Human Corticotropin-Releasing Hormone Test Research Articles

Human Corticotropin-Releasing Hormone Tests: 10 Years of Real-Life Experience in Pituitary and Adrenal Disease.

The human corticotropin-releasing hormone (CRH) test (hCRHtest) is used to differentiate Cushing disease (CD) from ectopic adrenocorticotropin (ACTH) secretion (EAS), to assess autonomous cortisol secretion by the adrenal glands, and to characterize pseudo-Cushing syndrome (CS) or adrenal insufficiency (AI). The main outcome measure of this study was to assess the diagnostic accuracy of the hCRHtest. We measured ACTH and cortisol levels; collected the peak values (peakACTH and peakcortisol), and calculated the percentage increases (∆%ACTH and ∆%cortisol) after an intravenous bolus of 100 μg hCRH. This cross-sectional study of hCRH tests from 2010 to 2019 took place in a referral university hospital center. We enrolled 200 patients: 86 CD, 15 EAS, 18 adrenal CS, 25 mild adrenal autonomous cortisol secretion, 31 pseudo-CS, and 25 suspected AI. The hCRHtest was performed mainly for the differential diagnosis of ACTH-dependent CS or adrenal lesions (P = .048). PeakACTH and peakcortisol were higher in CD, and ∆%ACTH and ∆%cortisol were able to differentiate CD from EAS with a sensitivity and specificity greater than 80%. In patients with low (< 10 pg/mL) or indeterminate (10-20 pg/mL) basalACTH levels, an absent or reduced peakACTH response was able to differentiate adrenal from ACTH-dependent forms. PeakACTH and peakcortisol after hCRHtest were lower in pseudo-CS than in CD, but ∆%ACTH and ∆%cortisol were similar. The role of hCRHtest in patients with AI was limited. The hCRHtest test is the mainstay of the differential diagnosis of ACTH-dependent CS. It is also useful for pointing to a diagnosis of CD in the event of bilateral adrenal masses, and in patients with low basalACTH.

Human corticotropin releasing hormone test performance in the differential diagnosis between Cushing's disease and pseudo-Cushing state is enhanced by combined ACTH and cortisol analysis

Corticotropin releasing hormone (CRH) test does not reliably distinguish Cushing's disease (CD) from normality or pseudo-Cushing state (PC). We assessed whether this could be achieved with a novel approach while preserving the ability of the test to distinguish CD from ectopic ACTH syndrome (EAS). Design Retrospective/prospective study. We studied 51 subjects with CD, 7 with EAS, 26 with PC, and 31 controls (CT). Human CRH (hCRH) test was performed at 0830 h by measuring plasma ACTH and serum cortisol at -15, 0, 15, 30, 45, 60, 90, and 120 min. The area under the curve-ACTH exhibited a significant negative correlation with baseline serum cortisol in CT and PC, but not in CD or EAS patients. ACTH response to hCRH was blunted in PC compared with CT, whereas peak serum cortisol was higher in PC than in CT subjects. These findings suggested that ACTH-dependent Cushing's syndrome can be diagnosed by the presence of two hCRH test parameters and excluded if either or both are absent. Application of i) basal serum cortisol >12 microg/dl and peak plasma ACTH >54 pg/ml, or ii) peak serum cortisol >21 microg/dl and peak plasma ACTH >45 pg/ml, had 91.3% (95% confidence intervals (CI) 81-97.1) and 94.8% (CI 85.6-98.9) sensitivity and 98.2% (CI 90.6-99.9) and 91.2% (CI 80.7-97) specificity respectively, in diagnosing ACTH-dependent Cushing's syndrome. The >14% serum cortisol increase from mean baseline values to the mean of 15 and 30 min values in patients who were positive for the test completely discriminated between CD and EAS. Simultaneous plasma ACTH and serum cortisol analysis enables the hCRH test to distinguish CD from PC and from normality, while preserving its ability to discriminate CD from EAS.

