cosyntropin and Adrenal-Insufficiency

Adrenal insufficiency can result in significant patient morbidity and mortality, but due to the range of symptoms and variable clinical course and etiologies, it can be a challenging condition to diagnose and manage.. This narrative review will discuss the evaluation of an adult patient at risk for a new diagnosis of adrenal insufficiency and the management of a patient with known or suspected adrenal insufficiency.. A new presentation of adrenal insufficiency can range from nonspecific, minor symptoms including fatigue, to a life-threatening adrenal crisis with hemodynamic instability. Due to the variety of signs and symptoms, the diagnosis is often missed. Those with known adrenal insufficiency are at risk for adrenal crisis, which may occur due to a variety of triggers. Initial evaluation includes assessment for the underlying etiology or concomitant condition, laboratory analysis, and imaging, when clinically indicated. Although not necessary for evaluation in the emergency department setting, the diagnosis is confirmed by specific testing such as the cosyntropin stimulation test. The mainstay of treatment in adrenal crisis is hydrocortisone, intravenous fluid, glucose repletion, and treatment of the underlying acute trigger.. Emergency clinicians must be prepared to recognize, evaluate, and manage those with known or suspected adrenal insufficiency or adrenal crisis.

Topics: Acute Disease; Adrenal Insufficiency; Adult; Cosyntropin; Emergency Service, Hospital; Glucose; Humans; Hydrocortisone

Adrenal insufficiency is a rare disease characterized by cortisol deficiency. The evaluation of patients suspected of having adrenal insufficiency can be challenging because of the rarity of the disease and limitations in the biochemical assessment of the cortisol status by either basal or dynamic testing [adrenocorticotropic hormone (ACTH) stimulation test]. Prompt and adequate diagnosis is of paramount importance to avoid adverse outcomes. We aimed to summarize the recent developments in the conduction and interpretation of the ACTH stimulation test for the diagnosis of adrenal insufficiency.. The ACTH stimulation test is commonly performed in patients suspected of having adrenal insufficiency when the basal serum cortisol levels are inconclusive. Recent literature has evaluated the impact of technical aspects such as time of the day the test is performed, type of assay and sample source used for cortisol measurement on the clinical value of this test, as well as the feasibility of reliable low dose ACTH testing.. Clinicians evaluating patients with suspected adrenal insufficiency should take into consideration the clinical presentation (likelihood of adrenal insufficiency before testing) when interpreting the results of the ACTH stimulation test and be aware of clinical and technical factors that can affect cortisol values and diagnostic accuracy of this test.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Blood Chemical Analysis; Cosyntropin; Diagnosis, Differential; Humans; Hydrocortisone; Pituitary-Adrenal Function Tests; Predictive Value of Tests; Risk Factors

Adrenal insufficiency in pregnancy, although relatively rare, has significant clinical implications on both maternal and fetal outcomes. Hypothalamo-pituitary-adrenal axis dynamics and physiological changes are complex, thus diagnosis and management of adrenal insufficiency in pregnancy remain challenging.. Studies consistently demonstrate a rise in total serum cortisol with pregnancy, but less data are available on free cortisol levels. Salivary cortisol values have been measured in normal pregnancy and in a few studies using healthy nonpregnant women controls. Although this adds to our current knowledge of hypothalamo-pituitary-adrenal axis changes in pregnancy, clear-cut cortisol reference ranges are yet to be established. Serum cortisol and the cosyntropin stimulation test (albeit with higher peak cortisol thresholds) are currently the diagnostic tests of choice. Hydrocortisone is the preferred glucocorticoid replacement in pregnancy as it is inactivated by placental 11-β-hydroxysteroid dehydrogenase 2; dose titration may be required, but should be individualized depending on clinical course and mode of delivery.. Further studies on the long-term effects of maternal glucocorticoid regimens on the fetus and potential modulators of fetal glucocorticoid sensitivity and placental 11-β-hydroxysteroid dehydrogenase 2 are needed and will be useful in guiding clinical management strategies in pregnant women with adrenal insufficiency.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cosyntropin; Diagnostic Techniques, Endocrine; Female; Glucocorticoids; Hormone Replacement Therapy; Humans; Hydrocortisone; Pregnancy; Pregnancy Complications

The diagnostic value of tests used in assessing hypothalamic-pituitary-adrenal axis (HPA) in children remains controversial.. A systematic review and meta-analysis with receiver-operated-characteristic curve was undertaken to assess the diagnostic values of conventional standard dose 250 μg tetracosactrin (ACTH), short Synacthen test (SSST) and/or low-dose Synacthen test (LDSST) in the assessment of HPA insufficiency in children. Studies eligible for inclusion were any study that compared the use of the LDSST and/or SSST in the assessment of central adrenal insufficiency in children compared with reference standard test.. There were no randomised trials found. SSST resulted in higher specificity and positive likelihood ratio than LDSST. The LDSST had a higher sensitivity (86% vs 61%) but a lower specificity (88% vs 99%) than the SSST, but there was high heterogeneity from the LDSST studies with various doses of Synacthen used.. Lack of standardisation of assays and protocols with regard to timing, frequency and dose has resulted in diagnostic inaccuracies. There is no clear evidence to indicate that LDSST is superior to SSST in the assessment of HPA axis in children. The choice of either SSST or LDSST should be individualised based on clinical judgement for each patient. This systematic review has identified the need for a well-designed, adequately powered, randomised controlled trial on the use of diagnostic tests used in assessing HPA axis in children.

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Child; Cosyntropin; Dose-Response Relationship, Drug; Hormones; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System

A prolonged treatment with anti-inflammatory corticosteroids induces an inhibition of ACTH secretion from pituitary corticotroph cells. An abrupt interruption of such a treatment potentially leads to the risk of an acute adrenal failure, in particular in stressing situations. The inertia in reactivation of the secretion of the stimulating hypothalamic factors (CRH and AVP) and consecutively of ACTH can be responsible for an inability to adapt the secretion of glucocorticoids in response to stress. A short-time treatment (<3 weeks) with anti-inflammatory corticoids does not expose to this risk. On the contrary, a more prolonged treatment, especially with high daily doses, needs to perform an evaluation of the level of corticotroph secretion. This evaluation should be done before to consider that either stopping the treatment is out of risk or if the initiation of a substitutive treatment with hydrocortisone is required. The measurement of morning plasma cortisol level already provides a significant information. As to whether that is needed, a dynamic evaluation can be performed. Among the available tests, the Synacthen(®)test, easy to perform and using at best 1μg of β1-24 ACTH, appears the most finely informative to answer this question and to choose the most adapted follow-up.

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Anti-Inflammatory Agents; Cosyntropin; Drug Administration Schedule; Humans; Hydrocortisone; Long-Term Care; Substance Withdrawal Syndrome

Synthetic glucocorticoids treatment for their antiinflammatory and immunosuppressive activities for more than 3 weeks decreases corticotropic axis and induces a risk of adrenal insufficiency upon treatment withdrawal. Dose, duration and unknown individual factors play a role in the occurrence of adrenal insufficiency. Serum cortisol at 7-8 am, possibly completed by an 1-24 ACTH stimulation test makes the diagnosis. A scheme for care of patients is included with a progressive decrease of synthetic glucocorticoids dose, a replacement of this medication with physiological doses of hydrocortisone (in case of adrenal insufficiency) and a follow-up of endogenous secretion for detection of adrenal function recovery.

Topics: Adrenal Insufficiency; Aged; Algorithms; Circadian Rhythm; Cosyntropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Glucocorticoids; Humans; Hydrocortisone; Substance Withdrawal Syndrome

Prolonged glucocorticoid therapy is considered to be the most common cause of secondary adrenal insufficiency. Despite this, its true incidence remains unknown and the risk of acute adrenal insufficiency seems to be overestimated. The cosyntropin stimulation test is a very valuable test to assess the adrenal reserve but not to predict the risk of acute adrenal insufficiency. Otherwise, this test is well correlated with the adrenal response to a stress but not with clinical events. The corticosteroid withdrawal modalities are very heterogeneous, non-consensual, and have never been strictly evaluated. Several studies have demonstrated that the need for glucocorticoids coverage during a stress has been overestimated and that hydrocortisone doses should not necessarily be markedly increased. A prospective study of patients after withdrawal would be the only mean to assess the true incidence of this complication and to propose a rational strategy to prevent it. Meanwhile, the education of patients and physicians should be a mandatory step in the management of the patients with a potential risk of adrenal insufficiency.

Topics: Adrenal Insufficiency; Anti-Inflammatory Agents; Cosyntropin; Diagnosis, Differential; Glucocorticoids; Humans; Hydrocortisone; Risk Factors; Stress, Physiological

In the last two decades there was important evolution on the knowledge of the function of the hypothalamic-pituitary-adrenal axis. In the last decade, the expression "relative adrenal insufficiency" (RAI) was created, and more recently "critical illness-related corticosteroid insufficiency" (CIRCI) was used to designate those patients in which cortisol production was not sufficiently increased in stress situations. Patients with CIRCI have elevated hospital morbidity and mortality. Currently, there is a wide discussion about diagnostic criteria for this dysfunction. Besides basal cortisol, some publications now study the role of other tests, such as cortrosyn test - either in low (1 μg) or high doses (250 μg); free cortisol, salivary cortisol, metyrapone test and others. With this review, we aimed at summarizing the results of the most influent papers that intended to define diagnostic criteria for CIRCI. We also suggest an approach for CIRCI diagnosis and make it clear that the decision about steroid therapy in septic shock patients is matter apart from RAI.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Arginine Vasopressin; Corticotropin-Releasing Hormone; Cosyntropin; Critical Care; Critical Illness; Humans; Hydrocortisone; Metyrapone; Pituitary Gland; Steroids

Moderate forms of 21-hydroxylase deficiency (D21OH-NC), the so-called non-classical or late-onset forms are a frequently reported cause of hyperandrogenism in women [1-5]. The purpose of this collective and synthetic work was to provide the endocrinologist, gynecologist and dermatologist with consensual information so as to detect the maximum cases with acceptable cost-benefit ratio and to define the main lines of optimal patient management, given the data currently available in medical literature.

Topics: Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Cosyntropin; Female; Genetic Counseling; Glucocorticoids; Hirsutism; Hormone Replacement Therapy; Humans; Hyperandrogenism; Infertility, Female; Steroid 21-Hydroxylase

Relative adrenal insufficiency is an increasingly documented phenomenon in acute illness. Recognizing and treating such adrenal insufficiency has the potential to improve outcome. A post-cosyntropin cortisol value greater than 20 microg/dl has been recognized as consistent with normal adrenal function. While the cosyntropin test remains a superb test of primary adrenal failure, its utilityin the diagnosis of secondary adrenal failure is less clearly defined. In the setting of acute illness, a number of other criteria such as increment from basal serum cortisol have been used; however, the criteria for establishing adrenal insufficiency remains less clearly defined. We report a 44-year-old Caucasian female who presented with hypoglycemia and hypotension. The patient had a basal cortisol of 1.6 ug/dl and a peak serum cortisol of 23.3 ug/dl after 250 ug of cosyntropin. Despite this apparent normal response to cosyntropin, the patient responded to glucocorticoids with an improvement in her clinical status. Pituitary MRI revealed a 7-mm pituitary cyst. Pending the availability of free cortisol levels, it is prudent not to disregard low basal cortisol levels, even in the presence of a normal cosyntropin response. We recommend that clinicians managing acutely ill patients have a low threshold for initiating glucocorticoid replacement in the presence of hypoglycemia and shock regardless of the peak cortisol values.

Topics: Acute Disease; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adult; Cosyntropin; Female; Hormones; Humans; Hydrocortisone

A morning serum cortisol level >13 mcg/dL reliably rules out adrenal insufficiency, and the test is easy and safe to perform. Because of low specificity, patients with a level of < or =13 mcg/dL need further evaluation with the cosyntropin stimulation test (CST). The 250 mcg CST requires intravenous (IV) or intramuscular (IM) administration of cosyntropin and multiple blood draws; a normal response reliably rules out primary adrenal insufficiency and moderately decreases the likelihood of secondary adrenal insufficiency. The 1 mcg CST has better diagnostic discrimination, but requires an extra step to dilute the cosyntropin.

Topics: Adrenal Insufficiency; Cosyntropin; Hormones; Humans; Hydrocortisone

This article will review the clinical presentation, diagnosis, and treatment of acute adrenal insufficiency and explore the concept of 'relative adrenal insufficiency' in the critically ill.. Current dogma suggests that as many as 70% of patients in intensive care units with the clinical syndromes of sepsis or cardiogenic shock have 'relative adrenal insufficiency'. This article will explore how this concept came into being and why the concept has no clinical utility.. This article will provide an approach to critically ill patients that will identify adrenal insufficiency when it is part of the pathophysiology of a given patient and, at the same time, prevent the unnecessary treatment of critically ill patients with high doses of glucocorticoids for 'stress' when adrenal insufficiency is not a factor in the illness.

Topics: Adrenal Glands; Adrenal Insufficiency; Cosyntropin; Critical Illness; Humans; Hydrocortisone; Pituitary-Adrenal Function Tests; Stress, Psychological

To review the available literature on the low-dose cosyntropin stimulation test (CST) for the diagnosis of primary and secondary adrenal insufficiency in both nonstressed and acutely ill patients.. We performed a MEDLINE search of all English-language literature, published between 1965 and 2007, in which the 1-microg and the 250-microg CSTs were compared in patients with primary and secondary adrenal insufficiency.. The majority of published evidence suggests that the 1-microg CST is more sensitive than the 250-microg CST for the diagnosis of secondary adrenal insufficiency in nonstressed patients. In patients with primary adrenal insufficiency, the low-dose CST is unlikely to add any diagnostic sensitivity to the high-dose CST. In critically ill patients, the 1-microg test is also likely to be more sensitive than the 250-microg test when an appropriate cutoff value is used (25 microg/dL).. The 1-microg CST with a cortisol level determined at 30 minutes after stimulation, with use of a cutoff level of 18 to 20 microg/dL in nonstressed patients and less than 25 microg/dL or an increment of less than 9 microg/dL from baseline in critically ill patients, is the best test that is currently available for establishing the diagnosis of secondary adrenal insufficiency.

Topics: Adrenal Insufficiency; Cosyntropin; Dose-Response Relationship, Drug; Humans; Predictive Value of Tests; Stimulation, Chemical

Secondary adrenal insufficiency (SAI) is a clinical disorder that results from hypothalamic or hypophyseal damage or from prolonged administration of supraphysiological doses of glucocorticoids. Since glucocorticoids are widely used for a variety of diseases, the prevalence of SAI is by far exceeding that of primary adrenal insufficiency. Although the presentation of adrenal insufficiency may be insidious and difficult to recognize, an appropriate adrenocortical hormone replacement could lead to a normal quality of life and longevity can be achieved. The spectrum of adrenal insufficiency ranges from overt adrenal crises to subtle dysfunctions in asymptomatic patients who may be at risk of developing acute adrenal insufficiency since their hypothalamic-pituitary-adrenal (HPA) axis cannot appropriately react to stress. Thus, identification of patients with subtle abnormalities of the HPA is mandatory for avoiding this life-threatening event in stressful conditions. The optimal tests and the optimal testing sequence for adrenal insufficiency are still matter of debate. Insulin tolerance test (ITT) could be the gold standard, as it tests the whole HPA axis, but there are some patients who pass the ITT failing the ACTH test. Various alternatives to the ITT, including the standard cosyntropin stimulation test (SST) and low-dose SST, have been proposed since the adrenal gland in SAI loses the capacity for a prompt response to ACTH stimulation. The standard ACTH dose, but not the 1 microg dose, increases adrenal blood flow and this may contribute to produce an early cortisol response of greater magnitude. Moreover, the loss of the early cortisol response to ACTH stimulation could be a specific property of adrenal insufficiency, thus being a sensitive and early marker of failing adrenal function. While the results of the SSTs are often positive in patients with long-standing and severe disease, in patients with mild or recent-onset SAI these tests, using either 250 microg or 1 microg ACTH, tend to give normal results; thus, a negative cosyntropin test result does not rule out the possibility of SAI. Further studies with a systematic comparison of the different tests in large series of patients submitted to a prolonged follow-up are needed to solve the controversy of the optimal diagnostic strategy of SAI.

Topics: Adrenal Insufficiency; Cosyntropin; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin; Saliva

The combination of autoimmune adrenal insufficiency with autoimmune thyroid disease and/or type 1 autoimmune diabetes mellitus defines autoimmune polyglandular syndrome, type II. The conditions may occur in any order, and diagnosis is confounded by the nonspecific nature of the symptoms of adrenal insufficiency and hypothyroidism. The disorder is not common, but consequences can be life threatening when the diagnosis is overlooked. The conditions usually present in midlife, and women are affected more often than men. The cosyntropin test is recommended for diagnosing adrenal insufficiency, which must be present to diagnose this syndrome. Hormone therapy for each condition is similar to treatment that would be provided if the conditions occurred separately, except that treatment for adrenal insufficiency must be given before thyroid therapy is started when the conditions occur together.

Topics: Adrenal Insufficiency; Cosyntropin; Hormones; Humans; Hydrocortisone; Polyendocrinopathies, Autoimmune

Topics: Acute Disease; Adrenal Cortex; Adrenal Insufficiency; Adrenalectomy; Chronic Disease; Cosyntropin; Delayed-Action Preparations; Hormones; Humans; Hydrocortisone; Prognosis

To evaluate the utility of cosyntropin 1 microg in assessing adrenal function in critically ill patients.. A computerized literature search using MEDLINE, EMBASE, International Pharmaceutical Abstracts, and the Cochrane Database (1966-August 2004) was undertaken for trials evaluating cosyntropin 1 mug using the following search terms: adrenocorticotropin-releasing hormone (ACTH), cosyntropin, adrenal insufficiency, cortisol, corticosteroids, glucocorticoids, sepsis, septic shock, diagnosis, critically ill, intensive care, and critical care. STUDY SELECTION AND DATA SYNTHESIS: Identifying patients with sepsis with relative adrenal insufficiency (AI) using cosyntropin testing may identify those likely to benefit from corticosteroids. The results of 5 heterogeneous studies in non-intensive care unit (ICU) patients suggest that both 1 microg and 250 microg of cosyntropin stimulate similar cortisol responses and that testing using both doses correlates well with results from insulin tolerance testing. Some data from non-ICU patients suggest that the 1-microg test may be more sensitive to detect AI; 3 heterogeneous studies in ICU patients confirmed the improved sensitivity of the 1-microg test.. Use of cosyntropin 1 microg should detect AI in all patients who would have been diagnosed using 250 microg. Unfortunately, all of the clinical trials evaluating the role of corticosteroids in septic shock that used the cosyntropin stimulation test administered 250 microg. Extrapolation of the existing guidelines to treat patients with septic shock testing positive for relative AI using the 1-microg test may provide effective therapy to appropriate patients not diagnosed by the 250-microg testing or may introduce additional adverse effects in patients who should not receive corticosteroids. Large-scale, head-to-head comparison data of steroid effectiveness after 1- and 250-microg ACTH stimulation tests are needed to expand upon these promising results.

Topics: Adrenal Insufficiency; Cosyntropin; Critical Illness; Humans

Although the true incidence of adrenal insufficiency in critically ill patients is unknown, there is evidence that even partial adrenal insufficiency in such patients is associated with increased mortality. But exactly how should adrenal insufficiency be defined and diagnosed, and who should receive treatment?

Topics: Adrenal Insufficiency; Algorithms; Cosyntropin; Critical Care; Critical Illness; Humans; Practice Guidelines as Topic

Topics: Acute Disease; Adrenal Cortex Hormones; Adrenal Insufficiency; Cosyntropin; Critical Illness; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Shock, Septic

The cosyntropin stimulation test is the initial endocrine evaluation of suspected primary or secondary adrenal insufficiency.. To critically review the utility of the cosyntropin stimulation test for evaluating adrenal insufficiency.. The MEDLINE database was searched from 1966 to 2002 for all English-language papers related to the diagnosis of adrenal insufficiency.. Studies with fewer than 5 persons with primary or secondary adrenal insufficiency or with fewer than 10 persons as normal controls were excluded. For secondary adrenal insufficiency, only studies that stratified participants by integrated tests of adrenal function were included.. Summary receiver-operating characteristic (ROC) curves were generated from all studies that provided sensitivity and specificity data for 250-microg and 1-microg cosyntropin tests; these curves were then compared by using area under the curve (AUC) methods. All estimated values are given with 95% CIs.. At a specificity of 95%, sensitivities were 97%, 57%, and 61% for summary ROC curves in tests for primary adrenal insufficiency (250-microg cosyntropin test), secondary adrenal insufficiency (250-microg cosyntropin test), and secondary adrenal insufficiency (1-microg cosyntropin test), respectively. The area under the curve for primary adrenal insufficiency was significantly greater than the AUC for secondary adrenal insufficiency for the high-dose cosyntropin test (P < 0.001), but AUCs for the 250-microg and 1-microg cosyntropin tests did not differ significantly (P > 0.5) for secondary adrenal insufficiency. At a specificity of 95%, summary ROC analysis for the 250-microg cosyntropin test yielded a positive likelihood ratio of 11.5 (95% CI, 8.7 to 14.2) and a negative likelihood ratio of 0.45 (CI, 0.30 to 0.60) for the diagnosis of secondary adrenal insufficiency.. Cortisol response to cosyntropin varies considerably among healthy persons. The cosyntropin test performs well in patients with primary adrenal insufficiency, but the lower sensitivity in patients with secondary adrenal insufficiency necessitates use of tests involving stimulation of the hypothalamus if the pretest probability is sufficiently high. The operating characteristics of the 250-microg and 1-microg cosyntropin tests are similar.

Topics: Adrenal Insufficiency; Cosyntropin; Humans; ROC Curve; Sensitivity and Specificity

The diagnosis of adrenal hypofunction is suggested by clinical features and confirmed by biochemical testing. The characteristic features of acute primary adrenal insufficiency include orthostatic hypotension, fever, and hypoglycemia. By contrast, patients with chronic primary adrenal insufficiency have a longer history of malaise, as well as fatigue, anorexia, diarrhea, weight loss, joint and back pain, and darkening of the skin. While the clinical presentation of secondary adrenal insufficiency is similar to that of primary adrenal insufficiency, there is no hyperpigmentation, and hypotension and orthostasis are less pronounced. As a result, patients often present with vague, non-specific symptoms and the diagnosis may not be entertained. There is considerable debate regarding the best dynamic test for the diagnosis of adrenal hypofunction. Optimally, a screening test would be economic, convenient and safe. It would have high sensitivity and specificity based on consensus criteria for interpretation. Unfortunately, to date no test meets all of these criteria. Measurement of basal cortisol is an inexpensive and convenient screening test that can include (< 3 microg/dl; 83 nmol/l) or exclude (> 19 microg/dl; 524 nmol/l) adrenal insufficiency. However, most patients will have intermediate values and will require dynamic testing. This review discusses the use of metyrapone, insulin, CRH and synthetic ACTH 1-24 as provocative agents for cortisol secretion. Although the insulin and metyrapone stimulation tests have the advantage of testing the entire hypothalamic-pituitary-adrenal axis, they are cumbersome and carry more risk than the other tests. The 250 microg ACTH test works well to identify primary adrenal hypofunction, but can only detect secondary adrenal hypofunction when there is sufficient time for the glands to atrophy because of reduced endogenous ACTH stimulation. The 1 microg ACTH test has been advocated in the setting of possible secondary adrenal insufficiency, but its widespread use has been mitigated by the lack of a commercial preparation of this small dose and controversy regarding diagnostic criteria. Ultimately, the choice of test should be individualized for each patient, with knowledge of the available reference assays and the vagaries of each test.

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Cosyntropin; Feedback, Physiological; Glucocorticoids; Glucose Tolerance Test; Humans; Hydrocortisone; Insulin; Metyrapone; Pituitary-Adrenal Function Tests

Adrenal insufficiency is known to be a complication of HIV infection, although estimates of its prevalence and severity vary. Adrenal insufficiency is the most serious endocrine complication that occurs in persons with HIV infection. Patients with acquired immune deficiency syndrome (AIDS) are considered to be at high risk for primary or secondary adrenal insufficiency. We describe 3 patients with AIDS who had clinical features suggestive of adrenal insufficiency, but their corticotropin (ACTH) stimulation tests were normal. Repeat testing confirmed the diagnosis in one patient, and further testing with the overnight metyrapone test revealed evidence of secondary adrenal insufficiency in the other patients. Persistent clinical improvement was evident on subsequent glucocorticoid therapy. A normal response to the ACTH stimulation test can be dangerously misleading. Patients with AIDS and suspected adrenal insufficiency who have normal screening by the ACTH stimulation test should undergo further testing for secondary adrenal disease.

Topics: Adrenal Glands; Adrenal Insufficiency; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Combined Modality Therapy; Cosyntropin; Cytomegalovirus Infections; Dexamethasone; False Negative Reactions; Fluid Therapy; HIV Infections; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Metyrapone; Mycobacterium avium-intracellulare Infection; Pituitary Gland; Pituitary-Adrenal System; Risk; Sarcoma, Kaposi; Stomach Neoplasms

The rapid cosyntropin stimulation test offers a simple means for detecting adrenal insufficiency. In contrast, assessment of suspected hypercortisolism (Cushing's syndrome) is difficult because cortisol levels fluctuate with intermittent release of corticotropin from the pituitary or from tumors. Also, a number of medications affect cortisol levels, leading to false-positive or false-negative results. The classic low-dose followed by high-dose dexamethasone test is cumbersome, and other, simpler studies, such as the overnight high-dose dexamethasone suppression test, may prove more practical and cost-effective. With both high and low levels of adrenal glucocorticoids, awareness and early recognition of the symptoms are important. An endocrinologist should be consulted when the overnight dexamethasone suppression test or the 24-hour urine cortisol collection is abnormal or if clinical suspicion is high despite normal results on screening tests.

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocortical Hyperfunction; Cosyntropin; Cushing Syndrome; Dexamethasone; Diagnosis, Differential; Humans; Hydrocortisone; Patient Care Team

Topics: Adrenal Cortex Diseases; Adrenal Insufficiency; Cosyntropin; Glucocorticoids; Humans; Metyrapone

Adrenocortical insufficiency causes difficulty in diagnosis and morbidity out of proportion to its rarity, because of the non-specific, multi-system nature of the clinical features. Most of these are due to cortisol deficiency. Prominent features are well-known ones such as weight loss and asthenia, and hypoglycaemia. Less prominent in recent accounts are those due to failure of cellular sodium export and to vasopressin excess, which are frequent and clinically significant. For this reason, the clinical features of isolated ACTH deficiency, isolated glucocorticoid deficiency and Addison's disease overlap greatly. In addition, cortisol deficiency has secondary endocrine effects, e.g. glucocorticoid-reversible hypothyroidism, hyperprolactinaemia and hypercalcaemia. Further overlap between the various steroid insufficiency syndromes occurs because of the association of various organ-specific autoimmune endocrinopathies with Addison's disease. Over 80% of Addison's disease is of the autoimmune type, though almost any systemic destructive process can cause similar steroid insufficiency. Demonstration of adrenal insufficiency requires various combinations of tetracosactrin adrenal stimulation tests, and hypoglycaemia or equivalent tests, if the cause is ACTH deficiency but the correct test can only be chosen to suit a firm clinical diagnosis. The treatment of adrenocortical insufficiency is described.

