Morning Serum Cortisol May Be Less Accurate for Diagnosing Adrenal Insufficiency in Hospitalized Patients, Particularly Those on Opioids

Abstract Introduction: The positive predictive value of a low morning serum cortisol to diagnose adrenal insufficiency (AI) is reported to be >90%, which is the basis for guidelines recommending morning cortisol as the first-line test for central AI. A level <3 µg/dL is considered diagnostic. However, studies that established this cut-off were conducted primarily in outpatients, not hospitalized patients in whom diurnal variation may be disrupted. Studies suggest that opioids suppress cortisol levels acutely, may disrupt diurnal cortisol rhythm, and cause adrenal insufficiency in 8–50% of chronically-exposed patients. The impact of hospitalization, particularly in the setting of opioid use, on the accuracy of diagnostics for AI is unknown. We hypothesized that low morning cortisol values in hospitalized patients, especially those prescribed opioids, do not accurately diagnose adrenal insufficiency, as determined by corticotropin stimulation test (CST) peak cortisol <18 µg/dL. Methods: We performed a retrospective analysis of CSTs in hospitalized patients in the Mass General Brigham health system from 5/2015 to 9/2020. Opioid-exposed adults who underwent CST were included if they had a morning cortisol (5–9 AM) result. Control patients were matched by age, gender and race and had no opioid prescriptions within 30 days of testing. Patients were excluded if tested in the outpatient or ICU setting, had a history of cirrhosis or pituitary disease, had an elevated ACTH, were prescribed oral estrogen, or received oral, IV or intraarticular glucocorticoids within 30 days. Results: The analysis included 124 opioid-exposed and 322 control patients, mean (±SD) age 60.8±14.4 and 63.8±15.3y, and 55.6% and 45.0% female, respectively. Twenty-two (17.7%) opioid-exposed and 33 (10.2%) control patients were diagnosed with AI by CST (p=0.031). Nineteen opioid-exposed (15.3%) and 22 control (6.8%) patients had morning cortisol of <3 µg/dL (p=0.005). A morning cortisol <3 µg/dL had a positive predictive value of 36.8% (CI 19.1–59.0%) for AI in opioid-exposed and 50.0% (CI 30.7–69.3%) in control patients. In opioid-exposed patients with low morning cortisol levels, mean daily morphine milligram equivalent and duration of opioid exposure did not differ between those with AI confirmed by CST and those with normal CST (p=0.13 and 0.38, respectively). Conclusion: Among hospitalized patients with suspected AI, those prescribed opioids have a higher prevalence of central AI than controls. Serum morning cortisol <3 µg/dL is not an accurate test for AI in hospitalized patients, including those prescribed opioids in whom low morning cortisol is more prevalent than in controls. Given the risks associated with misdiagnosis of AI, caution should be exercised in relying on morning cortisol values for the diagnosis of AI in hospitalized patients.

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Ambient air pollutants are associated with morning serum cortisol in overweight and obese Latino youth in Los Angeles

Environmental Health ◽

10.1186/s12940-021-00713-2 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

C. M. Toledo-Corral ◽

T. L. Alderete ◽

M. M. Herting ◽

R. Habre ◽

A. K. Peterson ◽

...

Keyword(s):

Hpa Axis ◽

Air Pollutants ◽

Latino Youth ◽

Serum Cortisol ◽

Ambient Air ◽

Pubertal Status ◽

Ambient Air Pollutants ◽

Morning Cortisol ◽

Morning Serum Cortisol ◽

Cortisol Levels

Abstract Background Hypothalamic-pituitary-adrenal (HPA)-axis dysfunction has been associated with a variety of mental health and cardio-metabolic disorders. While causal models of HPA-axis dysregulation have been largely focused on either pre-existing health conditions or psychosocial stress factors, recent evidence suggests a possible role for central nervous system activation via air pollutants, such as nitrogen dioxide (NO2), ozone (O3) and particulate matter (PM). Therefore, in an observational study of Latino youth, we investigated if monthly ambient NO2, O3, and PM with aerodynamic diameter ≤ 2.5 (PM2.5) exposure were associated with morning serum cortisol levels. Methods In this cross-sectional study, morning serum cortisol level was assessed after a supervised overnight fast in 203 overweight and obese Latino children and adolescents (female/male: 88/115; mean age: 11.1 ± 1.7 years; pre-pubertal/pubertal/post-pubertal: 85/101/17; BMI z-score: 2.1 ± 0.4). Cumulative concentrations of NO2, O3 and PM2.5 were spatially interpolated at the residential addresses based on measurements from community monitors up to 12 months prior to testing. Single and multi-pollutant linear effects models were used to test the cumulative monthly lag effects of NO2, O3, and PM2.5 on morning serum cortisol levels after adjusting for age, sex, seasonality, social position, pubertal status, and body fat percent by DEXA. Results Single and multi-pollutant models showed that higher O3 exposure (derived from maximum 8-h exposure windows) in the prior 1–7 months was associated with higher serum morning cortisol (p < 0.05) and longer term PM2.5 exposure (4–10 months) was associated with lower serum morning cortisol levels (p < 0.05). Stratification by pubertal status showed associations in pre-pubertal children compared to pubertal and post-pubertal children. Single, but not multi-pollutant, models showed that higher NO2 over the 4–10 month exposure period associated with lower morning serum cortisol (p < 0.05). Conclusions Chronic ambient NO2, O3 and PM2.5 differentially associate with HPA-axis dysfunction, a mechanism that may serve as an explanatory pathway in the relationship between ambient air pollution and metabolic health of youth living in polluted urban environments. Further research that uncovers how ambient air pollutants may differentially contribute to HPA-axis dysfunction are warranted.

