Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary disease: comparison between serum and salivary cortisol during the high-dose short synacthen test

Deutschbein, Timo; Unger, Nicole; Mann, Klaus; Petersenn, Stephan

doi:10.1530/eje-08-0600

Cited by 52Adrenal Hormones and DisordersStress Responses and CortisolPituitary Gland Disorders and Treatments

Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary disease: comparison between serum and salivary cortisol during the high-dose short synacthen test

Deutschbein, Timo, Unger, Nicole, Mann, Klaus, Petersenn, Stephan·2009·European Journal of Endocrinology

DOI 10.1530/eje-08-0600

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Abstract

OBJECTIVE: Accurate assessment of adrenal function is essential in patients with hypothalamic-pituitary-adrenal (HPA) disease. The measurement of salivary cortisol (SaC) instead of serum cortisol (SeC) offers several advantages, such as the determination of the free hormone. We evaluated the diagnostic value of SeC and SaC both unstimulated and during a high-dose short synacthen test (HDT) in comparison to the insulin tolerance test (ITT). DESIGN: Comparative study between 2005 and 2007. METHODS: Fifty-five patients with HPA impairment and 21 healthy controls were enrolled. Samples were collected in the early morning and over 120 min during the HDT. Receiver operating characteristic analysis revealed individual thresholds for four HDT periods (0-30, 0-60, 0-90, and 0-120 min). RESULTS: The ITT identified 30 subjects as adrenal insufficient. With respect to the four HDT periods, sensitivity and specificity were 67-79% and 71-88% for SeC, compared with 63-72% and 72-86% for SaC. If upper and lower thresholds (with specificities >95%) were applied, patients were diagnosed in 40-45% by SeC and in 25-31% by SaC. The combination of basal cortisol and HDT allowed a diagnosis in 47-49% (SeC) and in 42-45% (SaC) respectively. CONCLUSION: We suggest the determination of basal SeC or SaC as first-line test. In comparison to the ITT, the HDT has only limited value in screening for alterations of the HPA axis. If the HDT is performed, sampling may be limited to 30 min post-synacthen, using either SeC or SaC. Due to the ease of collection and the independence of binding proteins, SaC may be preferable.

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Most primary reports detailing the 140 nmol/L cutoff value are not based on subjects with PAI.
“Unfortunately, most of the primary reports detailing this cutoff value are not based on subjects with PAI (23,24,(61)(62)(63)(64).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [24]
The validity of the calculated lower reference limits for salivary cortisol and cortisone is strengthened by the similarities to previously published cutoffs.
“The validity of our calculated LRLs for salivary cortisol and cortisone is strengthened by the similarities to previously published cutoffs (25, 30, 36, 42).”
From Salivary Cortisol and Cortisone Can Circumvent Confounding Effects of Oral Contraceptives in the Short Synacthen Test (2024) · cites this paper as [36]
Whether salivary cortisol and cortisone levels are unaffected by estrogens during an SST remains to be established together with cutoffs for excluding adrenal insufficiency using salivary samples, since previous studies were based on few observations.
“Nonetheless, whether salivary cortisol and cortisone levels are unaffected by estrogens during an SST remains to be established together with cutoffs for excluding AI using salivary samples, since previous studies were based on few observations (35-37).”
From Salivary Cortisol and Cortisone Can Circumvent Confounding Effects of Oral Contraceptives in the Short Synacthen Test (2024) · cites this paper as [36]

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Result
A comparison of salivary steroid levels during diagnostic tests for adrenal insufficiency
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Diagnosis of Secondary Adrenal Insufficiency: Unstimulated Early Morning Cortisol in Saliva and Serum in Comparison with the Insulin Tolerance Test
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Diagnosis of secondary adrenal insufficiency: evaluation of the standard dose short synacthen test in comparison to the insulin tolerance test in patients with hypothalamic-pituitary disease
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A comparison of salivary steroid levels during diagnostic tests for adrenal insufficiency
Dušková, M., Šimůnková, K., Vítků, J., Sosvorová, L., Jandíková, H., Pospíšilová, H., Šrámková, M., Kosák, M., Kršek, M., Hána, V., et al. (2016) · Prague Medical Report · doi:10.14712/23362936.2016.2 · Cited by 11 · see citing works

Authors: Deutschbein, T., Unger, N., Mann, K., & Petersenn, S.
Affiliations: University of Duisburg-Essen (DE)
Corresponding author: Petersenn, Stephan
ORCID: Deutschbein, Timo
Unger, Nicole
Petersenn, Stephan
Venue: European Journal of Endocrinology
Publisher: Oxford University Press (OUP)
Published: 2009-01
Volume: 160
Issue: 1
Pages: 9-16
ISSN: 0804-4643 (ISSN-L)
1479-683X
DOI: 10.1530/eje-08-0600
OpenAlex: W2112399023
Cited by: 52
References: 48
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 5 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 2 · 2014: 5 · 2012: 4
FWCI: 3.38
Type: journal article
Language: en
Open access: closed
Locations: European Journal of Endocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords: secondary adrenal insufficiency, hypothalamic-pituitary-adrenal axis, salivary cortisol, serum cortisol, insulin tolerance test, adrenal function testing, diagnostic thresholds
MeSH terms: Adrenal Insufficiency, Adult, Algorithms, Cosyntropin, Female, Humans, Hydrocortisone, Hypothalamic Diseases, Insulin, Male, Middle Aged, Pituitary Diseases, Random Allocation, ROC Curve, Saliva, Sensitivity and Specificity, Area Under Curve

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Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary disease: comparison between serum and salivary cortisol during the high-dose short synacthen test

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