Acute Illness and Death in Children With Adrenal Insufficiency.

Background: Adrenal Insufficiency (AI) can lead to life-threatening Adrenal Crisis (AC) and Adrenal Death (AD). Parents are trained to prevent, recognise and react to AC but there is little available information on what parents are actually doing at home to manage symptomatic AI. Methods: Three approaches were taken: (A) A retrospective analysis of patient characteristics in children and young people with AD over a 13-year period, (B) An interview-aided questionnaire to assess the circumstances around AC in children currently in our adrenal clinic, and (C) a separate study of parent perceptions of the administration of parenteral hydrocortisone. Results: Thirteen patients died (median age 10 years) over a thirteen-year period resulting in an estimated incidence of one AD per 300 patient years. Those with unspecified adrenal insufficiency were overrepresented (P = 0.004). Of the 127 patients contacted, thirty-eight (30%) were identified with hospital attendance with AC. Responses from twenty patients (median age 7.5 years) with AC reported nausea/vomiting (75%) and drowsiness (70%) as common symptoms preceding AC. All patients received an increase in oral hydrocortisone prior to admission but only two received intramuscular hydrocortisone. Questionnaires revealed that 79% of parents reported confidence in the administration of intramuscular hydrocortisone and only 20% identified a missed opportunity for injection. Conclusions: In children experiencing AC, parents followed 'sick day' guidance for oral hydrocortisone, but rarely administered intramuscular hydrocortisone. This finding is discrepant from the 79% of parents who reported confidence in this task. Local training programmes for management of AC are comprehensive, but insufficient to prevent the most serious crises. New strategies to encourage use of parenteral hydrocortisone need to be devised.

Mortality Risk in Patients With Adrenal Insufficiency Using Prednisolone or Hydrocortisone: A Retrospective Cohort Study.

CONTEXT: Prednisolone has been recommended rather than hydrocortisone for glucocorticoid replacement in adrenal insufficiency due its longer duration of action and lower cost. OBJECTIVE: To determine mortality rates with prednisolone versus hydrocortisone. METHODS: In this observational study, we used data extracted from a UK primary care database (Clinical Practice Research Datalink) to measure the relative mortality of patients with primary and secondary adrenal insufficiency, who were treated with either prednisolone or hydrocortisone, and control individuals who were individually matched for age, sex, period, and place of follow-up. RESULTS: As expected, mortality in adrenal insufficiency irrespective of cause was increased, based on 5478 patients (4228 on hydrocortisone; 1250 on prednisolone) and 54 314 controls (41 934 and 12 380, respectively). Overall, the adjusted hazard ratio (HR) was similar with the 2 treatments (prednisolone, 1.76 [95% CI, 1.54-2.01] vs hydrocortisone 1.69 [1.57-1.82]; P = 0.65). This was also the case for secondary adrenal insufficiency. In primary disease (1405 on hydrocortisone vs 137 on prednisolone; 13 965 and 1347 controls, respectively), prednisolone users were older, more likely to have another autoimmune disease and malignancy, and less likely to have mineralocorticoid replacement. Nevertheless, after adjustment, the HR for prednisolone-treated patients remained higher than for those taking hydrocortisone (2.92 [2.19-3.91] vs 1.90 [1.66-2.16]; P = 0.0020). CONCLUSION: In primary but not in secondary adrenal insufficiency, mortality was higher with prednisolone. The study was large, but the number of prednisolone-treated patients was small, and they had greater risk factors. Nonetheless, the increased mortality associated with prednisolone persisted despite statistical adjustment. Further evidence is needed regarding the long-term safety of prednisolone as routine replacement.

Increased Mortality Risk in Patients With Primary and Secondary Adrenal Insufficiency.

