Prevalence Of Adrenal Insufficiency Research Articles

Low dose adrenocorticotropic hormone test and adrenal insufficiency in critically ill acquired immunodeficiency syndrome patients

Context:Prevalence of adrenal insufficiency (AI) is not uncommon in HIV infected population. However, AI is rarely diagnosed in clinical practice because many patients have non-specific symptoms and signs. Critical illness in such patients further complicates the evaluation of adrenal function. A 1μgm ACTH test can be used for diagnosis, since it results in more physiological levels of ACTH. A serum cortisol of <18 μg/dL, 30 or 60-minutes after ACTH test has been accepted as indicative of AI, but many experts advocate the normal cortisol response should exceed 25 μg/dL, in critically ill patients.Aim:To determine the prevalence of AI in critically ill AIDS patients, by using 1 μg ACTH test and also, to compare the diagnostic criteria for adrenal insufficiency between cortisol response of <18 μg/dL and <25 μg/dL.Settings and Design:This prospective study was done in the Department of Medicine.Materials and Methods:After taking blood for basal plasma cortisol from AIDS affected fifty adult men and women aged over 18 yrs, 1 μg ACTH was given intravenously, and blood samples were again collected at 30 and 60 minutes for plasma cortisol estimation.Statistical analysis:It was done by Mann-Whitney test.Results:Prevalence of AI was 74% (37 patients) and 92% (46 patients), when the peak stimulated cortisol level of <18 μg/dL and <25 μg/dL, respectively, was used.Conclusion:AI is more prevalent in critically ill AIDS patients. Hence, this test can be performed for early intervention and better management.

Baseline and Stimulated Cortisol Levels in Preterm Infants: Is There Any Clinical Relevance?

Background/Aim: To evaluate the association between the cortisol levels and clinical outcomes in preterm infants. Methods: Baseline adrenocorticotropic hormone (ACTH) and cortisol levels and ACTH-stimulated cortisol concentrations after low-dose synthetic ACTH (Synacthen®, 1 µg/kg) were measured in preterm infants <37 weeks of gestational age between the 5th and 7th days of life. Associations between cortisol concentrations and clinical outcomes were examined. The prevalence and prognostic utility of relative adrenal insufficiency (AI) were assessed. Results: Ninety-eight preterm infants were enrolled. Median baseline cortisol and ACTH levels were 13.7 µg/dl (25th-75th percentile, 9.7-21.1 µg/dl) and 11.5 pg/ml (25th-75th percentile, 6.9-22.6 pg/ml), respectively. Median peak cortisol level after ACTH stimulation was 33.6 µg/dl (25th-75th percentile, 27.2-40.2 µg/dl). The prevalence of relative AI, defined as baseline cortisol <15 µg/dl or Δ-cortisol <9 µg/dl, was 65%. Cortisol levels at baseline and at all time points during the test and relative AI were not associated with mortality or any other clinical outcomes. Conclusion: Neither baseline nor ACTH-stimulated cortisol levels were associated with clinical outcomes in preterm infants. A significant proportion of preterm infants hospitalized in the neonatal unit fulfilled the criteria for relative AI; however, relative AI did not affect outcome.

What Predicts Adrenal Insufficiency in Patients with Thalassemia Major?