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Functional Adrenal Insufficiency among Tuberculosis-Human Immunodeficiency Virus co-infected patients: A Cross-section study in Uganda

10.21203/rs.2.16756/v3 ◽

2020 ◽

Author(s):

Agnes Bwanika Bwanika Naggirinya ◽

Andrew Mujugira ◽

David B. Meya ◽

Irene Andia Biraro ◽

Ezekiel Mupere ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Clinical Signs ◽

Signs And Symptoms ◽

Serum Cortisol ◽

Early Morning ◽

Serum Cortisol Level ◽

Drug Resistant ◽

Morning Serum Cortisol ◽

Cortisol Levels ◽

Clinical Signs And Symptoms

Abstract Objective: Tuberculosis (TB) is the leading cause of adrenal insufficiency in resource-limited settings. The adrenal gland is the most commonly affected endocrine organ in TB infection. We assessed factors associated with functional adrenal insufficiency (FAI) among TB-HIV patients with and without drug-resistance in Uganda. Patients with drug-sensitive and drug-resistant TB were enrolled and examined for clinical signs and symptoms of FAI with an early morning serum cortisol level obtained. FAI was defined as early morning serum cortisol <414 nmol//L. Associations with FAI were modeled using multivariable logistic regression.Results: We screened 311 TB patients and enrolled 272. Of these, 117 (43%) had drug-resistant TB. Median age was 32 years (IQR 18-66) and 66% were men. The proportion with FAI was 59.8%. Mean cortisol levels were lower in participants with drug-resistant than susceptible TB (317.4 versus 488.5 nmol/L; p<0.001). In multivariable analyses, drug-resistant TB (aOR 4.61; 95% CI: 2.3-9.1; p<0.001), treatment duration > 1 month (aOR 2.86; 95% CI: 1.4-5.5; p=0.002) and abdominal pain (aOR 2.06; 95% CI: 1.04-4.09; p=0.038) were significantly associated with FAI. Early morning serum cortisol levels should be quantified in TB-HIV co-infected patients with drug-resistant TB.

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Functional Adrenal Insufficiency among Tuberculosis-Human Immunodeficiency Virus co-infected patients: A Cross-section study in Uganda

10.21203/rs.2.16756/v2 ◽

2020 ◽

Author(s):

Agnes Bwanika Bwanika Naggirinya ◽

Andrew Mujugira ◽

David B. Meya ◽

Irene Andia Biraro ◽

Ezekiel Mupere ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Adrenal Insufficiency ◽

Multivariable Analysis ◽

Serum Cortisol ◽

Early Morning ◽

Serum Cortisol Level ◽

Drug Resistant ◽

Immunodeficiency Virus ◽

Morning Serum Cortisol ◽

Cortisol Levels

Abstract Objective Tuberculosis (TB) is the leading cause of adrenal insufficiency in resource-limited settings. The adrenal gland is the most commonly affected endocrine organ in TB infection. We assessed prevalence and factors associated with functional adrenal insufficiency (FAI) among human immunodeficiency virus (HIV)-infected patients with drug-resistant and drug-susceptible TB in Uganda. Patients with drug-sensitive and -resistant TB were enrolled, examined for clinical signs and symptoms of FAI with an early morning serum cortisol level obtained. FAI was defined as early morning serum cortisol <414 nmol//L. Associations with FAI were modeled using multivariable logistic regression. Results : A total of 311 TB patients were screened, and 272 enrolled. Of these, 117 (43%) had drug-resistant TB. Median age was 32 years (IQR 18-66) and 66% were men. Prevalence of FAI was 59.8%. Mean cortisol levels were lower in participants with drug-resistant than susceptible TB (317.4 versus 488.5 nmol/L; p<0.001 ) . In multivariable analysis, drug-resistant TB (aOR 4.61; 95% CI: 2.3-9.1; p < 0.001), treatment duration > 1month (aOR 2.86 95% CI: 1.4- 5.5; p=0.002) and abdominal pain (aOR 2.06; 95% CI: 1.04-4.09; p=0.038) were significantly associated with FAI. Early morning serum cortisol levels should be quantified in TB-HIV co-infected patients.