CONTEXT: Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations. OBJECTIVE: To compare mortality risk and causes of death in adrenal insufficiency with an individually matched reference population. METHODS: A retrospective cohort study was done using a UK general practitioner database (CPRD). A total of 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) were compared with 67564 individually-matched controls (primary, 20366; secondary, 39134). Main outcomes were all-cause and cause-specific mortality, and hospital admission from adrenal crisis. RESULTS: With follow-up of 40 799 and 406 899 person-years for patients and controls respectively, the hazard ratio (HR [95% CI]) for all-cause mortality was 1.68 [1.58-1.77]. HRs were greater in primary (1.83 [1.66-2.02]) than in secondary (1.52 [1.40-1.64]) disease; primary versus secondary disease (1.16 [1.03-1.30]). The leading cause of death was cardiovascular disease (HR 1.54 [1.32-1.80]), along with malignant neoplasms and respiratory disease. Deaths from infection were also relatively high (HR 4.00 [2.15-7.46]). Adrenal crisis contributed to 10% of all deaths. In the first 2 years following diagnosis, the patients' mortality rate and hospitalization from adrenal crisis were higher than in later years. CONCLUSION: Mortality was increased in adrenal insufficiency, especially primary, even with individual matching and was observed early in the disease course. Cardiovascular disease was the major cause but mortality from infection was also high. Adrenal crisis was a common contributor. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality.

The management of glucocorticoid deficiency: Current and future perspectives.

Glucocorticoid deficiency is the clinical state characterised by inadequate cortisol production. It may occur due to the primary failure of the adrenal cortex or to lack of stimulation of the adrenal cortex by adrenocorticotropic hormone. The aim of treatment of glucocorticoid deficiency is to mimic the normal physiological secretion of cortisol, in order to normalise quality of life and reverse pathological sequelae. However, the diurnal rhythm of cortisol secretion is difficult to reproduce with exogenous glucocorticoid therapy. There is wide inter- and intra-individual variability of in the dynamics of physiological glucocorticoid secretion, and glucocorticoid preparations that are currently available cannot reproduce physiological profiles. In addition, there are no reliable biomarkers to determine the adequacy of treatment. The treatment of acute glucocorticoid deficiency/ adrenal crisis involves prompt recognition and administration of parenteral hydrocortisone, rehydration, and management of electrolyte abnormalities. In the management of chronic glucocorticoid deficiency, the prevention of adrenal crisis must be balanced with avoidance of the long-term adverse effects of over-replacement. This requires close collaboration with the patient, for whom education and empowerment in the management of glucocorticoid deficiency, and the prevention of crises, are crucial.

Adrenal Insufficiency and Response to Stress Dose Hydrocortisone in Patients With Cirrhosis and Vasopressor Dependency Using Cirrhosis-Specific Cortisol Thresholds.

Background: Cortisol thresholds defining adrenal insufficiency (AI) in some cirrhosis-specific studies differ from those recommended by the SCCM/ESICM (Society of Critical Care Medicine/European Society of Intensive Care Medicine) guidelines, which may influence treatment decisions. Objective: To determine if stress-dose hydrocortisone (HC) improves outcomes in vasopressor-dependent patients meeting cirrhosis-specific criteria for AI. Methods: In this retrospective study, AI was defined using criteria from 2 studies in critically ill cirrhosis patients showing mortality reduction with HC (random cortisol <20 µg/dL, or if a standard-dose cosyntropin test was performed, baseline cortisol <15 µg/dL or delta cortisol <9 µg/dL if baseline = 15-34 µg/dL). Use of HC was at the discretion of the intensivist. The primary endpoint was days of vasopressor therapy. Secondary endpoints included hospital mortality and newly acquired infections. Sixty-four patients were evaluated; 40 patients received HC and 24 did not. Results: Mean random cortisol was significantly lower in the HC group (9.8 ± 3.2 vs 12.0 ± 3.7 µg/dL, P = 0.04). Delta cortisol also tended to be lower in the HC group (8.2 ± 4.4 vs 11.3 ± 6.4 µg/dL, P = 0.25). Patients in the HC group exhibited significantly fewer median days of vasopressor therapy (4.0 [2.0-7.0] vs 7.0 [4.2-10.8], P = 0.006), lower mortality (22.5% vs 50%, P = 0.02), and a similar incidence of newly acquired infections. Conclusion and Relevance: The use of HC in patients meeting cirrhosis-specific criteria for AI resulted in significantly shorter duration of vasopressor therapy, lower mortality, and no increased risk of infection. Use of traditional AI definitions may exclude patients with cirrhosis that could benefit from HC therapy.