Hypothalamic-pituitary-adrenal axis dysfunction in critically ill patients with traumatic brain injury: incidence, pathophysiology, and relationship to vasopressor dependence and peripheral interleukin-6 levels.

To investigate hypothalamic-pituitary-adrenal axis function in patients requiring mechanical ventilation for traumatic brain injury and to assess the relation of hypothalamic-pituitary-adrenal axis abnormalities with vasopressor dependence and peripheral cytokine levels. Prospective study. General intensive care unit in a university teaching hospital. Forty patients (33 men and 7 women) with moderate to severe traumatic brain injury (mean age, 37 +/- 16 yrs) were studied the day after termination of mechanical ventilation (7-60 days after trauma). First, a morning blood sample was obtained to measure baseline cortisol, corticotropin, interleukin-6, and tumor necrosis factor alpha. Subsequently, 1 microg of synthetic corticotropin was injected intravenously, and 30 mins later, a second blood sample was drawn to determine stimulated plasma cortisol. Based on data derived from healthy volunteers, patients having stimulated cortisol levels <18 microg/dL were defined as nonresponders to the low-dose stimulation test. Thirty-one patients underwent also a human corticotropin releasing hormone test. In traumatic brain injury patients, mean baseline and low-dose stimulation test-stimulated cortisol levels were 17.2 +/- 5.4 microg/dL and 24.0 +/- 6.6 microg/dL, respectively. The median increment in cortisol was 5.9 microg/dL. Basal corticotropin levels ranged from 3.9 to 118.5 pg/mL. Six of the 40 patients (15%) failed the low-dose stimulation test. The human corticotropin releasing hormone test (performed in 26 responders and five nonresponders) revealed diminished cortisol release only in the low-dose stimulation test nonresponder patients. Corticotropin responses to corticotropin releasing hormone were consistent with both primary (three patients) and/or secondary (two patients) adrenal dysfunction. In retrospect, nonresponders to the low-dose stimulation test more frequently required vasopressors (6/6 [100%] vs. 16/34 [47%]; p =.02) and for a longer time interval (median, 0 vs. 293 hrs; p =.006) compared with responders. Furthermore, nonresponders had higher interleukin-6 levels compared with responders (56.03 vs. 28.04 pg/mL; p =.01), whereas tumor necrosis factor alpha concentrations were similar in the two groups (2.42 vs. 1.55 pg/mL; p =.53). Adrenal cortisol secretion after dynamic stimulation is deficient in a subset of critically ill patients with moderate to severe head injury. This disorder is associated with prior vasopressor dependency and higher interleukin-6 levels.

Reference ranges and factors affecting the human corticotropin-releasing hormone test in preterm, very low birth weight infants.