Topics: Addison Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aldosterone; Androstenedione; Animals; Autoimmune Diseases; Blood Volume; Body Water; Calcium; Catecholamines; Cosyntropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Delayed-Action Preparations; Disease Models, Animal; Glomerular Filtration Rate; Glucocorticoids; Humans; Hypoglycemia; Hyponatremia; Hypotension; Hypothalamo-Hypophyseal System; Kidney; Posture; Prolactin; Regional Blood Flow; Skin Pigmentation; Thyroid Gland; Tomography, X-Ray Computed; Water-Electrolyte Balance

The Short Synacthen Test (SST) is the gold standard for diagnosing adrenal insufficiency. It requires invasive administration of Synacthen, venous sampling, and is resource-intensive.. To develop a nasally administered SST, with salivary glucocorticoids measurement, to assess the adrenal response.. We conducted 5 studies: 4 open-label, sequence-randomized, crossover, pharmacodynamic studies testing 6 doses/formulations and a repeatability study. Additionally, pharmacokinetic analysis was undertaken using our chosen formulation, 500 µg tetracosactide with mucoadhesive chitosan, Nasacthin003, in our pediatric study.. Adult and children's clinical research facilities.. A total of 36 healthy adult males and 24 healthy children.. We administered all 6 nasal formulations using an European regulator endorsed atomization device. The IV comparators were 250 µg or 1 µg SST.. We analyzed paired blood and saliva samples for plasma cortisol and salivary cortisol and cortisone.. The addition of chitosan to tetracosactide and dose escalation increased peak cortisol response (P = 0.01 and 0.001, respectively). The bioavailability of Nasacthin003 was 14.3%. There was no significant difference in plasma cortisol at 60 minutes between 500 µg Nasacthin003 and 250 µg IV Synacthen (P = 0.17). The repeatability coefficient at 60 minutes was 105 nmol/L for IV Synacthen and salivary cortisol and cortisone was 10.3 and 21.1 nmol/L, respectively. The glucocorticoid response in children was indistinguishable from that of adults.. Nasal administration of Nasacthin003 generates equivalent plasma cortisol values to the 250-µg IV SST and, with measurement at 60 minutes of salivary cortisol or cortisone, provides a noninvasive test for adrenal insufficiency.

Topics: Administration, Intranasal; Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adult; Child; Chitosan; Cosyntropin; Cross-Over Studies; Female; Glucocorticoids; Humans; Male; Middle Aged; Saliva

Injectable tetracosactide hexa-acetate, ACTH 1-24 (Synacthen), is not marketed in many countries including India, whereas Injectable long acting porcine sequence, ACTH 1-39 (Acton Prolongatum®) is easily available and much cheaper. This study aimed to find the diagnostic accuracy of ACTH stimulation test using i.m. Acton Prolongatum® (acton prolongatum stimulation test, APST) in comparison with Synacthen (short synacthen test, SST) for the diagnosis of glucocorticoid insufficiency.. Subjects with a suspicion of adrenal insufficiency based on clinical features underwent a SST with 250 µg Synacthen followed by APST using 30 units of Acton Prolongatum®. Serum cortisol levels were measured at 60 and 120 min following injection of Acton Prolongatum®. Stimulated peak cortisol of less than 18 µg/dL on SST was considered as adrenal insufficiency.. Forty seven patients with mean age of 36.7 ± 14.4 years were enrolled for the study. Based on SST, twenty (n = 20) persons were classified as having adrenal insufficiency, whereas twenty-seven (n = 27) were found to be normal. Area under the curve of APST (at 120 min) was 0.986 when compared to SST, thus proving its high accuracy. A serum cortisol cut off value of 19.5 µg/dL at 120-min following stimulation with Acton Prolongatum® showed a sensitivity of 100% and specificity of 88%.. ACTH stimulation test using Acton Prolongatum® is an economical and accurate alternative to the short Synacthen test.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Cosyntropin; Humans; Hydrocortisone; Middle Aged; Young Adult

The appropriate cosyntropin dose during cosyntropin stimulation tests remains uncertain. We conducted a prospective, randomized pilot study to compare 1 μg IV low dose cosyntropin test, 25 μg IM medium dose cosyntropin test, and 250 μg IM standard dose cosyntropin test to evaluate secondary adrenal insufficiency. Insulin tolerance test was used as the gold standard.. The study included patients with hypothalamic/pituitary disease (n  = 10) with at least one pituitary axis deficiency other than ACTH deficiency and controls (n  = 12). All tests were done in random order. Sensitivity and specificity were calculated for total cortisol and serum free cortisol cut-off levels during cosyntropin stimulation tests.. The median (range) age and F/M sex ratios for patients and controls were 54 years (23-62), 2/8, and 33 years (21-51), 6/6, respectively. The best total cortisol cut-off during low dose cosyntropin test, medium dose cosyntropin test, 30 min and 60 min standard dose cosyntropin test were 14.6 μg/dL (100% sensitivity & specificity), 18.7 μg/dL (100% sensitivity, 88% specificity), 16.1 (100% sensitivity & specificity), and 19.5 μg/dL (100% sensitivity & specificity), respectively. There was no difference in the ROC curve for cortisol values between the cosyntropin stimulation tests (p  > 0.41). Using a cortisol cut-off of 18 μg/dL during cosyntropin stimulation tests, only cortisol level at 30 min during standard dose cosyntropin test provided discrimination similar to insulin tolerance test. The best peak free cortisol cut-off levels were 1 μg/dL for insulin tolerance test, 0.9 μg/dL for low dose cosyntropin test, 0.9 μg/dL for medium dose cosyntropin test, and 0.9 μg/dL and 1.3 μg/dL for 30 min and 60 min standard dose cosyntropin test, respectively.. All cosyntropin stimulation tests had excellent correlations with insulin tolerance test, when appropriate cut-offs were used. This pilot study does not suggest an advantage in using 25 μg cosyntropin dose during the cosyntropin stimulation test. A serum free cortisol cut-off of 0.9 μg/dL may be used as pass criterion during low dose cosyntropin test, standard dose cosyntropin test cosyntropin test, and 30 min standard dose cosyntropin test.

Topics: Adrenal Cortex; Adrenal Insufficiency; Adult; Cosyntropin; Dose-Response Relationship, Drug; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Pilot Projects; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Solubility; Stimulation, Chemical; Young Adult

Recent studies suggest using lower GH cut-points for the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD), especially in obese patients. There are limited data on evaluating GH and hypothalamic-pituitary-adrenal (HPA) axes using weight-based dosing for the GST.. To define GH and cortisol cut-points to diagnose adult GHD and secondary adrenal insufficiency (SAI) using the GST, and to compare fixed-dose (FD: 1 or 1.5 mg in patients >90 kg) with weight-based dosing (WB: 0.03 mg/kg). Response to the insulin tolerance test (ITT) was considered the gold standard, using GH and cortisol cut-points of ≥3 ng/ml and ≥18 µg/dL, respectively.. 28 Patients with hypothalamic-pituitary disease and 1-2 (n = 14) or ≥3 (n = 14) pituitary hormone deficiencies, and 14 control subjects matched for age, sex, estrogen status and body mass index (BMI) underwent the ITT, FD- and WB-GST in random order.. Age, sex ratio and BMI were comparable between the three groups. The best GH cut-point for diagnosis of GHD was 1.0 (92 % sensitivity, 100 % specificity) and 2.0 ng/mL (96 % sensitivity and 100 % specificity) for FD- and WB-GST, respectively. Age negatively correlated with peak GH during FD-GST (r = -0.32, P = 0.04), but not WB-GST. The best cortisol cut-point for diagnosis of SAI was 8.8 µg/dL (92 % sensitivity, 100 % specificity) and 11.2 µg/dL (92 % sensitivity and 100 % specificity) for FD-GST and WB-GST, respectively. Nausea was the most common side effect, and one patient had a seizure during the FD-GST.. The GST correctly classified GHD using GH cut-points of 1 ng/ml for FD-GST and 2 ng/ml for WB-GST, hence using 3 ng/ml as the GH cut-point will misclassify some GH-sufficient adults. The GST may also be an acceptable alternative to the ITT for evaluating the HPA axis utilizing cortisol cut-points of 9 µg/dL for FD-GST and 11 µg/dL for WB-GST.

Topics: Adenoma; Adrenal Insufficiency; Adult; Aged; Blood Glucose; Body Weight; Case-Control Studies; Central Nervous System Cysts; Cosyntropin; Craniopharyngioma; Dose-Response Relationship, Drug; Female; Glucagon; Hormones; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemic Agents; Hypopituitarism; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System; Reference Values; Sensitivity and Specificity

To examine serum cortisol responses to a simplified low-dose short Synacthen test (LDSST) in children treated with inhaled corticosteroids (ICS) for asthma and to compare these to early morning salivary cortisol (EMSC) and cortisone (EMSCn) levels.. Early morning salivary cortisol and EMSCn samples were collected for three consecutive days. On day three, Synacthen 500 ng/1·73 m(2) was administered intravenously. Samples were collected at 0, 15, 25, 35 min.. A total of 269 subjects (160 M: 109 F), median (range) age 10·0 (5·1-15·2) years were studied. Peak cortisol in the LDSST was <500 nmol/l in 101 subjects (37·5%) and <350 nmol/l in 12 subjects (4·5%). Basal cortisol correlated with peak cortisol: r = 0·55, (95% CI: 0·46, 0·63, P < 0·0001). Time at which peak cortisol concentration was achieved was significantly related to the value of peak cortisol (P < 0·0001), with higher cortisol peaks occurring later in the test and lower cortisol peaks occurring earlier. EMSC and EMSCn had no predictive value for the identification of patients with a peak cortisol <500 nmol/l. EMSCn was superior to EMSC in identifying patients with a peak cortisol <350 nmol/l: a minimum EMSCn cut-off value of 12·5 nmol/l gave a negative predictive value of 99·2% and positive predictive value of 30·1%.. Our data illustrate that basal measures of cortisol are likely to be of value in screening populations for patients at greatest risk of adrenal crisis. EMSCn shows promise as a screening tool for the identification of patients with severe adrenal insufficiency.

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Circadian Rhythm; Cortisone; Cosyntropin; Dose-Response Relationship, Drug; Fluticasone; Humans; Hydrocortisone; Pituitary-Adrenal Function Tests; Saliva

To investigate the impact of etomidate on the rate of hospital-acquired pneumonia (HAP) in trauma patients and the effects of hydrocortisone in etomidate-treated patients.. This was a sub-study of the HYPOLYTE multi-centre, randomized, double-blind, placebo-controlled trial of hydrocortisone in trauma patients (NCT00563303). Inclusion criterion was trauma patient with mechanical ventilation (MV) of ≥48 h. The use of etomidate was prospectively collected. Endpoints were the results of the cosyntropin test and rate of HAP on day 28 of follow-up.. Of the 149 patients enrolled in the study, 95 (64 %) received etomidate within 36 h prior to inclusion. 79 (83 %) of 95 patients receiving etomidate and 34 of the 54 (63 %) not receiving etomidate had corticosteroid insufficiency (p = 0.006). The administration of etomidate did not alter basal cortisolemia (p = 0.73), but it did decrease the delta of cortisolemia at 60 min (p = 0.007). There was a correlation between time from etomidate injection to inclusion in the study and sensitivity to corticotropin (R (2) = 0.19; p = 0.001). Forty-nine (51.6 %) patients with etomidate and 16 (29.6 %) patients without etomidate developed HAP by day 28 (p = 0.009). Etomidate was associated with HAP on day 28 in the multivariate analysis (hazard ratio 2.48; 95 % confidence interval 1.19-5.18; p = 0.016). Duration of MV with or without etomidate was not significantly different (p = 0.278). Among etomidate-exposed patients, 18 (40 %) treated with hydrocortisone developed HAP compared with 31 (62 %) treated with placebo (p = 0.032). Etomidate-exposed patients treated with hydrocortisone had fewer ventilator days (p < 0.001).. Among the patients enrolled in the study, etomidate did not alter basal cortisolemia, but it did decrease reactivity to corticotropin. We suggest that in trauma patients, etomidate is an independent risk factor for HAP and that the administration of hydrocortisone should be considered after etomidate use.

Topics: Adolescent; Adrenal Insufficiency; Adult; Aged; Anesthetics, Intravenous; Child; Child, Preschool; Cosyntropin; Cross Infection; Double-Blind Method; Etomidate; Female; Humans; Hydrocortisone; Male; Middle Aged; Pneumonia, Bacterial; Respiration, Artificial; Risk Factors; Wounds and Injuries; Young Adult

The diagnosis of central adrenal insufficiency (AI) continues to be challenging, especially when it is partial. We have recently demonstrated the value of measuring serum dehydroepiandrosterone sulfate (DHEA-S) in establishing the diagnosis of central AI. The current investigation examined the added value of measuring serum dehydroepiandrosterone (DHEA) levels during low-dose (1 μg) cosyntropin (LDC) stimulation in patients suspected to have central AI.. Baseline and LDC-stimulated cortisol, DHEA, and DHEA-S were measured preoperatively in 155 consecutive patients with pituitary masses and 63 healthy subjects. Hypothalamic-pituitary adrenal (HPA) function was normal (NL-HPA) in 97 of the patients and was impaired (impaired HPA) in 58 patients. Patients with NL-HPA underwent surgical removal of the sellar masses and received no glucocorticoids before, during, or after surgery.. Baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S in patients with NL-HPA were similar to those of normal subjects. In contrast, patients with impaired HPA had lower baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S levels. There were 18 subjects in the latter group whose LDC-stimulated serum cortisol levels were greater than 18.0 μg/dl. In those 18 subjects, baseline and LDC-stimulated DHEA and DHEA-S levels were similar to the whole group of patients with impaired HPA function. The molar ratio of cortisol to DHEA did not change with LDC stimulation in normal subjects and those with NL-HPA. In contrast, patients with impaired HPA had a higher baseline cortisol to DHEA molar ratio that increased further with LDC stimulation.. Patients with impaired HPA function have a more severe loss in DHEA secretion than that of glucocorticoids. Measurements of serum DHEA levels during LDC simulation provide additional valuable information that improves the diagnostic accuracy of LDC in patients suspected to have central AI. We recommend the inclusion of DHEA and DHEA-S measurements in the laboratory assessment of HPA function.

Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Adrenal Insufficiency; Adult; Aged; Chemistry, Clinical; Cosyntropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Diagnostic Techniques, Endocrine; Female; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Prolactinoma; Reproducibility of Results

High prevalence of "biochemical" adrenal insufficiency (AI) in thalassemics has been reported. However, "clinical" AI is rare.. The aim was to determine whether cortisol binding globulin (CBG) or tests used in assessing adrenal function contributed to the abnormally high prevalence of biochemical AI.. The study was conducted at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.. Participants included 56 children and adolescents with thalassemia and 44 controls.. Serum CBG and adrenal function test results assessed by 1 μg cosyntropin test and insulin tolerance test (ITT) were measured. Free cortisol index (FCI) calculated by total cortisol (TC)/CBG and calculated free cortisol (cFC) were determined.. Mean (sd) CBG levels were comparable between patients and controls [45.2 (11.0) vs. 47.0 (8.6) mg/liter]. Peak TC, FCI, and cFC after cosyntropin test were lower in thalassemics [TC, 15.2 (4.0) vs. 18.9 (3.1) μg/dl; FCI, 3.4 (0.8) vs. 4.2 (1.2) μg/mg, P <0.001; and cFC, 1.03 (0.38) vs. 1.44 (0.61) μg/dl, P = 0.008]. Thirty of 56 thalassemics (53.6%) had AI, defined as having peak TC of less than 16 μg/dl. ITT was performed in 26 of those 30 patients. Five of 26 patients had peak TC after an ITT of at least 20 μg/dl. As a result, the estimated frequency of AI in the entire patient group was reduced by approximately 10%.. The 1 μg cosyntropin test could be an adrenal function screening test in thalassemics. However, for definite diagnosis, ITT should be performed in those having peak total cortisol of less than 16 μg/dl after the 1 μg cosyntropin test.

Topics: Adolescent; Adrenal Insufficiency; Biomarkers; Carrier Proteins; Child; Child, Preschool; Cosyntropin; Cross-Sectional Studies; Diagnosis, Differential; Down-Regulation; Humans; Hydrocortisone; Pituitary-Adrenal Function Tests; Prevalence; Thalassemia

The occurrence of eight cases of adrenal deficit in children hospitalized for acute lymphoblastic leukemia (ALL) led us to conduct a prospective study from May 2006 to May 2007 to better characterize this corticoid-induced adrenal deficit. Forty of the 48 patients hospitalized for ALL were given a low-dose Synacthen test (1 μg), a mean 7 days after the induction phase. An adrenal deficit was diagnosed in 27 patients (67.5%). No significant clinical or hematological difference was identified between the "with deficit" (n = 27) and "without deficit" (n = 13) groups. The diagnosis of adrenal deficit was not more common for children who had received dexamethasone (13/19) or prednisone (14/21), or for those who had (19/29) or had not (8/11) experienced corticoid toxicity during induction. The clinical signs suggesting adrenal deficit were identical in the two groups and none of the children presented an acute episode. In biological terms, only hypoprotidemia was significantly more common in patients with adrenal deficit (p = 0.0004). Of 13 patients with a deficit at the end of the induction who had received a 2nd low-dose Synacthène(®) test before intensification no. 1, 3 weeks on average after the end of corticotherapy, only two still had a deficit. Thus, corticoid-induced adrenal deficit is a common complication in children treated for ALL, although it is not highly symptomatic. Most of these children recover normal adrenal function before intensification no. 1, but it does not eliminate the risk of a secondary deficit after other courses of corticotherapy. Systematic repeated Synacthène(®) tests in common practice among children treated for ALL does not seem justified. However, the results of this study encouraged us to propose a hydrocortisone substitution to children treated for ALL in the event of stress.

Topics: Adolescent; Adrenal Insufficiency; Child; Child, Preschool; Cosyntropin; Dexamethasone; Female; Glucocorticoids; Hormones; Humans; Infant; Inpatients; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prospective Studies; Risk; Treatment Outcome

Clobetasol propionate 0.05% emulsion foam was recently developed for use on multiple body sites.. We sought to evaluate safety and efficacy of clobetasol emulsion foam 0.05% to treat steroid-responsive dermatoses in multiple age groups.. A phase II open-label study evaluated the effect of clobetasol foam on the hypothalamic-pituitary-adrenal axis in 52 participants aged 6 years or older with mild-to-severe atopic dermatitis (AD). Cosyntropin stimulation test was used to determine the effect of clobetasol foam on hypothalamic-pituitary-adrenal axis, with a normal response considered to be a postinjection serum cortisol level greater than 18 mug/dL. Another phase II open-label pharmacokinetic safety study was conducted in 32 participants aged 12 years or older with mild-to-moderate plaque-type psoriasis. Pharmacokinetic parameters evaluated included maximal plasma concentration of clobetasol propionate, time to achieve maximum concentration, and area under the curve. Two phase III, randomized controlled studies assessed treatment success in participants aged 12 years or older with moderate-to-severe AD (N = 377) or mild-to-moderate plaque-type psoriasis (N = 497). In all studies, participants received study drug for 2 weeks. In the AD study, treatment success was determined using a composite end point requiring an Investigator's Static Global Assessment (ISGA) score of 0 or 1, erythema score of 0 or 1, induration/papulation score of 0 or 1, and improvement in the ISGA score of at least two grades from baseline. Likewise, the study in plaque-type psoriasis used a composite end point requiring an ISGA score of 0 or 1, erythema score of 0 or 1, scaling score of 0 or 1, plaque thickness score of 0, and improvement in the ISGA score of at least two grades from baseline.. Significantly more participants achieved treatment success on clobetasol foam than vehicle foam (P < .0001 and P = .0005 for each study). Reversible hypothalamic-pituitary-adrenal axis suppression was observed in 27% of participants aged 18 years or older and 47% in participants aged between 6 and younger than 12 years, but 0% in participants aged between 12 and younger than 18 years.. The studies evaluated short-term use only.. Clobetasol emulsion formulation foam is safe and effective for treatment of moderate-to-severe AD and mild-to-moderate plaque-type psoriasis in patients aged 12 years or older.

Topics: Administration, Cutaneous; Adolescent; Adrenal Insufficiency; Adult; Age Factors; Aged; Area Under Curve; Biological Availability; Child; Clobetasol; Cosyntropin; Dermatitis, Atopic; Emulsions; Humans; Hydrocortisone; Immunosuppressive Agents; Middle Aged; Pituitary-Adrenal Function Tests; Psoriasis; Treatment Outcome

Severe systemic infection leads to hypercortisolism. Reduced cortisol binding proteins may accentuate the free cortisol elevations seen in systemic infection. Recently, low total cortisol increments after tetracosactrin have been associated with increased mortality and hemodynamic responsiveness to exogenous hydrocortisone in septic shock (SS), a phenomenon termed by some investigators as relative adrenal insufficiency (RAI).. Free plasma cortisol may correspond more closely to illness severity than total cortisol, comparing SS and sepsis (S).. This was a prospective study.. This study took place in a tertiary teaching hospital.. Patients had SS (n = 45) or S (n = 19) or were healthy controls (HCs; n = 10).. The aim of the study was to compare total with free cortisol, measured directly and estimated by Coolens' method, corticosteroid-binding globulin (CBG), and albumin in patients with SS (with and without RAI) and S during acute illness, recovery, and convalescence.. Comparing SS, S, and HC subjects, free cortisol levels reflected illness severity more closely than total cortisol (basal free cortisol, SS, 186 vs. S, 29 vs. HC, 13 nmol/liter, P < 0.001 compared with basal total cortisol, SS, 880 vs. S, 417 vs. HC, 352 nmol/liter, P < 0.001). Stimulated free cortisol increments varied greatly with illness category (SS, 192 vs. S, 115 vs. HC, 59 nmol/liter, P = 0.004), whereas total cortisol increments did not (SS, 474 vs. S, 576 vs. HC, 524 nmol/liter, P = 0.013). The lack of increase in total cortisol with illness severity is due to lower CBG and albumin. One third of patients with SS (15 of 45) but no S patients met a recently described criterion for RAI (total cortisol increment after tetracosactrin < or = 248 nmol/liter). RAI patients had higher basal total cortisol (1157 vs. 756 nmol/liter; P = 0.028) and basal free cortisol (287 vs. 140 nmol/liter; P = 0.017) than non-RAI patients. Mean cortisol increments in RAI were lower (total, 99 vs. 648 nmol/liter, P < 0.001; free, 59 vs. 252 nmol/liter, P < 0.001). These differences were not due to altered CBG or albumin levels. Free cortisol levels normalized more promptly than total cortisol in convalescence. Calculated free cortisol by Coolens' method compared closely with measured free cortisol.. Free cortisol is likely to be a better guide to cortisolemia in systemic infection because it corresponds more closely to illness severity. The attenuated cortisol increment after tetracosactrin in RAI is not due to low cortisol-binding proteins. Free cortisol levels can be determined reliably using total cortisol and CBG levels.

Topics: Adrenal Insufficiency; Aged; Cosyntropin; Female; Humans; Hydrocortisone; Male; Microdialysis; Middle Aged; Prospective Studies; Reproducibility of Results; Sepsis; Serum Albumin; Shock, Septic; Transcortin

No consensus exists until now about the suitable dose of tetracosactin in the ACTH stimulation test for detecting adrenal insufficiency. Our aim was to characterize both the ACTH(1-24) and the cortisol profiles after standard high-dose test (250 microg) (HDT) and low-dose test (1 microg) (LDT) in healthy subjects in order to provide a deeper knowledge about the relationship between stimulus and response.. ACTH tests were performed in 10 healthy volunteers (five men, five women) with at least 1 week of difference.. Plasma ACTH(1-24) and ACTH(1-39) and serum cortisol were measured before tetracosactin i.v. injection and at 5, 15, 30, 45, 60, 75 and 90 min after stimulus. Area under the curve (AUC) of ACTH(1-24) and cortisol, as well as mean residence time (MRT) for ACTH(1-24) were calculated in both tests.. Elimination of ACTH(1-24) was faster in HDT than in LDT (MRTs of 0.14 vs 0.37, respectively, P = 0.008), but plasma concentrations were higher up to 60 min cortisol production in HDT reaching a higher maximum concentration (Cmax: 1144 vs 960 nmol/l) but delayed in time (75 vs 52.5 min). No significant relationship was observed between AUC or Cmax of ACTH(1-24) and AUC, Cmax and increment of cortisol in any of the tests. However, a negative correlation of basal cortisol values was observed with relative cortisol increment (HDT: r = 0.77 P = 0.009; LDT: r = 0.94 P < 0.0001), but not so with Cmax (HDT: r = 0.22 P = 0.55; LDT: r = 0.57 P = 0.09).. The elimination rate of ACTH in healthy volunteers was significantly lower in LDT than in HDT, but cortisol production rate appears to be identical in both tests, so that a maximum adrenal stimulation seems to exist. The use of LDT may be more adequate, although data from patients need studying.

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Area Under Curve; Cosyntropin; Drug Administration Schedule; Female; Hormones; Humans; Hydrocortisone; Male; Metabolic Clearance Rate

Inhaled corticosteroids (ICs) are considered first-line therapy for persistent asthma. At medium to high doses, ICs can suppress the hypothalamic-pituitary-adrenal (HPA) axis. Various provocative stimuli have been used to evaluate HPA axis function, but they are labor intensive and time-consuming. Dehydroepiandrosterone sulfate (DHEA-S) is a corticotropin-dependent adrenal androgen precursor that is suppressible in patients treated with ICs.. To evaluate DHEA-S as a possible marker for HPA axis dysfunction in children treated with ICs.. Children with moderate-to-severe persistent asthma and a history of medium- to high-dose IC exposure for at least 6 months were evaluated using low-dose and standard high-dose cosyntropin stimulation testing to assess adrenal function, and DHEA-S levels were compared with the results.. Thirteen (59%) of 22 patients exhibited an abnormal cortisol response to cosyntropin. Age- and sex-specific mean DHEA-S z scores were significantly lower in cosyntropin abnormal responders (-1.2822) compared with normal responders (0.2964) (P = .008). The receiver operating characteristic curve for DHEA-S z scores had an area of 0.786 (95% confidence interval, 0.584-0.989), reaching 100% sensitivity with a DHEA-S z score of -1.5966 or less and 100% specificity with a DHEA-S z score greater than 0.0225.. Most children develop biochemical evidence of adrenal suppression after treatment with medium to high doses of ICs. The presence of low DHEA-S levels can be used as a screening test to identify the child who needs more formal testing of the HPA axis.

Topics: Administration, Inhalation; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Asthma; Biomarkers; Child; Cosyntropin; Dehydroepiandrosterone Sulfate; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Mass Screening; Pituitary-Adrenal System; ROC Curve

A short course of moderately early dexamethasone therapy with a starting dose of 0.5 mg/kg/day improves lung compliance and shortens the duration of ventilatory support in preterm infants with respiratory distress syndrome (RDS). We conducted a double-blind, randomized study to evaluate whether a moderately early 14-day weaning course of low-dose dexamethasone affects adrenal function and facilitates weaning from the ventilator.. Thirty-six preterm infants with a gestational age < or =32 weeks who required ventilatory support for RDS on days 7-14 were randomized to a 14-day treatment course with dexamethasone (0.2 mg/kg/day start, tapering doses) or placebo (equivalent amounts of normal saline). Prior to the first study treatment and the day after completion of the treatment course, adrenal function was assessed from serum cortisol levels drawn before and 30 min after intravenous administration of 0.1 mg Cortrosyn. Extubation rate during treatment in both groups was compared.. In both groups baseline serum cortisol levels decreased significantly during treatment, but stimulated cortisol levels did not change. After the 14-day treatment course, stimulated cortisol levels increased significantly from baseline levels in both groups (p<0.001), following Cortrosyn administration. More infants in the dexamethasone group were extubated within 7-14 days of study entry than in the placebo group (p<0.05). Hyperglycemia was more frequently diagnosed in the dexamethasone group and open-label dexamethasone treatment was given more frequently in the control group.. A moderately early 14-day weaning course of low-dose dexamethasone does not significantly suppress the adrenal function of very preterm infants with RDS, but accelerates weaning from the ventilator.