Impact of underlying chronic adrenal insufficiency on clinical course of hospitalized patients with adrenal crisis: A nationwide cohort study.

BACKGROUND: Chronic adrenal insufficiency (AI) is an established risk factor for adrenal crisis (AC). However, the proportion of patients with newly diagnosed chronic AI during admission for AC is unclear. METHODS: This retrospective cohort study used a Japanese claims database involving 7.39 million patients at 145 acute care hospitals between 2003 and 2014. Study patients with AC met these criteria: 1) newly coded in claims as AI; 2) glucocorticoid therapy administered; 3) admission; and 4) age ≥ 18 years. We investigated the prevalence of underlying chronic AI and assessed in-hospital mortality. Additionally, we explored risk factors for in-hospital mortality through multivariate analysis using a Cox proportional hazards model. RESULTS: Among 504 patients with AC, chronic AI was diagnosed before and during admission in 73 (14.5%) and 86 (17.1%) patients, respectively. In-hospital mortality rates were 1.4% and 5.8%, respectively, lower than that of the total population (14.1%). Significant risk factors for increased mortality were: age (hazard ratio [HR] 1.45/10 years; 95% confidence interval [CI] 1.17-1.78), requiring mechanical ventilation (HR 3.81; 95% CI 1.88-7.72), vasopressor administration (HR 2.05; 95% CI 1.16-3.64), sepsis (HR 3.79; 95% CI 1.57-9.14), AI-related symptoms (HR 2.00; 95% CI 1.02-3.93), and liver disease (HR 3.24; 95% CI 1.10-9.58). CONCLUSIONS: Relative to patients without chronic AI, those diagnosed before admission tended to survive to discharge; however, the difference with those diagnosed during admission was not significant. Hospital admission due to nonspecific AI-related symptoms was associated with an increased risk of in-hospital mortality.

Adrenal insufficiency in systematic lupus erythematosus (SLE) and antiphospholipid syndrome (APS): A systematic review.

BACKGROUND: Adrenal insufficiency (AI) is associated with high morbidity and mortality. The aim of this systematic review was to enhance diagnostic approaches and summarize therapeutic strategies in the management of AI in patients with systematic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). METHODS: A literature search of PubMed and Medline databases was performed and 91 publications containing 105 cases were included for the final analysis. RESULTS: The following frequency of clinical signs and symptoms was noted: abdominal pain (39.04%) was the leading symptom, followed by fever (33.33%), vomiting (23.81%), and nausea (19.05%). APS was present in 73%, SLE in 17% of the patients, while 2% had a diagnosis of both, SLE and APS. ACTH stimulation test (ACTHst) was performed in 18% of cases and 76.6% of them were unresponsive towards stimulation. Variable treatment approaches were used: hydrocortisone was most commonly used (38.09%), followed by fludrocortisone (26.67%), prednisolone (20.00%) and volume replacement treatment (11.43%), respectively. CONCLUSIONS: This analysis highlights the importance of an early diagnosis and initiation of therapeutic management when AI is suspected. In line, signs and symptoms related to autoimmune diseases in patients with AI should be reviewed crtitically.

Adrenal Crises in Children: Perspectives and Research Directions.