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An approach to stress assessment during hunting: Cortisol levels of wild boar (Sus scrofa) during drive hunts

10.1101/2020.03.11.987628 ◽

2020 ◽

Author(s):

Justine Güldenpfennig ◽

Marion Schmicke ◽

Martina Hoedemaker ◽

Ursula Siebert ◽

Oliver Keuling

Keyword(s):

Wild Boar ◽

Cortisol Level ◽

Age Groups ◽

Serum Cortisol ◽

Well Being ◽

Lower Saxony ◽

Pregnant Females ◽

Wildlife Species ◽

Cortisol Levels ◽

The Impact

AbstractOnly little is known about the effect of stress (both short-term and long-term) on wildlife species. To get an idea of stress in wildlife, we investigated the cortisol level of wild boar during drive hunts in Lower Saxony, Germany. Cortisol as one of the main stress hormone in mammals is considered to have negative impacts on the animal’s well-being if expressed excessively (repeatedly over a longer period). We analysed serum cortisol levels of 115 samples using a radioimmunoassay and compared sampling month, hunting grounds, age classes and sexes, as well as possible correlations between cortisol level and weight and pregnancy status of female wild boar. We found that cortisol levels during these drive hunts exhibit wide variation. The mean cortisol level was 411.16 nmol/L with levels ranging from 30.60 nmol/L (minimum) to 1,457.92 nmol/L (maximum). Comparing age groups and sexes, we found significant differences between the sexes, with females having a higher cortisol levels than males. After grouping age groups and sexes together, we also found significant differences based on the age-sex group. We found no correlation between cortisol levels and weight, but significantly higher cortisol levels in pregnant females compared to non-pregnant females. No differences were found between sampling months and locations, respectively. These results show the impact of drive hunts on stress in wild boar; nevertheless, this impact of drive hunts as performed in most parts of Central Europe seems to be not as high as imagined. Still, we need more information about cortisol levels and stress in (hunted) wildlife species.

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ICD-10 codes are a valid tool for identification of pneumonia in hospitalized patients aged ⩾65 years

Epidemiology and Infection ◽

10.1017/s0950268807008564 ◽

2007 ◽

Vol 136 (2) ◽

pp. 232-240 ◽

Cited By ~ 65

Author(s):

S. A. SKULL ◽

R. M. ANDREWS ◽

G. B. BYRNES ◽

D. A. CAMPBELL ◽

T. M. NOLAN ◽

...

Keyword(s):

Positive Predictive Value ◽

Negative Predictive Value ◽

Medical Record ◽

Chest Radiograph ◽

Predictive Value ◽

Hospitalized Patients ◽

Radiology Reports ◽

Cohort Design ◽

Icd 10 ◽

Symptoms And Signs

SUMMARYThis study examines the validity of using ICD-10 codes to identify hospitalized pneumonia cases. Using a case-cohort design, subjects were randomly selected from monthly cohorts of patients aged ⩾65 years discharged from April 2000 to March 2002 from two large tertiary Australian hospitals. Cases had ICD-10-AM codes J10–J18 (pneumonia); the cohort sample was randomly selected from all discharges, frequency matched to cases by month. Codes were validated against three comparators: medical record notation of pneumonia, chest radiograph (CXR) report and both. Notation of pneumonia was determined for 5098/5101 eligible patients, and CXR reports reviewed for 3349/3464 (97%) patients with a CXR. Coding performed best against notation of pneumonia: kappa 0·95, sensitivity 97·8% (95% CI 97·1–98·3), specificity 96·9% (95% CI 96·2–97·5), positive predictive value (PPV) 96·2% (95% CI 95·4–97·0) and negative predictive value (NPV) 98·2% (95% CI 97·6–98·6). When medical record notation of pneumonia is used as the standard, ICD-10 codes are a valid method for retrospective ascertainment of hospitalized pneumonia cases and appear superior to use of complexes of symptoms and signs, or radiology reports.