Topics: Adrenal Glands; Adrenal Insufficiency; Anti-Inflammatory Agents; Cosyntropin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrocortisone; Infant, Newborn; Injections, Intravenous; Intensive Care Units, Neonatal; Male; Pituitary-Adrenal System; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Ventilator Weaning

In suspected adrenal insufficiency, the ideal test for assessing the hypothalamo-pituitary-adrenal axis is controversial. Therefore, three tests were compared in patients presenting with symptoms suggestive of adrenal insufficiency.. Responses to the standard short Synacthen test (SSST), the low dose Synacthen test (LDST), and the 08:00 hour serum cortisol concentration were measured in 32 patients. A normal response to the synacthen test was defined as a peak serum cortisol of >/= 500 nmol/l and/or incremental concentration of >/= 200 nmol/l. The sensitivity and specificity of the 08:00 hour serum cortisol concentration compared with other tests was calculated.. Three patients had neither an adequate peak nor increment after the SSST and LDST. All had a serum 08:00 hour cortisol concentration of < 200 nmol/l. Eight patients had abnormal responses by both criteria to the LDST but had normal responses to the SSST. Three reported amelioration of their symptoms on hydrocortisone replacement. Twenty one patients had a normal response to both tests (of these, 14 achieved adequate peak and increment after both tests and seven did not have an adequate peak after the LDST but had a normal increment). The lowest 08:00 hour serum cortisol concentration above which patients achieved normal responses to both the LDST and SSST was 500 nmol/l. At this cut off value (compared with the LDST), the serum 08:00 hour cortisol concentration had a sensitivity of 100% but specificity was only 33%.. The LDST revealed mild degrees of adrenal insufficiency not detected by the SSST. The value of a single 08:00 hour serum cortisol concentration is limited.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Biomarkers; Child; Child, Preschool; Circadian Rhythm; Cosyntropin; Female; Humans; Hydrocortisone; Male; Sensitivity and Specificity

Recently the rapid low-dose (1 microgram) cosyntropin test has been found to be superior to the standard (250 micrograms) rapid cosyntropin test for evaluating the hypothalamic-pituitary-adrenal axis. Because the 1-microgram test has not been studied in postoperative patients, we evaluated the test after major abdominal surgery.. We performed rapid 1-microgram cosyntropin tests in 20 patients aged 65 years or older immediately and 24 hours after uncomplicated elective abdominal surgery (group A) and in 10 patients who were suspected of having adrenal insufficiency after abdominal surgery (group B). Subsequently, 250 micrograms of cosyntropin was infused over 8 hours on 2 successive days in group B patients.. Ninety-five percent of group A patients had normal rapid 1-microgram cosyntropin test results immediately after surgery and 90% had normal test results 24 hours postoperatively. Six group B patients had abnormal rapid 1-microgram cosyntropin test results. Additional testing indicated primary adrenal insufficiency in 2 patients and central adrenal insufficiency in 1 patient; another patient probably had primary adrenal insufficiency and 2 patients appeared to be euadrenal. Four group B patients had normal rapid 1-microgram cosyntropin test results. After additional testing, 3 of these patients appeared to have normal adrenal function; 1 probably had primary adrenal insufficiency.. The rapid 1-microgram cosyntropin test accurately evaluated adrenal gland function in selected patients after uncomplicated surgery. The test, however, was difficult to interpret in unselected seriously ill postoperative patients. Therefore we recommend that postoperative patients with unexplained hypotension or other features suggestive of adrenal insufficiency who have random plasma cortisol levels less than 20 micrograms/dL be treated with glucocorticoids and the hypothalamic-pituitary-adrenal axis be studied by standard tests after recovery.

Topics: Abdominal Neoplasms; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Carcinoma; Colectomy; Colonic Neoplasms; Cosyntropin; Female; Humans; Hydrocortisone; Hypotension; Hypothalamo-Hypophyseal System; Male; Postoperative Complications

To investigate adrenocortical function in patients with ruptured aneurysm of the abdominal aorta.. Prospective clinical investigation.. Surgical intensive care unit in a university teaching hospital and intensive care unit in a general hospital.. 54 patients with a documented rupture of the abdominal aorta.. A short adrenocorticotrophic hormone (ACTH) stimulation test was performed.. Patients were studied within 24 h of admission to the hospital. Blood samples for the measurement of cortisol and ACTH were collected at 0800 h. Subsequently 0.25 mg tetracosactrin (Synacthen) was injected i.v. and after 60 min cortisol measurement was repeated. The criterion for a normal short ACTH test was: stimulated or unstimulated cortisol levels > or = 0.55 mumol/l. For the group as a whole, an unstimulated plasma cortisol level of 0.76 mumol/l was comparable to that in other groups of critically ill patients with similar severity of illness. Between survivors and non survivors, significant differences were found between unstimulated plasma cortisol levels (0.70 vs 1.03 mumol/l), stimulated plasma cortisol levels (1.00 vs 1.30 mumol/l), and plasma ACTH levels (72 vs 133 ng/l). One patient did not meet the criteria for normal adrenocortical function: unstimulated plasma cortisol 0.26 mumol/l, stimulated plasma cortisol 0.47 mumol/l.. In the patients studied with ruptured aneurysm of the abdominal aorta, adrenocortical response was comparable to that in other groups of critically ill patients with similar severity of illness. High cortisol levels were associated with mortality. One patient did not meet the criteria for normal adrenocortical function but survival without steroid treatment.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Aged, 80 and over; Anesthetics, Intravenous; Aorta, Abdominal; Aortic Rupture; APACHE; Cosyntropin; Critical Illness; Etomidate; Female; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Postoperative Complications; Prospective Studies

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adult; Clinical Trials as Topic; Cosyntropin; Double-Blind Method; Female; Humans; Hydrocortisone; Injections, Intramuscular; Injections, Intravenous; Male; Random Allocation

While it has been established within the first 4 months of life that there is no circadian rhythm, what is unclear is the usefulness of a random serum cortisol (rSC) level in determining neonatal central adrenal insufficiency (CAI). The objective of the study is to determine the utility of using rSC in infants less than 4 months old in the evaluation of CAI.. Retrospective chart review of infants who underwent a low dose cosyntropin stimulation test ≤4 months of life with rSC taken as baseline cortisol before stimulation. Infants were divided into three groups: those diagnosed with CAI, those at risk for CAI (ARF-CAI) and a non-CAI group. Mean rSC for each group was compared, and ROC analysis was used to identify rSC cut-off for the diagnosis of CAI.. Two hundred and fifty one infants with the mean age of 50.5 ± 38.08 days, and 37% of these were born at term gestation. The mean rSC were lower in the CAI group (1.98 ± 1.88 mcg/dl) as compared to the ARF-CAI (6.27 ± 5.48 mcg/dl, p = .002) and non-CAI (4.6 ± 4.02 mcg/dl, p = .007) groups. ROC analysis identified a cut-off of rSC level of 5.6 mcg/dL is associated with 42.6% sensitivity and 100% specificity for the diagnosis of CAI in term infants.. This study demonstrates that though an rSC can be used within the first 4 months of life, its value is best when done ≤30 days of life. Moreover, a diagnostic cut-off for CAI using rSC levels was identified for term infants.

Topics: Adolescent; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Child; Cosyntropin; Humans; Hydrocortisone; Infant; Infant, Newborn; Middle Aged; Retrospective Studies; Sensitivity and Specificity; Young Adult

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cosyntropin; Humans; Hydrocortisone; Pituitary-Adrenal System

Current peak serum cortisol cutoffs for the diagnosis of adrenal insufficiency (AI) after Cosyntropin stimulation have been established using polyclonal antibody (pAb) immunoassays. However, new and highly specific cortisol monoclonal antibody (mAb) immunoassays are being used more widely, which can potentially yield higher false positive rates. Thus, this study aimed to redefine the biochemical diagnostic cutoff points for AI in children when using a highly specific cortisol mAb immunoassay and liquid chromatography tandem mass spectrometry (LC/MS) to avoid unnecessary steroid use.. Cortisol levels from 36 children undergoing 1 mcg Cosyntropin stimulation tests to rule out AI were measured using pAb immunoassay (Roche Elecsys Cortisol I), mAB immunoassay (Roche Elecsys Cortisol II), and LC/MS. Logistic regression was used to predict AI using the pAB as the reference standard. A receiver operator characteristic curve, area under the curve (AUC), sensitivity, specificity, and kappa agreement were also calculated.. Using a peak serum cortisol cutoff value of 12.5 μg/dL for the mAb immunoassay provided 99% sensitivity and 94% specificity for diagnosing AI, when compared to the historical pAb immunoassay cutoff of 18 μg/dL (AUC=0.997). Likewise, a cutoff of value of 14 μg/dL using the LC/MS, provided 99% sensitivity and 88% specificity when compared to the pAb immunoassay (AUC=0.995).. To prevent overdiagnosis of AI in children undergoing 1 mcg Cosyntropin stimulation test, our data support using a new peak serum cortisol cutoff of 12.5 μg/dL and 14 μg/dL to diagnose AI when using mAb immunoassays and LC/MS in children, respectively.

Topics: Adrenal Insufficiency; Child; Chromatography, Liquid; Cosyntropin; Humans; Hydrocortisone; Immunoassay

Increasing referrals to Endocrinology with nonspecific symptoms of suspected adrenal insufficiency (AI) has increased use of the short-synacthen test (SST). Prevailing resource and safety concerns emphasise importance of patient selection criterion to optimise SST use. This study aimed to (1) document the adverse event profile of the SST (2) identify any pretest predictors of SST outcome.. Retrospective data analysis of all patients referred for SST in Oxford from 2017 to 2021. Pretest clinical variables (age, sex, BMI, blood pressure and electrolytes), symptoms (fatigue, dizziness, weight loss) and pretest morning cortisol were included in the statistical model with the aim of identifying any variables that could predict SST outcome in Group 1 primary AI, Group 2 central AI and Group 3 glucocorticoid induced AI. Symptoms and signs during and post SST were also noted with the aim of describing adverse effects to synacthen across a large cohort.. A total 1480 SSTs (Males:38%, age 52 [39-66] years) were performed: 505 (34.1%) in Group 1, 838 (57%) in Group 2, and 137 (9.3%) in Group 3. Adverse-effects were recorded in 1.8% of tests, including one episode of anaphylaxis. Pretest morning-cortisol was the only predictor for an "SST pass" (whole cohort: B = 0.015, p < 0.001, Group 1: B = 0.018, p < .001; Group 2: B = 0.010, p < 0.012; Group 3: B = 0.018, p = <.001). A threshold of ≥343 nmol/l (receiver-operating characteristic [ROC] area under the curve [AUC] = 0.725, 95% confidence interval [CI] 0.675-0.775, p < 0.001) for the whole cohort, ≥300 nmol/L (ROC AUC = 0.763, 95% CI 0.675 to 0.850, p < 0.001) for Group 1, ≥340 nmol/L (ROC AUC = 0.688, 95% CI 0.615 to 0.761, p < 0.001) for Group2, and ≥376 nmol/L [baseline cortisol] (ROC AUC = 0.783, 95% CI 0.708 to 0.859, p < 0.001) for Group 3, predicted an 'SST pass' with 100% specificity.. Adverse effects to synacthen are rare. Pretest morning cortisol is a reliable predictor for SST outcome and is a helpful tool to rationalise use of the SST. Predictive morning-cortisol thresholds vary according to the aetiology of AI.

Topics: Adrenal Insufficiency; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged; Retrospective Studies; Tertiary Care Centers

Adrenal function tests (Synacthen test) in chronic hemodialysis (HD) patients are currently performed off dialysis. The study aimed to demonstrate equivalence of serum cortisol concentrations pre- and during HD, each for standard-dose (250 µg) and low-dose (1 µg) Synacthen test.. In a single-center cross-over diagnostic equivalence study, Synacthen tests were performed in four settings, in standard- and low-dose as well as pre- and during HD. Serum cortisol concentration was measured at 30 and 60 min after Synacthen administration, and additionally at 20 min in low dose test. Based on a multivariable linear mixed model the means of cortisol concentration on log-scale were estimated in each dose and test time combination. Differences in means were calculated and the TOST approach was applied to test for equivalence. Equivalence was proven if the 90% confidence interval of the difference of two cortisol means was entirely between - 0.22 and 0.22.. In 28 chronic HD patients, serum cortisol concentrations at 30 and 60 min after Synacthen administration in both standard- and low-dose were shown to be equivalent pre- and during HD. In 10 of 56 low-dose tests, the cortisol peak was already reached after 20 min. However, cortisol concentrations at 20 and 30 min after low-dose Synacthen test pre- and during HD showed no significant difference.. These results suggest that the adrenal function test may be carried out during an ongoing HD session, leading to a more patient-friendly performance of the test, less organizational effort and potentially earlier diagnosis of adrenal insufficiency.

Topics: Adrenal Insufficiency; Cosyntropin; Humans; Hydrocortisone; Renal Dialysis; Time Factors

We aimed to (1) examine the diagnosis of opioid-induced adrenal insufficiency, and (2) investigate the diagnostic value of a morning cortisol <83 nmol/L (3 µg/dl) for the diagnosis of adrenal insufficiency, using newer more specific cortisol assays and cut-offs.. Retrospective study (5/2015-10/2020).. Cohort 1 (N = 75): adults who underwent cosyntropin stimulation testing and opioid exposure for >30 days. Cohort 2 (N = 854): adults, with or without opioid exposure, who had a morning cortisol level measured the same day as stimulation testing.. Peak cortisol during cosyntropin stimulation testing. Sensitivity and specificity of morning serum cortisol for adrenal insufficiency.. The prevalence of adrenal insufficiency in patients with chronic opioid exposure who underwent cosyntropin stimulation testing was 4.0% using a cortisol cutoff of <405 nmol/L (14.7 µg/dl) versus 19% using the traditional cutoff of <500 nmol/L (18.1 µg/dl). For hospitalized patients with and without opioid-exposure, 14 of 22 (64%) patients with morning cortisol levels of <83 nmol/L (3 µg/dl) passed cosyntropin stimulation testing. A morning cortisol level of <348 nmol/L (12.6 µg/dl) had 100% sensitivity (95% confidence interval: 84.5%-100%) for the diagnosis of adrenal insufficiency.. Applying a cutoff of <405 nmol/L (14.7 µg/dl), opioid-induced adrenal insufficiency is rare. Nearly 1 out of 6 patients would be reclassified as having adrenal insufficiency applying the guideline-recommended cutoff of <500 nmol/L (18.1 µg/dl). Serum morning cortisol <83 nmol/L (3 µg/dl) is not a valid diagnostic test for adrenal insufficiency in hospitalized patients, whether or not receiving opioids.

Topics: Adrenal Insufficiency; Adult; Analgesics, Opioid; Cosyntropin; Hospitalization; Humans; Hydrocortisone; Retrospective Studies

An institutional study previously demonstrated that cosyntropin stimulation testing on postoperative day 1 (POD1-CST) identified patients at risk for adrenal insufficiency (AI) following unilateral adrenalectomy (UA) for adrenal-dependent hypercortisolism (HC) and primary aldosteronism (PA), allowing for selective glucocorticoid replacement (GR).. This study re-evaluates the need for GR following UA for patients with HC and PA in a larger cohort.. A prospective database identified 108 patients who underwent UA for mild autonomous cortisol excess (MACE) (n = 47), overt hypercortisolism (OH) (n = 27), PA (n = 22), and concurrent PA/HC (n = 12) from September 2014 to October 2020; all underwent preoperative evaluation for HC. MACE was defined by the 1 mg dexamethasone suppression test (cortisol >1.8 μg/dL), with ≥5 defined as OH. GR was initiated for basal cortisol ≤5 or stimulated cortisol ≤14 (≤18 prior to April 2017) on POD1-CST.. Fifty-one (47%) patients had an abnormal POD1-CST; 54 (50%) were discharged on GR (27 MACE, 20 OH, 1 PA, 6 PA/HC). Median duration of GR was OH: 6.0 months, MACE: 2.1 months, PA: 1 month, PA/HC: 0.8 months. Overall, 26% (n = 7) of patients with OH and 43% (n = 20) of patients with MACE did not require GR. Two (2%) patients with OH had normal POD1-CST but developed AI several weeks postoperatively requiring GR. None experienced life-threatening AI.. POD1-CST identifies patients with HC at risk for AI after UA, allowing for selective GR. One-quarter of patients with OH and nearly half of patients with MACE can forgo GR after UA. Patients with PA do not require evaluation for AI if concurrent HC has been excluded preoperatively.

Topics: Adrenal Glands; Adrenal Insufficiency; Adrenalectomy; Aged; Cosyntropin; Cushing Syndrome; Female; Glucocorticoids; Hormone Replacement Therapy; Humans; Hyperaldosteronism; Male; Middle Aged; Postoperative Complications; Postoperative Period; Prospective Studies; Retrospective Studies; Risk Assessment

The diagnosis of adrenal insufficiency relies on clear cut-offs and accurate measurement of cortisol levels. Newer monoclonal antibody assays may increase the rate of diagnosis of adrenal insufficiency if traditional cortisol cut-off levels <18 mcg/dL (500 nmol/L) are applied. We aimed to determine if the rate of diagnosis of adrenal insufficiency using a 1 mcg Cosyntropin stimulation test varied with the change in cortisol assay from a polyclonal to a monoclonal antibody assay.. Cortisol levels obtained during the 1 mcg Cosyntropin stimulation test performed in the last semester of 2016 using a polyclonal antibody cortisol assay were compared to tests performed using a monoclonal antibody cortisol assay during the first semester of 2017. Cosyntropin tests included cortisol values obtained at baseline, 20 min and 30 min after IV administration of 1 mcg Cosyntropin. Peak cortisol cut-off value <18 mcg/dL was used to diagnose adrenal insufficiency.. Stimulated cortisol values after 1 mcg Cosyntropin using the monoclonal assay in 2017 (n=38) were significantly lower (33%) compared to those obtained with the polyclonal assay in 2016 (n=27) (p-value <0.001). The number of passing tests with a peak cortisol value >18 mcg/dL fell from 74% in 2016 (20 out of 27 tests) to 29% in 2017 (11 out of 38 tests).. The change in cortisol assay substantially increased the number of patients diagnosed with adrenal insufficiency after 1 mcg Cosyntropin stimulation testing. Standardization of cortisol assays and diagnostic criteria is critical for the accurate diagnosis of adrenal insufficiency.

Topics: Adrenal Insufficiency; Cosyntropin; Humans; Hydrocortisone

The accurate interpretation of the cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation test requires method- and assay-specific cutoffs of the level of cortisol. Compared with a historical cutoff (18 μg/dL) for polyclonal antibody-based immunoassays, lower thresholds were proposed for the Roche Elecsys II assay, which uses a monoclonal antibody. However, cutoffs for other commonly adopted, monoclonal antibody-based cortisol assays were not yet available. Here, we established the thresholds for the level of cortisol specific to the Abbott Architect immunoassay by comparing the measurements of the level of cortisol using 3 immunoassays.. The ACTH stimulation test was performed in patients with suspected adrenal insufficiency (n = 50). The serum cortisol level was measured using the Abbott Architect, Roche Elecsys II, and Siemens Centaur assays. The results of the Abbott assay were also compared with those of liquid chromatography-tandem mass spectrometry. The receiver operating characteristic analysis was performed to derive new diagnostic thresholds for the Abbott assay using the polyclonal antibody-based Siemens assay as the reference method.. The concentrations of cortisol measured using the Abbott assay were similar to those measured using liquid chromatography-tandem mass spectrometry and the Roche Elecsys II assay but significantly lower than those measured using the Siemens assay. The optimized threshold for cortisol using the Abbott assay was 14.6 μg/dL at 60 minutes after stimulation (sensitivity, 92%; specificity, 96%) and 13.2 μg/dL at 30 minutes after stimulation (sensitivity, 100%; specificity, 89%).. We recommend a threshold of 14.6 μg/dL for the level of cortisol at 60 minutes after ACTH stimulation for the Abbott assay. In comparison with the historical threshold of 18 μg/dL, the application of the new cutoff may significantly decrease false-positive results due to ACTH stimulation testing. The use of assay-specific cutoffs will be essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Antibodies, Monoclonal; Cosyntropin; Humans; Hydrocortisone; Immunoassay

There is emerging speculation that the inflammatory state associated with SARS-CoV-2 infection may trigger autoimmune conditions, but no causal link is established. There are reports of autoimmune thyroiditis and adrenal insufficiency in adults post-COVID-19. We describe the first pediatric report of adrenal insufficiency and autoimmune hypothyroidism after COVID-19.. A 14-year-old previously healthy girl, with vitiligo, presented in shock following 1 week of fever, lethargy, diarrhea, and vomiting. Three weeks prior, she had congestion and fatigue and known familial exposure for COVID-19. Labs were remarkable for sodium 129 mmol/L, K 4.3 mmol/L, creatinine 2.9 mg/dL, hemoglobin 8.3 g/dL, and positive COVID-19 PCR and SARS-CoV-2 IgG. She was resuscitated with normal saline and required pressor support. EKG showed abnormal repolarization presumed secondary to myocarditis. She met the criteria for multisystem inflammatory syndrome in children (MIS-C), received intravenous immune globulin and IL-1R antagonist and was admitted for intensive care. Persistent hypotension despite improved inflammatory markers and undetectable cortisol led to initiation of hydrocortisone. She was then able to rapidly wean off pressors and hydrocortisone within 48 h. Thereafter, tests undertaken for persistent bradycardia confirmed autoimmune hypothyroidism with TSH 131 μU/mL, free T4 0.85 ng/dL, and positive thyroid autoantibodies. Basal and stimulated cortisol were <1 μg/dL on a standard 250 μg cosyntropin stimulation test, with baseline ACTH >1,250 pg/mL confirming primary adrenal insufficiency. Treatment was initiated with hydrocortisone, levothyroxine, and fludrocortisone. Adrenal sonogram did not reveal any hemorrhage and anti-adrenal antibody titers were positive. The family retrospectively reported oligomenorrhea, increased salt craving in the months prior, and a family history of autoimmune thyroiditis. The cytokine panel was notably different from other cases of MIS-C.. This is the first pediatric report, to our knowledge, of primary adrenal insufficiency and hypothyroidism following COVID-19, leading to a unique presentation of autoimmune polyglandular syndrome type 2. The initial presentation was attributed to MIS-C, but the subsequent clinical course suggests the possibility of adrenal crisis. It remains unknown if COVID-19 had a causal relationship in triggering the autoimmune adrenal insufficiency and hypothyroidism.

Topics: Addison Disease; Adolescent; Adrenal Insufficiency; Adult; Autoantibodies; Child; Cosyntropin; COVID-19; Creatinine; Cytokines; Female; Fludrocortisone; Hashimoto Disease; Humans; Hydrocortisone; Hypothyroidism; Immunoglobulins, Intravenous; Retrospective Studies; Saline Solution; SARS-CoV-2; Sodium; Systemic Inflammatory Response Syndrome; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine

To examine adrenal cortex reserve in patients with rheumatic and musculoskeletal diseases (RMD) who relapse upon tapering of low glucocorticoid dose, despite concomitant treatment with disease-modifying anti-rheumatic drugs (DMARDs).. A morning standard dose of 250 mcg tetracosactide (Synacthen test) was given in 25 consecutive patients (13 rheumatoid arthritis, 2 psoriatic arthritis, 5 systemic lupus erythematosus, 2 dermatomyositis, 1 systemic sclerosis, 2 temporal arteritis) at the time of relapse upon small reductions (1-2 mg daily) of low prednisolone dose (<7.5 mg daily), while being on stable concomitant treatment with methotrexate, leflunomide, hydroxychloroquine, azathioprine, mycophenolate, tofacitinib, belimumab, anti-TNF, anti-IL-6 or anti-IL-1 regimens (n=14; 3; 9; 1; 2; 1; 1; 5; 2; 1, respectively). Sex-matched apparently healthy individuals (n=45) served as controls.. Baseline cortisol levels and time-integrated cortisol response to tetracosactide were lower in patients than controls (12.01±4.47 vs. 15.63±4.16 mcg/dl, p=0.001, and 1050±286 vs. 1284±182, p<0.001, respectively). No significant associations were observed between the cortisol response to tetracosactide and age, duration of disease or glucocorticoid treatment. An abnormal Synacthen test, indicative of adrenal insufficiency, presumably secondary to chronic glucocorticoid administration, was noted in 5/25 patients. The remaining 20 patients (80%) had normal Synacthen test demonstrating, however, lower cortisol response than controls, independently of age (β-coefficient=-0.373, p=0.033).. Patients with RMD in remission under DMARDs who relapse upon concomitant low glucocorticoid dose tapering should be tested for iatrogenic adrenal insufficiency. Whether a marginally normal Synacthen test should discourage further attempts to withdraw glucocorticoid treatment in these patients warrants further investigation.

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Adrenal Insufficiency; Antirheumatic Agents; Arthritis, Rheumatoid; Azathioprine; Chronic Disease; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone; Hydroxychloroquine; Leflunomide; Methotrexate; Prednisolone; Recurrence; Tumor Necrosis Factor Inhibitors

We report here a woman in her 70s presenting with adrenal insufficiency secondary to a primary adrenal lymphoma. The patient had a previous history of aphthous ulcers on dexamethasone and was referred to endocrinology with symptoms of fatigue and orthostasis. Subsequent Cosyntropin stimulation showed primary adrenal insufficiency and adrenal CT demonstrated large infiltrative masses. Adrenal biopsy confirmed the diagnosis of primary adrenal lymphoma of the B-cell type. This case demonstrates the importance of including lymphoma in the differential diagnosis of adrenal insufficiency, particularly in the elderly population and in the setting of negative 21-hydroxlyase antibody results.

Topics: Addison Disease; Adrenal Gland Neoplasms; Adrenal Insufficiency; Aged; Cosyntropin; Dexamethasone; Female; Humans; Lymphoma; Lymphoma, B-Cell; Tomography, X-Ray Computed

The short Synacthen test (SST) is widely used to assess the hypothalamus-pituitary-adrenal axis in the outpatient setting. However, in the inpatient setting, technical difficulties to adhere to the protocol may pose a challenge for using this test.. To find the most suitable basal serum cortisol (BSC) cut-off for predicting an adequate response to the SST in non-critically inpatients without conducting the actual test.. Information was retrieved retrospectively from medical files of 197 patients who had had a 250 μg SST between the years 2000 and 2016 at the Shaare Zedek Medical Center. BSC, electrolytes, creatinine, thyroid-stimulating hormone, blood counts and blood pressure values were evaluated for a correlation with the results of the SST.. A BSC cut-off of 280 nmol/L provides a negative predictive value of 94% for adrenal insufficiency (AI). Using a cut-off of 380 nmol/L increases the sensitivity to 96% and yields a negative predictive value of 95.8%.. In this study, we found two suitable BSC cut-offs for predicting an adequate response to the SST in hospitalised patients. We suggest using the lower cut-off (280 nmol/L) for patients with a low level of suspicion for AI and using the higher cut-off (380 nmol/L) for patients with a higher level of suspicion. A BSC above this cut-off makes the diagnosis of AI very unlikely and precludes the need for a Synacthen test.

Topics: Adrenal Insufficiency; Cosyntropin; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Retrospective Studies

The short synacthen test (SST) is widely used across the UK to assess adrenal reserve. The main objective of our study was to determine the morning serum cortisol level that will predict adrenal insufficiency (AI) thus reducing our reliance on SST.. This was a single centre retrospective study of 393 SST tests measuring 0 and 60 min cortisol levels after administration of 250 μg of synacthen (synthetic ACTH).. All the SST tests for patients suspected of primary or secondary AI between April 2016 and October 2018 were included in this study. We used serum to determine circulating cortisol by a newer generation competitive electrochemiluminescence immunoassay (ECLIA) (Roche Diagnostics). A post-ACTH cortisol response of ≥420 nmol/L at 60 min was considered adequate to rule out AI. The data were analysed to ascertain the relationship between 0 min and 60 min serum cortisol.. A total of 393 SST results were included in this study. Overall, a total of 332 (84.5%) subjects achieved sufficient serum cortisol level at 60 min, while 61 subjects (15.5%) showed insufficient response. Using the logistic regression, we determined that a morning basal serum cortisol level of ≥354 nmol/L was able to predict normal adrenal function with 100% sensitivity. We were unable to find a lower cut-off value below which SST will not be required. By using this proposed cut-off point, approximately 37% of the SSTs tests could be avoided.. Basal morning serum cortisol can be safely used as a first step in the evaluation of patients with suspected AI. This will enhance the number of patients being screened for this condition.

Topics: Adrenal Insufficiency; Adult; Aged; Cosyntropin; Diagnostic Tests, Routine; Female; Humans; Hydrocortisone; Male; Middle Aged; Retrospective Studies

Topics: Adrenal Insufficiency; Cortisone; Cosyntropin; Humans; Hydrocortisone

Topics: Acute Disease; Adrenal Insufficiency; Cosyntropin; Humans; Hydrocortisone

BACKGROUND This case report illustrates the difficulties that arise during diagnosis of adrenal insufficiency, especially in the general medicine setting. Symptoms can often be nonspecific, and when a serum cortisol level is checked, further difficulty exists as to how to interpret the results. The 250-μg cosyntropin dose or 1-μg dose are available for use in the diagnosis of adrenal insufficiency, but each test has its own indications, which will be discussed. CASE REPORT A 45-year-old woman presented with nausea, emesis, chills, and diaphoresis, symptoms that concerning for adrenal insufficiency. Her random serum cortisol levels were relatively low. Her ACTH levels were within normal range. She received additional testing with the ACTH stimulation test using both the 1-μg and the 250-μg dose. The 1-μg test was performed in the evening and showed an inadequate adrenal response. The 250-μg dose test, which is the criterion standard, was performed the following morning and excluded adrenal insufficiency. CONCLUSIONS With the use of the high-dose ACTH stimulation test performed in the early morning, this patient was able to avoid lifelong steroid replacement therapy that could potentially suppress the hypothalamic-pituitary-adrenal (HPA) axis, which of itself can lead to adrenal insufficiency. Careful consideration is needed in choosing the right modalities for diagnosis of adrenal insufficiency.