Adrenal crises (AC) are life-threatening physiological disturbances that occur at a rate of 5-10/100 patient years in patients with adrenal insufficiency (AI). Despite their seriousness, there is a paucity of information on the epidemiology of AC events in the paediatric population specifically, as most investigations have focused on AI and ACs in adults. Improved surveillance of AC-related morbidity and mortality should improve the delineation of AC risk overall and among different subgroups of paediatric patients with AI. Valid incidence measures are essential for this purpose and also for the evaluation of interventions aimed at reducing adverse health outcomes from ACs. However, the absence of an agreed AC definition limits the potential benefit of research and surveillance in this area. While approaches to the treatment and prevention of ACs have much in common across the lifespan, there are important differences between children and adults with regards to the physiological, psychological, and social milieu in which these events occur. Education is considered to be an essential element of AC prevention but studies have shown that ACs occur even among well-educated patients, suggesting that new strategies may be needed. In this review, we examine the current knowledge regarding AC events in children with AI; assess the existing definitions of an AC and offer a new definition for use in research and the clinic; and suggest areas for further investigation that are aimed at reducing the incidence and health impact of ACs in the paediatric age group.

Relative Adrenal Insufficiency Is Associated With Prolonged Postoperative Hemodynamic Instability.

BACKGROUND: We assessed the hypothesis that a significant proportion of patients undergoing cardiac surgery have postoperative relative adrenal insufficiency (RAI), and that this puts them at higher risk of persistent hemodynamic instability. METHODS: A prospective study included 135 patients who underwent cardiac surgery using cardiopulmonary bypass between July 2006 and December 2007. Adrenal function was assessed 36 hours after surgery using a 1-µg cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation test. Relative adrenal insufficiency was defined as a peak cortisol level inferior to 500 nmol/L or an increase in cortisol of less than 250 nmol/L, or both, compared with baseline. The primary endpoint was hemodynamic instability at 48 hours after surgery, defined as persistent requirement for any vasoactive drug. The secondary endpoint was long-term survival. RESULTS: Postoperative RAI was diagnosed in 75 patients (56%). Compared with patients who showed a normal response to the ACTH stimulation test, patients with RAI had significantly higher rates of hemodynamic instability at 48 hours (40% versus 22%, p = 0.03). On multivariable analysis, adrenal response to the ACTH test was a significant independent predictor of hemodynamic instability at 48 hours after surgery (odds ratio 1.06 [95% confidence interval: 1.02 to 1.11] per 10 nmol/L cortisol decrease; p = 0.002). At a mean follow-up of 8.3 ± 2.8 years, patients without perioperative RAI had survival equivalent to that of the general population, whereas patients with RAI had lower than expected survival. CONCLUSIONS: Postoperative RAI is common among patients undergoing cardiac surgery and is associated with an increased risk of persistent hemodynamic instability.

Acute adrenal crisis and mortality in adrenal insufficiency: Still a concern in 2018!

Despite established replacement therapy, mortality in patients suffering from chronic adrenal insufficiency is increasing. This may be partly explained by the fact that lack of adrenal stress hormones impairs the body's capacity to deal adequately with stress situations, resulting in life-threatening adrenal crises. Since many such situations are of rapid onset, concepts that allow for quick response to emergencies are particularly important. Optimal education for patients and relatives, improved awareness on the part of health professionals and the development of new easy-to-use drugs for acute therapy are of prime importance.

Mortality data from the European Adrenal Insufficiency Registry-Patient characterization and associations.

