Download PDF
Exp Clin Endocrinol Diabetes 2025; 133(01): 25-33
DOI: 10.1055/a-2444-4386
Article

Can Salivary Cortisol be Used in Diagnosing Adrenal Insufficiency During the Acute and Subacute Phases of Traumatic Brain Injury?

Emre Urhan 
1   Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey (Ringgold ID: RIN64212)
,
Gulsah Elbuken 
2   Department of Endocrinology, Tekirdag Namik Kemal University Medical School, Tekirdag, Turkey (Ringgold ID: RIN162334)
,
Zuleyha Karaca
1   Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey (Ringgold ID: RIN64212)
,
Kursad Unluhizarci
1   Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey (Ringgold ID: RIN64212)
,
Mustafa Kula
3   Department of Nuclear Medicine, Erciyes University Medical School, Kayseri, Turkey (Ringgold ID: RIN52958)
,
Ahmed Selcuklu
4   Department of Neurosurgery, Erciyes University Medical School, Kayseri, Turkey
,
Fahrettin Kelestimur
5   Department of Endocrinology, Yeditepe University Medical School, Istanbul, Turkey
› Author AffiliationsSupported by: Erciyes University Council of Scientific Investigations project code: TSA-10-2909
› Further Information
Also available at
    Permissions and Reprints

Abstract

Introduction The diagnosis of adrenal insufficiency (AI) related to traumatic brain injury (TBI) remains a challenge. We investigated the basal and low-dose adrenocorticotropic hormone (ACTH)-stimulated serum cortisol and salivary cortisol (SaC) levels and the diagnostic utility of SaC levels during 28 days following TBI.

Materials and Methods Blood samples were collected for basal levels [sequentially from day 1 (D1) to D7 and on D28)] and for peak serum cortisol and SaC responses to the low-dose ACTH stimulation test (on D1, D7, and D28). After the patient enrollment period was completed, patients were retrospectively categorized as AI or AS (adrenal sufficiency) for each day separately, based on a basal serum cortisol cut-off level of 11 µg/dL, and data analysis was performed between the groups.

Results Thirty-seven patients and 40 healthy controls were included. Median basal serum cortisol levels were higher in patients on D1 but were similar on other days. Median basal SaC levels were higher in patients on D1 and D2 but were similar on other days. Median peak serum cortisol and SaC levels were similar on D1 but were lower in patients on D7 and D28. Median basal SaC levels were higher in the AS group than in the AI group on all days.

Discussion and Conclusions When evaluating AI during the course of TBI, the cut-off for basal SaC levels is 0.5–0.6 µg/dL throughout the first week, except for 1.38 µg/dL on D2. SaC levels may serve as a surrogate marker for accurately reflecting circulating glucocorticoid activity.

Keywords

Traumatic brain injury - HPA axis - serum cortisol - salivary cortisol - ACTH stimulation test