Topics: Adrenal Insufficiency; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Pituitary-Adrenal System

Tuberculosis of the adrenal glands may cause overt or subclinical adrenal insufficiency. An algorithm-based approach including assessment of paired basal cortisol and plasma adrenocorticotropic hormone (ACTH), short Synacthen, and plasma renin activity assays could be useful to diagnose all forms of adrenal insufficiency.. This cross-sectional study included consecutive, treatment-naive subjects diagnosed with pulmonary tuberculosis. Tuberculosis severity was classified by radiological criteria. Baseline parameters plus morning (8 am) serum cortisol and paired plasma ACTH were measured in all patients. Synacthen stimulation tests and plasma renin activity assays were performed as required.. Eighty-four treatment-naive consecutive cases of pulmonary tuberculosis were evaluated for adrenal insufficiency. Twenty-seven (32.14%) subjects had normal adrenocortical function and 8 (9.5%), 7 (8.3%), 40 (47.6%), and 2 (2.4%) subjects had stage 1, stage 2, stage 3, and stage 4 adrenal insufficiency, respectively. Serum cortisol was negatively correlated with radiological severity (P = .01) and duration of illness (P = .001). Adrenal dysfunction was present in 27.3%, 82.5%, and 80% of those with radiologically minimal, moderately advanced, and far-advanced disease, respectively. Mean cortisol was 19.74 ± 5.52, 17.42 ± 8.53, and 15.71 ± 7.14 (μg/dL) in the 3 groups, respectively (P = .042). Hyponatremia was present in 83.3% of the patients. Serum sodium was negatively correlated with severity but not with the duration of disease.. The prevalence of overt and subclinical adrenal dysfunction in pulmonary tuberculosis was high and was correlated with disease severity and duration. An algorithmic approach may be useful to detect the same and may have important clinical implications.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cosyntropin; Cross-Sectional Studies; Humans; Hydrocortisone; Tuberculosis, Pulmonary

Cortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center.. Data were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing's syndrome were excluded.. The median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement.. Synacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Insufficiency; Adrenalectomy; Adult; Aged; Cosyntropin; Cushing Syndrome; Dexamethasone; Endocrinology; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Pheochromocytoma; Postoperative Period; Retrospective Studies

In recent years, the short Synacthen test (SS) has become the most widely used test to assess adrenal reserve. Despite its frequent use, there are still several areas related to the short Synacthen test (SST), which have no consensus including the optimum sampling times, that is, whether a 60 min post-Synacthen administration cortisol is necessary or not.. We performed a retrospective data analysis of 492 SSTs performed on adult patients in a tertiary referral teaching hospital in Ireland. The SSTs were performed in the inpatient and outpatient setting and included patients across all medical disciplines and not exclusively to the endocrinology department.. 313 patients had 0, 30 and 60 min samples available for analysis. A total of 270/313 (82%) were deemed to pass the test, that is, cortisol ≥500 nmol/L at both 30 and 60 min. Of the 313 patients, 19 (6%) patients had an indeterminate response, cortisol <500 nmol/L at 30 min, but rising to ≥500 nmol/L on the 60 min sample. Of these 19 patients, only 9/19 patients had a serum cortisol level at 30 min <450 nmol/L, requiring clinical treatment with glucocorticoid replacement. All 24/313 (8%) patients who had insufficient responses at 60 min were also insufficient at 30 min sampling. No individuals passed (≥500 nmol/L) at 30 min and then failed (<500 nmol/L) at 60 min.. Using the 30 min cortisol sample post-Synacthen administration alone identifies clinically relevant adrenal insufficiency in the majority of cases. A small subset of patients have a suboptimal response at 30 min but have a 60 min cortisol concentration above the threshold for a pass. Data regarding the long-term outcomes and management of such patients are lacking and require further study.

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Adult; Aged; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Retrospective Studies; ROC Curve; Time Factors

Fatigue is a common symptom in patients visiting the clinic of psychosomatic medicine. A 250-μg synthetic ACTH (1-24) test (rapid ACTH test) and Beck depression inventory (BDI) were performed for 62 patients presenting with fatigue who visited the Department of Psychosomatic Medicine at Fukuoka Tokushukai Hospital. Patients were divided into 3 groups according to the serum cortisol response to the rapid ACTH test; those with a peak serum cortisol level of <15 μg/dL were defined as the adrenal insufficiency (AI) probable group, ≥15 μg/dL and <18 μg/dL as the AI suspected group, and ≥18 μg/dL as the non-AI group. Patients prescribed anti-depressants, had a BDI ≥16, and/or met the full criteria for major depression were diagnosed with depression. Five (8.0%) and 7 patients (11.3%) were assigned to the AI probable and AI suspected groups, respectively. All others were assigned to the non-AI group. Depression was observed in 37 patients (59.6%; 4 in the AI probable group [80.0%], 4 in the AI suspected group [57.1%], and 29 in the non-AI group [58.0%]). Users of exogenous steroids, such as inhaled steroids for bronchial asthma, were seen in the AI probable group (2; 40.0%), the AI suspected group (3; 42.8%), and the non-AI group (7; 14.0%) (χ

Topics: Administration, Inhalation; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Antidepressive Agents; Cosyntropin; Depressive Disorder; Fatigue; Female; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Psychosomatic Medicine

While the ACTH1-24 test has some well-documented shortcomings, it is the most widely used test to diagnose primary and secondary adrenal insufficiency. However, this synthetic ACTH preparation is not readily available in some countries. Research from India has demonstrated that using a long-acting porcine sequence ACTH has similar diagnostic performance to ACTH1-24 at around 25% of the cost. This may allow access to a robust test for adrenal insufficiency to developing countries and potentially allow thousands of patients to be identified and appropriately treated.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Animals; Cosyntropin; India; Swine

The short synacthen test (SST) is widely used across the UK to assess adrenal reserve but there remains no consensus on the timing of cortisol sampling to help diagnose adrenal insufficiency. The main objective of our study was to see if both 30 and 60 min sample are required following administration of synacthen to investigate suspected adrenal insufficiency (AI).. This was a single-centre retrospective study of 393 SSTs measuring 0, 30 and 60 min cortisol levels after administration of 250 µg of synacthen.. All the SSTs for patients suspected of primary or secondary AI between April 2016 and October 2018 were included in this study. The tests were performed as per our hospital protocol. A post-adrenocorticotropic hormone (ACTH) cortisol response of 420 nmol/L at any time point was considered adequate to rule out AI. The data were analysed to ascertain the proportion of patients who achieved this level at 30 and/or 60 min.. A total of 393 SST results were included in this study. Patients were divided into two groups depending on whether (group A) or not (group B) they were on steroids. Overall, a total of 313 (79.6%) subjects achieved cortisol level of ≥420 nmol/L at 30 and 60 min while 19 (4.8%) had late response (ie, insufficient 30 min cortisol levels, rising to ≥420 nmol/L at 60 min). Another 61 subjects (15.5%) showed insufficient response at both 30 and 60 min (ie, failed to achieved level of ≥420 nmol/L). Importantly, there was no patient in either group who had adequate response at 30 min and then failed at 60 min. Patients in group A were more likely to have inadequate response at both 30 and 60 min while patients in group B were more likely to have normal response at both time points.. Our results suggest that about 5% of people undergoing SST may be inappropriately diagnosed as having AI (and subjected to long-term unnecessary steroid treatment) if the 60 min sample is not maintained. We suggest that 30 min sample does not add any additional diagnostic utility and can be omitted thus simplifying SST even further and saving on cost and resources. We propose that single measurement after 60 min of administration of synthetic ACTH is a sufficient screening test for AI.

Topics: Adrenal Insufficiency; Adult; Aged; Cosyntropin; Diagnostic Tests, Routine; Female; Humans; Hydrocortisone; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; United Kingdom

To determine if treatment with ACTH for infantile spasms (IS) is associated with secondary adrenal insufficiency.. This is a retrospective study of patients diagnosed with infantile spasms and treated with ACTH between 2007 and 2018 at Soroka University Medical Center (SUMC). We reviewed the records of patients who had a post-hormonal laboratory assessment of their adrenal function; either a low dose ACTH test or a random morning cortisol level and looked for laboratory or clinical signs of adrenal insufficiency.. Between the years 2007 and 2018, 45 children were diagnosed with IS at our Pediatric Neurology Unit, 20 patients were treated with ACTH, of them 14 children met the inclusion criteria and had a post-treatment laboratory assessment of adrenal function by low dose ACTH test or morning cortisol level. Five children had a normal low dose ACTH test, two had normal morning cortisol level, five were not conclusive, and two had subnormal levels of cortisol. None of the children showed clinical signs of adrenal insufficiency.. Our study adds to the limited literature on this topic and in contrast to previous publications suggests that adrenal suppression should not occur after ACTH treatment.

Topics: Adrenal Glands; Adrenal Insufficiency; Cohort Studies; Cosyntropin; Female; Hormones; Humans; Infant; Male; Retrospective Studies; Spasms, Infantile

Synacthen stimulated salivary cortisol has been previously evaluated and found beneficial in the diagnosis of adrenal insufficiency (AI), especially in situations with altered cortisol-binding protein (CBG) levels. Unfortunately, Synacthen is not marketed in many parts of the world whereas porcine sequence corticotrophin (Acton Prolongatum) is readily available. This study aimed to find the diagnostic accuracy of Acton prolongatum stimulated salivary cortisol test (APSST) compared to the short synacthen test (SST).. Consecutive outpatients with suspected AI underwent SST initially, followed by APSST after 3 days. For APSST, saliva was collected at 0, 60 and 120 minutes after administering 30 units Acton Prolongatum intramuscularly. Serum and salivary cortisol were estimated using electrochemiluminescence assay. (Cobas e 411, Elecsys Cortisol II kits) RESULTS: Sixty-seven patients with clinically suspected AI were enrolled for the study. Based on SST, 35 patients were classified as having AI [primary AI (n=19) and secondary AI (n=16)] whereas 32 had normal glucocorticoid reserve. The area under receiver operator curve of 0.99 and 0.98 was observed for salivary cortisol values at 60 and 120 minutes, respectively, for APSST. A cut-off value of 18.5 nmol/L (0.67 µg/dL) and 29.3 nmol/L (1.06 µg/dL) at 60 and 120 minutes, respectively, had a sensitivity as well as specificity of 93%-100% in diagnosing AI.. Salivary cortisol estimation following stimulation using intramuscular porcine ACTH (Adrenocorticotrophic hormone) (30 units) is an economical and accurate alternative to SST in the diagnosis of AI, m and its level of 30 nmol/L or more at 2 hours confirms adrenal sufficiency.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Animals; Cosyntropin; Humans; Hydrocortisone; Saliva; Swine

Topics: Adrenal Insufficiency; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone

To assess and compare diagnostic value of 30-minute cortisol level over 60-minute level in the diagnosis of adrenal insufficiency.. The comparative cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from August 2017 to May 2018, and comprised patients referred to the facility for short synacthen test with suspicion of adrenal insufficiency. Blood samples for serum cortisol were taken at time-0 and then 30 and 60 minutes after the adreno-cortico-tropic hormone injection. Total serum cortisol was measured. Adrenal insufficiency was defined as stimulated cortisol level <500 nmol/l at 30 and 60 minutes post-stimulation. SPSS 24 was used for data analysis.. Of the 111 subjects, 56(50.4%) were males and 55(49.5%) were females. Overall mean age was 34±20 years. Mean basal serum cortisol level was 110±98 nmol/l in patients with adrenal insufficiency and it was 294±164 nmol/l in patients with intact adrenal functions. Cortisol level at both 30 and 60 minutes was significant (p<0.001). Receiver Operating Characteristics curve was plotted which showed area under curve of 0.83 and 0.82 for 60 and 30 minutes respectively.. The 30-minute cortisol level post-stimulation carried no diagnostic value . Measuring cortisol level once at 60-minute post-stimulation would be of more value apart from being cost-effective in the diagnosis of adrenal insufficiency.

Topics: Adolescent; Adrenal Insufficiency; Adult; Cosyntropin; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Male; Middle Aged; Pituitary-Adrenal Function Tests; Predictive Value of Tests; Young Adult

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cosyntropin; Humans

Earlier research on 1 μg low-dose test (LDT) performed using 20.3 cm plastic IV tubing on healthy volunteers, has shown that afternoon testing was associated with a sevenfold increased likelihood of failing the test. Nevertheless, it has been claimed that subnormal cortisol response using plastic tubes might have resulted from cosyntropin adherence to the tube and, thus, loss of the delivered dosage. Following from our previous study, which showed that using a short (2.5 cm) plastic tube does not alter in-vitro-cosyntropin dosage delivery or healthy-volunteers' morning cortisol responses, we predicted that, when using the same short plastic tube, LDT would show comparable morning and afternoon cortisol stimulation. The current study was designed to investigate this prediction by comparing morning and afternoon cortisol responses in healthy volunteers during LDT, using a short plastic tube.. Thirteen healthy adult volunteers were recruited for the study. Each subject underwent morning and afternoon LDT via 25 mm plastic intravenous line tube. Baseline serum cortisol (SC) in addition to SC and salivary free cortisol (SFC) 30-minute responses were determined.. Mean baseline morning SC concentration was higher in the morning than in the afternoon (13.63±3.42 and 9.18±2.78 μg/dL, respectively; P<0.001); however, mean absolute SC-concentration increment between baseline and 30-minute time point was higher in the afternoon than in the morning (11.89±3.50 and 7.71±3.12 μg/dL, respectively; P=0.002). Subsequently, LDT resulted in comparable morning and afternoon 30-minute SC (21.33±3.08 and 21.08±3.43 μg/dL, respectively; P=0.782) and SFC concentration (0.939±0.256 and 1.036±0.372 μg/dL, respectively; P=0.463).. In healthy volunteers, using a 2.5 cm plastic tube, LDT provides comparable morning and afternoon 30-minute stimulated SC and SFC concentration.

Topics: Adrenal Insufficiency; Adult; Cosyntropin; Female; Healthy Volunteers; Humans; Hydrocortisone; Male; Middle Aged; Saliva; Time Factors

Topics: Adolescent; Adrenal Insufficiency; Child; Cosyntropin; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Female; Hormones; Humans; Hydrocortisone; Male

Glucocorticoids (GCs) are frequently used to treat glomerular diseases but are associated with multiple adverse effects including hypothalamic-pituitary-adrenal axis inhibition that can lead to adrenal insufficiency (AI) on withdrawal. There is no agreed GC tapering strategy to minimise this risk.. This is a single centre retrospective study, between 2013 to 2016, of patients with glomerular disease on GC therapy for more than 3 months screened for GC induced AI with short synacthen stimulation tests (SSTs) done prior to complete GC withdrawal. We investigated the prevalence of AI, predictors, choice of screening tool and recovery.. Biochemical evidence of GC induced AI was found in 57 (46.3%) patients. Total duration of GC did not differ between those with and without AI (p = 0.711). Patients with GC induced AI had a significantly lower pre-synacthen baseline cortisol as compared to patients without AI. A cut off pre-synacthen baseline cortisol of ≥223.5 nmol/l had a specificity of 100% for identifying individuals without biochemical AI. Patients with GC induced AI took a mean of 8.7 ± 4.6 months (mean ± SD) to recover. Patients with persistent AI had a significantly lower index post-synacthen cortisol measurement.. We demonstrate that biochemically proven GC induced AI is common in patients with glomerular diseases, is not predicted by daily dose or duration and takes a considerable time to recover. The study supports the use of morning basal cortisol testing as an appropriate means to avoid the need for SSTs in all patients and should be performed in all patients prior to consideration of GC withdrawal after 3 months duration.

Topics: Adrenal Insufficiency; Biomarkers; Cosyntropin; Female; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Kidney Diseases; Kidney Glomerulus; Male; Methylprednisolone; Middle Aged; Pituitary-Adrenal System; Prednisolone; Retrospective Studies; ROC Curve; Time Factors

Central adrenal insufficiency (AI) can be diagnosed with the low-dose ACTH stimulation test (LDST). Protocols determining timing of cortisol sampling vary, with 30 minutes after stimulation being most common.. To determine optimal times to draw cortisol levels and factors predicting timing of peak cortisol levels in children undergoing LDST.. Retrospective chart review of LDSTs between February 2014 and September 2017.. The Children's Hospital of Eastern Ontario.. Patients 3 months to 20 years who underwent LDSTs.. LDSTs were performed with cortisol levels at 0, 15, 30, and 60 minutes after 1 μg cosyntropin. Cortisol values <18 μg/dL (500 nmol/L) determined AI.. The incremental value of testing cortisol at 15 or 60 minutes, in addition to the standard 30-minute sample, was estimated.. A total of 221 patients met inclusion criteria. The mean age was 9.7 years, and 32% were female. Peak cortisol levels were 19%, 67%, and 14% at 15, 30, and 60 minutes, respectively. One false positive LDST result would be prevented for every 24 (95% CI, 13 to 46) or 55 (95% CI, 22 to 141) patients tested at 15 or 60 minutes in addition to the standard 30-minute test. Of the 122 patients who passed the LDST, discontinuing the 15- and 60-minute samples would have misdiagnosed 12 patients (9.8%). Glucocorticoid exposure, age, and body mass index z scores were independent predictors of peak cortisol timing.. Although the majority of patients peak 30 minutes after cosyntropin administration, testing cortisol levels at 15 and 60 minutes reduces the risk of false positive LDSTs.

Topics: Adolescent; Adrenal Insufficiency; Adrenocorticotropic Hormone; Child; Child, Preschool; Cosyntropin; Female; Glucocorticoids; Humans; Hydrocortisone; Infant; Male; Retrospective Studies; Time Factors; Young Adult

Topics: Adrenal Insufficiency; Cosyntropin; Glucocorticoids; Humans; Pituitary-Adrenal System; Pneumonia

The ACTH. Case-control study in a clinical research facility. Eighty-seven patients with suspected cortisol deficiency, twenty-four healthy controls, and ten healthy women on the oral contraceptive (OC) underwent an intravenous 250 µg ACTH. There was a significant difference in serum cortisol between the healthy volunteers and the women on the OC (P < 0.001) but no difference in salivary cortisol. The lower limit of the reference interval for salivary cortisol at 60 min was 26 nmol/L. 27/89 (30%) of tests with suspected HPA axis disorder failed the 60 min serum cortisol cut-off of 500 nmol/L. Of these, 24/27 (89%) had a salivary cortisol of <26 nmol/L. In contrast, 12/19 (63%) tests and 5/43 (12%) tests where the 60 min serum cortisol was 500-599 and ≥600 nmol/L, respectively had a salivary cortisol of <26 nmol/L.

Topics: Adolescent; Adrenal Insufficiency; Adult; Cosyntropin; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Saliva; Young Adult

We retrospectively evaluated the diagnoses and outcomes in 68 infants who had a SDST at age <6 months from 2011 to 2014.. Specific aetiology can be identified in a third of infants with a subnormal SDST. When the aetiology remains elusive, adrenal function should be reassessed as the problem can be transient.

Topics: Adrenal Cortex; Adrenal Insufficiency; Cosyntropin; Diagnosis, Differential; Diagnostic Techniques, Endocrine; Female; Gestational Age; Hormones; Humans; Infant; Infant, Premature; Male

The short synacthen test (SST) is widely used to assess patients for adrenal insufficiency, but the frequency and protocols used across different centres for the low-dose test (LDT) are unknown. This study aimed to survey centres and test the accuracy of ten different synacthen preparation strategies used for the LDT.. Members of 6 international endocrine societies were surveyed regarding diagnostic tests used for adrenal insufficiency, and in particular the SST. Synacthen was diluted for the LDT and concentrations measured using a synacthen ELISA.. Survey responses were received from 766 individuals across 60 countries (52% adult, 45% paediatric endocrinologists). The SST is used by 98% of centres: 92% using high-dose (250 μg), 43% low-dose and 37% both. Ten low-dose dilution methods were assessed and variation in synacthen concentration was demonstrated with intramethod coefficients of variation (CV) ranging from 2.1% to 109%. The method using 5% dextrose as a diluent was the least variable (CV of 2.1%). The variation in dilution methods means that the dose of synacthen administered in a LDT may vary between 0.16 and 0.81 μg.. The high-dose SST is the most popular diagnostic test of adrenal insufficiency, but up to 72% of paediatric endocrinologists use a LDT. There is considerable variation observed both within and between low-dose synacthen dilution methods creating considerable risk of inaccurate dosing and thereby invalid results.

Topics: Adrenal Insufficiency; Adult; Cosyntropin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Surveys and Questionnaires

Cosyntropin stimulation testing (CST) is used to screen patients for adrenal insufficiency (AI). Traditionally, CST includes baseline cortisol concentration, the administration of cosyntropin, and cortisol concentration at 30 and 60 minutes poststimulation. There is debate surrounding the utility of testing and cut-off points for concentrations at each time point.. To determine if a single cortisol measurement at 30 or 60 minutes could replace the traditional approach.. looked retrospectively at inpatients who underwent standard, high-dose CST (n = 702) and evaluated the number of patients who would screen positive for AI by using a single time point (30 or 60 minutes) compared with the traditional CST.. A tertiary-care, academic medical center.. Hospital inpatients present between January 2012 and September 2013.. Of tests, 84.3% were normal, which was defined as at least 1 cortisol concentration of 18 mcg/dL or higher at any time after stimulation. The average 60-minute concentration was higher than the average 30-minute concentration (P < .001). A single 60-minute concentration is 100% concordant with the full CST in the intensive care unit (ICU) subgroup and 99.6% concordant in floor patients. A single 30-minute concentration is significantly less concordant, 91.9% and 86.9%, in the ICU and floor subgroups, respectively.. Overall, a single 60-minute cortisol concentration to screen for AI was 99.7% concordant with the traditional CST, and the positive percent agreement was 98%. Fewer false-positive screens would occur with a single 60-minute cortisol concentration compared with a single 30-minute concentration (P < .001). High-dose CST screening may safely be interpreted with single 60-minute poststimulation cortisol serum concentrations.

Topics: Adrenal Insufficiency; Cosyntropin; Female; Hospital Units; Humans; Hydrocortisone; Male; Mass Screening; Middle Aged; Patients; Retrospective Studies; Time Factors

The cosyntropin test is used to diagnose adrenal insufficiency (AI) and nonclassical congenital adrenal hyperplasia (NCCAH). Current cutoffs for cortisol and 17-hydroxyprogesterone (17-OHP) are derived from nonstandardized immunoassays. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers direct measurement of steroids, prompting the need to re-establish normal ranges.. The goal of this study was to define cutoff values for cortisol and 17-OHP in serum by LC-MS/MS 30 and 60 minutes after intravenous administration of 250 µg tetracosactide acetate to healthy volunteers and to compare the results with LC-MS/MS with routine immunoassays.. Cosyntropin testing was performed in healthy subjects (n = 138) and in patients referred for evaluation of adrenocortical function (n = 94). Steroids were assayed by LC-MS/MS and compared with two immunoassays used in routine diagnostics (Immulite and Roche platforms). The cutoff level for cortisol was defined as the 2.5% percentile in healthy subjects not using oral estrogens (n = 121) and for 17-OHP as the 97.5% percentile.. Cortisol cutoff levels for LC-MS/MS were 412 and 485 nmol/L at 30 and 60 minutes, respectively. Applying the new cutoffs, 13 of 60 (22%) subjects who had AI according to conventional criteria now had a normal test result. For 17-OHP, the cutoff levels were 8.9 and 9.0 nmol/L at 30 and 60 minutes, respectively.. LC-MS/MS provides cutoff levels for cortisol and 17-OHP after cosyntropin stimulation that are lower than those based on immunoassays, possibly because cross-reactivity between steroid intermediates and cortisol is eliminated. This reduces the number of false-positive tests for AI and false-negative tests for NCCAH.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Chromatography, Liquid; Cosyntropin; Female; Humans; Hydrocortisone; Male; Middle Aged; Reference Values; Tandem Mass Spectrometry; Young Adult

Despite widespread use of the 250-mcg Cosyntropin test (ACTH test) for the diagnosis of adrenal insufficiency (AI), the effect of time of day and the utility of performing both 30- and 60-min serum cortisol values remains unclear.. We conducted a retrospective cohort study of all ACTH testing at the Halifax Neuropituitary Program, Nova Scotia, Canada between January 2006 and April 2016. Data were collected on age, gender, medication history, serum cortisol levels at 0, 30 and 60 min after ACTH administration, as well as time of and indication for testing.. There were 336 tests performed, divided by time of day (0800-1000 h, 1001-1200 h, and after 1200 h). There were no differences in mean cortisol levels at 30 (574.5, 559, 534 nmol/L, respectively; p = 0.25) and 60 min (642, 623, 619 nmol/L, respectively; p = 0.63) between groups. When comparing 30- vs. 60-min values using a cut-off of ≥500 nmol/L, 45 patients (13.4%) failed to reach the cut-off at 30 min but met the cut-off at 60 min. Conversely, only 2 patients (0.6%) who met the cut-off at 30 min failed to reach it at 60 min.. We found that outcomes from ACTH testing are not affected by time of day. Furthermore, using a 30-min cortisol level in isolation results in more than one in seven patients having a false positive diagnosis of AI; a 60-min value of ≥500 nmol/L alone may be sufficient to diagnose AI in >99% of cases.

Topics: Adrenal Insufficiency; Adult; Aged; Cosyntropin; Female; Humans; Hydrocortisone; Male; Middle Aged; Retrospective Studies; Time Factors

Topics: Adrenal Insufficiency; Cortisone; Cosyntropin; Humans; Hydrocortisone

Aiming to validate the use of a single poststimulus sampling protocol for cosyntropin test short standard high-dose test (SST) in our institution, our primary objectives were (1) to determine the concordance between 30 and 60 min serum cortisol (SC) measurements during SST; and (2) to evaluate the diagnostic agreement between both sampling times when using classic or assay-specific and sex-specific SC cut-off values. The secondary objectives included (1) estimating the specificity and positive predictive value of 30 and 60 min sampling times while considering the suspected origin of adrenal insufficiency (AI); and (2) obtaining assay-specific cut-off values for SC after SST in a group of subjects with normal hypothalamic-pituitary-adrenal (HPA) axis.. This is a retrospective chart review study conducted at a Spanish academic hospital from 2011 to 2015.. Two groups were evaluated: (1) a main study group including 370 patients in whom SC was measured at 30 and 60 min during SST; and (2) a confirmative group that included 150 women presenting with a normal HPA axis in whom SST was conducted to rule out late-onset congenital adrenal hyperplasia. Diagnostic agreement between both sampling times was assessed by considering both classic (500 nmol/L) and assay-specific SC cut-off concentrations.. Diagnostic agreement between both sampling times was greater when applying sex-specific and assay-specific cut-off values instead of the classic cut-off values. For suspected primary AI, 30 min SC determination was enough to establish a diagnosis in over 95% of cases, without missing any necessary treatment. When central AI is suspected, 60 min SC measurement was more specific, establishing a diagnosis in over 97% of cases.. Sex-specific and assay-specific SC cut-off values improve the diagnostic accuracy of SST. For primary disease, a subnormal SC response at 30 min is a reliable marker of adrenal dysfunction. On the contrary, when central AI is suspected, 60 min SC measurement improves the diagnostic accuracy of the test.

Topics: Adrenal Cortex Function Tests; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Cosyntropin; Female; Hospitals, Teaching; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Reference Values; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Sex Factors; Spain

It is well known that adrenal insufficiency is common in septic shock or hemodynamically unstable patients. But, there is as yet no sufficient clinically significant data about the exact prevalence or differences in the cause of cirrhosis with adrenal insufficiency. To investigate adrenal insufficiency prevalence in hemodynamically stable patients with cirrhosis and determine differences based on cirrhosis severity or etiology.From July 2011 to December 2012, 69 hemodynamically stable patients with cirrhosis without infection admitted at Hallym University Medical Center were enrolled. Adrenal insufficiency was defined as a peak cortisol level < 18 μg/dL, 30 or 60 minutes after 250 μg Synacthen injection.The study included 55 male patients (79.7%), and the mean age was 57.9 ± 12.9 years. Cirrhosis etiology was alcohol consumption, HBV, HCV, both viral and alcohol related, and cryptogenic in 49, 15, 7, 11, 9 patients, respectively. Adrenal insufficiency occurred in 24 patients (34.8%). No differences were found in age, sex, mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption, encephalopathy, variceal bleeding history, or hepatocellular carcinoma between patients with or without adrenal insufficiency. Serum albumin level was lower (P < .05), and INR was higher (P < .05) in patients with than in those without adrenal insufficiency. However, multivariate analysis revealed no independent adrenal insufficiency predictor. Significant negative correlations were found between Child-Pugh score and peak cortisol levels (γ=-0.365, P = .008).Adrenal insufficiency was frequent even in hemodynamically stable patients with cirrhosis and tended to be associated with only liver disease severity, being unrelated to cirrhosis etiology.