OBJECTIVE: Mortality from primary and secondary adrenal insufficiency (AI; PAI and SAI, respectively) is 2-3-fold higher than in the general population. Mortality relates to cardiovascular disease, acute adrenal crisis (AC), cancer and infections; however, there has been little further characterization of patients who have died. DESIGN/METHODS: We analysed real-world data from 2034 patients (801 PAI, 1233 SAI) in the European Adrenal Insufficiency Registry (EU-AIR; NCT01661387). Baseline clinical and biochemical data of patients who subsequently died were compared with those who remained alive. RESULTS: From August 2012 to June 2017, 26 deaths occurred (8 PAI, 18 SAI) from cardiovascular disease (n = 9), infection (n = 4), suicide (n = 2), drug-induced hepatitis (n = 2), and renal failure, brain tumour, cachexia and AC (each n = 1); cause of death was unclear in 5 patients. Patients who died were significantly older at baseline than alive patients. Causes of AI were representative of patients with SAI; however, 3-quarters of deceased patients with PAI had undergone bilateral adrenalectomy (3 with uncontrolled Cushing's disease, 3 with metastatic renal cell cancer). There were no significant differences in body mass index, blood pressure, low-density lipoprotein cholesterol, total cholesterol or electrolytes between deceased and alive patients. Deceased patients with SAI were more frequently male individuals, were receiving higher daily doses of hydrocortisone (24.0 ± 7.6 vs 19.3 ± 5.7 mg, P = .0016) and experienced more frequent ACs (11.1 vs 2.49/100 patient-years, P = .0389) than alive patients. CONCLUSIONS: This is the first study to provide detailed characteristics of deceased patients with AI. Older, male patients with SAI and frequent AC had a high mortality risk.

Group 1. Epidemiology of primary and secondary adrenal insufficiency: Prevalence and incidence, acute adrenal insufficiency, long-term morbidity and mortality.

The prevalence of primary adrenal insufficiency is estimated at between 82-144/million, with auto-immunity being the most common cause in adults and genetic causes, especially enzyme defects, being the most common cause in children. The prevalence of secondary adrenal deficiency is estimated to be between 150-280/million. The most frequent occurrence is believed to be corticosteroid-induced insufficiency, despite the incidence of clinically relevant deficiency after cessation of glucocorticoid treatment being widely debated. Data on mortality in adrenal insufficiency are contradictory, with studies from Sweden suggesting a two-fold increase in comparison to the general population, but this is not consistently reported in all studies. However, increased mortality has been consistently reported in young patients, associated with infection and/or acute adrenal insufficiency. Acute adrenal deficiency (adrenal crisis) occurs in primary as well as secondary adrenal insufficiency. Its incidence, mostly determined in retrospective studies, is estimated in Europe at 6-8/100 patients/year. A prospective study reported 0.5 deaths/100 patient-years from adrenal crisis. Long-term morbidity of adrenal insufficiency is not well-established, the increased cardiovascular risk or bone demineralization which are not consistently reported may also be due to a supraphysiological glucocorticoid replacement therapy. However, alteration in quality of life, both in physical and mental health components, has been demonstrated by several studies in both primary and secondary adrenal insufficiency.

Steroid use for refractory hypotension in congenital diaphragmatic hernia.

PURPOSE: Guidelines for diagnosis and treatment of adrenal insufficiency (AI) in newborns with congenital diaphragmatic hernia (CDH) are poorly defined. METHODS: From 2002 to 2016, 155 infants were treated for CDH at our institution. Patients with shock refractory to vasopressors (clinically diagnosed AI) were treated with hydrocortisone (HC). When available, random cortisol levels <10 µg/dL were considered low. Outcomes were compared between groups. RESULTS: Hydrocortisone was used to treat AI in 34% (53/155) of patients. That subset of patients was demonstrably sicker, and mortality was expectedly higher for those treated with HC (37.7 vs. 17.6%, p = 0.0098). Of the subset of patients with random cortisol levels measured before initiation of HC, 67.7% (21/31) had low cortisol levels. No significant differences were seen in survival between the high and low groups, but mortality trended higher in patients with high cortisol levels that received HC. After multivariate analysis, duration of HC stress dose administration was associated with increased risk of mortality (OR 1.11, 95% CI 1.02-1.2, p = 0.021), and total duration of HC treatment was associated with increased risk of sepsis (OR 1.04, 95% CI 1.005-1.075, p = 0.026). CONCLUSION: AI is prevalent amongst patients with CDH, but prolonged treatment with HC may increase risk of mortality and sepsis.

Relative Adrenal Insufficiency is Associated with the Clinical Outcome in Patients with Stable Decompensated Cirrhosis.