Abstract 5299 Background:Thalassemia is one of the most common genetic blood disorders worldwide. With recent improvements in medical therapy, patients with transfusion-dependent thalassemia, i.e., thalassemia major, are living longer. As a result, there is a greater need to address endocrine complications related to chronic iron overload. Adrenal insufficiency (AI), in particular, is important to identify because therapies are available and can be life-saving. Objectives:The objectives of this study are to determine the prevalence of AI in our population of subjects with thalassemia major; to identify risk factors that predict AI in these individuals; and to localize the origin of the AI within the hypothalamic-pituitary-adrenal (HPA) axis. Methods:This is a prospective study of individuals with thalassemia major with an enrollment goal of 30 subjects. All subjects enrolled were initially tested for AI using a glucagon stimulation test. Those found to have AI (stimulated cortisol <18 mcg/dL) subsequently underwent an ovine corticotrophin-releasing hormone (oCRH) stimulation test for confirmatory purposes and to define the physiological basis for the AI. Results:Eleven subjects (8 - 29 years old, 6 female) have been enrolled to date. In our population of patients with TM, the prevalence of AI was 55%. There was no correlation between age, number of years transfused, or ferritin levels and AI. All male patients failed the glucagon stimulation test, whereas 5 of 6 females passed the glucagon stimulation test, p = 0.0024. There was no correlation between 8 AM ACTH levels and 8 AM cortisol levels. There was a significant correlation (p = 0.025) between 8 AM cortisol level and peak cortisol level following glucagon stimulation testing. Of the six subjects with AI, two subjects subsequently failed the oCRH stimulation test (peak cortisol < 21.9 mcg/dL). In these two subjects, peak oCRH ACTH levels were elevated, 144 and 164 pg/mL, respectively, suggesting primary adrenal insufficiency. Conclusions:We conclude that 8 AM cortisol level is a good predictor of adrenal insufficiency in our population, and can potentially be used as a simple screening test for AI with a strong negative predictive value. There appears to be a male predominance of AI in our population. This may indicate a protective role of female sex in this population. Two subjects had classic primary AI with robust ACTH levels in the face of inadequate cortisol production following oCRH testing. Four subjects (all males) who failed the glucagon stimulation test subsequently demonstrated normal ACTH and cortisol response to oCRH, indicating a possible hypothalamic origin to their AI. This dysfunction is likely independent of iron overload and warrants further investigation. Alternatively, these subjects may have impaired sympathetic nervous system function leading to hypoglycemic unawareness. Both outcomes are novel to the field and of medical significance. Disclosures:Geffner:Daiichi- Sankyo: Steering Committee for Clinical Trial; Eli Lilly, Inc.: Research Contract; Endo Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ipsen: Data Safety Monitoring Board and Research Contract; Novo Nordisk: Research Funding; Pfizer, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Free Cortisol and Accuracy of Total Cortisol Measurements in the Diagnosis of Adrenal Insufficiency in Brain-dead Patients

After brain death, adrenal insufficiency (AI) is very common and may be one of the mechanisms that contributes to hemodynamic instability and loss of potential organ donors. However, when diagnosed by total cortisol measurement, critically ill patients may be overdiagnosed as having AI. The aims of this study were to assess the prevalence of AI when diagnosed using free cortisol measurement and the accuracy of total cortisol measurement to diagnose AI in brain-dead patients. All consecutive brain-dead patients were included in this single-center noninterventional clinical observation study. Assessment of adrenocorticotropin, corticosteroid-binding globulin, baseline and tetracosactin-stimulated serum free and total cortisol concentrations were performed. AI was defined as a baseline free cortisol concentration ≤ 55 nM(-1) and/or Δ free cortisol ≤ 55 nM(-1). Patients were considered to have a low albumin concentration if less than 25 g · L(-1) and a low corticosteroid-binding globulin concentration if less than 27 mg · L(-1) in men or 31 mg · L(-1) in women. Among the 42 included patients, the incidence of AI was 83% (95% CI, 69-93%). Baseline total cortisol was correlated with baseline free cortisol, whatever the albumin or corticosteroid-binding globulin concentration. The area under the receiver operating characteristic curve of baseline total cortisol measurement to diagnose AI was 0.94 (95% CI, 0.81-0.98). The optimal cutoff was 485 nM(-1), providing a sensitivity and a specificity of 89% and 100%, respectively. Total baseline cortisol measurement is accurate and sufficient to diagnose AI in brain-dead patients, even if albumin or corticosteroid-binding globulin concentrations are low.

Characterising adrenal function using directly measured plasma free cortisol in stable severe liver disease

Adrenal insufficiency (AI) has been reported in patients with advanced liver disease. Diagnosing AI is problematic owing to controversies in using total serum cortisol as a measure of adrenal function. No published data exist on directly measured plasma free cortisol (PFC) in patients with liver disease. This prospective study compared serum total and measured plasma free cortisol to evaluate adrenal function in clinically stable cirrhotic patients and healthy controls. Cortisol levels were measured at baseline and following 250 μg corticotrophin. AI was defined by total cortisol increments (delta cortisol) of less than 250 nmol/L, or a peak total cortisol under 500 nmol/L after cosyntropin. We used a peak plasma free cortisol concentration of 33 nmol/L as the threshold for AI. Forty-three consecutive patients and 10 healthy controls were studied. Cirrhotic patients had significantly lower peak (526 vs. 649 nmol/L, p=0.004) and delta total cortisol (264 vs. 397 nmol/L, p = 0.002) responses compared to healthy controls. However, basal plasma free cortisol was higher in patients (10.9 vs. 6.4 nmol/L, p = 0.03), and there were no differences in peak plasma free cortisol (p = 0.69) between the two groups. The prevalence of AI using total cortisol criteria was 58% compared to 12% using free cortisol (p<0.001). In patients with stable severe liver disease, a significant discrepancy exists between the rates of diagnosis of AI using the total and free cortisol criteria. We would advise caution in the interpretation of adrenal function testing using total cortisol measurements in this group.