Topics: Adrenal Insufficiency; Aged; Alcohol Drinking; Cosyntropin; Female; Hemodynamic Monitoring; Hormones; Humans; Hydrocortisone; International Normalized Ratio; Liver; Liver Cirrhosis; Male; Middle Aged; Prevalence; Prospective Studies; Serum Albumin; Severity of Illness Index

Low-dose ACTH stimulation testing would lower cost and may increase sensitivity for identification of partial ACTH deficiency.. (1) The low-dose ACTH stimulation test will provide comparable results to the standard-dose ACTH stimulation test in dogs suspected of hypoadrenocorticism and (2) partial ACTH deficiency exists in dogs and can result in chronic, intermittent gastrointestinal signs.. Thirty-one client-owned dogs suspected of having hypoadrenocorticism.. Prospective study. Dogs suspected of having hypoadrenocorticism received 1 μg/kg cosyntropin IV for the first ACTH stimulation test; the second test was performed 4 h later and dogs received 5 μg/kg cosyntropin IV. Blood samples were obtained pre-ACTH and 1 hour post-ACTH for each dose (4 measurements total). Samples for endogenous ACTH measurement were obtained at the time of initial blood collection.. No significant difference was observed in the basal cortisol concentration before administration of a 1 μg/kg versus before a 5 μg/kg dose of cosyntropin (P = .544). For dogs suspected of having hypoadrenocorticism, the ACTH-stimulated cortisol concentrations in response to both doses of ACTH were equivalent (90% confidence interval [CI], 80.5-97.2%; P = .04). No cases with partial ACTH deficiency were identified conclusively.. A 1 μg/kg dose of cosyntropin is equivalent to a 5 μg/kg dose of cosyntropin for screening dogs suspected of hypoadrenocorticism. The existence of partial ACTH deficiency was not identified in this small group of dogs.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Animals; Cosyntropin; Dog Diseases; Dogs; Female; Hydrocortisone; Male; Prospective Studies; Reproducibility of Results

The occurrence of endocrine diseases in people who are infected with HIV is traditionally thought to occur in the setting of AIDS with opportunistic infections and malignancies. However, recent studies find the correlation between hypocortisolism and stage of HIV (CD4 count and WHO clinical stage) inconsistent.. This descriptive cross-sectional study included three hundred and fifty (350) consecutive patients with HIV infection. They were interviewed, and subsequently underwent laboratory evaluation for the detection of hypocortisolism. Blood samples for serum cortisol estimation were taken at baseline and at 30 minutes following the administration of 1µg of tetracosactrin (Synacthen). In addition, the patients had blood samples taken at 0 minutes (baseline) for CD4+ lymphocyte cell counts.. At baseline, 108 (30.9%) participants had serum cortisol levels below 100 µg/L with a median value of 55.48 µg/L (11.36-99.96 µg/L), but only 57 (16.3%) study participants had stimulated serum cortisol levels below 180 µg/L with median of 118 µg/L (19.43-179.62). There was no significant difference in the occurrence of clinical features between participants with low and normal serum cortisol, nor WHO clinical stage, CD4 count and ART regimen. The occurrence of hypocortisolism was higher among participants who had been on ART for a longer period of time.. There is a high prevalence of hypocortisolism among HIV patients by biochemical testing, especially those who have been on ARVs for a longer duration. Hypocortisolism cannot be predicted based on the participants' WHO clinical stage of disease, CD4 cell count, or the treatment regimen.. Personal Funds.

Topics: Adrenal Insufficiency; Adult; Antiviral Agents; CD4 Lymphocyte Count; Cosyntropin; Cross-Sectional Studies; Female; HIV Infections; Humans; Hydrocortisone; Logistic Models; Male; Middle Aged; Nigeria; Prevalence; Time Factors

Studies on 1 μg low-dose test showed that among 1 μg cosyntropin samples pushed through long IV plastic tubing, some adrenocorticotropic hormone dosage was not recovered, and in healthy volunteers it provided subnormal cortisol responses. The aim of the current study is to assess whether there is any loss in adrenocorticotropic hormone 1-24 concentration when pushed through a short plastic tube, and to assess serum and salivary cortisol responses in low-dose test among healthy volunteers, using a similar short plastic tube vs. direct intravenous consyntropin injection.. We evaluated in vitro if adrenocorticotropic hormone was absorbed in a 2.5 cm plastic tube by measuring adrenocorticotropic hormone 1-24 concentration in a 1 μg/ml adrenocorticotropic hormone aliquot solution before and after being flushed through the plastic tube. For the in vivo study, we recruited 20 healthy adult volunteers. Each subject underwent low-dose test via 2.5 cm plastic tube via plastic tube and via direct intravenous injection by a metal syringe via direct intravenous injection, and cortisol responses were determined.. Mean adrenocorticotropic hormone 1-24 concentration did not differ significantly when flushed via plastic tube or measured in the aliquot solution (P = 0.25). In vivo, mean 30-min serum cortisol concentrations were 20.47 ± 2.87 and 21.62 ± 3.89 μg/dl in via plastic tube and in via direct intravenous injection tests, respectively, and did not show a significant difference (P = 0.16).. In low-dose test, using a 2.5 cm plastic tube ensures completeness of the intravenous adrenocorticotropic hormone injection dosage and provides equivalent cortisol responses.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Cosyntropin; Diagnostic Tests, Routine; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Male; Middle Aged; Saliva; Sensitivity and Specificity; Young Adult

Adrenocorticotrophic hormone (ACTH) stimulation testing is the current standard for assessing primary and secondary adrenal insufficiency (AI). We aimed to investigate the value of basal cortisol level for prediction of AI.. We retrospectively analyzed 804 consecutive patients who had high-dose (250 μg, HDT) or low-dose (1 μg, LDT) ACTH testing as part of their diagnostic work-up. Site-specific cut-off levels for AI were <550 in and <500 nmol/L in HDT and LDT, respectively.. Overall, 70/400 (17.5%) in the LDT group and 118/404 (29.2%) in the HDT group showed an insufficient increase of cortisol and were categorized as AI. The receiver operating characteristic curve analysis showed an overall area under the curve (AUC) for basal cortisol of 0.88, which was comparable in LDT (area under the curve [AUC] 0.88) and HDT (AUC 0.88). If basal cortisol levels were ≥450 nmol/L (n = 234/804, 29.1%), the negative predictive value to rule out AI was 98.7%. If cortisol was ≤100 nmol/L (n = 69/804, 8.6%) the positive predictive value was 93.2% to rule in AI. There was a minimal additional value of the 30-minute cortisol level in HDT as compared to the 60-minute result, as well as for delta values.. Basal cortisol levels ≤100 and ≥450 nmol/L were found in almost half of patients tested for possible AI and had high diagnostic accuracy, abolishing the need for formal ACTH testing. The 30-minute cortisol value in HDT did not increase diagnostic accuracy. These data may help guide clinicians when testing can safely be omitted, thereby reducing expenses and simplifying test protocols.. ACTH = adrenocorticotropic hormone AI = adrenal insufficiency AUC = area under the curve CI = confidence interval HDT = high-dose test HPA axis = hypothalamus-pituitary-adrenal axis ITT = insulin tolerance test LDT = low-dose test NR = normal responders LR+/- = positive/negative likelihood ratio NPV = negative predictive value PPV = positive predictive value.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Area Under Curve; Cohort Studies; Cosyntropin; Female; Humans; Hydrocortisone; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; ROC Curve; Sensitivity and Specificity

Cardiopulmonary bypass (CPB) may lead to adrenal insufficiency (AI). Emerging evidence supports association of AI with morbidity after cardiac surgery.. The aim of this study was to define AI incidence in neonates undergoing complex cardiac surgery with CPB and its association with intraoperative post-CPB outcomes.. Forty subjects enrolled in a prior randomized control trial who received preoperative methylprednisolone as part of our institutional neonatal bypass protocol were included. No intraoperative steroids were given. ACTH stimulation tests were performed: preoperatively and 1 h after separation from CPB. AI was defined as <9 μg·ml. 2/40 (5%) subjects had preoperative AI vs 13/40 (32.5%) post-CPB AI, P ≤ 0.001. No significant difference was observed in age, gestational age, weight, CPB time, circulatory arrest, or STAT category between subjects with or without post-CPB AI. ACTH decreased from preoperative values 127.3 vs 35 pcg·ml. Neonatal cardiac surgery with CPB and preoperative methylprednisolone leads to AI as determined by low-dose ACTH stimulation test in one-third of patients. AI is associated with increased serum lactate and colloid resuscitation in OR. Impact of preoperative methylprednisolone on results is not defined. Benefit of postoperative steroid administration in neonates with post-CPB AI warrants further investigation.

Topics: Adrenal Insufficiency; Alabama; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cosyntropin; Female; Heart Defects, Congenital; Hormones; Humans; Incidence; Infant, Newborn; Male; Postoperative Complications

Clinical practice shows that many low-dose short synacthen tests (LD-SSTs) for diagnosing adrenal insufficiency in an outpatient setting have a normal outcome and could be considered superfluous. The objective of this study is to provide a guideline to safely reduce the number of unnecessarily performed LD-SSTs.. Data of LD-SSTs performed in outpatients were collected. Optimal morning cortisol cut-off values were determined using ROC analysis. Subsequently the predictive value of several variables was tested using univariable and multivariable logistic regression analyses.. A morning cortisol lower cut-off value of 145 nmol/l (specificity 89.9%, positive predictive value 90.0%) and an upper cut-off value of 375 nmol/l (sensitivity 100.0%, negative predictive value 100.0%) were found. Chronic fatigue symptoms and symptoms of hypotension or orthostasis as the main reason for performing the test predict a normal outcome. The use of glucocorticosteroids predicts an abnormal outcome of the LD-SST. Oral, topical, nasal and inhaled glucocorticosteroids are each significant predictors when analysed specifically for predicting central adrenal insufficiency.. By using morning cortisol cut-off values of 145 nmol/l and 375 nmol/l instead of the conventional cut-off values, the number of LD-SSTs performed in an outpatient setting can be reduced by 12%, while maintaining high sensitivity and specificity. Furthermore, the outcome of the LD-SST can be predicted by additional variables such as the indication for performing the test and the use of glucocorticosteroids. Different routes of administration of glucocorticosteroids such as inhalation or topical use should be taken into account when central insufficiency is suspected.

Topics: Adrenal Insufficiency; Adult; Cosyntropin; Female; Glucocorticoids; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Predictive Value of Tests; Reference Values; Retrospective Studies; ROC Curve; Time Factors

Topics: Adrenal Cortex Hormones; Adrenal Cortex Neoplasms; Adrenal Insufficiency; Adrenalectomy; Cosyntropin; Cushing Syndrome; Female; Humans; Male

Secondary adrenal insufficiency (AI) can occur after unilateral adrenalectomy for adrenal-dependent hypercortisolism. Postoperative glucocorticoid replacement (GR), although given routinely, may not be necessary. We sought to identify factors that, in combination with postoperative day 1 cosyntropin stimulation testing (POD1-CST), would predict the need for GR.. We reviewed 31 consecutive patients who underwent unilateral adrenalectomy for hypercortisolism (study patients) or hyperaldosteronism (control patients). A standard POD1-CST protocol was used. Hydrocortisone was started for clinical evidence of AI, basal plasma cortisol ≤ 5 (μg/dL), or a stimulated plasma cortisol <18.. A normal POD1-CST was found in all nine control patients and 11 of 22 patients (50%) with Cushing's syndrome; the other 11 study patients (50%) received GR based on the POD1-CST. These patients were younger (51 vs 62 years; P = .017), had a higher body mass index (BMI; 31 vs 29 kg/m(2)), and smaller adrenal neoplasms (16.9 vs 33.0 g; P = .009) than non-GR study patients.. After unilateral adrenalectomy for hypercortisolism, only 50% of patients received GR. No preoperative biochemical characteristics were associated with postoperative AI, although patients who received GR were younger, and tended to have a higher BMI and smaller adrenal nodules. Use of this novel protocol for postoperative dynamic adrenal function testing prevented unnecessary GR in 50% of patients and allowed for individualized patient care.

Topics: Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Cortex Neoplasms; Adrenal Insufficiency; Adrenalectomy; Adult; Aged; Clinical Protocols; Cosyntropin; Cushing Syndrome; Female; Hormone Replacement Therapy; Humans; Male; Middle Aged; Retrospective Studies; Young Adult

Serum free cortisol (SFF) responses to cosyntropin simulation test (CST) may more accurately assess adrenal function than total cortisol (TF).. The objective of the study was to evaluate the diagnostic utility of SFF responses during a 250-μg CST.. We recruited healthy volunteers (HV; n = 27), patients with primary and secondary adrenal insufficiency (n = 19 and n = 24, respectively), and subjects with Child-Pugh class A cirrhosis (CH; n = 15). Each received 250 μg cosyntropin with measurement of ACTH and corticosteroid binding globulin (CBG) at time 0 and TF and SFF at 0, 30, and 60 minutes. Salivary cortisol was measured at all time points in CH subjects.. Peak SFF and TF were significantly higher in HVs vs both AI groups (P < .05). Peak SFF and TF (6.8 μg/dL vs 2.2 μg/dL; [188 nmol/L vs 62 nmol/L]; P < .01) were significantly higher in the secondary adrenal insufficiency vs primary adrenal insufficiency patients. The optimal peak SFF criterion to identify adrenal insufficiency patients vs HV was 0.9 μg/dL (25 nmol/L) (sensitivity of 95%, specificity of 100%). Mean CBG and albumin levels were similar among all four groups. CH patients had a higher peak SFF than HV (2.4 vs 2.0 μg/dL; P = .02. In the CH patients, peak salivary cortisol levels correlated well with peak SFF (rs = 0.84, P = .005). CBG levels were similar among the groups.. We provide normative data for SFF values in HV and AI during the CST. Normal CBG levels in mild cirrhosis did not affect the interpretation of the CST.

Topics: Addison Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Hepatitis, Viral, Human; Humans; Hydrocortisone; Liver Cirrhosis; Male; Middle Aged; Saliva; Transcortin

Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis). The gold standard is still considered the insulin tolerance test (ITT), but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD±4.8) years, and mean/median BMI (body mass index) 25.38/24.82 (SD±3.2) kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 μg, 10 μg, and 250 μg Synacthen (ACTH) tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone) were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 μg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results.

Topics: Adrenal Insufficiency; Adult; Chromatography, Liquid; Cosyntropin; Dehydroepiandrosterone; Diagnostic Tests, Routine; Healthy Volunteers; Hormones; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Pregnenolone; Saliva

To validate the diagnostic utility of Cortrosyn(™) stimulated aldosterone in the differentiation of primary (PAI) and secondary adrenal insufficiency (SAI) and to evaluate the effect of urine sodium levels and posture on test performance.. Cross-sectional study.. Healthy volunteers (HV; n = 46) and patients with PAI (n = 26) and SAI (n = 29) participated in the study. Testing included cortisol and aldosterone (by liquid-chromatography tandem mass spectrometry) measurements at baseline and 30 and 60 min after 250 μg Cortrosyn(™). Plasma corticotropin (ACTH), renin activity (PRA) and urine spot sodium as a proxy for 24-h urine sodium excretion were measured at baseline. The effect of a sitting or semifowlers posture was evaluated in healthy volunteers.. A Cortrosyn(™)-stimulated aldosterone level of 5 ng/dl (0·14 nmol/l) had 88% sensitivity and positive predictive value and 89·7% specificity and negative predictive value for distinguishing PAI from SAI. Spot urine sodium levels showed a strong correlation with peak aldosterone levels (r = -0·55, P = 0·02, n = 18) in the SAI but not PAI or HV groups. Posture did not have a significant effect on results.. Once diagnosed with adrenal insufficiency, a stimulated aldosterone value of 5 ng/dl (0·14 nmol/l) works well to differentiate PAI from SAI. However, clinicians should be aware of the possible effect of total body sodium as reflected by spot urine sodium levels on aldosterone results. A 24-h urine sodium measurement may be helpful in interpretation.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aldosterone; Cosyntropin; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Male; Middle Aged; Pituitary-Adrenal Function Tests; Reference Values; Renin; Reproducibility of Results; Sensitivity and Specificity; Sodium; Tandem Mass Spectrometry

Controversy persists regarding the use of the low-dose adrenocorticotropic hormone (ACTH) stimulation test (LDST) for the diagnosis of adrenal insufficiency (AI) and optimal test result interpretation. However, many centers are now using the LDST to assess cortisol secretion adequacy, and some only use a 30-minute cortisol level to determine adrenal sufficiency or AI. This study examined both 30- and 60-minute cortisol levels to assess whether the interpretation of the test was affected when both cortisol levels were taken into consideration.. Data were obtained by retrospective chart review from a single pediatric endocrinology unit over a 7-year period. We identified 82 patients who completed the LDST. Their mean age was 11.7 years, and 37% were female. Cortisol levels were evaluated at baseline and 30 and 60 minutes after cosyntropin administration. A cutoff value ≥18 μg/dL was used to define adrenal sufficiency.. We found that 54% of patients reached peak cortisol levels at 60 minutes, and 11 patients who did not pass the test at 30 minutes did so at 60 minutes. The only predictive characteristic was weight status; overweight and obese individuals tended to peak at 30 minutes, and normal and underweight individuals tended to peak at 60 minutes.. Although further studies are necessary to confirm our findings, it appears that measuring cortisol both 30 and 60 minutes following synthetic ACTH administration may be necessary to avoid overdiagnosing AI.

Topics: Adolescent; Adrenal Insufficiency; Body Weight; Child; Cosyntropin; Female; Humans; Hydrocortisone; Kinetics; Male; Obesity; Overweight; Retrospective Studies; Time Factors

To establish cutoff values for salivary liquid chromatography tandem mass spectroscopy cortisol and cortisone in defining adequate adrenocortical function during a standard synacthen test.. We compared salivary liquid chromatography tandem mass spectroscopy cortisol and cortisone responses to those of serum cortisol measured on the Roche E170 immunoassay analyser and the Abbott Architect i2000 before and 30 min and 60 min following 0.25 mg of intravenous synacthen.. Correlations of salivary cortisol and cortisone were bimodal and linear, respectively. Based on these correlations, adequate salivary cortisol and cortisone responses to synacthen were extrapolated from a serum cortisol (Roche) cut-off of 550 nmol/L and defined as 15 nmol/L and 45 nmol/L, respectively. The Abbott method correlated well with the Roche but gave results that were about 20% lower than the Roche method.. Measurement of salivary cortisol and cortisone responses offers an alternative to those of serum cortisol during a synacthen test in the investigation of adrenal hypofunction.

Topics: Administration, Intravenous; Adolescent; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Cortisone; Cosyntropin; Female; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Saliva; Young Adult

Up to 3% of US and UK populations are prescribed glucocorticoids (GC). Suppression of the hypothalamo-pituitary-adrenal axis with the potential risk of adrenal crisis is a recognized complication of therapy. The 250 μg short Synacthen stimulation test (SST) is the most commonly used dynamic assessment to diagnose adrenal insufficiency. There are challenges to the use of the SST in routine clinical practice, including both the staff and time constraints and a significant recent increase in Synacthen cost.. We performed a retrospective analysis to determine the prevalence of adrenal suppression due to prescribed GCs and the utility of a morning serum cortisol for rapid assessment of adrenal reserve in the routine clinical setting.. In total, 2773 patients underwent 3603 SSTs in a large secondary/tertiary centre between 2008 and 2013 and 17.9% (n=496) failed the SST. Of 404 patients taking oral, topical, intranasal or inhaled GC therapy for non-endocrine conditions, 33.2% (n=134) had a subnormal SST response. In patients taking inhaled GCs without additional GC therapy, 20.5% (34/166) failed an SST and suppression of adrenal function increased in a dose-dependent fashion. Using receiver operating characteristic curve analysis in patients currently taking inhaled GCs, a basal cortisol ≥348 nmol/l provided 100% specificity for passing the SST; a cortisol value <34 nmol/l had 100% sensitivity for SST failure. Using these cut-offs, 50% (n=83) of SSTs performed on patients prescribed inhaled GCs were unnecessary.. Adrenal suppression due to GC treatment, particularly inhaled GCs, is common. A basal serum cortisol concentration has utility in helping determine which patients should undergo dynamic assessment of adrenal function.

Topics: Administration, Inhalation; Adrenal Insufficiency; Adult; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Prevalence; Retrospective Studies; United Kingdom

Free cortisol (FC) is potentially superior to total cortisol (TC) measurements in selected clinical settings; however, the advantages of uniform use of FC in outpatient settings are unclear. The objectives of this study were to describe the dynamic response of FC during cosyntropin stimulation testing (CST) compared to TC and to determine the rates of discordance.. This is a cross-sectional study of 295 stable patients who underwent CST in an outpatient Endocrine Testing Center. The main outcome measures were TC and FC measurements during CST.. The mean age of the 295 subjects was 49.1 (16.9) years. Of 218 females, 43 were taking estrogen therapy (ET) at the time of testing. Adrenal insufficiency (AI) was diagnosed in 41/295 (14%) patients. The FC concentrations were associated with TC concentrations at baseline (R(2) = 0.77, P<.001), 30 minutes (R(2) = 0.87, P<.001), and 60 minutes (R(2) = 0.90, P<.001). The FC cutoffs for AI were 873 and 1,170 ng/dL at 30 and 60 minutes, respectively. The FC had a more pronounced fold change from baseline to peak than TC (median 3.2 vs. 1.7, P<.001). Both TC and FC at baseline were higher in females on ET compared to those who were not and to males; however, peak TC and FC values were similar. In 3/43 females on ET, FC, and TC results were discordant (P = .003).. We report 99% concordance of TC and FC measurements in a large outpatient cohort. The discordant rates were high in females treated with ET (7%). The FC measurements during CST in females on ET may provide a more rapid and accurate diagnosis of AI.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Cosyntropin; Cross-Sectional Studies; False Positive Reactions; Female; Humans; Hydrocortisone; Male; Middle Aged; Outpatients; Pituitary-Adrenal Function Tests; ROC Curve; Young Adult

Topics: Adrenal Insufficiency; Cosyntropin; Female; Humans; Hydrocortisone; Male

Adrenal insufficiency is often present in cirrhosis. We hypothesize that a prolonged adrenocorticotropic hormone (ACTH) stimulus can restore cellular capacity of adrenal glands to secrete cortisol. Aim of our study was to assess adrenal responsiveness to prolonged ACTH stimulation in cirrhotics.. Prospective observational study in 121 consecutively admitted cirrhotic patients undergoing a low dose short synacthen test and plasma ACTH measurement using a chemiluminescence immunoassay. Long synacthen test was performed if the low dose was abnormal.. 46 patients had abnormal low dose short test (38%), and 29 underwent the long test: 41% showed normal response (Group 1), 55% showed delayed response (Group 2) and 1 had abnormal response (4%). Baseline ACTH levels did not significantly differ between the two groups. Median basal cortisol was higher in Group 1 (296 vs. 198 nmol/L; p=0.02). Using ROC curve basal cortisol <254 nmol/L was associated with a delayed long synacthen test response (AUC 0.78, p=0.001) with good accuracy (sensitivity 67%, specificity 81%).. A delayed cortisol response after a prolonged ACTH stimulation is found in over fifty percent of cirrhotics with abnormal low dose short synacthen test, confirming that the mechanism of hypoadrenalism in these patients could be related both to adrenal cellular dysfunction and hypothalamus-pituitary adrenal axis impairment.

Topics: Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Liver Cirrhosis; Male; Middle Aged; Pituitary-Adrenal System; Prospective Studies; ROC Curve; Sensitivity and Specificity

Topics: Adrenal Insufficiency; Cosyntropin; Female; Humans; Hydrocortisone; Male; Pituitary-Adrenal Function Tests

Topics: Adrenal Insufficiency; Cosyntropin; Female; Humans; Hydrocortisone; Male

Topics: Adrenal Insufficiency; Cosyntropin; Female; Humans; Hydrocortisone; Male

Topics: Adrenal Insufficiency; Cosyntropin; Female; Humans; Hydrocortisone; Male

Topics: Adrenal Insufficiency; Cosyntropin; Female; Humans; Hydrocortisone; Male

Topics: Adrenal Insufficiency; Cosyntropin; Female; Humans; Hydrocortisone; Male

Previous studies have demonstrated that a morning serum cortisol of <100 nmol/l makes further dynamic testing such as the Synacthen stimulation test (SST) unnecessary to confirm adrenal insufficiency. The morning cortisol level that reliably predicts adrenal sufficiency (AS) is less well established, and values ranging from 300 to 500 nmol/l have been proposed.. The aim of this study was to determine the ambulatory morning cortisol level that predicts adrenal sufficiency, as defined by an adequate response to SST, using a receiver operating characteristics (ROC) curve.. Observational retrospective cross-sectional study.. We conducted a retrospective audit of SST performed at PathWest Laboratory QEII from January 2006 to August 2008. A total of 761 results were obtained. Patients who were acutely ill or in intensive care, on glucocorticoid therapy, and those with inadequate data or multiple records were excluded from the analysis leaving 505 available for analysis. Baseline serum was obtained prior to intramuscular injection of 250 mcg Synacthen, and a second sample was obtained 30 min post-Synacthen. AS was defined as a 30-min post-Synacthen cortisol of >550 nmol/l; values ≤550 nmol/l were considered inadequate.. Based on SST criteria, of the 505 patients included in the study, 350 patients (69%) were adrenal sufficient and 155 (31%) had adrenal insufficiency. Using the minimum ROC distance criterion, a basal cortisol value of >236 nmol/l was identified to predict AS with sensitivity 84% and specificity 71%. However, to increase the specificity to 95%, we recommend a basal cortisol cut-off of >375 nmol/l. For patients with known pituitary disease (n = 152), basal cortisol of >214 nmol/l (sensitivity 85% and specificity 71%) may obviate the need for SST in the appropriate clinical context, although 330 nmol/l gives a specificity of 95%.. Basal morning cortisol is a viable first step in the evaluation of patients with suspected adrenal insufficiency.

Topics: Adolescent; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Child; Cosyntropin; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Injections, Intramuscular; Male; Middle Aged; Pituitary-Adrenal Function Tests; Retrospective Studies; Time Factors; Young Adult

The short Synacthen test (SST) is widely used as alternative test to the insulin tolerance test (ITT) to investigate central adrenal insufficiency (CAI), but the methodology and cut-off values of the SST are controversial. Our aim was to evaluate the cut-off value of the ITT in normal subjects and to assess the different cut-off values of the high-dose SST (250 μg, HDT) and the low-dose SST (1 μg, LDT) in subjects with suspected CAI.. We conducted ITTs in 208 normal subjects to establish the cut-off value for the ITT, and 28 of those subjects underwent the HDT and LDT. From 1999 to 2007, 182 patients with suspected CAI were recruited and underwent ITTs, LDTs and HDTs to establish cut-off values and compare the diagnostic accuracy between the LDT and HDT.. The 95th percentile of the peak cortisol level during the ITT in the normal control subjects was 14·8 μg/dl. Receiver operator characteristics (ROC) analysis revealed that the optimal cut-off values of peak cortisol in the LDT and HDT in patients with suspected CAI were 15·8 and 17·4 μg/dl, respectively. However, the cut-off values from normative data (mean - 2 SD) were 18·3 μg/dl for the LDT and 20·5 μg/dl for the HDT in normal control.. The optimal cut-off values of SSTs needed to be individualized according to the type of SST and tested patient population.

