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Reliability of hypothalamic–pituitary–adrenal axis assessment methods for use in population-based studies

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Abstract

Population-based studies have been hampered in exploring hypothalamic–pituitary–adrenal axis (HPA) activity as a potential explanatory link between stress-related and metabolic disorders due to their lack of incorporation of reliable measures of chronic cortisol exposure. The purpose of this review is to summarize current literature on the reliability of HPA axis measures and to discuss the feasibility of performing them in population-based studies. We identified articles through PubMed using search terms related to cortisol, HPA axis, adrenal imaging, and reliability. The diurnal salivary cortisol curve (generated from multiple salivary samples from awakening to midnight) and 11 p.m. salivary cortisol had the highest between-visit reliabilities (r = 0.63–0.84 and 0.78, respectively). The cortisol awakening response and dexamethasone-suppressed cortisol had the next highest between-visit reliabilities (r = 0.33–0.67 and 0.42–0.66, respectively). Based on our own data, the inter-reader reliability (rs) of adrenal gland volume from non-contrast CT was 0.67–0.71 for the left and 0.47–0.70 for the right adrenal glands. While a single 8 a.m. salivary cortisol is one of the easiest measures to perform, it had the lowest between-visit reliability (R = 0.18–0.47). Based on the current literature, use of sampling multiple salivary cortisol measures across the diurnal curve (with awakening cortisol), dexamethasone-suppressed cortisol, and adrenal gland volume are measures of HPA axis tone with similar between-visit reliabilities which likely reflect chronic cortisol burden and are feasible to perform in population-based studies.

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Abbreviations

ACTH:

Adrenocorticotrophic hormone

ARIC:

Atheroslerosis Risk In Communities Study

AUC:

Area under the curve

BMI:

Body mass index

CAR:

Cortisol awakening response

CBG:

Corticotrophin binding globulin

CRH:

Corticotrophin releasing hormone

CT:

Computed tomography

HPA:

Hypothalamic–pituitary–adrenal axis

ICC (R):

Intraclass correlation coefficient

MESA:

Multi-Ethnic Study Atherosclerosis

MRI:

Magnetic resonance imaging

R:

Pearson’s linear correlation coefficient

rs :

Spearman’s ordinal correlation coefficient

UFC:

Urine free cortisol

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Acknowledgments

This review and accompanying studies were supported by the National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health (K23 DK071565 to SHG) and by the National Institute of Alcohol Abuse and Alcoholism (RO1 AA10158 to GW).

Author information

Authors and Affiliations

  1. Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Sherita Hill Golden & Gary S. Wand

  2. Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA

    Sherita Hill Golden

  3. Department of Radiology, Johns Hopkins University, Baltimore, MD, USA

    Ihab Kamel & Karen Horton

  4. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Saurabh Malhotra

  5. Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 2024 E. Monument Street, Suite 2-600, Baltimore, MD, 21287, USA

    Sherita Hill Golden

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  1. Sherita Hill Golden
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  4. Ihab Kamel
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Corresponding author

Correspondence to Sherita Hill Golden.

Appendix: medline search strategy

Appendix: medline search strategy

“Salivary cortisol”[tiab] OR “Daytime cortisol”[tiab] OR “morning cortisol”[tiab] OR “Awakening cortisol”[tiab] OR “Free cortisol”[tiab] OR “diurnal cortisol”[tiab] OR “cortisol”[ti] OR “cortisol response”[ti] OR “Cortisol levels”[tiab] OR “Cortisol rhythms”[tiab] OR “Cortisol rhythm”[tiab] OR “Cortisol secretion”[tiab] OR “Dexamethasone”[ti] OR “hydrocortisone”[tiab] OR “adrenocorticotropic hormone”[tiab] OR “Saliva/chemistry”[majr] OR “Saliva/drug effects”[majr] OR “adrenocortical stress capacity”[All Fields] OR “magnetic resonance imaging”[tiab] AND (“Adrenal Gland Volume”[tiab] OR “adrenal insufficiency”[tiab] OR “Adrenocortical Insufficiency”[tiab] OR “Adrenocorticotropic hormone deficiency”[All] OR “ACTH deficiency”[tiab] OR “Adrenocortical Hyperplasia”[tiab] OR “adrenocortical activity”[tiab] OR “adrenal incidentaloma”[tiab] OR “Adrenalectomy”[tiab] OR “Hypercortisolism”[tiab] OR “Cushing’s syndrome”[tiab] OR “Hypothalamic Pituitary Adrenal Axis”[tiab] OR “Hypothalamic pituitary axis”[tiab] OR “Hypothalamic pituitary adrenocortical system”[tiab] OR “pituitary adrenal cortical axis”[tiab] OR “Hypothalamo-pituitary-adrenal axis”[tiab] OR “hypothalamus–pituitary–adrenal axis”[tiab] OR “hypothalamo-pituitary-adrenal”[tiab] OR “major depression”[ti] OR “depressive illness”[ti] OR “major depressive disorder”[ti] OR “depressed”[ti] OR “antidepressant treatment”[ti] OR “salivary cortisol”[ti] OR “reliability”[ti] OR “cortisol response”[ti]) AND (“humans”[MeSH Terms] AND English[lang] AND “adult”[MeSH Terms] AND (“1982”[PDAT] : “2010/06/30”[PDAT])) NOT review[ptyp].

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Golden, S.H., Wand, G.S., Malhotra, S. et al. Reliability of hypothalamic–pituitary–adrenal axis assessment methods for use in population-based studies. Eur J Epidemiol 26, 511–525 (2011). https://doi.org/10.1007/s10654-011-9585-2

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