Circadian rhythm of salivary cortisol, plasma cortisol, and plasma ACTH in end-stage renal disease

Hershel Raff,Hariprasad Trivedi

doi:10.1530/ec-12-0058

Hershel Raff, Hariprasad Trivedi

Open Access

https://doi.org/10.1530/ec-12-0058

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Abstract

ObjectivePatients with end-stage renal disease (ESRD) can display the features of endogenous hypercortisolism but are difficult to evaluate for Cushing's syndrome. We evaluated the circadian rhythm of plasma compared with salivary cortisol in subjects with ESRD.DesignPlasma and salivary cortisol and plasma ACTH samples were drawn frequently over 24 h in an inpatient research unit in stable ESRD subjects on daytime chronic hemodialysis (n=16) vs controls (n=8).MethodsPlasma cortisol was measured every 2 h from 0800 to 0600 h the following day. Salivary cortisol was measured every 2 h, except between 2400 and 0400 h (sleep time). Plasma ACTH measured in a subset of samples and C-reactive protein (CRP) was measured as a marker of a subclinical inflammatory state in all subjects.ResultsESRD subjects had a discernable circadian rhythm in plasma and salivary cortisol, but with a significantly higher nadir (1800–2400 h) compared with the controls (P=0.016–<0.001). After excluding four ESRD subjects without a normal circadian rhythm, the ESRD subjects still had higher nadir plasma and salivary cortisol and plasma ACTH compared with controls. There was no difference in the correlation of salivary and plasma cortisol in control vs ESRD subjects. ESRD subjects had higher CRP levels compared with controls.ConclusionsESRD subjects had increased late-night plasma and salivary cortisol and plasma ACTH levels. Late-night salivary cortisol is a reliable index of plasma cortisol in ESRD patients.

Highlights

The measurement of salivary cortisol has emerged as a first-line test in the evaluation of the hypothalamic– pituitary–adrenal (HPA) axis in humans and, in particular, for the diagnosis of endogenous hypercortisolism (Cushing’s syndrome) [1, 2, 3, 4, 5, 6, 7]
The initial purpose of this study was to evaluate the usefulness of salivary cortisol to evaluate the HPA axis in subjects with end-stage renal disease (ESRD)
We have clearly demonstrated that salivary cortisol is a useful surrogate for plasma cortisol in ESRD patients in agreement with many previous studies of patients with Cushing’s syndrome, hypoalbuminemia, corticosteroid-binding globulin mutations, and adrenal insufficiency [6, 7, 18, 19]

Summary

Introduction

The measurement of salivary cortisol has emerged as a first-line test in the evaluation of the hypothalamic– pituitary–adrenal (HPA) axis in humans and, in particular, for the diagnosis of endogenous hypercortisolism (Cushing’s syndrome) [1, 2, 3, 4, 5, 6, 7]. In patients with normal renal function, salivary cortisol concentration is highly correlated with plasma free cortisol [7]. Our reference laboratory often receives inquiries as to whether late-night salivary cortisol can be used to evaluate the possibility of endogenous Cushing’s syndrome in patients with chronic kidney failure and we have been unable to provide a definitive answer based on previous studies [1, 2]

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