Publication History

Received: 07 June 2024

Accepted after revision: 17 October 2024

Accepted Manuscript online:
17 October 2024

Article published online:
16 January 2025

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Srivastava A, Chandra A, Yadav A. et al. Dynamic change in cortisol levels associated with severity, progression, and survival of patients with traumatic brain injury. Clin Neurol Neurosurg 2022; 222: 107419
    CrossrefPubMedSearch in Google Scholar
  • 2 Kokshoorn NE, Wassenaar MJ, Biermasz NR. et al. Hypopituitarism following traumatic brain injury: Prevalence is affected by the use of different dynamic tests and different normal values. Eur J Endocrinol 2010; 162: 11-18
    CrossrefPubMedSearch in Google Scholar
  • 3 Tanriverdi F, Senyurek H, Unluhizarci K. et al. High risk of hypopituitarism after traumatic brain injury: A prospective investigation of anterior pituitary function in the acute phase and 12 months after trauma. J Clin Endocrinol Metab 2006; 91: 2105-2111
    CrossrefPubMedSearch in Google Scholar
  • 4 Klose M, Juul A, Poulsgaard L. et al. Prevalence and predictive factors of post-traumatic hypopituitarism. Clin Endocrinol (Oxf) 2007; 67: 193-201
    CrossrefPubMedSearch in Google Scholar
  • 5 Schneider HJ, Schneider M, Saller B. et al. Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury. Eur J Endocrinol 2006; 154: 259-265
    CrossrefPubMedSearch in Google Scholar
  • 6 Bernard F, Outtrim J, Menon DK. et al. Incidence of adrenal insufficiency after severe traumatic brain injury varies according to definition used: Clinical implications. Br J Anaesth 2006; 96: 72-76
    CrossrefPubMedSearch in Google Scholar
  • 7 Renner CI. Interrelation between neuroendocrine disturbances and medical complications encountered during rehabilitation after TBI. J Clin Med 2015; 4: 1815-1840
    CrossrefPubMedSearch in Google Scholar
  • 8 Tanriverdi F, Ulutabanca H, Unluhizarci K. et al. Pituitary functions in the acute phase of traumatic brain injury: Are they related to severity of the injury or mortality?. Brain Inj 2007; 21: 433-439
    CrossrefPubMedSearch in Google Scholar
  • 9 Mirzaie B, Mohajeri-Tehrani MR, Annabestani Z. et al. Traumatic brain injury and adrenal insufficiency: Morning cortisol and cosyntropin stimulation tests. Arch Med Sci 2013; 9: 68-73
    CrossrefPubMedSearch in Google Scholar
  • 10 Daneva E, Makris K, Korompeli A. et al. Saliva cortisol levels and physiological parameter fluctuations in mild traumatic brain injury patients compared to controls. Int J Neurosci 2021; 20: 1-9
    PubMedSearch in Google Scholar
  • 11 Hannon MJ, Sherlock M, Thompson CJ. Pituitary dysfunction following traumatic brain injury or subarachnoid haemorrhage-in “Endocrine Management in the Intensive Care Unit”. Best Pract Res Clin Endocrinol Metab 2011; 25: 783-798
    CrossrefPubMedSearch in Google Scholar
  • 12 Hacioglu A, Kelestimur F, Tanriverdi F. Long-term neuroendocrine consequences of traumatic brain injury and strategies for management. Expert Rev Endocrinol Metab 2020; 15: 123-139
    CrossrefPubMedSearch in Google Scholar
  • 13 Tanriverdi F, Unluhizarci K, Kelestimur F. Pituitary function in subjects with mild traumatic brain injury: A review of literature and proposal of a screening strategy. Pituitary 2010; 13: 146-153
    CrossrefPubMedSearch in Google Scholar
  • 14 Pastores SM, Annane D, Rochwerg B. Corticosteroid Guideline Task Force of SCCM and ESICM. Guidelines for the diagnosis and management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in critically Ill patients (Part II): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Crit Care Med 2017; 46: 146148
    PubMedSearch in Google Scholar
  • 15 Tanriverdi F, Kelestimur F. Pituitary dysfunction following traumatic brain injury: Clinical perspectives. Neuropsychiatr Dis Treat 2015; 11: 1835-1843
    CrossrefPubMedSearch in Google Scholar
  • 16 Elbuken G, Tanriverdi F, Karaca Z. et al. Comparison of salivary and calculated free cortisol levels during low and standard dose of ACTH stimulation tests in healthy volunteers. Endocrine 2015; 48: 439-443
    CrossrefPubMedSearch in Google Scholar
  • 17 Arafah BM, Nishiyama FJ, Tlaygeh H. et al. Measurement of salivary cortisol concentration in the assessment of adrenal function in critically ill subjects: A surrogate marker of the circulating free cortisol. J Clin Endocrinol Metab 2017; 92: 2965-2971
    CrossrefPubMedSearch in Google Scholar
  • 18 Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med 2004; 350: 1629-1638
    CrossrefPubMedSearch in Google Scholar
  • 19 Raff H. Utility of salivary cortisol measurements in Cushing’s syndrome and adrenal insufficiency. J Clin Endocrinol Metab 2009; 94: 3647-3655
    CrossrefPubMedSearch in Google Scholar
  • 20 Zhang Q, Dou J, Gu W. et al. Reassessing the reliability of the salivary cortisol assay for the diagnosis of Cushing syndrome. J Int Med Res 2013; 41: 1387-1394
    CrossrefPubMedSearch in Google Scholar
  • 21 Karaca Z, Lale A, Tanriverdi F. et al. The comparison of low and standard dose ACTH and glucagon stimulation tests in the evaluation of hypothalamo-pituitary-adrenal axis in healthy adults. Pituitary 2011; 14: 134-140
    CrossrefPubMedSearch in Google Scholar
  • 22 Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2: 81-84
    CrossrefPubMedSearch in Google Scholar
  • 23 Topkas E, Keith P, Dimeski G. et al. Evaluation of saliva collection devices for the analysis of proteins. Clin Chim Acta 2012; 413: 1066-1070
    CrossrefPubMedSearch in Google Scholar
  • 24 Gozansky WS, Lynn JS, Laudenslager ML. et al. Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic-pituitary-adrenal axis activity. Clin Endocrinol (Oxf) 2005; 63: 336-341
    CrossrefPubMedSearch in Google Scholar
  • 25 Simunkova K, Hampl R, Hill M. et al. Salivary cortisol in low dose (1 microg) ACTH test in healthy women: comparison with serum cortisol. Physiol Res 2007; 56: 449-454
    CrossrefPubMedSearch in Google Scholar
  • 26 Elbuken G, Karaca Z, Tanriverdi F. et al. Comparison of total, salivary and calculated free cortisol levels in patients with severe sepsis. J Intensive Care 2016; 4: 1-10
    CrossrefPubMedSearch in Google Scholar