Prevalence of Adrenal Insufficiency Following Systemic Glucocorticoid Therapy in Infants With Hemangiomas

Prevalence of Adrenal Insufficiency Following Systemic Glucocorticoid Therapy in Infants With Hemangiomas

Prevalence of Adrenal Insufficiency Following Systemic Glucocorticoid Therapy in Infants With Hemangiomas

Prevalence of Adrenal Insufficiency Following Systemic Glucocorticoid Therapy in Infants With Hemangiomas

Adrenal Insufficiency in the Elderly: A Nationwide Study of Hospitalizations in Taiwan

Adrenal insufficiency (AI), a life-threatening disorder, usually starts with variable nonspecific symptoms and signs of poor appetite, fatigue, fever, and gastrointestinal discomfort, and may progress to adrenal crisis with complications of electrolyte imbalance, change of consciousness or even shock. Epidemiological data about AI in the elderly population are limited. Based on nationwide hospitalization datasets in Taiwan, we retrospectively analyzed the annual incidence of AI among the elderly population (> or = 60 years old), as well as co-morbidities. The prevalence of AI increased from 6.5/10(5) (n = 1,293) in 1996 to 20.8/10(5) (n = 4,681) in 2007. In 2006, AI was newly diagnosed in 3,494 patients (1,701 women and 1,793 men), which represented an incidence of 15.5/10(5) in the whole population. Nearly four fifths (1,349 women and 1,429 men) of the patients were 60 years old and over, corresponding to an incidence of 92.4/10(5) in the elderly population. The most common co-morbidities were pneumonia (8.6%, n = 238) and urinary tract infections (6.9%, n = 193). Within the one-year observation after discharge, pneumonia was also the most frequent diagnosis in subsequent hospitalizations; besides, 178 (6.5%) patients died in the hospital and the common causes of death were respiratory failure (n = 34), septicemia (n = 23), pneumonia (n = 16), and chronic obstructive pulmonary disease (n = 9). In conclusion, the majority of the elderly have co-morbidities when AI was initially diagnosed. Infectious and pulmonary diseases as the most common co-morbidities also play a major role in subsequent hospitalizations and in-hospital deaths.

Inhaled Corticosteroids and Adrenal Insufficiency

Adrenal insufficiency (AI) is a potentially life-threatening condition. It is known that high doses of inhaled corticosteroids (ICS) can induce systemic adverse effects. Currently, there are no data on the prevalence of AI associated with the use of ICS. This study aimed to investigate the prevalence and clinical presentation of AI (associated or not associated with exogenous Cushing's syndrome) in patients who were prescribed ICS by French physicians during the period 2000-5. All metropolitan French paediatricians, endocrinologists, pulmonologists and intensive care physicians (n = 11 783) were mailed questionnaires requesting information regarding cases of AI associated or not associated with exogenous Cushing's syndrome between 2000 and 2005. Data collected included patient demographics, oral corticosteroid or ICS used during the year preceding the diagnosis of AI, underlying condition(s), concomitant treatment(s), presenting clinical signs and symptoms, results of laboratory investigations and outcome. The French pharmacovigilance database was screened for spontaneous reports to determine the frequency of AI associated with the use of ICS, using the capture-recapture method. Forty-six cases of AI were identified. Twenty-three cases presented with clinical symptoms of AI alone and 23 with exogenous Cushing's syndrome. ICS prescribed were fluticasone propionate (n = 24), budesonide (n = 12) and beclometasone dipropionate (n = 5). In 82% (n = 32) of cases for which data were available, ICS were prescribed at high doses. A potential drug interaction was found in 12 cases. Thirteen cases of AI were identified in the French pharmacovigilance database, one of which was common with the questionnaire survey. The capture-recapture method provided an estimation of 598 (95% CI 551, 648) cases of AI associated with the use of ICS for the 2000-5 period in France. The results of this study confirm the occurrence of adrenal insufficiency in patients treated with ICS. Although the prevalence of ICS-induced AI reported in this study is low, the likelihood of under-diagnosis underlines the need to consider this risk in patients when prescribing these drugs.

