Update on adrenal insufficiency in patients with liver cirrhosis

Table 1 Prevalence of adrenal insufficiency in critically ill patients with liver cirrhosis

Ref.	No. of patients (type of cirrhosis)	Diagnosis and definition of AI	Prevalence of AI
Harry et al[14]	20 (ALF/CLD)	SD-SST: Peak cortisol < 500 nmol/L1	69%
Marik et al[12]	340 (ALF: 24)(CLD: 146)(recent LT: 119)(remote LT: 51)	LD-SST: Peak cortisol < 552 nmol/L orrandom cortisol level < 414 nmol/L in non-stressed patients orrandom cortisol level < 552 nmol/L in stressed patients	72%33%66%92%61%
Tsai et al[8]	101 (cirrhosis+ severe sepsis)	SD-SST: Baseline cortisol < 414 nmol/L ordelta cortisol < 250 nmol/L if baseline cortisol between 414 and 938 nmol/L	51%
Fernandez et al[13]	25 (cirrhosis + septic shock)	SD-SST: Baseline cortisol < 414 nmol/L ordelta cortisol < 250 nmol/L if baseline cortisol between 414 and 966 nmol/L	68%
Thierry et al[64]	14 (cirrhosis + septic shock)	SD-SST: Baseline cortisol < 414 nmol/L; delta cortisol < 250 nmol/L	77%
du Cheyron et al[65]	50 (critically ill cirrhosis)	SD-SST: Baseline cortisol < 414 nmol/L; delta cortisol < 250 nmol/L if baseline cortisol between 414 and 938 nmol/L	82%
Vasu et al[86]	24 (critically ill cirrhotics)	SD-SST: Definition of AI was not reported	62%
Arabi et al[29]	75 (cirrhosis + septic shock)	SD-SST: Delta cortisol < 250 nmol/L	76%
Mohamed et al[85]	15 (cirrhosis+septic shock)	SD-SST: Definition of AI was not reported	87%
Thevenot et al[74]	30 (cirrhosis + sepsis)	SD-SST: Peak serum total cortisol < 510 nmol/L	10%
Acevedo et al[89]	166 (decompensated cirrhosis)	SD-SST: Delta cortisol < 250 nmol/L	26%
Graupera et al[20]	37 (severe acute bleeding)	SD-SST: Baseline cortisol < 414 nmol/L and/or delta cortisol < 250 nmol/L	38%
Triantos et al[16]	20 (cirrhosis with variceal bleeding)	SD-SST: Baseline cortisol < 276 nmol/L or delta cortisol < 250 nmol/LLD-SST: Peak serum cortisol < 690 nmol/L or a delta cortisol < 250 nmol/L	30%60%
El Damarawy et al[66]	45 (cirrhosis with septic shock or HRS, cirrhosis without septic shock or HRS)	SD-SST: Baseline cortisol < 414 nmol/L or delta cortisol < 250 nmol/L in patients with baseline cortisol < 966 nmol/L	73%

¹To convert serum total cortisol concentrations from nanomoles per liter to micrograms per deciliter divide by 27.59[79]. ALF: Acute liver failure; CLD: Chronic liver disease; HRS: Hepatorenal syndrome; LT: Liver transplant; AI: Adrenal insufficiency; SD-SST: Standard dose short synacthen test; LD-SST: Low dose short synacthen test.

Table 2 Prevalence of adrenal insufficiency in patients with liver cirrhosis, not critically ill

