A subnormal peak cortisol response to stimulation testing does not predict a subnormal cortisol production rate (original) (raw)
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Universal Journal of Medical Science, 2015
Background and objectives: Hypoglycemia in the body is controlled by counter regulatory hormones. Serum cortisol is one among them not subjected to extensive study, in Type 2 diabetes mellitus cases. Cortisol responses among non diabetics and type 1 diabetics have been studied to a certain extent. The primary objective of our study was to identify the serum cortisol levels in hypoglycemic patients with or without type 2 diabetes and to find out the correlation between the mean cortisol responses in the two groups. Methodology: A total population of 51 symptomatic hypoglycemic patients meeting Whipple's criteria were studied in the ER of a medical college hospital at Kochi. Forty patients were diabetic and 11 non diabetic. Previous history, present illness, comorbidities, medical history and reasons for hypoglycemia were considered. Laboratory investigations on RFT, 7 AM serum cortisol and RBS were made and the results analysed applying standard statistical methods and SPSS II software. Results and discussion: Male female ratio in the diabetic and non diabetic groups was 3:1 and 10:1 respectively. Hypoglycemia was more among males, especially in the diabetic group due to decreased food intake(49%) or concurrent illness(51%), the mean age being 65.7 years in these cases. Hypoglycemia was more frequent in those on sulfonylurea (61.9%), and in habitual insulin users (42.5%). In non diabetic patients, hypoglycemia was caused by renal failure(27.27%), insulinoma(27.27%) or sepsis(18.18%). The mean serum cortisol among the diabetic group was subnormal(17.47), and in the non diabetic group it was 28.56. Age, sex, serum creatinine, GCS, period of stay and condition at discharge showed no correlation with serum cortisol levels. RBS, period of stay and condition at discharge showed no correlation with diabetic status. Conclusion: Diabetic patients with acute symptomatic hypoglycemia demonstrated a subnormal serum cortisol response as compared to non diabetic hypoglycemic patients.
European journal of endocrinology, 2010
Objective: Relative corticosteroid insufficiency may be common in critically ill patients and is associated with a poor outcome; however, the response of the hypothalamic-pituitary-adrenal (HPA) axis in nursed patients is not known. Our aim was to evaluate the response of HPA axis to the severity of illness in non-critically ill nursed (NCIN) patients and the clinical outcome. Subjects and methods: Fifty-six nursed patients who were divided into four groups (stroke, mild disease, sepsis and severe sepsis) as well as a control group (nZ15) were studied. At admission (day 1), cortisol and ACTH were measured and a low-dose (1 mg) corticotrophin test was performed, followed 2 h later by a standard-dose (250 mg) corticotrophin test. Diurnal variation of cortisol was obtained on day 2. A second identical set of low-dose and standard-dose corticotrophin tests were performed on day 5 or 6 (recovery phase). Results: In patients with stroke and severe sepsis, cortisol had the highest values and its diurnal variation was abolished. Dissociation of ACTH and cortisol was found in all patients. The D max of cortisol after the 1-mg corticotrophin test did not differ among the groups, while after the 250-mg corticotrophin test, it was borderline higher in controls. The ratio of responders (D max of cortisol R9 mg/dl) to non-responders after 1-or 250-mg corticotrophin test did not differ among patients and controls. All patients had a good outcome without glucocorticoid treatment. Conclusions: Depending on the severity of illness, mild alterations in the HPA axis occurred. However, relative corticosteroid insufficiency was not confirmed in NCIN patients.
PLOS ONE, 2015
Background Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over-or under-replacement but have been poorly evaluated. Methods Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m 2 /d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients' cortisol AUC in the control range. Results Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients' cortisol AUC to
The Journal of Pediatrics, 2013
Objectives To determine which biological or clinical variables may predict cortisol response to low-dose adrenocorticotropic hormone (ACTH) stimulation following supraphysiological doses of glucocorticoids in children. Study design This retrospective study included all patients who underwent ACTH testing (1 mg) between October 2008 and June 2010 at the Sainte-Justine University Hospital Center, Montreal, after supraphysiological doses of glucocorticoids. Results Data from 103 patients (median age, 8.0 years; range, 0.6-18.5 years; 57 girls) were analyzed, revealing growth deceleration in 37% and excessive weight gain in 33%. Reasons for glucocorticoid treatment included asthma (n = 30) and hematologic (n = 22), dermatologic (n = 19), rheumatologic (n = 16), and miscellaneous (n = 16) disorders. The following information was recorded: duration of glucocorticoid treatment (median, 374 days; range, 5-4226 days); duration of physiological hydrocortisone replacement (median, 118 days; range, 0-1089 days); maximum daily (median, 200 mg/m 2 /day; range, 12-3750 mg/m 2 /day) and cumulative (median, 16 728 mg/m 2 ; range, 82-178 209 mg/m 2) doses, in hydrocortisone equivalents; and interval since the last dose (median, 43 days; range, 1-1584 days). Sixty-two patients (58%) exhibited a normal response (ie, peak cortisol >500 nmol/L) to ACTH stimulation. Peak cortisol level was not related to sex, prior morning cortisol level, duration of treatment, or cumulative glucocorticoid dose; 28% of the patients with normal baseline cortisol levels nevertheless demonstrated a subnormal response to ACTH. Conclusion Given the absence of clinical or biological predictors of the cortisol response to ACTH after suppressive doses of glucocorticoids, physicians have only 2 options: (1) empirically advocate glucocorticoid stress coverage during 18 months after cessation of high-dose glucocorticoid treatment; or (2) perform serial ACTH testing in all such patients until a normal peak cortisol level is attained.