Topics: Adolescent; Adrenal Insufficiency; Adult; Aged; Cosyntropin; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Sensitivity and Specificity; Young Adult

This study investigated the significance of baseline cortisol levels and adrenal response to corticotropin in shocked patients after acute myocardial infarction (AMI).. A short corticotropin stimulation test was performed in 35 patients with cardiogenic shock after AMI by intravenously injecting of 250 μg of tetracosactrin (Synacthen). Blood samples were obtained at baseline (T0) before and at 30 (T30) and 60 (T60) minutes after the test to determine plasma total cortisol (TC) and free cortisol concentrations. The main outcome measure was in-hospital mortality and its association with T0 TC and maximum response to corticotropin (maximum difference [Δ max] in cortisol levels between T0 and the highest value between T30 and T60).. The in-hospital mortality was 37%, and the median time to death was 4 days (interquartile range, 3-9 days). There was some evidence of an increased mortality in patients with T0 TC concentrations greater than 34 μg/dL (P=.07). Maximum difference by itself was not an independent predictor of death. Patients with a T0 TC 34 μg/dL or less and Δ max greater than 9 μg/dL appeared to have the most favorable survival (91%) when compared with the other 2 groups: T0 34 μg/dL or less and Δ max 9 μg/dL or less or T0 34 μg/dL or higher and Δ max greater than 9 μg/dL (75%; P=.8) and T0 greater than 34 μg/dL and Δ max 9 μg/dL or less (60%; P=.02). Corticosteroid therapy was associated with an increased mortality (P=.03). There was a strong correlation between plasma TC and free cortisol (r=0.85).. A high baseline plasma TC was associated with a trend toward increased mortality in patients with cardiogenic shock post-AMI. Patients with lower baseline TC, but with an inducible adrenal response, appeared to have a survival benefit. A prognostic system based on basal TC and Δ max similar to that described in septic shock appears feasible in this cohort. Corticosteroid therapy was associated with adverse outcomes. These findings require further validation in larger studies.

Topics: Acute Disease; Adrenal Insufficiency; Aged; Biomarkers; Cosyntropin; Female; Hormones; Hospital Mortality; Humans; Hydrocortisone; Injections, Intravenous; Male; Middle Aged; Myocardial Infarction; Pilot Projects; Prognosis; Prospective Studies; Shock, Cardiogenic; Shock, Septic; Time Factors

Suppressed adrenal responses associated with inhaled steroid use have been reported in patients with bronchiectasis and have been shown to be associated with poor quality of life. This study was undertaken to examine the prevalence of suppressed cortisol responses in stable bronchiectasis and determine their correlation with the use of inhaled corticosteroids, radiologic severity of bronchiectasis and quality of life (QOL) scores.. In this case-control study, cases were patients with bronchiectasis and suppressed cortisol responses and controls were healthy volunteers, and patients with bronchiectasis without suppressed cortisol responses. Symptoms, lung function test values, exercise capacity, HRCT severity scores for bronchiectasis, exacerbations, inhaled corticosteroid use and quality of life scores were compared between patients with and without suppressed cortisol values.. Forty consecutive patients with bronchiectasis and 40 matched controls underwent 1-μg cosyntropin testing. Baseline cortisol (mean difference -2.0 μg/dl, P=0.04) and 30-minute stimulated cortisol (mean difference -3.73 μg/dl, P=0.001) were significantly lower in patients with bronchiectasis. One patient had absolute adrenal insufficiency and 39.5 per cent (15/38) patients with bronchiectasis had impaired stimulated responses. Baseline and stimulated cortisol responses were unaffected by inhaled steroids (O.R 1.03, P=0.96). SGRQ scores were negatively correlated with body mass (r= -0.51, P=0.001) and bronchiectasis severity (r=0.37, P=0.019), but not related to baseline or stimulated cortisol responses.. Our results showed that the impaired adrenal responses to 1-μg cosyntropin were common in patients with bronchiectasis. This was not associated with the use of inhaled steroids or severity of bronchiectasis. Poor health status was associated with advanced disease and not with cortisol responses to the 1-μg cosyntropin test.

Topics: Administration, Inhalation; Adrenal Insufficiency; Bronchiectasis; Cosyntropin; Forced Expiratory Volume; Humans; Hydrocortisone; India; Interviews as Topic; Quality of Life; Respiratory Function Tests; Spirometry; Statistics, Nonparametric; Surveys and Questionnaires; Vital Capacity

A 61-year-old female with cervical stenosis underwent an elective cervical laminectomy with post-op worsening upper extremity weakness. Over the first 3 weeks post-op, she received two separate courses of intravenous steroids. Two days after cessation of steroids, she presented with non-specific symptoms of adrenal insufficiency (AI). Initial formal diagnostic tests of random cortisol level and 250 µg cosyntropin challenge were non-diagnostic; however, symptoms resolved with the initiation of empiric treatment with hydrocortisone. Ten days later, repeat cosyntropin (adrenocortocotropic hormone stimulation) test confirmed the diagnosis of AI.. AI is a potentially life-threatening complication of acute spinal cord injury (ASCI), especially in those receiving steroids acutely. Only three cases have been reported to date of AI occurring in ASCI after steroid treatment. The presenting symptoms can be non-specific (as in this patient) and easily confused with other common sequelae of ASCI such as orthostasis and diffuse weakness. The 250 µg cosyntropin simulation test may not the most sensitive test to diagnose AI in ASCI.. The non-specific presentations and variability of diagnosis criteria make diagnosis more difficult. One microgram cosyntropin simulation test may be more sensitive than higher dose. Clinicians should be aware that AI can be a potential life-threatening complication of ASCI post-steroid treatment. Prompt diagnosis and treatment can reverse symptoms and minimize mortality.

Topics: Adrenal Insufficiency; Anti-Inflammatory Agents; Cosyntropin; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Middle Aged; Spinal Cord Injuries; Time Factors

In clinical practise the high dose ACTH stimulation test (HDT) is frequently used in the assessment of adrenal insufficiency (AI). However, there is uncertainty regarding optimal time-points and number of blood samplings. The present study compared the utility of a single cortisol value taken either 30 or 60 minutes after ACTH stimulation with the traditional interpretation of the HDT.. Retrospective analysis of 73 HDT performed at a single tertiary endocrine centre. Serum cortisol was measured at baseline, 30 and 60 minutes after intravenous administration of 250 µg synthetic ACTH1-24. Adrenal insufficiency (AI) was defined as a stimulated cortisol level <550 nmol/l.. There were twenty patients (27.4%) who showed an insufficient rise in serum cortisol using traditional HDT criteria and were diagnosed to suffer from AI. There were ten individuals who showed insufficient cortisol values after 30 minutes, rising to sufficient levels at 60 minutes. All patients revealing an insufficient cortisol response result after 60 minutes also had an insufficient result after 30 minutes. The cortisol value taken after 30 minutes did not add incremental diagnostic value in any of the cases under investigation compared with the 60 minutes' sample.. Based on the findings of the present analysis the utility of a cortisol measurement 30 minutes after high dose ACTH injection was low and did not add incremental diagnostic value to a single measurement after 60 minutes.

Topics: Adrenal Insufficiency; Adult; Aged; Biomarkers; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Retrospective Studies; Time Factors

Topics: Adrenal Insufficiency; Aged, 80 and over; Biomarkers; Comorbidity; Cosyntropin; Dexamethasone; Diagnosis, Differential; Drug Therapy, Combination; Female; Glucocorticoids; Hormones; Humans; Megestrol Acetate

Recent studies in critically ill populations have suggested both adrenal insufficiency (AI) and vitamin D deficiency to be associated with worse clinical outcome. There are multiple mechanisms through which these pleiotropic hormones might synergistically influence critical illness.. The aim of the study was to investigate potential relationships between vitamin D status, adrenal status, and cardiovascular dysfunction in critically ill children.. We conducted a secondary analysis of data from a prospective cohort study.. The study was conducted on 319 children admitted to 6 Canadian tertiary-care pediatric intensive care units.. Vitamin D status was determined through total 25-hydroxyvitamin D (25OHD) levels. AI was defined as a cortisol increment under 9 μg/dL after low-dose cosyntropin. Clinically significant cardiovascular dysfunction was defined as catecholamine requirement during pediatric intensive care unit admission.. Using 3 different thresholds to define vitamin D deficiency, no association was found between vitamin D status and AI. Furthermore, linear regression failed to identify a relationship between 25OHD and baseline or post-cosyntropin cortisol. However, the association between AI and cardiovascular dysfunction was influenced by vitamin D status; compared to children with 25OHD above 30 nmol/L, AI in the vitamin D-deficient group was associated with significantly higher odds of catecholamine use (odds ratio, 5.29 vs 1.63; P = .046).. We did not find evidence of a direct association between vitamin D status and critical illness-related AI. However, our results do suggest that vitamin D deficiency exacerbates the effect of AI on cardiovascular stability in critically ill children.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adrenal Cortex; Adrenal Insufficiency; Calcifediol; Canada; Cardiovascular Diseases; Cardiovascular System; Catecholamines; Child; Child, Preschool; Cohort Studies; Cosyntropin; Hormones; Humans; Hydrocortisone; Infant; Intensive Care Units, Pediatric; Nutritional Status; Prospective Studies; Tertiary Care Centers; Vitamin D Deficiency

Despite the widespread use of the short synacthen test (SST), there remains no clear consensus on sampling times for the measurement of serum cortisol that best determines adrenal reserve. We set out to establish whether there is any value in measuring serum cortisol at 60 min following administration of synacthen.. Retrospective data analysis of 500 SST results measuring 0, 30 and 60 min cortisol levels after administration of 250 μg of synacthen at 2 large urban National Health Teaching Hospitals in the UK.. Individuals thought to have primary or secondary adrenal insufficiency given 250 μg of synacthen.. Serum cortisol levels measured at 0, 30 and 60 min, looking to see how many people who had adrenal insufficiency at the 30 min sample but in whom the 60 min sample showed adequate adrenal reserve.. The results from 384 people were analysed. A total of 276 had normal responses at 30 min and also at 60 min. A sum of 33 individuals had 'insufficient' (i.e., <550 nmol/l) 30 min cortisol levels, rising to ≥ 550 nmol/l at the 60 min test. All 75 individuals who were insufficient at 60 min were also insufficient at 30 min. No individuals passed (≥550 nmol/l) at 30 min and then failed (<550 nmol/l) at 60 min.. These results suggest that a significant proportion of people undergoing a SST may be inappropriately diagnosed as having adrenal insufficiency if the 60 min sample is not measured. We suggest that the 60 min sample is measured in all individuals having a SST to prevent unnecessary over-diagnosis of adrenal insufficiency.

Topics: Adrenal Insufficiency; Adult; Aged; Cosyntropin; Female; Hormones; Hospitals, Teaching; Humans; Hydrocortisone; Male; Middle Aged; Retrospective Studies; ROC Curve; Time Factors; United Kingdom

Despite the low prevalence (0.008%) of adrenal insufficiency (AI) in the general population, this disorder was recently diagnosed in a substantial number of sickle cell disease (SCD) patients at our hospital. The main objective of this study was to assess the prevalence of AI in SCD patients.. All adult patients admitted to the Department of Medicine at Interfaith Medical Center from October 2010 to November 2011 were eligible for this retrospective study. Medical records of adult SCD patients hospitalized for painful crisis and who had undergone cosyntropin testing were reviewed. Adult non-SCD patients hospitalized for painful crisis and who had undergone cosyntropin testing served as controls. The result of the cosyntropin test was the primary outcome. The prevalence of positive cosyntropin tests was compared between the 2 groups by using Student's t-test, and odds ratios.. 62 adult SCD patients were enrolled in the study. 15 underwent cosyntropin testing and 12 (19.4%) of these patients were found to have AI. AI was also diagnosed in 1 of 1,340 non-SCD patients. The odds ratio for AI in SCD to non-SCD patients [(12/62)/(1,340)] was 259. The odds ratio for the prevalence of AI in SCD patients in our study (19.4%) vs. the general population (approximately 0.008%) was 2,375.. AI occurred in 19.4% of SCD patients included in this study. These patients thus have a 2,375-fold higher risk of developing AI than the general population, and a 259-fold greater risk of developing AI than do hospitalized non-SCD patients.

Topics: Adolescent; Adrenal Insufficiency; Adult; Anemia, Sickle Cell; Cosyntropin; Female; Hormones; Hospitalization; Hospitals, Community; Humans; Male; New York City; Prevalence; Retrospective Studies; Risk Factors

Critically ill cancer patients with sepsis represent a high-risk sub-group for the development of critical illness-related corticosteroid insufficiency (CIRCI); however, the incidence of CIRCI in this population is unknown. The purpose of this study was to determine the incidence of CIRCI in cancer patients with severe sepsis or septic shock.. A single-center, retrospective, observational study was conducted in a 52-bed medical-surgical intensive care unit of a National Cancer Institute-recognized academic oncology institution. Eighty-six consecutive patients with a diagnosis of severe sepsis or septic shock who received a high-dose 250-μg cosyntropin stimulation test were included. CIRCI was identified by a maximum delta serum cortisol of 9 μg/dL or less post cosyntropin.. Overall, 59% (95% CI, 48-70%) of cancer patients with severe sepsis or septic shock were determined to have CIRCI. When compared to patients without CIRCI, patients with CIRCI had higher baseline serum cortisol (median, 26.3 versus 14.7 μg/dL; p = 0.002) and lower delta cortisol levels (median, 3.1 versus 12.5 μg/dL; p < 0.001). Mortality did not differ between the two groups. An inverse relationship was identified between baseline serum cortisol and maximum delta cortisol (maximum delta cortisol = -0.27 × baseline cortisol + 14.30; R (2) = 0.208, p < 0.001).. The incidence of CIRCI in cancer patients with severe sepsis or septic shock appears high. Further large-scale prospective trials are needed to confirm these findings.

Topics: Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Cosyntropin; Critical Illness; Female; Humans; Hydrocortisone; Incidence; Male; Middle Aged; Retrospective Studies; Sepsis; Severity of Illness Index; Shock, Septic; Young Adult

The pathophysiology of adrenal insufficiency, common in surgical intensive care units, has not been fully elucidated.. Patients at risk (age > 55 years, in the surgical intensive care unit >1 week, baseline cortisol < 20 μg/dL) were enrolled. After measuring cortisol and adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH) was administered. ACTH and cortisol were measured over 120 minutes. Short and long cosyntropin stimulation tests determined adrenal function. Area under the curve (AUC) and mixed linear models were used to compare cortisol and ACTH responses. Patients were grouped according to survival and response to stimulation testing. Chi-square and t tests were performed, and P values < .05 were considered statistically significant.. Six of 25 patients responded poorly to cosyntropin, and 5 died compared with 3 after a normal response (P < .01). ACTH (AUC) and ACTH peak were increased in nonsurvivors after CRH administration. Cortisol peak and AUC were not different.. ACTH responsiveness was increased in nonsurvivors and may predict mortality.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Aged, 80 and over; Area Under Curve; Corticotropin-Releasing Hormone; Cosyntropin; Critical Illness; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Intensive Care Units; Linear Models; Male; Middle Aged; Pituitary-Adrenal System; Postoperative Complications; Prognosis

Transsphenoidal surgery (TS) is the treatment of choice for many pituitary tumors. Because TS may cause pituitary insufficiency in some of these patients, early postoperative assessment of pituitary function is essential for appropriate endocrine management. The aim of our study was to evaluate the clinical relevance of the CRH-stimulation test in assessing postoperative pituitary-adrenal function. We performed a retrospective analysis of 144 patients treated by TS between January 1990 and November 2009, in whom a CRH-test and a second stimulation test was performed to assess adrenal function during follow-up. Patients with Cushing's disease were excluded. Hydrocortisone substitution was started if peak cortisol levels were <550 nmol/L. The cortisol response was insufficient in 42(29%) and sufficient in 102 patients at the postoperative CRH-test. Thirteen of 42(30%) demonstrated a normal cortisol response during a second cortisol stimulation test. In 75 of the 102 patients with a sufficient response to CRH repeat testing revealed an insufficient cortisol response in 14 patients (14%). All but one had concomitant pituitary hormone deficits. There were no cases of adrenal crises during follow-up. Additional pituitary insufficiency was significantly more present (P < 0.001) in the group of patients with an abnormal response to CRH directly after surgery. In this study a substitution strategy of hydrocortisone guided by the postoperative cortisol response to CRH appeared safe and did not result in any case of adrenal crises. However, the early postoperative CRH-test does not reliably predict adrenal function after TS for pituitary adenomas in all patients and retesting is mandatory.

Topics: Adenoma; Adolescent; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Corticotropin-Releasing Hormone; Cosyntropin; Female; Humans; Hydrocortisone; Hypopituitarism; Insulin; Male; Metyrapone; Middle Aged; Pituitary Neoplasms; Postoperative Period; Retrospective Studies

Adrenal insufficiency in patients with liver failure, referred to as hepatoadrenal syndrome, is well characterized in adult patients but has not yet been described in children. We present 22 pediatric subjects with end-stage liver disease and adrenal insufficiency, diagnosed using the cosyntropin stimulation test.. A retrospective chart review using inpatient records from a pediatric intensive care unit in an academic medical center with a busy pediatric transplant program.. Most were infants with anatomical short gut and severe, total parenteral nutrition-induced liver failure awaiting liver transplantation. Many were critically ill; 68% required mechanical ventilation and 59% required vasopressors.. None.. All patients had low baseline cortisol levels and ten also had an abnormal cosyntropin stimulation test. Cortisol levels at baseline and increments of serum cortisol at 30 and 60 mins post cosyntropin were 9.3 ± 5 μg/dL, 9.3 ± 4 μg/dL, and 10.7 ± 6 μg/dL, respectively, compared to these values in five patients with liver failure and normal adrenal function (21.3 ± 3 μg/dL, 10.5 ± 5 μg/dL, and 12.7 ± 3 μg/dL, respectively). Baseline cortisol levels were higher in patients who required vasopressors (11.1 ± 5 μg/dL) compared to those who did not (6.6 ± 4.3 μg/dL, p = .04), and 60-min increment cortisol levels were lower in nonsurvivors compared to survivors (8.6 ± 4.8 μg/dL vs. 15.1 ± 5.1 μg/dL, p = .002). The severity of adrenal insufficiency did not correlate with the degree of hepatic decompensation. Clinical characteristics, including serum electrolytes and vasopressor requirements, were similar in patients with hepatoadrenal syndrome and patients with liver failure and normal adrenal function. Twelve (55%) of the patients died in the hospital, 11 without receiving a transplant. Hydrocortisone therapy permitted rapid weaning of vasopressor therapy but did not affect survival.. Children with end-stage liver disease are at risk for hepatoadrenal syndrome and should have their cortisol levels monitored since clinical manifestations may not be diagnostic.

Topics: Adrenal Insufficiency; Biomarkers; Child, Preschool; Cosyntropin; End Stage Liver Disease; Female; Hormones; Humans; Hydrocortisone; Infant; Male; Retrospective Studies; Severity of Illness Index

Stress situations such as septic shock are accompanied by activation of the HPA axis. Some patients do not activate this axis in stress situations. This blunted response is currently designated as critical illness-related corticosteroid insufficiency (CIRCI). Currently the 250 μg cosyntropin stimulation test is the preferred diagnostic test for CIRCI. Few papers explored the role of the 1 μg cosyntropin test in septic shock patients. In this study, we compared both tests in septic shock patients taking a special interest in the population with intermediary baseline cortisol. Prospective noninterventional study included 74 septic shock patients. After measurement of baseline cortisol all patients received 1 μg of cosyntropin i. v. and 4 h later 249 μg of cosyntropin. We compared the cortisol increase after each test and its relation to mortality and vasopressor therapy. There was a moderate correlation in response to low and high dose cosyntropin, r(s)=0.55. This correlation in patients with baseline cortisol between 10-34 μg/dl is, r(s)=0.67. The increase induced by both tests was equally accurate to identify mortality and time of vasopressor withdrawal. Low and high dose cosyntropin tests presented a moderate correlation in patients with baseline cortisol between 10-34 μg/dl. Both tests are equally accurate to identify mortality and time of vasopressor therapy. These results suggest that both tests could be used to diagnose CIRCI.

Topics: Adrenal Insufficiency; Adult; Aged; Cosyntropin; Female; Humans; Male; Middle Aged; Prospective Studies; Shock, Septic

To investigate if in preterm newborns, an early adrenocorticotropin hormone (ACTH) test can identify possible transient adrenal insufficiency (TAI), using significant hypotension as a clinical marker.. We studied 40 premature newborns born 24 to 29 weeks gestational age (GA) before 8 h of life. Serum cortisol levels were obtained before and 40 min after administration of 1.0 mcg kg(-1) cosyntropin. Inotropes were used to treat hypotension based on clinical assessment following no response to fluid boluses. Functional echocardiogram was used to support the clinical diagnosis of hypotension. The accuracy of the ACTH test was evaluated using receiver operating characteristic (ROC) curve.. Study patients had mean GA of 26.6 weeks and birth weight of 876 g. In all, 30% required inotropes. The area under the ROC curve for the ACTH test was 87%. Using a cutoff of an increase in cortisol below 12% from baseline had 75% sensitivity and 93% specificity for detecting hypotension. This cutoff was associated with bronchopulmonary dysplasia (8/12 vs 7/28, 95% CI: 0.1 to 0.72), but not with other morbidities or death.. An early ACTH test using the above cutoff has high specificity for detecting hypotension, and thus, can serve as a marker for potential TAI in preterm newborns. Future studies should focus on identifying those newborns for which steroid supplementation would be most beneficial.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Biomarkers; Bronchopulmonary Dysplasia; Cosyntropin; Early Diagnosis; Echocardiography; Female; Humans; Hydrocortisone; Hypotension; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Pregnancy; Prospective Studies; ROC Curve; Sensitivity and Specificity

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cosyntropin; Female; Humans; Hydrocortisone; Hypotension; Infant, Premature, Diseases; Male; Pregnancy

Supported by meta-analyses, the low-dose Synacthen test (LDST) has gained in popularity, with many believing it to be more sensitive than the supraphysiological standard (250 µg) short ST (SSST), particularly when assessing children prescribed high-dose inhaled corticosteroids (HDICS). However, consensus is lacking about its specific clinical application, what is considered 'low dose' and how that dose is made up.. To ascertain current use of the short Synacthen test (SST), a questionnaire was emailed to members of the British Society of Paediatric Endocrinology and Diabetes in the UK and Ireland (N=257), requesting a response from each department (N=92). A reminder was sent a month later to members of departments which had not responded.. The authors received 39 replies, giving a response rate of 42%. All departments use the SST: 82% use an LDST, 87% use the SSST and 69% use both. The 1 µg dose was used by 44% of hospitals, with the other 56% using seven different doses based on age, weight and body surface area. There were 14 different methods of preparing the low dose test. Additionally, variations in the timings of cortisol sampling and the diagnostic cut-offs for adrenal insufficiency were found. Increased requests for SSTs in children with asthma prescribed HDICS were noted by 44% of respondents, with 67% reporting the detection of adrenal suppression in this group.. Standardisation of the SST is required to address the considerable variation in the methodology and application of this test in the UK and Ireland.

Topics: Adrenal Insufficiency; Asthma; Child; Cosyntropin; Dose-Response Relationship, Drug; Hormones; Humans; Ireland; Meta-Analysis as Topic; Sensitivity and Specificity; Surveys and Questionnaires; United Kingdom

  There is no consensus among pediatric endocrinologists in using low-dose (LD) versus high-dose (HD) cosyntropin to test for secondary/tertiary adrenal insufficiency. This paper compares LD and HD cosyntropin stimulation testing in children for evaluation of hypothalamic-pituitary-adrenal axis (HPAA) and suggests a new peak cortisol cut-off value for LD stimulation testing to avoid false positivity..   Data of 36 children receiving LD (1 µg) and HD (249 µg) cosyntropin consecutively during growth hormone (GH) stimulation testing were analyzed in two groups. Group A were patients who passed GH stimulation testing and were not on oral, inhaled or intranasal steroids (intact hypothalamic-pituitary axis, n= 19). Group B were patients who failed GH stimulation testing and/or were on oral, inhaled or intranasal steroids (impaired hypothalamic-pituitary axis, n= 17)..   In group A, the mean peak cortisol response in LD cosyntropin was 18.5 ± 2.4 µg/dL and that for the HD cosyntropin was 24.8 ± 3.1 µg/dL (r: 0.76, P≤ 0.05). In group B, the mean peak cortisol response in LD cosyntropin was 15.7 ± 6.1 µg/dL and that for HD cosyntropin was 21.7 ± 7.9 µg/dL (r: 0.98, P≤ 0.05). When a standard cut-off of 18 µg/dL was used, 37% of the patients with intact HPAA failed LD cosyntropin testing, but a cut-off of 14 µg/dL eliminated false positive results..   LD cosyntropin stimulation testing results should be interpreted cautiously when used alone to prevent unnecessary long-term treatment. Using a lower cut-off for LD (≥14 µg/dL) seems to avoid false positive results and still detects most cases of impaired HPAA.

Topics: Adolescent; Adrenal Insufficiency; Child; Child, Preschool; Cosyntropin; False Positive Reactions; Female; Hormones; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immunoassay; Male; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Retrospective Studies

Prader-Willi syndrome (PWS) is a genetic disease associated with hypogonadism and partial GH insufficiency, possibly explained in part by a hypothalamic dysfunction. Partial insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis has recently been suggested.. The objective of the study was to further explore the HPA axis in PWS by use of routine tests.. Nonselected PWS patients were examined with a standard high-dose synacthen test or the insulin tolerance test (ITT). A random serum (s) cortisol was measured in case of acute illness.. The study was conducted at university hospitals in Denmark and Sweden.. Sixty-five PWS patients with a confirmed genetic diagnosis participated in the study.. A s-cortisol value above 500 nmol/liter as well as an increase of 250 nmol/liter or greater was considered a normal response.. Fifty-seven PWS patients (median age 22 yr, total range 0.5-48 yr) were examined with the high-dose synacthen test. The median s-cortisol at the time of 30 min was 699 (474-1578) nmol/liter. Only one patient had a s-cortisol level below 500 nmol/liter but an increase of 359 nmol/liter. This patient subsequently showed a normal ITT response. Two patients had increases less than 250 nmol/liter but a time of 30-min s-cortisol values of 600 nmol/liter or greater. These three patients were interpreted as normal responders. Eight patients [aged 26 (16-36) yr] examined with the ITT had a median peak s-cortisol of 668 (502-822) nmol/liter. Four children admitted for acute illnesses had s-cortisol values ranging from 680 to 1372 nmol/liter.. In this PWS cohort, the function of the HPA axis was normal, suggesting that clinically significant adrenal insufficiency in PWS is rare.

Topics: Adolescent; Adrenal Insufficiency; Adult; Child; Child, Preschool; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immunoassay; Infant; Insulin; Male; Middle Aged; Pituitary Function Tests; Pituitary-Adrenal System; Prader-Willi Syndrome

Patients with cortisol deficiency poorly tolerate any systemic inflammatory response syndrome (SIRS), and may die if not treated with sufficient exogenous glucocorticoids. Controversy surrounds what constitutes a 'normal' adrenal response in critical illness. This study uses conventional tests for adrenal insufficiency to investigate cortisol status in patients undergoing elective coronary artery bypass surgery, a condition frequently associated with SIRS.. A prospective, observational study.. Thirty patients with impaired left ventricular function (ejection fraction >23% <50%) underwent basal ACTH measurement, and a short cosyntropin test (250 μg, i.v.) 1 week preoperatively, and at +4 h following induction of general anaesthesia. Preoperatively, a 30 min cortisol level post cosyntropin >550 nmol/l was taken as a normal response.. Prior to surgery, all patients had a normal response to cosyntropin. Postoperatively, eight patients (26.7%) did not achieve stimulated cortisol levels >550 nmol/l and the mean peak cortisol postoperatively was lower (1048 vs 730 nmol/l; P<0.001). There was a significant rise in ACTH after surgery (21 vs 184 ng/l; P=0.007) and reduction in Δ-cortisol post cosyntropin (579 vs 229 nmol/l; P<0.001). There was no change in basal cortisol pre- and post-operatively (447 vs 501; P=0.4). All patients underwent routine, uneventful postoperative recovery.. Up to one quarter of patients with a normal cortisol status preoperatively demonstrated a raised ACTH and deficient cortisol response postoperatively. Despite these responses, all patients had uneventful outcomes. These data reinforce the need for caution when interpreting results of endocrine testing following major surgery or in the intensive care environment, and that prognostic value of these results may be of limited use.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Aged, 80 and over; Coronary Artery Bypass; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Systemic Inflammatory Response Syndrome

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Cosyntropin; Depression; Humans; Male; Middle Aged; Stupor

Topics: Adrenal Insufficiency; Aged, 80 and over; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Shock

We present the first national audit of the Short Synacthen Test (SST), identifying the clinical, analytical and interpretative procedures adopted by 89 laboratories.. The SST has replaced the insulin stress test as the first-line test to assess adrenal insufficiency and has received considerable attention regarding its sensitivity and specificity. Concerns regarding this test include the bias of cortisol methods, cut-off values used, contraindications and the limitations of the test in diagnosing recent, mild secondary adrenal insufficiency. The audit took into consideration the protocols used by laboratories, the advice provided prior and after the SST and the analytical bias of the methods used.. A web-based questionnaire using Microsoft FrontPage(TM) was prepared to collect data from laboratories and provided drop-down lists and other form-field elements to capture additional comments. The resultant data were exported to Microsoft Excel(TM) for data clean-up and analysis.. The workloads were highly variable; however, most laboratories were in general agreement to the indications, contraindications, timing and reference ranges. In contrast, there was variability in the bias of the cortisol methods, which had not been translated to the cut-off values used by the majority of laboratories.. The audit has shown that though the preanalytical procedures were similar in most laboratories, there is a requirement to recognize the effect that method bias may have on the reference ranges and consequently on the diagnosis of adrenal insufficiency. There is a need to develop consensus guidelines, which can aid both clinicians and laboratories.

