Salivary Cortisol Determination in ACTH Stimulation Test to Diagnose Adrenal Insufficiency in Patients with Liver Cirrhosis

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 μg intravenous ACTH test and to estimate the prevalence of AI in noncritically 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 μg ACTH [30’(T30), 60’(T60), and 90’(T90)]. Results. Based on the findings in healthy subjects and patients with known AI, we defined AI in cirrhotic patients as SaC-T0< 0.08 μg/dL (2.2 nmol/L), SaC-T60 < 1.43 μg/dl (39.5 nmol/L), or ΔSaC<1 μg/dl (27.6 nmol/L). We compared AI determination in cirrhotic patients with the ACTH test using these SaC thresholds versus established TSC thresholds (TSC-T0< 9 μg/dl [248 nmol/L], TSC-T60 < 18 μg/dl [497 nmol/L], or ΔTSC<9 μg/dl [248 nmol/L]). SaC correlated well with TSC. The prevalence of AI in cirrhotic patients was higher when determined by TSC (48.7%) than by SaC (30.8%); however, this difference did not reach statistical significance. AI was associated with sex, cirrhosis etiology, and Child-Pugh classification. Conclusions. Measuring SaC was more accurate than TSC in the ACTH stimulation test. Measuring TSC overestimated the prevalence of AI in noncritically ill cirrhotic patients.

Assessment of adrenal response in patients with stable cirrhosis and ascites using different short Synacthen tests and definitions

“…In our study, 52.4% of patients were classified as having RAI according to LDSST/SalC definition. By contrast, only 20% of patients had RAI according to SDSST/SalC criteria, which is consistent with previous observations [5,16]. Notably, no healthy subject had RAI according to SalC criteria after both SSTs.…”

Relative adrenal insufficiency in the non‐critically ill patient with cirrhosis: A systematic review and meta‐analysis

“…Child–Pugh classification was reported in 17 studies ( n = 1334) with following breakdown: A – 22%, B – 42% and C – 36%. Four studies evaluated outpatients with stable cirrhosis, 13,17,21,34 compared to 18 studies investigating inpatients without critical illness 7,9,15,16,18,20,23,35–45 . All studies were observational and single centre, including 14 prospective cohort studies 7,9,13,15–18,35,36,39,41–43,45 and eight cross‐sectional studies 20,21,23,34,37,38,40,44 .…”

“…Three studies utilized both a SD‐SST and LD‐SST to evaluate for RAI 7,17,45 ; data for each SST type were included in pooled subgroup analyses. The most common criteria to define RAI was delta cortisol ( n = 15), 9,13,15–18,20,21,36,38,40–42,45 with 13 studies using peak TC instead or as an alternative criterion 7,13,17,20,21,23,37–40,42,44,45 . Peak levels of PFC were utilized in five studies, 13,21,34,37,39 whereas four studies described use of SC to define RAI 17,20,36,40 .…”

“…After excluding 21 studies for selection of a non-target population (n = 8), unclear or unusual AI definition (n = 6), being a systemic review (n = 4) or unclear study methodology (n = 3), 22 studies were included in the final analysis (see Figure 1). 7,9,13,[15][16][17][18]20,21,23,[34][35][36][37][38][39][40][41][42][43][44][45]…”

“…14 In the 5-year interim since its publication, however, an additional 11 studies have been published on the topic. 10,[15][16][17][18][19][20][21][22][23][24] Given the influx of this recent literature and uncertainty surrounding the concept of RAI in patients with cirrhosis but without critical illness, we undertook an updated systematic review and meta-analysis. We restricted our analysis to patients in either the outpatient or acute care (but not intensive care) setting to reduce the known suppressive effects of critical illness on hypothalamic-pituitary-adrenal (HPA) axis functionality.…”