BACKGROUND: The clinical impact of relative adrenal insufficiency (AI) on patients with stable decompensated cirrhosis (DeCi) has not been yet elucidated. AIM: Explore the association between AI and outcome [death or liver transplantation (LT)] in patients with DeCi. MATERIAL AND METHODS: Patients with DeCi presenting no active complication have been included. Clinical and laboratory data, including serum levels of corticosteroid-binding globulin (CBG), interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNFα) were recorded in each participant. Salivary cortisol (SC) and serum total cortisol (STC) were assessed at (T0) and 1 h (T60) after intravenous injection of 250 µg corticotropin. RESULTS: 113 consecutive patients were totally tested. Median SC was 3.9 ng/mL and 15.5 ng/mL and median STC was 10.7 µg/dL and 22.7 µg/dL at T0 and T60 respectively. The patients with AI [group 1, n = 34 (30%)] had significantly lower systolic blood pressure (106 ± 12 vs. 113 ± 13 mmHg, p = 0.05), serum sodium (133 ± 7 vs. 137 ± 12 mEq/ L, p = 0.04), HDL (29.9 ± 14 vs. 38.6 ± 18 mg/dL, p = 0.034) and albumin (2.7 ± 0.5 vs. 3.1 ± 0.5 g/dL, p = 0.002), but higher direct bilirubin (median: 1.6 vs. 0.8 mg/dL, p = 0.029) compared to those without AI [group 2, n = 79 (70%)]. Moreover, group 1 patients presented more frequently past history of spontaneous bacterial peritonitis (SBP) [10/34 (29.4%) vs. 6/79 (7.5%), p = 0.002]. AI was significantly associated with death [HR = 2.65, 95% C.I.: 1.55 - 4.52, p = 0.003 over a follow up period of 12 (6-48) months.] Conclusions. The presence of AI in patients with stable DeCi predispose to obvious clinical implications since it is associated with circulatory dysfunction, previous history of SBP and worse survival.

Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans.

It is well established that somatic genomic changes can influence phenotypes in cancer, but the role of adaptive changes in developmental disorders is less well understood. Here we have used next-generation sequencing approaches to identify de novo heterozygous mutations in sterile α motif domain-containing protein 9 (SAMD9, located on chromosome 7q21.2) in 8 children with a multisystem disorder termed MIRAGE syndrome that is characterized by intrauterine growth restriction (IUGR) with gonadal, adrenal, and bone marrow failure, predisposition to infections, and high mortality. These mutations result in gain of function of the growth repressor product SAMD9. Progressive loss of mutated SAMD9 through the development of monosomy 7 (-7), deletions of 7q (7q-), and secondary somatic loss-of-function (nonsense and frameshift) mutations in SAMD9 rescued the growth-restricting effects of mutant SAMD9 proteins in bone marrow and was associated with increased length of survival. However, 2 patients with -7 and 7q- developed myelodysplastic syndrome, most likely due to haploinsufficiency of related 7q21.2 genes. Taken together, these findings provide strong evidence that progressive somatic changes can occur in specific tissues and can subsequently modify disease phenotype and influence survival. Such tissue-specific adaptability may be a more common mechanism modifying the expression of human genetic conditions than is currently recognized.

Clinical features and practice patterns of treatment for adrenal crisis: a nationwide cross-sectional study in Japan.

