Abstract

Purpose. The prevalence of adrenal insufficiency (AI) in patients with decompensated liver cirrhosis is unknown. Because these patients have lower levels of cortisol-binding carrier proteins, their total serum cortisol (TSC) correlates poorly with free serum cortisol (FC). Salivary cortisol (SaC) correlates better with FC. We aimed to establish SaC thresholds for AI for the 250 g intravenous ACTH test and to estimate the prevalence of AI in non-critically ill cirrhotic patients. Methods. We included 39 patients with decompensated cirrhosis, 39 patients with known AI, and 45 healthy volunteers. After subjects fasted ≥8 hours, serum and saliva samples were collected for determinations of TSC and SaC at baseline 0’ (T0) and at 30-minute intervals after intravenous administration of 250

Introduction

Adrenal insufficiency (AI) is common in patients with liver disease; AI is present in both patients with severe cirrhosis admitted to intensive care units and stable patients [1–3]. Relative AI in patients with cirrhosis is a sum of primary (lack of steroid precursors, such as cholesterol) and secondary (impairment of CRH-ACTH axis) AI. The lack of specific symptoms of acute and chronic AI makes the diagnosis difficult.

The insulin tolerance test is considered the gold standard for evaluating the hypothalamus-pituitary–adrenal axis. However, in clinical practice, the short ACTH stimulation test is more widely used because it is better tolerated and has fewer contraindications. Both tests are based on the analysis of serum cortisol, and the correlation between the two is well studied; most clinical guidelines support the use of the ACTH

Serum cortisol is mostly bound to carrier proteins such as cortisol-binding globulin (CBG) and albumin [6]. Free cortisol (FC), the biologically active unbound fraction, rep- resents about 5% to 10% of total serum cortisol (TSC) [7, 8]. Various conditions affect protein synthesis. For instance, cirrhosis, malnutrition, and critical illness reduce it, whereas oral contraceptives and pregnancy increase it. Thus, TSC does not accurately reflect FC, increasing the risk of misdiagnosis [9–11]. Rauschecker et al. [12] recently demonstrated that measuring FC in response to ACTH stimulation is a good alternative to TSC for diagnosing AI. However, FC analysis is time-consuming and expensive, hindering its use for routine laboratory testing. The FC fraction can be calculated using the Coolens’ equation, but the results are unsatisfactory [13]. An easier, less expensive approach is to determine FC indirectly by measuring salivary cortisol (SaC), a surrogate of plasma FC [14]

Late-night (23:00–24:00 h) SaC is widely used to detect hypercortisolism when Cushing’s syndrome is suspected [15]. Various authors have proposed using SaC instead of TSC after ACTH stimulation tests [15–17], but limited data are available to validate this approach

We aimed to determine the reference values for SaC after stimulation with 250