufficiency in kidney transplant patients during low-dose prednisolone therapy: a cross-sectional case–control study

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz180 ◽

2019 ◽

Vol 35 (12) ◽

pp. 2191-2197 ◽

Cited By ~ 2

Author(s):

Amalie Valentin ◽

Stina Willemoes Borresen ◽

Marianne Rix ◽

Thomas Elung-Jensen ◽

Søren Schwartz Sørensen ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Low Dose ◽

Case Control Study ◽

Case Control ◽

Adrenal Crisis ◽

Control Group ◽

Cross Sectional ◽

Prednisolone Treatment ◽

Synacthen Test ◽

Control Study

Abstract Background Maintenance immunosuppressive regimens after renal transplantation (RTx) most often include prednisolone, which may induce secondary adrenal insufficiency, a potentially life-threatening side effect to glucocorticoid (GC) treatment due to the risk of acute adrenal crisis. We investigated the prevalence of prednisolone-induced adrenal insufficiency in RTx patients receiving long-term low-dose prednisolone treatment. Methods We performed a case–control study of patients on renal replacement therapy differing in terms of GC exposure. The study included 30 RTx patients transplanted >11 months before enrolment in the study and treated with prednisolone (5 or 7.5 mg prednisolone/day for ≥6 months) and 30 dialysis patients not treated with prednisolone. Patients underwent testing for adrenal insufficiency by a 250-µg Synacthen test performed fasting in the morning after a 48-h prednisolone pause. Normal adrenal function was defined as P-cortisol ≥420 nmol/L 30 min after Synacthen injection. This cut-off is used routinely for the new Roche Elecsys Cortisol II assay and is validated locally based on the Synacthen test responses in 100 healthy individuals. Results Thirteen RTx patients {43% [95% confidence interval (CI) 27–61]} had an insufficient response to the Synacthen test compared with one patient in the control group [3% (95% CI 0.6–17)] (P = 0.0004). Insufficient responses were seen in 9/25 and 4/5 RTx patients treated with 5 and 7.5 mg prednisolone/day, respectively. Conclusions We found a high prevalence of adrenal insufficiency among RTx patients receiving low-dose prednisolone treatment. We therefore advocate for increased clinical alertness towards prednisolone-induced adrenal insufficiency in RTx patients and thus their potential need of rescue GC supplementation during stress.

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