Topics: Addison Disease; Adrenal Insufficiency; Cosyntropin; Hematologic Tests; Humans; Laboratories; Medical Audit; Reference Values; Surveys and Questionnaires; United Kingdom

The objectives of this study were to determine the risk factors for relative adrenal insufficiency in cardiopulmonary bypass patients and the impact on postoperative vasopressor requirements.. Prospective cohort study on cardiopulmonary bypass patients who received etomidate or not during anesthetic induction. Relative adrenal insufficiency was defined as a rise in serum cortisol

Topics: Adrenal Insufficiency; Anesthetics, Intravenous; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cosyntropin; Etomidate; Humans; Hydrocortisone; Postoperative Care; Postoperative Complications; Risk Factors; Vasoconstrictor Agents

The frequency of adrenal insufficiency after a prolonged, continuous course of oral high-dose corticosteroids is poorly documented. We evaluated it retrospectively in our internal medicine department.. The patients were included between February 2000 and June 2007 and were administered a Synacthene 250 microg test (ST250) before tapering prednisone dose below 5mg per day. A non-responsive test was defined by a cortisol increase below 18 microg/dL, 60 min after stimulation. We also studied the risk factors associated with biological adrenal insufficiency by a multivariate logistic regression analysis.. Hundred patients were included (mean age: 61.5+/-16.3 years). Mean initial dose of corticosteroids was 65.5+/-112 mg/d. Forty-five patients failed to respond to the ST250. A normal ST250 was negatively associated with a duration of corticosteroids therapy longer than 19.5 months (OR=0.38 [0.15-0.94]; p=0.04) and positively with an age over 63.5 years (OR=2.5 [1.1-6.4]; p=0.05). Two patients experienced a clinical adrenal insufficiency crisis.. Biological adrenal insufficiency is very common after a prolonged course of oral high-dose corticosteroids. The risk does not seem to increase with age. The clinical benefit of a systematic ST250 at the time of corticosteroids withdrawal followed by hydrocortisone substitution if the test is non responsive remains unknown, and this practice is still a matter of debate.

Topics: Adrenal Insufficiency; Aged; Cohort Studies; Cosyntropin; Female; France; Glucocorticoids; Hormones; Humans; Incidence; Male; Middle Aged; Prednisone; Retrospective Studies; Risk Factors

Topics: Addison Disease; Adrenal Insufficiency; Adult; Cosyntropin; Female; Humans; Hydrocortisone; Male; Reference Values; Young Adult

Topics: Adrenal Glands; Adrenal Insufficiency; Animals; Cosyntropin; Critical Care; Hydrocortisone; Hypnotics and Sedatives; Intubation, Intratracheal; Respiration, Artificial; Time Factors

Topics: Adolescent; Adrenal Insufficiency; Adult; Child; Cosyntropin; Humans; Hydrocortisone; Insulin; Obesity; Pituitary-Adrenal System; Prader-Willi Syndrome; Prevalence; Retrospective Studies; Scotland

Accurate assessment of adrenal function is essential in patients with hypothalamic-pituitary-adrenal (HPA) disease. The measurement of salivary cortisol (SaC) instead of serum cortisol (SeC) offers several advantages, such as the determination of the free hormone. We evaluated the diagnostic value of SeC and SaC both unstimulated and during a high-dose short synacthen test (HDT) in comparison to the insulin tolerance test (ITT).. Comparative study between 2005 and 2007.. Fifty-five patients with HPA impairment and 21 healthy controls were enrolled. Samples were collected in the early morning and over 120 min during the HDT. Receiver operating characteristic analysis revealed individual thresholds for four HDT periods (0-30, 0-60, 0-90, and 0-120 min).. The ITT identified 30 subjects as adrenal insufficient. With respect to the four HDT periods, sensitivity and specificity were 67-79% and 71-88% for SeC, compared with 63-72% and 72-86% for SaC. If upper and lower thresholds (with specificities >95%) were applied, patients were diagnosed in 40-45% by SeC and in 25-31% by SaC. The combination of basal cortisol and HDT allowed a diagnosis in 47-49% (SeC) and in 42-45% (SaC) respectively.. We suggest the determination of basal SeC or SaC as first-line test. In comparison to the ITT, the HDT has only limited value in screening for alterations of the HPA axis. If the HDT is performed, sampling may be limited to 30 min post-synacthen, using either SeC or SaC. Due to the ease of collection and the independence of binding proteins, SaC may be preferable.

Topics: Adrenal Insufficiency; Adult; Algorithms; Area Under Curve; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamic Diseases; Insulin; Male; Middle Aged; Pituitary Diseases; Random Allocation; ROC Curve; Saliva; Sensitivity and Specificity

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Cosyntropin; Humans; Hydrocortisone; Shock, Septic

To evaluate baseline plasma cortisol and ACTH concentrations and responses to low-dose ACTH stimulation testing in ill foals.. Cross-sectional study.. 58 ill foals.. Baseline cortisol and ACTH concentrations and cortisol concentrations after administration of a low dose of cosyntropin were determined within 6 hours after admission. Foals were assigned to 4 groups on the basis of age (

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocorticotropic Hormone; Age Factors; Animals; Animals, Newborn; Area Under Curve; Cosyntropin; Cross-Sectional Studies; Female; Horse Diseases; Horses; Hydrocortisone; Male

To determine the prevalence of adrenal insufficiency in infants with hemangiomas following treatment with systemic glucocorticoids (GCs).. Prospective study for 18 months.. Hemangioma and vascular malformation center at a tertiary care children's hospital.. Sixteen infants with hemangiomas had an adrenal axis evaluation as soon as possible following the completion of GC therapy. Ten healthy control infants were also evaluated for comparison.. Prednisolone at a starting dose of 2 to 3 mg/kg/d for 4 weeks, followed by a tapering period. The mean duration of GC treatment was 7.2 months.. Prevalence of adrenal insufficiency in GC-treated subjects as assessed by a combination low-dose/high-dose corticotropin stimulation test.. Subjects underwent corticotropin testing at a mean of 13 days after the completion of therapy. Only 1 of the 16 GC-treated infants (6%) had adrenal insufficiency. This subject was tested 1 day after GC treatment was stopped, and results from retesting 3 months later were normal. All control subjects had normal adrenal function.. Infants with hemangiomas are at low risk of adrenal insufficiency following the completion of GC therapy, as used in our hemangioma center.

Topics: Adrenal Insufficiency; Cosyntropin; Female; Glucocorticoids; Hemangioma; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Infant; Male; Pituitary-Adrenal System; Prednisolone; Skin Neoplasms

Acute adrenal insufficiency in the trauma patient is underrecognized and the impact poorly understood. Our hypothesis was that the identification and treatment of acute adrenal insufficiency reduces mortality in trauma patients. Institutional Review Board approval for the retrospective review of a prospective database from a Level 1 trauma center for 2002 to 2004 was obtained. The study population included patients receiving a cosyntropin stimulation test (250 microg) and/or random cortisol level based on our practice management guideline and an intensive care unit stay longer than 24 hours. Demographic, acuity, and outcome data were collected. The nonresponders had baseline cortisol levels less than 20 microg/dL or poststimulation rise less than 9 microg/dL. Independent t tests and chi2 statistics were used. One hundred thirty-seven patients had cosyntropin stimulation tests performed. Eighty-two (60%) patients were nonresponders of which 66 were treated with hydrocortisone and 16 went untreated as a result of the discretion of the attending physician. The 55 (40%) responders showed no statistical differences in outcome variables whether or not they received hydrocortisone. The untreated adrenal-insufficient patients had significantly higher mortality, longer hospital length of stay, intensive care unit days, and ventilator-free days. Conclusions were: (1) treatment of acute adrenal insufficiency reduces mortality by almost 50 per cent in the trauma patient; and (2) acute adrenal insufficiency recognized by low random cortisol levels or nonresponse to a stimulation tests should be considered for treatment.

Topics: Acute Disease; Adrenal Insufficiency; Adult; Cosyntropin; Drug Therapy, Combination; Glucocorticoids; Hormones; Humans; Hydrocortisone; Length of Stay; Middle Aged; Prevalence; Prospective Studies; Survival Rate; Trauma Centers; Trauma Severity Indices; Treatment Outcome; United States; Wounds and Injuries

In order to identify whether low-dose (1 microg) tetracosactide (Synacthen) testing may be preferable to high-dose (250 microg) testing in the diagnosis of adrenal insufficiency in traumatic brain injury (TBI), as suggested by studies in other forms of critical illness.. We retrospectively reviewed the results of modified tetracosactide tests (involving administration of both low-dose and high-dose tetracosactide) conducted for clinical indications in patients in a neurocritical care unit within 10 days of TBI. Sixty-three modified tests were included and cortisol concentrations before and after administration of tetracosactide were extracted from the hospital records. Data were also extracted regarding hemodynamic response to empirical corticosteroid therapy, based on rapid weaning from vasoactive drugs.. Cortisol increments at 30 and 60 min following tetracosactide correlated well in the low-dose test (r(2) = 0.875, P < 0.0001). The mean cortisol concentration was 581 nmol/l at 30 min and 556 nmol/l at 60 min in the low-dose test. Cortisol increments following low-dose and high-dose testing correlated well overall (r(2) = 0.839, P < 0.0001), but results were discordant in 27 of 63 cases (43%) when the same diagnostic threshold was used. ROC curve analysis showed that both tests performed poorly in identifying hemodynamic steroid responsiveness (AUC 0.553 and 0.502, respectively).. In the low-dose tetracosactide test, it is sufficient to determine cortisol concentrations at baseline and at 30 min. Low-dose and high-dose tests give discordant results in a significant proportion of cases when using the same diagnostic threshold. Neither test can be used to guide the initiation of corticosteroid therapy in acute TBI.

Topics: Acute Disease; Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Brain Injuries; Cosyntropin; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Hemodynamics; Humans; Hydrocortisone; Kinetics; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Young Adult

To assess the repeatability of low-dose Synacthen test (LDST) in asthmatic children receiving high-dose fluticasone propionate (FP).. Low-dose Synacthen test was performed on 18 children with stable chronic asthma treated with FP at a constant daily dose of > or =500 microg and repeated 1 month later. Repeatability was assessed using the Kappa statistic for categorical variables.. Fifteen patients had consistent results (either two normal or two abnormal responses) and three patients had inconsistent results (one normal and one abnormal response). The Kappa statistic was 0.56 indicating fair to good agreement between the tests.. The results of adrenal function testing in patients on inhaled steroids can have major implications for patient management, making it important to use a test with excellent repeatability. The LDST conducted using our protocol does not fulfil this criterion.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Cosyntropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Male; Reproducibility of Results

Topics: Adrenal Glands; Adrenal Insufficiency; Cosyntropin; Glucocorticoids; Hormones; Humans; Hypothalamo-Hypophyseal System; Practice Guidelines as Topic

This study investigates the hypothesis that an adrenocorticotropic hormone-analog therapy may ameliorate relative adrenal insufficiency in the early phase of acute necrotizing pancreatitis (NP) by boosting endogenous glucocorticoid production.. Forty Wistar rats with taurocholate-induced NP were divided into 5 groups: the first group received low-dose Synacthen (0.5 mg/kg); the second, high-dose Synacthen (5mg/kg); the third,low-dose cortisol (10 mg/kg); the fourth, high-dose cortisol (100 mg/kg); and the fifth, the control group, received no treatment. All animals were killed after 6 hours: concentrations of plasma corticosterone, interleukin 1 (IL-1), IL-6, IL-10, tumor necrosis factor alpha, amylase, and lipase in ascites, myeloperoxidase activity in the pancreas, and a histological score were evaluated.. Corticosterone increased neither in the low-dose nor in the high-dose Synacthen group. Synacthen did not improve the early course of NP in terms of laboratory and histological results. A reduction of pancreatic necrosis and inflammation was observed in the low-dose cortisol group.. Endogenous glucocorticoid release seemed to be at its maximum during the early stage of NP and could not be further increased by Synacthen. Low-dose exogenous cortisol ameliorated the disease. These findings support the existence of relative adrenal insufficiency in the early phase of acute NP.

Topics: Adrenal Insufficiency; Amylases; Animals; Cosyntropin; Cytokines; Disease Models, Animal; Disease Progression; Female; Hydrocortisone; Lipase; Pancreas; Pancreatitis, Acute Necrotizing; Peroxidase; Rats; Rats, Wistar; Taurocholic Acid; Time Factors

Topics: Adrenal Insufficiency; Contraindications; Cosyntropin; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System

The hypothalamic-pituitary-adrenal axis is an important part of the body's natural response to acute illness. Adrenal insufficiency has the potential to lead to hemodynamic instability and electrolyte imbalances, limit the body's ability to respond to stress, and worsen overall clinical outcome. In this case series, we describe 16 patients evaluated for acute adrenal insufficiency after aneurysmal subarachnoid hemorrhage.. Over a 2-year period, the medical records of 16 patients admitted to the adult neurosurgery service for aneurysmal subarachnoid hemorrhage who were nonresponsive to vasopressor therapy and received cosyntropin for the evaluation of adrenal insufficiency within 14 days of their event were reviewed.. The median baseline cortisol in this population was 22.5 microg/dL, with a poststimulation cortisol level of 31 microg/dL. Of the population surveyed, a total of 11 patients met the preestablished criteria for adrenal insufficiency, 3 with baseline cortisol levels of less than 15 microg/dL and 11 with poststimulation concentration changes of less than 9 microg/dL. Baseline serum cortisol concentrations were significantly correlated with hospital stay (P = 0.045), intensive care unit stay (P = 0.005), and ventilator days (P = 0.006).. To date, this is the only investigation evaluating the incidence of acute relative adrenal insufficiency in this population. In our cohort, 69% of the patients met the preestablished criteria for relative adrenal insufficiency. The impact of low-dose corticosteroid therapy in this population also needs review, as it could have significant implications for the management of cerebral vasospasm.

Topics: Acute Disease; Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Comorbidity; Cosyntropin; Female; Hospital Mortality; Humans; Hydrocortisone; Incidence; Intracranial Pressure; Length of Stay; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Subarachnoid Hemorrhage; Treatment Outcome

There are few data in the paediatric literature on the normal cortisol response to stimulation during the low dose synacthen test (LDST) (1 microg).. To examine the cortisol responses in children, subsequently presumed to be normal, who had an LDST during anterior pituitary function tests (APFTs).. A retrospective review of results in children with short stature and normal growth hormone levels.. Of 33 children tested, seven had suboptimal cortisol responses based on accepted criteria (peak <500 nmol/l)--a false positive rate of 21%. Only three of these children had a repeat LDST, which was normal in all cases. The peak cortisol response (median 633, range, 417-1052 nmol/l) was inversely correlated with age (r = -0.44, p < 0.05).. One in five tests did not meet normal criteria. This false positive rate (21%) should be borne in mind when interpreting synacthen tests to prevent overdiagnosis of adrenal insufficiency.

Topics: Adolescent; Adrenal Insufficiency; Child; Child, Preschool; Cosyntropin; Dose-Response Relationship, Drug; False Positive Reactions; Female; Humans; Hydrocortisone; Male; Pituitary Function Tests; Pituitary Gland, Anterior; Reproducibility of Results; Retrospective Studies

Suppression of the adrenal axis may occur frequently in post-cardiac arrest patients. Physiological doses of corticosteroids have been shown to reverse hypotension and decrease mortality in other forms of shock. We sought to investigate current clinical practice pertaining to the evaluation for relative adrenal insufficiency in post-cardiac arrest shock.. We performed a retrospective analysis of post-cardiac arrest patients in an urban emergency department. Inclusion criteria included pre-hospital cardiac arrest patients over the age of 18 with a sustained return of spontaneous circulation that required vasopressor support. Exclusion criteria were traumatic arrest and cardiac arrest in the presence of healthcare personnel. The primary endpoint was the percent of patients in refractory shock that either had their adrenal axis tested or were treated for presumed relative adrenal insufficiency. Data analysis was descriptive in nature.. A total of 79 post-cardiac arrest patients were analyzed. Of the 79 patients, 69 were vasopressor-dependent. Of this group, 13% (9/69) had a cortisol level checked (with or without cosyntropin stimulation). Of those who had a cosyntropin stimulation test performed, 86% met biochemical criteria for relative adrenal insufficiency. Seventeen percent of vasopressor-dependent patients received corticosteroids explicitly for their shock state. Overall, only 32% of patients in refractory shock had testing for relative adrenal insufficiency or received corticosteroids for shock.. Though vasopressor-dependent shock is common in post-cardiac arrest patients, adrenal insufficiency was not considered in the majority of cases.

Topics: Adrenal Insufficiency; Biomarkers; Cosyntropin; Female; Follow-Up Studies; Heart Arrest; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Prognosis; Retrospective Studies

Cirrhosis of the liver is associated with an increased susceptibility to bacterial infections capable of causing septic shock and with a basal hyperdynamic circulatory state. The primary objective of this study was to delineate the echocardiographic characteristics and outcomes of septic shock in patients with liver cirrhosis. The secondary objective was to determine whether adrenal insufficiency, which may contribute to hyperdynamic syndrome, was more marked in patients with cirrhosis than in other patients with septic shock.. Prospective single-center cohort study.. Thirty-four patients admitted to the intensive care unit (ICU) for septic shocks were included, 14 with and 20 without liver cirrhosis. Echocardiography was performed within the first 24 h to measure the cardiac index (CI), systolic index (SI), and left ventricular ejection fraction (LVEF). A Synacthen test was performed.. Patients with cirrhosis had higher values for the CI (3.69+/-1.0 vs. 2.86+/-0.8 l/min/m(2); P=0.02), SI (37.5+/-8 vs. 32.4+/-7 ml/m(2); P=0.04), and LVEF (67+/-7 vs. 55.9+/-12%; P=0.005). ICU mortality was 53% overall, 64% in patients with cirrhosis, and 45% in patients without cirrhosis (P=0.27). Serum cortisol levels under basal conditions (H0) and after stimulation (H1) showed no significant differences between patients with and without cirrhosis. The proportion of patients with no response to Synacthen was 77% among patients with cirrhosis and 50% among patients without cirrhosis (P=0.18).. In a population with septic shock, left ventricular function was more hyperdynamic in the subset with cirrhosis. Relative adrenal insufficiency occurred in similar proportions of patients with and without cirrhosis.

Topics: Adrenal Cortex; Adrenal Insufficiency; Adult; Aged; Body Surface Area; Cardiac Output; Cohort Studies; Cosyntropin; Echocardiography; Female; Humans; Hydrocortisone; Intensive Care Units; Liver Cirrhosis; Male; Middle Aged; Paris; Prospective Studies; Shock, Septic; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left

Relative adrenal insufficiency (RAI) is a common complication during septic shock and may be more frequent in specific subgroups. The main objectives of this study were to determine the adrenal function and the RAI incidence in different subgroups of septic shock patients considering: main admission categories (medical, elective or emergency surgery); source of infection; nosocomial or community-acquired infections; gender, age <65 years or >65 years; and the presence or absence of neurological diseases, acute respiratory distress syndrome (ARDS) and bacteremia.. Prospective study in a medical-surgical ICU, including adults with septic shock, from May 2002 to May 2005. All patients had total serum cortisol measured at baseline and 60 min after a high-dose ACTH test within the first 96 h of shock onset. RAI was defined as a serum cortisol increment after ACTH test (Deltamax(249)) <90 microg/l.. One hundred and two subjects were enrolled, and the overall RAI incidence was 22.5%. Patients with ARDS before ACTH test or bacteremia showed lower Deltamax(249) values than patients with ARDS after ACTH test (96 vs. 153 microg/l, P=0.02) or without bacteremia (140 vs. 175 microg/l, P=0.04). Multivariate regression analysis revealed that female gender, development of ARDS before ACTH test, and bacteremia were associated with greater RAI incidence. There was no difference in RAI incidence considering neurological diseases, age, type and source of infection and the main admission categories.. Female gender, bacteremia and early-onset ARDS were variables independently associated with greater RAI incidence in septic shock patients. There was no difference in the RAI incidence concerning other subgroups.

Topics: Adrenal Cortex; Adrenal Insufficiency; Adult; Aged; Bacteremia; Brazil; Community-Acquired Infections; Cosyntropin; Cross Infection; Elective Surgical Procedures; Emergencies; Female; Humans; Hydrocortisone; Inpatients; Intensive Care Units; Male; Middle Aged; Nervous System Diseases; Postoperative Complications; Prospective Studies; Respiratory Distress Syndrome; Shock, Septic

The insulin tolerance test (ITT) has become less popular in paediatrics because of the risks associated with hypoglycaemia. Human corticotrophin-releasing hormone (hCRH) test results correlate with the ITT and may be an acceptable method to test for central adrenal insufficiency (CAI). Simpler tests, such as the low dose Synacthen test (LDST) and 9am cortisol, have also been proposed.. To compare the ability of the hCRH test, LDST, 9am cortisol level and 24-h cortisol profiles to diagnose CAI in a paediatric population.. A cross-sectional study in a tertiary paediatric endocrine clinic.. Thirty-one children and adolescents (aged 2.3-18.3 years) with CAI risk factors had an hCRH test, LDST, 9am cortisol and 24-h cortisol profile performed.. Of 23 patients with confirmed CAI (hCRH peak cortisol < 400 nmol/), 19 failed the LDST (peak cortisol < 267 nmol/l, i.e. 10th percentile for controls). Nineteen would have failed based on the 10th percentile cut point for 9am cortisol (< 140 nmol/l). Using receiver operating characteristic (ROC) curve coordinates, a 9am cortisol < 108 nmol/l was sensitive (83%) and specific (99%) for CAI. The 9am cortisol levels measured on two occasions were repeatable (94%) and correlated (r = 0.83, P = 0.01). All eight adrenally sufficient patients (hCRH peak cortisol > or = 400 nmol/l) passed the LDST. Seven had normal 9am cortisol (> or = 140 nmol/l). The 24-h cortisol area under the curve (AUC) for these patients was within the 10th-90th percentiles for control subjects' AUC. The peak cortisol to hCRH and LDST were correlated (r = 0.88, P = 0.01), with no difference between the peaks (mean difference -5.3 nmol/l, P = 0.69).. In children with CAI risk factors, the diagnosis can be made if unstressed 9am cortisol is < 108 nmol/l. As cortisol levels > 381 nmol/l are highly suggestive of normal hypothalamic-pituitary-adrenal (HPA) function, stimulation testing need only be performed if 9am cortisol is 108-381 nmol/l. The LDST should be interpreted cautiously because mild CAI may be missed. When stimulation results are marginal, 24-h cortisol profiles can provide reassurance of normal cortisol status.

Topics: Adolescent; Adrenal Insufficiency; Child; Child, Preschool; Corticotropin-Releasing Hormone; Cosyntropin; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Sensitivity and Specificity

Timely diagnosis and treatment of adrenal insufficiency (AI) dramatically reduces mortality in trauma patients. We sought to identify risk factors and populations with a high risk of developing AI.. Retrospective registry study.. Academic level I trauma center.. All trauma patients in the intensive care unit who underwent cosyntropin stimulation testing (CST) for presumed AI from January 1, 2002, through December 31, 2004.. Cosyntropin stimulation testing, in which response was defined as an increase of 9 mug/dL (248 nmol/L) or more in cortisol level.. Risk factors for developing AI in critically ill trauma patients.. In 137 patients, CST was performed; 83 (60.6%) were nonresponders and 54 (39.4%) were responders. Age, sex, race, trauma mechanism, Injury Severity Score, and Revised Trauma Score were not statistically different between the groups. Rates of sepsis/septic shock, mechanical ventilation, and mortality were also similar between the 2 groups. However, rates of hemorrhagic shock on admission (45 [54%] vs 16 [30%]), requirement of vasopressor support (65 [78%] vs 28 [52%]), and etomidate exposure (59 [71%] vs 28 [52%]) were all significantly higher in the nonresponder group (P < .01). The increased risk of AI remained after controlling for potential confounding covariates (age, mechanism, Injury Severity Score, and Revised Trauma Score).. Exposure to etomidate is a modifiable risk factor for the development of AI in this sample of critically injured patients. The use of etomidate for procedural sedation and rapid-sequence intubation in this patient population should be reevaluated.