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The impact of HIV-related neuropsychological dysfunction on driving behavior

Journal of the International Neuropsychological Society ◽

10.1017/s1355617700677111 ◽

2000 ◽

Vol 6 (7) ◽

pp. 854-854 ◽

Cited By ~ 5

Author(s):

THOMAS D. MARCOTTE ◽

ROBERT K. HEATON ◽

TANYA WOLFSON ◽

MICHAEL J. TAYLOR ◽

OMAR ALHASSOON ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Positive Predictive Value ◽

Predictive Value ◽

Visual Inspection ◽

Driving Behavior ◽

Personality Change ◽

Impaired Consciousness ◽

Neuropsychological Dysfunction ◽

Gcs Score ◽

The Impact

The following is a correction for an error that occurred in the Journal of the International Neuropsychological Society, Vol. 6, No. 3. The error occurred in the article titled “Personality change disorder in children and adolescents following traumatic brain injury,” pp. 279–289, by Max et al. On page 285, under the subheading “Injury Factors,” beginning with the second sentence in the first paragraph, the statement should read:Visual inspection of the distribution of PC relative to lowest post-resuscitation GCS scores revealed that a cut-off of lowest post-resuscitation GCS score of 4 or less versus more than 4 yielded a sensitivity for a diagnosis of persistent PC of 9/14 (64.3%), specificity of 18/23 (78.3%), and a positive predictive value of 0.64 (9.14).A cut-off of duration of impaired consciousness of 100 hr or less versus more than 100 hr yielded a sensitivity for a diagnosis of persistent PC of 11/14 (78.6%), specificity of 20/23 (87.0%), and a positive predictive value (PPV) of 0.79 (11/14).

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False‐Positive Gonorrhea Test Results with a Nucleic Acid Amplification Test: The Impact of Low Prevalence on Positive Predictive Value

Clinical Infectious Diseases ◽

10.1086/381895 ◽

2004 ◽

Vol 38 (6) ◽

pp. 814-819 ◽

Cited By ~ 34

Author(s):

Alan R. Katz ◽

Paul V. Effler ◽

Roy G. Ohye ◽

Barbara Brouillet ◽

Maria Veneranda C. Lee ◽

...

Keyword(s):

Nucleic Acid ◽

Positive Predictive Value ◽

Predictive Value ◽

False Positive ◽

Nucleic Acid Amplification Test ◽

Nucleic Acid Amplification ◽

Test Results ◽

Low Prevalence ◽

The Impact

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Investigating the impact of disease and health record duration on the eMERGE algorithm for rheumatoid arthritis

Journal of the American Medical Informatics Association ◽

10.1093/jamia/ocaa014 ◽

2020 ◽

Vol 27 (4) ◽

pp. 601-605

Author(s):

Vanessa L Kronzer ◽

Liwei Wang ◽

Hongfang Liu ◽

John M Davis ◽

Jeffrey A Sparks ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Positive Predictive Value ◽

Negative Predictive Value ◽

Predictive Value ◽

Index Date ◽

Model Performance ◽

Area Under The Curve ◽

Population Based ◽

Health Record ◽

The Impact

Abstract Objective The study sought to determine the dependence of the Electronic Medical Records and Genomics (eMERGE) rheumatoid arthritis (RA) algorithm on both RA and electronic health record (EHR) duration. Materials and Methods Using a population-based cohort from the Mayo Clinic Biobank, we identified 497 patients with at least 1 RA diagnosis code. RA case status was manually determined using validated criteria for RA. RA duration was defined as time from first RA code to the index date of biobank enrollment. To simulate EHR duration, various years of EHR lookback were applied, starting at the index date and going backward. Model performance was determined by sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve (AUC). Results The eMERGE algorithm performed well in this cohort, with overall sensitivity 53%, specificity 99%, positive predictive value 97%, negative predictive value 74%, and AUC 76%. Among patients with RA duration <2 years, sensitivity and AUC were only 9% and 54%, respectively, but increased to 71% and 85% among patients with RA duration >10 years. Longer EHR lookback also improved model performance up to a threshold of 10 years, in which sensitivity reached 52% and AUC 75%. However, optimal EHR lookback varied by RA duration; an EHR lookback of 3 years was best able to identify recently diagnosed RA cases. Conclusions eMERGE algorithm performance improves with longer RA duration as well as EHR duration up to 10 years, though shorter EHR lookback can improve identification of recently diagnosed RA cases.

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Adrenal Insufficiency in the Critically Ill Trauma Population

The American Surgeon ◽

10.1177/000313480607200501 ◽

2006 ◽

Vol 72 (5) ◽

pp. 373-376 ◽

Cited By ~ 6

Author(s):

T.A. Gannon ◽

R.C. Britt ◽

L.J. Weireter ◽

F.J. Cole ◽

J.N. Collins ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Critically Ill ◽

Serum Cortisol ◽

Total Serum ◽

Trauma Patients ◽

Total N ◽

Trauma Population ◽

Number Of Patients ◽

Low Cortisol ◽

The Impact

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.

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