CONTEXT: Adrenal crisis is an endocrine emergency that requires prompt diagnosis and treatment. However, the clinical features and practice patterns of treatment for adrenal crisis are not completely understood. OBJECTIVE: To investigate patient characteristics, comorbidities and treatments of adrenal crisis. METHODS: We conducted a cross-sectional study of patients who received intravenous glucocorticoids for adrenal crisis at admission from 1 July 2007 to 31 March 2014, using a national inpatient database in Japan. RESULTS: Among approximately 34 million inpatients in the database, we identified 799 patients diagnosed with adrenal crisis and coexisting primary or secondary adrenal insufficiency at admission. The median (interquartile range) age was 58 (28-73) years, and the overall in-hospital mortality was 2.4% (19 of 799 patients). The most common comorbidity at admission was infections excluding pneumonia and gastroenteritis (15.0%). There were 68 (8.5%) patients with gastroenteritis, and no deaths occurred among these patients. The patients with secondary adrenal insufficiency showed significantly higher proportions of admission to ICU, extracellular fluid resuscitation, insulin therapy and catecholamine use than the patients with primary adrenal insufficiency. There were no significant between-group differences in mortality rate and variation in intravenous glucocorticoids (short-acting glucocorticoid, hydrocortisone; moderate-acting glucocorticoid, prednisolone or methylprednisolone; long-acting glucocorticoid, dexamethasone or betamethasone). Of the 19 dead patients, 15 were aged above 60 years, 12 had impaired consciousness at admission and 13 received insulin therapy. CONCLUSIONS: Clinicians should be aware that older patients with impaired consciousness and diabetes mellitus are at relatively high risk of death from adrenal crisis.

[Adrenal insufficiency in cirrhotic patients]. / Insuficiencia suprarrenal relativa en pacientes cirróticos.

Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 υg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh = 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with = 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.

Insuficiencia suprarrenal relativa en pacientes cirróticos / Adrenal insufficiency in cirrhotic patients

La insuficiencia suprarrenal relativa (ISR) es frecuente en pacientes cirróticos con sepsis grave, asociándose a un pobre pronóstico. Se desconoce su importancia en condiciones de enfermedad estable. El objetivo del trabajo ha sido evaluar la prevalencia de la ISR en una serie de pacientes cirróticos estables y su relación con el deterioro de la función hepática. Se determinó el impacto de la ISR en la supervivencia y se correlacionaron los niveles entre el cortisol basal en plasma y saliva en sujetos controles y cirróticos. Fueron incluidos 47 pacientes ambulatorios y 16 controles. La funcionalidad del eje hipotalámico-pituitario-suprarrenal se valoró mediante la prueba de estimulación con 250 μg de ACTH sintética EV, definiendo la ISR como delta cortisol < 9 μg/dl. Respecto al grado de deterioro de la función hepática, 22 tenían un Child-Pugh ≤ 8 y 25 pacientes = 9. La prevalencia de ISR fue de un 22%, siendo significativamente más elevada en aquellos con mayor deterioro de la función hepática (8/32 vs. 3/13, p < 0.05). Se observó correlación entre el cortisol salival y el plasmático basal (r = 0.6, p < 0.0004). Por último, la supervivencia fue más elevada en los pacientes sin ISR al año (97%) y a los tres años (91%) que aquellos que desarrollaron esta complicación (79 % y 51%, p < 0.05, respectivamente). En resumen, la prevalencia de ISR es elevada en los pacientes con cirrosis estable y se relaciona con un deterioro de la función hepática y una mayor mortalidad.

Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 μg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh ≤ 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with ≤ 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.

Quality of Life and Life Expectancy in Patients with Adrenal Insufficiency: What Is True and What Is Urban Myth?

For a long time it has been assumed that patients with chronic adrenal insufficiency under established replacement therapy have a normal life expectancy and a normal everyday life. Recent studies now indicate both an impairment of quality of life (QoL) with a negative impact on daily life and increased mortality in a significant number of patients. The clinical presentation of patients varies considerably. While some neither suffer from reduced QoL nor from adrenal crisis, others are significantly more affected by the disease. Long-term management of patients is thus more challenging and goes far beyond identification of the correct maintenance dose of corticosteroids. The mortality from adrenal crisis is still high and prevention should be a top priority for endocrinologists. Concepts of replacement therapy as well as patient education and emergency equipment are currently being reassessed. Developments to improve patient care and treatment comprise novel glucocorticoid preparations that are closer to the physiological circadian cortisol profile, a uniform European emergency card and more standardized crisis prevention measures.