Adrenal insufficiency in early phase of pediatric acute lung injury/acute respiratory distress syndrome

Introduction Adequate adrenal function is essential to survive critical illness. Several recent articles have reported the significant effect of adrenal insufficiency (AI) in patients with sepsis. However, the prevalence of AI in pediatric acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is so far still scanty. Thus, we elected to study its prevalence and its clinical outcome. Methods This is a cross-sectional observational study. We enrolled eligible infants and children aged between 1 month and 15 years who were admitted to our tertiary pediatric intensive care unit from February 1, 2005, to December 31, 2005, with ALI or ARDS diagnosed by the American-European Consensus criteria. A short corticotropin stimulation test (250 μg) was done within 24 hours of enrollment, and all clinical data were also recorded. Cortisol levels were measured at baseline, 30 minutes, and 60 minutes posttest. Adrenal insufficiency was defined as a baseline cortisol level of less than 15.1 μg/dL or an increment of cortisol level of less than 9 μg/dL after the adrenocorticotropic hormone stimulation test. Results Of 507 patients admitted to the pediatric intensive care unit, there were 20 diagnosed with ALI/ARDS. Of 20 children, 16 met the inclusion criteria and had none of the exclusion criteria. Of 16, there were 9 (56%) with ARDS, and 7 (44%) of 12 had ALI. The prevalence of AI was observed in 37.5% (6/16), diagnosed by baseline level criteria in 25% (4/16) and by incremental criteria in 12.5% (2/16). The Baseline level of the adrenocorticotropic hormone was 7.8 ± 5 (nmol/L). The median age in the AI group was 2 months. Of 6 children, 5 (83.3%) were in the ARDS group. Pediatric Risk of Mortality III score was significantly higher in the AI group compared with that in the non-AI ( P < .05). Initial Pa o 2/fraction of inspired oxygen ratio tended to be lower in the AI group (123.2 ± 62.2) compared with that in the non-AI group (183.8 ± 79.1), although not statistically significant ( P = .1). The mortality was also not statistically different between the AI (1/6, 16.7%) and the non-AI groups (1/10, 10%). Conclusions Our study demonstrated that the prevalence of AI was common in pediatric ALI/ARDS. These results would be an initial step to further study the impact of AI on clinical outcomes of these children in a larger scale.

Adrenal Insufficiency in the Critically Ill Trauma Population

Acute adrenal insufficiency has been demonstrated in a number of patients with shock. This study was designed to evaluate the rate of occult adrenal insufficiency in the critically ill trauma population and to determine the impact of hypoproteinemia on the use of random cortisol levels as a marker for adrenal insufficiency. Forty-four patients were prospectively enrolled on admission to the trauma intensive care unit, with three excluded, for a total n of 41. Random total serum cortisol and albumin levels were drawn on hospital Days 1, 4, 8, and 14. Occult adrenal insufficiency was defined as a cortisol less than 25 mcg/dL in the setting of an albumin greater than 2.5 g/dL. The prevalence of cortisol less than 25 mcg/dL ranged from 51 to 81 per cent during the study period, and peaked on Days 4 and 8. Albumin 2.5 g/dL or less ranged from 37 to 60 per cent, and this prevalence also peaked on Days 4 and 8. The patients with a low albumin had a high prevalence of low cortisol, ranging from 67 to 100 per cent. The prevalence of adrenal insufficiency, with low cortisol and normal albumin, ranged from 41 to 82 per cent during the study period. None of our patients with occult adrenal insufficiency were treated with steroids, which was a decision made by the treating physicians. Among the patients with occult adrenal insufficiency, survival was 100 per cent. Occult adrenal insufficiency is common in critically ill trauma patients, and is a dynamic entity that can be acquired and even resolved during critical illness. Random cortisol of 25 mcg/dL may actually not be an adequate marker of occult adrenal insufficiency. Low albumin predicts a low cortisol. Hemodynamically stable occult adrenal insufficiency should not be treated with steroid replacement in the critically ill trauma patient, as survival in our series was 100 per cent without replacement.