This prospective study aims to investigate the factors that influence the human CRH (hCRH) test and to provide reference ranges for plasma corticotropin (ACTH) and serum cortisol concentrations of the stimulation test in preterm, very low birth weight (VLBW) infants. Two hundred twenty-six hCRH tests were performed on 137 VLBW infants at d 7 and 14 of life. Plasma ACTH did not differ significantly between infants whose mothers did not receive antenatal corticosteroids (group 1) and those whose mothers received one or two doses (group 2) or more than two doses (group 3) of the drug. However, plasma ACTH levels at d 7 were found to be significantly higher in infants with severe lung disease who required intermittent positive-pressure ventilation (IPPV) or high-frequency oscillation ventilation (HFOV), compared with those who had milder pulmonary disease and did not require mechanical ventilation or needed only continuous positive airway pressure (CPAP) support (P < 0.011). A significantly higher rate of increase in plasma ACTH concentration at d 7 was also observed in infants whose mothers suffered from antepartum hemorrhage (P < 0.016). In contrast, infants in group 2 had significantly lower serum cortisol, compared with group 1 infants (P < 0.05), whereas group 3 infants did not have serum cortisol levels significantly different from those of patients in group 1 or 2. Significant positive correlation between serum cortisol at d 7 and the time interval between the last dose of antenatal dexamethasone and delivery was also observed in group 3 infants (r > 0.33, P < 0.045). In addition, infants who required IPPV or HFOV had significantly lower serum cortisol at d 7 (P < 0.0001), but this pattern of cortisol response was reversed on d 14, with infants requiring IPPV or HFOV having significantly higher serum cortisol (P < 0.036). The reference ranges for plasma ACTH and serum cortisol concentrations of the hCRH test at d 7 and 14 were also provided for group 1 and group 2 infants. This study demonstrates that even one or two doses of antenatal corticosteroids cause adrenal suppression in VLBW infants. Maternal antepartum hemorrhage also influences the pituitary response of preterm newborns in the first week of life. The change in the pattern of cortisol response in sick ventilated (IPPV or HFOV) infants during the first 2 wk of life suggests that a proportion of preterm infants may have inadequate adrenal response to stress in early postnatal life, but it is likely that rapid adaptation of the hypothalamic-pituitary-adrenal axis results in enhanced and more appropriate cortisol response by d 14. The percentile distribution of plasma ACTH and serum cortisol responses provides useful statistical reference data for interpretation of the hCRH test in VLBW infants and may also assist in facilitating the use of corticosteroids replacement therapy in cases with clinical manifestations suggestive of adrenal insufficiency.

Prevalence of abnormal adrenocortical function in human immunodeficiency virus infection by low-dose cosyntropin test.

Recent evidence suggests that 10 microg cosyntropin test has higher sensitivity for detecting hypothalamus-hypophysis-adrenal axis (HHA-A) dysfunction. Our objective was to determine prevalence of glucocorticoid insufficiency with the 10 microg cosyntropin test and the level of the HHA-A defect. One hundred and four HIV-infected patients underwent the 10 microg cosyntropin test. In abnormal and borderline respondents, insulin-induced hypoglycaemia test and human corticotropin releasing hormone test were used to confirm and localize the level of the HHA-A defect. Thirty-two patients with HIV infection and 72 with AIDS were identified. Prevalence of glucocorticoid insufficiency by the 10 microg cosyntropin test was 21.2%. By clinical categories, the frequency in AIDS and HIV infection patients was 26.4% and 9.4%, respectively. Confirmed glucocorticoid insufficiency by insulin-induced hypoglycaemia test was found in 16 out of 19 cases. Twelve cases had primary glucocorticoid insufficiency, 7 had secondary glucocorticoid insufficiency and 3 were false positive. In conclusion, adrenocortical dysfunction occurs in approximately 20% of the cases with HIV disease. Clinical findings commonly occurring in HIV disease as well as adrenocortical insufficiency are not reliable indicators for performing adrenocortical laboratory assessment. Our results suggest screening all AIDS patients with the 10 microg cosyntropin test.

Human corticotropin-releasing hormone test in normal subjects and patients with hypothalamic, pituitary or adrenocortical disorders.

Human corticotropin-releasing hormone (hCRH) test was performed in 57 normal volunteers and 102 patients with hypothalamic, pituitary and adrenocortical diseases. Intravenous bolus injection of synthetic hCRH, 100 micrograms for adults or 1.5 micrograms/kg for children, increased plasma ACTH and cortisol levels in about 90% of normal subjects. In 47 patients with Cushing's disease, plasma ACTH tended to show an exaggerated response to hCRH and peak ACTH was the most frequent abnormal component among the several reaction parameters. Poor responders among normal subjects and patients with Cushing's disease had significantly higher plasma cortisol levels before CRH administration. Patients with hypothalamic hypopituitarism showed exaggerated response, whereas patients with primary pituitary lesion, isolated ACTH deficiency or adrenal Cushing's syndrome showed no ACTH response. These differences in the response of patients suggest the value of the hCRH test in their differential diagnosis.