European Journal of Epidemiology

, Volume 26, Issue 7, pp 511–525

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

  • Sherita Hill Golden
  • Gary S. Wand
  • Saurabh Malhotra
  • Ihab Kamel
  • Karen Horton
METHODS

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.

Keywords

Adrenal gland volume Cortisol awakening response Cortisol diurnal curve Dexamethasone suppression test Reliability Salivary cortisol 

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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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Sherita Hill Golden
    • 1
    • 2
    • 5
  • Gary S. Wand
    • 1
  • Saurabh Malhotra
    • 4
  • Ihab Kamel
    • 3
  • Karen Horton
    • 3
  1. 1.Department of MedicineJohns Hopkins UniversityBaltimoreUSA
  2. 2.Department of EpidemiologyJohns Hopkins UniversityBaltimoreUSA
  3. 3.Department of RadiologyJohns Hopkins UniversityBaltimoreUSA
  4. 4.Department of MedicineIndiana University School of MedicineIndianapolisUSA
  5. 5.Division of Endocrinology and MetabolismJohns Hopkins University School of MedicineBaltimoreUSA

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