Cortisol levels in patients with severe community-acquired pneumonia

To evaluate cortisol levels and prevalence of adrenal insufficiency in patients with severe community-acquired pneumonia (CAP). Retrospective cohort study in a 24-bed medical-surgical intensive care unit (ICU). Forty patients with severe CAP admitted to the ICU from March 2003 and May 2005. Random cortisol levels were measured up to 72 h after ICU admission. A threshold of 20 microg/dl was considered for the diagnosis of adrenal insufficiency. Median cortisol levels were 15.5 microg/dl (IQR 10.8-25.1), and 26 patients (65%) met the criteria for adrenal insufficiency. Other cutoff levels of cortisol were evaluated, and 30 patients (75%) had cortisol levels below 25 microg/dl and 19 (47.5%) had cortisol levels below 15 microg/dl. When only patients with septic shock (n=19) were evaluated, 12 (63%) had adrenal insufficiency. Relative adrenal insufficiency occurs in a high proportion of patients with severe CAP. This finding highlights the importance of measuring cortisol levels and may help explain the potential benefits of hydrocortisone infusion in these patients.

Survey of oral hydrocortisone utilization in Madrid (Spain)

A progressive 69% increase in sales of hydrocortisone tablets was observed in Spain from 1988 to 1995. But there were no data suggesting an increase in the number of adrenal insufficiency cases. We aimed to assess the hydrocortisone prescription habits of physicians in 1996 in Madrid (Spain). An anonymous mail questionnaire was sent to 6130 randomly selected physicians (3345 generalists and 2785 specialists) of Madrid. Five hundred and forty-six questionnaires (8.8%) were returned. Three hundred and eighteen physicians (58.2%) sometimes prescribed oral hydrocortisone. 70.8% of these physicians prescribed hydrocortisone for chronic adrenal insufficiency, 17.3% for acute adrenal insufficiency, 7.9% for congenital adrenal hyperplasia, and 30.2% for inflammatory diseases (asthma, allergic diseases, urticaria, rheumatic diseases, ulcerative colitis). Prescription for inflammatory diseases was more frequent in male physicians, physicians older than 40 years, and general practitioners. We can conclude that the main indication for hydrocortisone prescription was chronic adrenal insufficiency but there was a significant number of physicians that used the drug in inflammatory diseases. As a drastic increase in prevalence of adrenal insufficiency seems unlikely, the augmentation in sales of hydrocortisone could be explained by its prescription for other pathologies.

Adrenocortical function in patients with macrometastases of the adrenal gland.

Metastases of the adrenal gland are a frequent finding in patients with malignant tumors like bronchogenic carcinoma or breast cancer. Only limited and conflicting data on adrenocortical function in these patients are available. Cross-sectional study. We investigated the impact of adrenal macrometastases on adrenocortical function in a series of 28 tumor patients using the ACTH(1-24) stimulation test and dexamethasone suppression test. Seven normal controls (Con), eleven patients without adrenal metastases (No Met), eight patients with unilateral (Uni Met) and nine patients with bilateral adrenal metastases (Bil Met) were investigated. The prevalence of adrenal insufficiency was low in our study population, with only two of nine patients with bilateral metastases having subclinical adrenocortical insufficiency. In the remaining patients with uni- or bilateral metastases, baseline and stimulated cortisol concentrations were higher than in controls and cancer patients without metastases (baseline cortisol (in nmol/l): Con: 307+/-33.2 vs Uni Met: 440+/-53.5, and Bil Met: 637.6+/-92.1, P=0.04 by ANOVA; cortisol 60 min after ACTH(1-24): Con: 794.6+/-41.2 vs Uni Met: 990.8+/-92.9, and Bil Met: 1151.4+/-155.5, P=0.03 by ANOVA). Simultaneously, baseline and stimulated serum aldosterone concentrations were significantly blunted in the tumor groups. Adrenal insufficiency is infrequent and develops only in patients with bilateral metastases. However, the majority of patients have activation of the hypothalamic-pituitary-adrenal axis despite adrenal metastases with strongly elevated cortisol concentrations.