Cortisol correlates with metabolic disturbances in a population study of type 2 diabetic patients
European Journal of Endocrinology, 2006
Objective: The prevalence of type 2 diabetes mellitus is increasing rapidly in industrialized countries, and adrenal glucocorticoids may intensify this disease. We sought to assess the relationship between diabetes-associated metabolic disturbances and cortisol concentrations in patients with type 2 diabetes. Design: We investigated 190 type 2 diabetic patients who volunteered from a population study of 12 430 people in Luebeck and its suburbs. The target population comprised men and women born between 1939 and 1958 who initially received a postal questionnaire about their health status. We identified 346 subjects with confirmed diabetes mellitus and 216 patients participated in the study. Patients with type 1 diabetes were excluded. Methods: Five salivary cortisol samples were collected before and after lunch, in the evening and then the next morning before and after standing. Clinical variables associated with diabetes were measured and correlated with cortisol concentrations. Results: None of the cohort had salivary cortisol concentrations that exceeded the normally accepted range. Based on cortisol samples collected just prior to a standard lunch, the cohort was divided into tertiles. Cortisol was positively related to: fasting blood, urinary and postprandial glucose; glycosylated hemoglobin; and systolic and diastolic blood pressures (all P , 0.05). Cortisol concentrations also correlated with the relative abdominal mass (P , 0.05) when patients with marked glucosuria were excluded. Conclusions: The degree of severity of several clinical measures of type 2 diabetes correlates with cortisol concentrations. Moreover, the results provide evidence for a positive relationship between metabolic disturbances and cortisol concentrations that are within the accepted normal range.
Predicting Recovery Of The Hypothalamic-Pituitary-Adrenal Axis After Prolonged Glucocorticoid Use
Endocrine Practice, 2018
Objective: Prolonged exposure to glucocorticoids lead to hypothalamic-pituitary-adrenal (HPA) axis suppression that recovers after cessation of treatment. We aimed to identify the predictive factors for HPA axis recovery after prolonged glucocorticoid use. Methods: Retrospective review of patients who had undergone first short Synacthen test (SST) to assess HPA axis recovery after prolonged use of glucocorticoids. Results: A total of 61% (20/33) of patients had adequate SST response at a median time of 2 years after diagnosis of adrenal insufficiency. Those who had adequate response during SST had higher ambulatory early morning cortisol (P<.01), shorter duration of exposure to glucocorticoids (P = .01), and lower final cumulative hydrocortisone replacement dose (P = .03). Age, gender, body mass index, indications for glucocorticoid use, and basal adrenocorticotropic hormone levels were not predictive of HPA axis recovery. On multivariate analysis, ambulatory early morning cortisol was the only independent predictor of adequate SST response (odds ratio, 1.02; 95% confidence interval, 1.01 to 1.04; P = .02). Using receiver operating characteristic curve analysis, ambulatory early morning cortisol of 8.8 µg/dL predicted a positive SST response with a sensitivity of 70% and specificity of 93%. Conclusion: Early morning ambulatory cortisol could be used to decide on timely SST in order to prevent complications from unnecessary replacement with glucocorticoids.