Ref.	No. of patients (type of cirrhosis)	Diagnosis and definition of AI	Prevalence of AI
McDonald et al[69]	38 (stable cirrhosis)	IIHT: Reduction in maximal increments of plasma cortisolSD-SST: Reduction in maximal increments of plasma cortisol	64%39%
Zietz et al[112]	52 (stable cirrhosis)	CRHT: Peak cortisol < 550 nmol/L or an increase < 250 nmol/L1rise of plasma ACTH < twice the baseline	58%42%
Sigalas et al[87]	47 (stable cirrhosis)	SD-SST: Baseline cortisol < 250 nmol/L and delta cortisol < 250 nmol/L	36%
Alessandria et al[88]	25 (cirrhosis and ascites)	SD-SST: Delta cortisol < 250 nmol/L	36%
Jang et al[63]	18 (stable cirrhosis)	SD-SST: Baseline cortisol < 414 nmol/L delta cortisol < 250 nmol/L	83%
Acevedo et al[19]	198 (10 compensated and 188 decompensated cirrhosis)	SD-SST: Baseline cortisol < 414 nmol/Ldelta cortisol < 250 nmol/L	64%27%
Galbois et al[45]	88 (stable cirrhosis)	SD-SST: (1) Serum total cortisol: Baseline cortisol < 250 nmol/L or peak cortisol < 500 nmol/L or delta cortisol < 250 nmol/L(2) Salivary cortisol: Basal salivary cortisol < 1.8 ng/mL or post-stimulation values < 12.7 ng/mL or increase values < 3 ng/mL	33% 9%
Tan et al[15]	43 (stable cirrhosis)	SD-SST: Peak total cortisol < 500 nmol/L; delta cortisol < 250 nmol/L; peak plasma free cortisol < 33 nmol/L; any set of criteria	39%47%12%58%
Thevenot et al[67]	95 (stable cirrhosis)	LD-SST: Baseline cortisol < 138 nmol/L; < 440 nmol/L after stimulation; ≤ 500 nmol/L after stimulation; delta cortisol < 250 nmol/L	7%19%27%49%
Fede et al[17]	101 (stable cirrhosis)	LD-SST: Peak serum cortisol < 500 nmol/L; peak serum cortisol < 442 nmol/L; delta cortisol < 250 nmol/L	38%29%60%
Triantos et al[16]	60 (stable cirrhosis)	SD-SST: Peak serum cortisol < 500 nmol/LLD-SST: Peak serum cortisol < 500 nmol/L	30%48%
Mohamed et al[85]	15 (stable cirrhosis)	SD-SST: Definition of AI was not reported	53%
Risso et al[18]	85 (cirrhosis with ascites, without sepsis or shock)	SD-SST: Delta cortisol < 250 nmol/L and/or peak cortisol < 500 nmol/L	39%
Vincent et al[73]	26 (liver impairment)	SD-SST: Serum total cortisol < 550 nmol/L; free cortisol index < 12	46%13%

¹To convert serum total cortisol concentrations from nanomoles per liter to micrograms per deciliter divide by 27.59[79]. AI: Adrenal insufficiency; SD-SST: Standard dose short synacthen test; LD–SST: Low dose short synacthen test; CRHT: Corticotropin-releasing hormone test; IIHT: Insulin-induced hypoglycemia test; ACTH: Adrenocorticotropic hormone.

Table 3 Published studies on corticosteroid therapy in patients with liver cirrhosis

Ref.	No. of patients (type of cirrhosis)	Study design	Steroid dose	Outcomes
Harry et al[14]	20 (ALF or ACLF)	Retrospective	Hydrocortisone 300 mg/d	Reduction in vasopressor doses, but higher incidence of infection and no survival benefit
Marik et al[12]	140 (ALF or CLD)	Not RCT	Hydrocortisone 300 mg/d	Reduction in the dose of norepinephrine at 24 h, and lower mortality rate increased survival
Fernandez et al[13]	17 (cirrhosis and septic shock)	Prospective but not RCT	Hydrocortisone 200 mg/d	Significant increase in shock resolution and high hospital survival rate
Arabi et al[29]	39 (cirrhosis and septic shock)	RCT	Hydrocortisone 200 mg/d	Reduction in vasopressor doses and higher rates of shock reversal, but no benefit in 28 d mortality, increase in gastrointestinal bleeding and shock relapse

ALF: Acute liver failure; ACLF: Acute-on-chronic liver failure; CLD: Chronic liver disease; RCT: Randomized controlled trial.