Clinical Endocrinology, 2008
Objective The insulin tolerance test (ITT) is the gold standard for assessing GH and cortisol production in pituitary disease. However, areas of uncertainty remain regarding its safety in older people, the optimal duration of the test and its performance in insulin resistant states. Whether basal cortisol concentration can reliably predict an adequate adrenal response to hypoglycaemia remains to be determined.Patients and design We performed a cross-sectional retrospective examination of 197 consecutive patients (mean age 41·8 ± 16·4, range 13–76 years) with pituitary disease who underwent the ITT over 18 months. The standard intravenous insulin dose administered was 0·15 units/kg body weight. Patients with acromegaly or with type 2 diabetes received 0·2 units/kg; those with basal cortisol < 100 nmol/l received 0·1 units/kg.Results Adequate hypoglycaemia (nadir glucose < 2·2 mmol/l) was achieved in 87% of patients, amongst whom 17% did not achieve peak cortisol until 120 min. There were no significant adverse events, even in those ≥ 65 years. Of the 18 patients who had basal cortisol < 100 nmol/l, 78% achieved adequate hypoglycaemia; 29% of those had an adequate peak cortisol response ≥ 500 nmol/l. A receiver operating characteristics curve identified a basal cortisol of ≥ 393 nmol/l to predict a normal peak cortisol response to hypoglycaemia.Conclusions In specialized units, the ITT is safe even in elderly patients and those with hypocortisolaemia. The standard 90-min. cut-off for the ITT misses one in six peak cortisol responses. Some patients with basal cortisol < 100 nmol/l had a normal cortisol response to hypoglycaemia.
Cortisol Levels in Central Adrenal Insufficiency: Light and Shade
Evaluating children or adolescents with central adrenal insufficiency (CAI) is a difficult task in clinical practice, especially in subjects with hypothalamic-pituitary diseases and partial ACTH deficiency, or in those with recent pituitary surgery or brain irradiation when the adrenal cortex may still be responsive to stress. In 2008, a meta-analysis reported a three-step approach for evaluating patients at risk for CAI with no acute illness. In particular, the authors recommended the evaluation of morning cortisol, a low dose ACTH test (LDST) and the “gold standard” insulin tolerance test or metyrapone test if the low LDCT was not diagnostic. Cortisol and ACTH secretion exhibit significant fluctuation throughout the day. The reference ranges supplied by labs are so wide that they only flag up extremely low cortisol levels. Interpreting the results correctly can be difficult for a physician without an experience in adrenal dysfunctions. The lack of uniformity in these cut-off levels could in part be attributed to differences in study populations, variability of dynamic tests, the use of different serum cortisol assays and dissimilar cut-off peak serum cortisol response indicative of a normal axis response and the difference in the clinical context in which the studies were done. Therefore, laboratories have to advertise the need to establish reference values for given populations, both for basal or stimulated hormone levels. Failure to apply this rule may elicit false-positive and more critically, falsenegative results. LDST (1 μg synthetic ACTH as iv bolus with measurement of serum cortisol) has been proposed as a sensitive test for the diagnosis of CAI. However, the advantage of LDST compared with the high dose test may be offset by the technical difficulties inherent to dilution of 250 μg ampoules. Clinical judgement remains imperative especially regarding the use of glucocorticoid supplementation during extreme stress.
Effect of glucocorticoid excess on the cortisol/cortisone ratio
Steroids, 2001
Objective: The conversion of cortisol, which binds avidly to the mineralocorticoid receptor, to cortisone, which no longer has mineralocorticoid function, is predominantly catalyzed by the 11-hydroxysteroid dehydrogenase type 2 (11-HSD 2). It was the objective of the present study to examine the impact of different forms of glucocorticoid excess on the cortisol/cortisone ratio and to differentiate their role in the genesis of hypertension. Design and methods: Plasma cortisol and cortisone levels were determined in 12 adults with Cushing's disease, 12 adults with hypercortisolism due to an adrenal tumor, and 20 healthy volunteers before and after an intravenous ACTH test, using specific radioimmunoassays after automated Sephadex LH 20 chromatography. Results: The cortisol/cortisone ratios were significantly higher in patients with Cushing's disease (13.9 Ϯ 1.1), adrenal tumors (11.5 Ϯ 2.3), and in healthy volunteers after ACTH stimulation (14.1 Ϯ 2.0) than in untreated controls (6.0 Ϯ 0.5) (P Ͻ 0.001, P Ͻ 0.05, and P Ͻ 0.001, respectively). Similar differences were seen for cortisol plasma concentrations, whereas cortisone concentrations did not differ among the groups. Conclusions: Our data suggest that the excessive mineralocorticoid effects in patients with hypercortisolism are inflicted by elevated cortisol/cortisone ratios possibly due to an insufficient conversion of cortisol to cortisone by 11-HSD 2. This may provide a possible explanation for the occurrence of hypertension. This effect seems to be independent of the role of ACTH in the mechanism of hypercortisolism.