Topics: Academic Medical Centers; Adolescent; Adrenal Insufficiency; Adult; Aged; APACHE; Cosyntropin; Etomidate; Female; Follow-Up Studies; Humans; Hypnotics and Sedatives; Injury Severity Score; Intubation, Intratracheal; Male; Middle Aged; Multiple Trauma; Poisson Distribution; Probability; Registries; Retrospective Studies; Risk Assessment; Statistics, Nonparametric; Survival Analysis; Trauma Centers

Topics: Adrenal Insufficiency; Aged; Cosyntropin; Critical Illness; Female; Humans; Male; Middle Aged; Retrospective Studies; Shock, Septic

There is paucity of data on the magnitude of absolute or relative adrenal insufficiency in septic shock, especially in children. We conducted a prospective study to determine the prevalence of adrenal insufficiency in children with septic shock using a low-dose Synacthen (1 microg) stimulation test.. Cross-sectional study.. Pediatric intensive care unit in a tertiary care hospital in northern India.. Children with septic shock.. None.. We performed cortisol estimation at baseline and after low-dose Synacthen (1 microg) stimulation at 30 and 60 mins in children with fluid refractory septic shock admitted to our pediatric intensive care unit. Basal cortisol levels <7 microg/dL and peak cortisol level <18 microg/dL were used to define adrenal insufficiency. An increment of <9 microg/dL after stimulation was used to diagnose relative adrenal insufficiency. As there is lack of consensus on the cutoffs for defining relative adrenal insufficiency using the low-dose adrenocorticotropic hormone test, we evaluated different cutoff values (increment at 30 mins, increment at 60 mins, greater of the two increments) and evaluated their association with the incidence of catecholamine refractory shock and outcomes. Children with sepsis but without septic shock were sampled for baseline cortisol levels as a comparison. Thirty children (15 girls) with septic shock were included; median age (95% confidence interval) was 36.5 (9.39- 58.45) months. Median Pediatric Risk of Mortality score was 22.5 (14.13-24.87). Fifteen (50%) children survived. The median (95% confidence interval) cortisol values at baseline and 30 mins and 60 mins after stimulation were 71 (48.74-120.23) microg/dL, 78.1 (56.9-138.15) microg/dL, and 91 (56.17-166.44) microg/dL, respectively. The median baseline cortisol value in age- and gender-matched children with sepsis was 11.5 microg/dL. None of the children with septic shock fulfilled the criteria for absolute adrenal insufficiency. However, nine (30%) patients had relative adrenal insufficiency (increment in cortisol <9 microg/dL). Of these nine patients, five (56%) died; of the 21 patients with a greater increment in cortisol after stimulation, ten died (p = .69). Compared with patients in septic shock with normal adrenal reserve, those with relative adrenal insufficiency had a higher incidence of catecholamine refractory shock (p = .019) but no difference in mortality rate (p = .69). On the sensitivity and specificity analysis using various cutoffs of increment, the best discrimination for catecholamine refractory shock was obtained with a peak increment <6 microg/dL.. Relative adrenal insufficiency is common in children with septic shock and is associated with catecholamine refractory shock.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Age Factors; Child; Child, Preschool; Confidence Intervals; Cosyntropin; Cross-Sectional Studies; Data Interpretation, Statistical; Female; Humans; Hydrocortisone; Infant; Intensive Care Units, Pediatric; Male; Prospective Studies; Sensitivity and Specificity; Sex Factors; Shock, Septic; Time Factors

Glucocorticoids are the main drug used to control vasogenic edema in patients with brain tumor. Rapid GC tapering may not only decompensate intracranial pressure, but also unmask SAI, and some symptoms of SAI can be mistakenly attributable to increased intracranial pressure or side effects of chemotherapy and radiation therapy.. The University of Virginia Neuro-Oncology Database was reviewed from February 2002 to January 2006, and 5 neuro-oncology patients with clinical and laboratory evidence of SAI were identified.. In our experience, 1% of neuro-oncology patients treated with GC developed SAI. Symptoms resembled increased intracranial pressure or side effects of antineoplastic treatment.. A healthy index of suspicion for this complication and use of pharmacologic testing will help avert misattribution of symptoms of SAI and its deleterious consequences.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Brain Edema; Brain Neoplasms; Causality; Cosyntropin; Drug Administration Schedule; Female; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Intracranial Hypertension; Male; Middle Aged; Patient Selection; Substance Withdrawal Syndrome

Previous studies have indicated that most individuals reach peak cortisol levels in 60 minutes during the short Synacthen test (SST) done to exclude adrenal insufficiency. Therefore, measuring serum cortisol at only 60 minutes may suffice. This study was carried out to evaluate the significance of the 60-minute serum cortisol level in SST as a reliable and cost-effective screening test in comparison to the conventional SST.. A cross-sectional study was conducted from January 2000 to September 2004, in which data was collected by reviewing medical records of all patients who underwent SST at the Aga Khan University Hospital, Karachi. A total of 236 patients suspected of having adrenal insufficiency were included. Values of serum cortisol at baseline, 30 and 60 minutes post-250 ug-injection Synacthen were recorded. The cortisol level was measured through fluorescence polarisation immunoassay. The cut-off value of 20 ug/dL was used to differentiate normal individuals from hypoadrenal individuals.. Out of 236 study participants, 93 (39 percent) were males and 143 (61 percent) were females. The mean age and standard deviation was 44.4 +/- 21 years. Cortisol concentration increased significantly from baseline to 30 minutes and 60 minutes after injecting Synacthen (p-value is less than 0.001 for each). The majority of the patients reached the cortisol peak of greater than 20 ug/dL (555 nmol/L) at 60 minutes. Normal responses were found in 148 patients (63.1 percent) at both 30 and 60 minutes, while 27 participants (12 percent) reached a peak greater than 20 ug/dL (555 nmol/L) at 60 minutes but were less than 20 ug/dL (555 nmol/L) at 30 minutes. In the deficient cases, SST showed abnormal responses in 60 cases (25 percent) at both 30 and 60 minutes. However, there was only one patient who reached a peak value of 21 ug/dL (589 nmol/L) at 30 minutes, which reduced to 17 ug/dL (485 nmol/L) at 60 minutes.. This study showed that a 60-minute cortisol value during SST was reliable enough in identifying normal subjects for excluding adrenal insufficiency, and was equally effective in identifying abnormal cases, as compared to values at both 30 and 60 minutes. It is therefore suggested that a single 60-minute post-Synacthen serum cortisol level may suffice, as compared to the conventional SST. This is also significant as a cost-effective measure, especially in third world countries where cost is a major issue for diagnosing and treating patients.

Topics: Adrenal Insufficiency; Adult; Cost-Benefit Analysis; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Male; Mass Screening; Middle Aged; Time Factors

Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose.. Children recorded as prescribed FP > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l).. A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6-19.3 years) were successfully tested. Of 194 receiving FP > or = 500 microg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of > or = 1000 microg/day.. Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cosyntropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluticasone; Humans; Hydrocortisone

A 21-year-old man with a C6 American Spinal Injury Association A spinal cord injury (SCI) developed symptomatic hypotension resistant to vasopressors and volume replacement 2 weeks after injury and was diagnosed with adrenal insufficiency by cosyntropin test. Adrenal insufficiency has been documented in chronic SCI; this case shows documented adrenal insufficiency in acute SCI.. Case report.. Secondary adrenal insufficiency complicated the medical and rehabilitative course of this patient with SCI. During 2 infectious episodes, this patient's dosage of hydrocortisone had to be doubled to control symptomatic hypotension, lethargy, diffuse weakness, and anorexia.. The nonspecific symptomatology of adrenal insufficiency can be easily overlooked in patients with SCI. Low basal cortisol levels may be an important clue to this disorder. Low-dose adrenocorticotropic hormone stimulation may be more sensitive than high doses for detecting subclinical adrenal insufficiency. A high index of clinical suspicion is needed for the correct diagnosis of acute and chronic adrenal insufficiency.

Topics: Adrenal Insufficiency; Adult; Cervical Vertebrae; Cosyntropin; Dose-Response Relationship, Drug; Humans; Hydrocortisone; Hypotension; Male; Neurologic Examination; Spinal Cord Injuries; Spinal Fractures

Diagnosis of adrenal insufficiency in critically ill patients has relied on random or cosyntropin-stimulated cortisol levels, and has not been corroborated by a more accurate diagnostic standard.. We used the overnight metyrapone stimulation test to investigate the diagnostic value of the standard cosyntropin stimulation test, and the prevalence of sepsis-associated adrenal insufficiency.. This was an inception cohort study.. In two consecutive septic cohorts (n = 61 and n = 40), in 44 patients without sepsis and in 32 healthy volunteers, we measured (1) serum cortisol before and after cosyntropin stimulation, albumin, and corticosteroid-binding globulin levels, and (2) serum corticotropin, cortisol, and 11beta-deoxycortisol levels before and after an overnight metyrapone stimulation. Adrenal insufficiency was defined by postmetyrapone serum 11beta-deoxycortisol levels below 7 microg/dl. More patients with sepsis (31/61 [59% of original cohort with sepsis] and 24/40 [60% of validation cohort with sepsis]) met criteria for adrenal insufficiency than patients without sepsis (3/44; 7%) (p < 0.001 for both comparisons). Baseline cortisol (< 10 microg/dl), Delta cortisol (< 9 microg/dl), and free cortisol (< 2 microg/dl) had a positive likelihood ratio equal to infinity, 8.46 (95% confidence interval, 1.19-60.25), and 9.50 (95% confidence interval, 1.05-9.54), respectively. The best predictor of adrenal insufficiency (as defined by metyrapone testing) was baseline cortisol of 10 microg/dl or less or Delta cortisol of less than 9 microg/dl. The best predictors of normal adrenal response were cosyntropin-stimulated cortisol of 44 microg/dl or greater and Delta cortisol of 16.8 microg/dl or greater.. In sepsis, adrenal insufficiency is likely when baseline cortisol levels are less than 10 microg/dl or delta cortisol is less than 9 microg/dl, and unlikely when cosyntropin-stimulated cortisol level is 44 microg/dl or greater or Delta cortisol is 16.8 microg/dl or greater.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Cosyntropin; Female; Humans; Hydrocortisone; Male; Metyrapone; Middle Aged; Sepsis; Serum Albumin; Shock, Septic; Transcortin

To determine the impact of physiologic doses of hydrocortisone on neurologic outcome after traumatic brain injury (TBI).. We conducted a retrospective study in a neurocritical care unit at a university teaching hospital. We included 29 patients with moderate and severe TBI requiring vasoactive drugs to maintain adequate arterial blood pressure who received corticosteroid. Infected patients were excluded. Blood cortisol levels were measured before and 30 and 60 minutes after the administration of a high-dose corticotropin stimulation test (HDST). Patients received hydrocortisone replacement therapy (200-300 mg/day) and vasoactive drugs requirements were noted. Intracranial pressure was managed according to a predefined protocol.. A total of 14 out of 29 (48%) of patients were classified as responders to hydrocortisone (stopping vasoactive drugs within 3 days of starting hydrocortisone). The Glasgow Outcome Score (GOS) was used to assess neurologic outcome at 6 months. A favorable outcome (GOS 4 and 5) was observed in 11 out of 14 (79%) of responders and five out of 15 (33%) of nonresponders (p = 0.03). Of the responders, 12 out of 14 (85%) had a baseline cortisol below 414 nmol/L, and five out of 14 (36%) had primary adrenal insufficiency (AI) (primary AI: low baseline cortisol, and poor response to the HDST). Age, severity of injury, and response to hydrocortisone were predictive of outcome in multiple logistic regression analysis.. Adrenal insufficiency is frequent after TBI, and hydrocortisone replacement therapy seems to be associated with a favorable neurologic outcome.

Topics: Adrenal Insufficiency; Adult; Anti-Inflammatory Agents; Blood Pressure; Brain Injuries; Brain Injury, Chronic; Cosyntropin; Dose-Response Relationship, Drug; Female; Glasgow Outcome Scale; Humans; Hydrocortisone; Male; Middle Aged; Neurologic Examination; Prognosis; Retrospective Studies; Vasoconstrictor Agents

Patients with organic growth hormone deficiency (GHD) or with structural hypothalamic-pituitary abnormalities may have additional anterior pituitary hormone deficits, and are at risk of developing complete or partial corticotropin (ACTH) deficiency. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis (HPA) is essential in these patients because, although clinically asymptomatic, their HPA cannot appropriately react to stressful stimuli with potentially life-threatening consequences.. In this study we evaluated the integrity of the HPA in 24 patients (age 4.2-31 years at the time of the study) with an established diagnosis of GHD and compared the reliability of the insulin tolerance test (ITT), short synacthen test (SST), low-dose SST (LDSST), and corticotropin releasing hormone (CRH) test in the diagnosis of adrenal insufficiency.. At a cortisol cut-off for a normal response of 550 nmol/l (20 microg/dl), the response to ITT was subnormal in 11 subjects, 6 with congenital and 5 with acquired GHD. Four patients had overt adrenal insufficiency, with morning cortisol concentrations ranging between 66.2-135.2 nmol/l (2.4-4.9 microg/dl) and typical clinical symptoms and laboratory findings. In all these patients, a subnormal cortisol response to ITT was confirmed by LDSST and by CRH tests. SST failed to identify one of the patients as adrenal insufficient. In the seven asymptomatic patients with a subnormal cortisol response to ITT, the diagnosis of adrenal insufficiency was confirmed in one by LDSST, in none by SST, and in five by CRH tests. The five patients with a normal cortisol response to ITT exhibited a normal response also after LDSST and SST. Only two of them had a normal response after a CRH test. In the seven patients with asymptomatic adrenal insufficiency mean morning cortisol concentration was significantly higher than in the patients with overt adrenal insufficiency. ITT was contraindicated in eight patients, and none of them had clinical symptoms of overt adrenal insufficiency. One of these patients had a subnormal cortisol response to LDSST, SST, and CRH, and three exhibited a subnormal response to CRH but normal responses to LDSST and to SST.. We conclude that none of these tests can be considered completely reliable for establishing or excluding the presence of secondary or tertiary adrenal insufficiency. Consequently, clinical judgment remains one of the most important issues for deciding which patients need assessment or re-assessment of adrenal function.

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Child; Child, Preschool; Corticotropin-Releasing Hormone; Cosyntropin; Diagnostic Techniques, Endocrine; Female; Human Growth Hormone; Humans; Hypoglycemia; Hypoglycemic Agents; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Insulin; Male; Pituitary Diseases; Pituitary-Adrenal System; Reproducibility of Results

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocortical Hyperfunction; Animals; Cats; Cosyntropin; Dogs

Autoimmune polyglandular syndromes are fairly common diseases that are classified into four constellations based on the clinical clustering of the various component diseases. In types 1, 2, and 4, primary adrenal insufficiency due to an autoimmune process is usually present, but its diagnosis is often delayed because it is difficult to detect in a subclinical phase. It is widely accepted that the classical dose of 250 microg ACTH(1-24) is supramaximal, whereas 0.06 microg has been shown to be one of the lowest ACTH doses that is able to stimulate adrenal secretion in normal young subjects. The aim of this study was to clarify the sensitivity and maximal secretory response of the adrenal gland to ACTH in a group of patients with at least two autoimmune diseases, without clinical signs and symptoms of overt or subclinical hypocortisolism. Cortisol (F), aldosterone (A), and dehydroepiandrosterone (DHEA) responses to the sequential administration of very low and supramaximal ACTH(1-24) doses [0.06 microg followed by 250 microg ACTH(1-24) i.v. at 0 and +60 min] were studied in 18 patients with at least two autoimmune diseases (AP; age, 20-40 yr; body mass index, 22-26 kg/m(2)). The results in the patients were compared with the results recorded in 12 normal age-matched control subjects (CS; age, 22-34 yr; body mass index, 20-25 kg/m(2)). At baseline, ACTH levels in AP were within the normal range but higher (P < 0.05) than in CS, whereas F, A, DHEA, urinary-free F, and plasma renin activity were similar in both groups. F, A, and DHEA responses to ACTH were dose dependent in both groups. However, in AP, F, A, and DHEA levels showed no response to the 0.06- micro g ACTH dose, which, in turn, elicited clear responses (P < 0.01) in CS. On the other hand, F, A, and DHEA responses to 250 microg ACTH in AP were not different from those in CS. In conclusion, patients with autoimmune diseases who displayed a normal basal adrenal function showed a loss of F, A, and DHEA response to the very low ACTH dose, although they were normal responders to the high ACTH dose. These data are likely to indicate that a reduced sensitivity to ACTH in all adrenal zones occurs in patients with different types of autoimmune disease.

Topics: Adrenal Cortex Function Tests; Adrenal Glands; Adrenal Insufficiency; Adult; Aldosterone; Case-Control Studies; Cosyntropin; Dehydroepiandrosterone; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Male; Polyendocrinopathies, Autoimmune

Topics: Adrenal Insufficiency; Cosyntropin; Humans; Sensitivity and Specificity

Because more than 90 percent of circulating cortisol in human serum is protein-bound, changes in the binding proteins can alter measured serum total cortisol concentrations without influencing free concentrations of this hormone. We investigated the effect of decreased amounts of cortisol-binding proteins on serum total and free cortisol concentrations during critical illness, when glucocorticoid secretion is maximally stimulated.. Base-line serum total cortisol, cosyntropin-stimulated serum total cortisol, aldosterone, and free cortisol concentrations were measured in 66 critically ill patients and 33 healthy volunteers in groups that were similar with regard to sex and age. Of the 66 patients, 36 had hypoproteinemia (albumin concentration, 2.5 g per deciliter or less), and 30 had near-normal serum albumin concentrations (above 2.5 g per deciliter).. Base-line and cosyntropin-stimulated serum total cortisol concentrations were lower in the patients with hypoproteinemia than in those with near-normal serum albumin concentrations (P<0.001). However, the mean (+/-SD) base-line serum free cortisol concentrations were similar in the two groups of patients (5.1+/-4.1 and 5.2+/-3.5 microg per deciliter [140.7+/-113.1 and 143.5+/-96.6 nmol per liter]) and were several times higher than the values in controls (0.6+/-0.3 microg per deciliter [16.6+/-8.3 nmol per liter], P<0.001 for both comparisons). Cosyntropin-stimulated serum total cortisol concentrations were subnormal (18.5 microg per deciliter [510.4 nmol per liter] or less) in 14 of the patients, all of whom had hypoproteinemia. In all 66 patients, including these 14 who had hypoproteinemia, the base-line and cosyntropin-stimulated serum free cortisol concentrations were high-normal or elevated.. During critical illness, glucocorticoid secretion markedly increases, but the increase is not discernible when only the serum total cortisol concentration is measured. In this study, nearly 40 percent of critically ill patients with hypoproteinemia had subnormal serum total cortisol concentrations, even though their adrenal function was normal. Measuring serum free cortisol concentrations in critically ill patients with hypoproteinemia may help prevent the unnecessary use of glucocorticoid therapy.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Aldosterone; APACHE; Cosyntropin; Critical Illness; Humans; Hydrocortisone; Hypoalbuminemia; Hypoproteinemia; Middle Aged; Pituitary-Adrenal System; Regression Analysis

We hypothesized that hypothyroidism and adrenal insufficiency frequently occur together in critically ill patients.. A prospective observational study.. Surgical intensive care unit of a university-affiliated tertiary referral center.. Sixty-six consecutive patients with severe sepsis, septic shock, and hemorrhagic shock who required pulmonary artery catheterization for resuscitation were studied.. Thyrotropin and baseline cortisol levels were obtained at 3 am followed by intravenous injection of 250 mug of cosyntropin, a synthetic adrenocorticotropic hormone derivative. A second measurement of the cortisol level was performed 1 hour later.. Incidence of hypothyroidism and adrenal insufficiency and mortality.. Mean (SD) age was 62 (19) years. The mean (SD) Acute Physiology and Chronic Health Evaluation II score was 21 (5). Twenty-seven patients (40.9%) had severe sepsis, 31 (46.9%) had septic shock, and 8 (12.1%) had hemorrhagic shock. Five patients (7.6%) had hypothyroidism alone and 35 (53.0%) had only adrenal insufficiency. Eight patients (12.1%) had both hypothyroidism and adrenal insufficiency. All patients with endocrine abnormalities were treated. Mortality for the total group was 15 (22.7%) of 66 patients.. There is a 12% incidence of simultaneous hypothyroidism and adrenal insufficiency in our study and the routine testing for both may be indicated in this population of critically ill patients.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Cosyntropin; Critical Illness; Female; Humans; Hydrocortisone; Hypothyroidism; Incidence; Injections, Intravenous; Male; Middle Aged; Prospective Studies; Sepsis; Shock, Hemorrhagic; Shock, Septic; Thyrotropin; Wounds and Injuries

It is widely accepted that the classical dose of 250.0 microg ACTH (1-24) (tetracosactin) is clearly supra-maximal while 1.0 and 0.03 microg have been shown as the maximal and the lowest stimulatory ACTH doses for cortisol (F) secretion in normal young subjects. Testing with low ACTH dose would better evaluate adrenal sensitivity to corticotropin. The aims of the present study were: a) to clarify the adrenal sensitivity to ACTH in patients with different duration of corticotroph insufficiency by testing with low and very low tetracosactin doses; and b) to evaluate diagnostic implication regarding the ability of ACTH tests to distinguish patients with corticotroph insufficiency from normal subjects. In 24 hypopituitaric patients (HYPOPIT, 15 male and 9 female, age 22-50 yr, BMI: 22-26 kg/m2) with corticotrophin deficiency we studied the F, DHEA and aldosterone (A) responses to challenges with low ACTH doses (0.06 or 0.5 microg iv at 0 min) followed by 250 microg iv (at +60 min). The results in HYPOPIT were compared with those recorded in 12 normal controls (NS, 6 male and 6 female, age 22-34 yr, BMI: 20-25 kg/m2). Basal F and DHEA levels in HYPOPIT were lower than in NS, while A levels were similar in both groups. The F responses to ACTH in HYPOPIT were dose-independent and markedly lower (p < 0.0001) than in NS. After the 0.06 and 0.5 microg ACTH dose, 16% of HYPOPIT patients showed AF peak within the range of normal response. No HYPOPIT showed AF peak within the normal range after 250 microg ACTH. The DHEA responses to ACTH in HYPOPIT were dose-independent and markedly lower than in NS (p < 0.0001). Overlap between individual DHEA responses in HYPOPIT and NS was present after 0.06 microg and 0.5 microg but not after 250 microg tetracosactin. The A responses in HYPOPIT were dose-dependent and overlapped with those in NS. The adrenal responses to ACTH in HYPOPIT were not associated with the duration of the disease. In conclusion, the present study shows that the mean F and DHEA but not the A responses to ACTH (1-24) are markedly impaired in hypopituitaric patients with corticotroph insufficiency independently of the duration of the disease. The impaired F and DHEA response to ACTH is also independent of the dose, suggesting the existence of relatively enhanced sensitivity of the fasciculata and reticularis adrenal zone to ACTH but meantime remarkable impairment of the adrenal function due to corticotrophin deficiency. In the present study, testing with sub

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aldosterone; Area Under Curve; Cosyntropin; Dehydroepiandrosterone; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Hypopituitarism; Male; Middle Aged

Recently, there has been renewed interest in corticosteroid therapy for patients with septic shock. The cortisol response to a tetracosactide stimulation test, otherwise known as a short synacthen test, may identify which patients are most likely to benefit from corticosteroid replacement. Controversy over interpretation of the cortisol response and the correct tetracosactide dose remains. We retrospectively analysed all septic shock patients who had full cortisol results following a 1- micro g short synacthen test. All cortisol results were re-evaluated by three common ways of interpreting the cortisol response to a short synacthen test. The thresholds were a cortisol rise >/= 250 nmol x l(-1), a peak cortisol >/= 550 nmol x l(-1) and a peak cortisol >/= 700 nmol x l(-1). We found a significant relationship between the peak cortisol results and haemodynamic improvement in patients given corticosteroids. There was no association between a cortisol rise >/= 250 nmol x l(-1) and haemodynamic improvement after corticosteroids. A postal questionnaire was sent to adult intensive care units in the United Kingdom to assess national practice. Sixty per cent of intensive care units use corticosteroids in septic shock patients, but only 22% use a short synacthen test to guide therapy.

Topics: Adrenal Insufficiency; Adult; Cosyntropin; Critical Care; Drug Administration Schedule; Health Care Surveys; Hemodynamics; Humans; Hydrocortisone; Practice Guidelines as Topic; Professional Practice; Retrospective Studies; Shock, Septic; Surveys and Questionnaires

Although widely used, the effects of steroid "bursts" on the hypothalamic-pituitary-adrenal axis, especially with long-term, concomitant topical steroids use, have not been studied.. To examine the effect of a prednisone burst, long-term intranasal steroids, and inhaled fluticasone propionate on the suppression and recovery of adrenal function.. Adult patients taking long-term intranasal steroids, either moderate-dose (440 microg/d) or high-dose (880 microg/d) inhaled fluticasone propionate, underwent a low-dose cosyntropin stimulation test (LDCST) before and 2 days after a prednisone burst. Suppressed adrenal responses were monitored with a weekly LDCST. Persistent abnormal LDCST results were confirmed by 8-hour cosyntropin infusion. Inhaled fluticasone dosages were decreased; adrenal recovery was evaluated by a monthly LDCST. Adverse effects of steroids were monitored by questionnaires.. Sixty-three patients participated in the study. Three of 31 patients not taking inhaled steroids and 1 of 13 patients taking moderate-dose fluticasone had abnormal LDCST results on day 2 after the prednisone burst, which normalized by the second week. In the high-dose fluticasone group, 14 of 19 patients had suppressed LDCST responses on day 2 and adrenal function recovered in 10 of 19 patients by the fourth week. These patients complained significantly of decreased libido (P = 0.02), listlessness (P = 0.03), and weight loss (P = 0.05). High-dose fluticasone (r = 0.66, P < 0.001) and duration of use (r = 0.32, P = 0.01) were statistically correlated with adrenal impairment. Of the 4 patients with persistent adrenal impairment, 3 patients successfully reduced dosages of inhaled fluticasone and adrenal function recovered in 2 to 10 months.. Prednisone bursts induce brief adrenal impairment. Intranasal steroids and moderate-dose fluticasone had no effect on adrenal function. High-dose, inhaled fluticasone caused mild-to-significant adrenal suppression and delayed the recovery after a steroid burst. Avoiding or limiting the duration of high-dose inhaled steroids would minimize systemic adverse effects.

Topics: Administration, Intranasal; Adrenal Glands; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Cosyntropin; Female; Fluticasone; Humans; Male; Middle Aged; Prednisone; Respiratory Tract Diseases

Topics: Adrenal Insufficiency; Coma; Cosyntropin; Humans; Hydrocortisone; Hypoglycemia; Hypopituitarism; Treatment Outcome

The aim was to reevaluate a group of adults treated for idiopathic childhood onset GH deficiency (GHD) after 18 yr without GH treatment. Twenty-six (11 females) patients participated. All but two had isolated GHD. Childhood diagnosis was established by insulin tolerance test (ITT). The patients were retested with an ITT to evaluate adult GH status. In five patients, an arginine and a synacthen test were performed instead of an ITT. Eleven of 25 patients had a subnormal cortisol response to ITT or synacthen. Ten patients had a GH peak less than 3.0 microg/liter (0.5. +/- 0.5 microg/liter), whereas 16 patients displayed a normal GH response (12.3 +/- 10.6 microg/liter) after ITT. IGF-I values were decreased in the patients with a pathological retest as well as in patients with a normal GH response compared with controls (P < 0.005). In 26 idiopathic childhood onset GHD patients, 44% of the patients had developed adrenal insufficiency; 38.5% had persistent GHD in adulthood, using the same test in both childhood and adulthood. Patients having a normal GH test had decreased IGF-I levels, compared with controls, indicating impaired function of a seemingly normal GH axis. It is imperative that pituitary axes other than the GH axis are tested at regular intervals, even in the absence of GHD in adulthood.

Topics: Adrenal Insufficiency; Adult; Cosyntropin; Cross-Sectional Studies; Female; Human Growth Hormone; Humans; Hydrocortisone; Insulin; Insulin-Like Growth Factor I; Male; Metabolism, Inborn Errors; Risk Assessment

Acute liver failure and septic shock share many clinical features, including hyperdynamic cardiovascular collapse. Adrenal insufficiency may result in a similar cardiovascular syndrome. In septic shock, adrenal insufficiency, defined using the short synacthen test (SST), is associated with hemodynamic instability and poor outcome. We examined the SST, a dynamic test of adrenal function, in 45 patients with acute hepatic dysfunction (AHD) and determined the association of these results with hemodynamic profile, severity of illness, and outcomes. Abnormal SSTs were common, occurring in 62% of patients. Those who required noradrenaline (NA) for blood pressure support had a significantly lower increment (median, 161 vs. 540 nmol/L; P <.001) following synacthen compared with patients who did not. Increment and peak were lower in patients who required ventilation for the management of encephalopathy (increment, 254 vs. 616 nmol/L, P <.01; peak, 533 vs. 1,002 nmol/L, P <.01). Increment was significantly lower in those who fulfilled liver transplant criteria compared with those who did not (121 vs. 356 nmol/L; P <.01). Patients who died or underwent liver transplantation had a lower increment (148 vs. 419 nmol/L) and peak (438 vs. 764 nmol/L) than those who survived (P <.01). There was an inverse correlation between increment and severity of illness (Sequential Organ Failure Assessment, r = -0.63; P <.01). In conclusion, adrenal dysfunction assessed by the SST is common in AHD and may contribute to hemodynamic instability and mortality. It is more frequent in those with severe liver disease and correlates with severity of illness.

Topics: Adolescent; Adrenal Insufficiency; Adult; Aged; Bacterial Infections; Cosyntropin; Critical Care; Female; Hemodynamics; Humans; Hydrocortisone; Kidney Diseases; Liver Failure, Acute; Liver Transplantation; Male; Middle Aged; Pregnancy; Respiration, Artificial; Severity of Illness Index; Treatment Outcome

Topics: Adrenal Insufficiency; Adrenocortical Hyperfunction; Animals; Cosyntropin; Dog Diseases; Dogs; Female; Hydrocortisone; Infusions, Intravenous; Leukocyte Count; Pilot Projects; Predictive Value of Tests; Reference Values

To examine the incidence and response to treatment of adrenal insufficiency (AI) in high-risk postoperative patients.. Prospective observational case series.. Large urban tertiary-care surgical ICU (SICU).. Adults > 55 years of age who required vasopressor therapy after adequate volume resuscitation in the immediate postoperative period.. Each patient underwent a cosyntropin (ACTH) stimulation test; at the discretion of the clinical team, some patients were empirically given hydrocortisone (100 mg IV q8h for three doses) before serum cortisol values became available.. Adrenal dysfunction (AD), defined as serum cortisol < 20 microg/dL at all time points, with Delta cortisol (60 min post-ACTH minus baseline) of < or = 9 microg/dL; functional hypoadrenalism (FH), defined as serum cortisol < 30 microg/dL at all time points or Delta cortisol (60 min post-ACTH minus baseline) < or = 9 microg/dL; and AI, as the presence of either AD or FH.. One hundred four patients were enrolled with a mean age (SD) of 65.2 +/- 16.9 years. AI (AD plus FH) was found in 34 of 104 patients (32.7%): AD was found in 9 patients (8.7%), FH in 25 patients (24%), and normal adrenal function in 70 patients (67.3%). The absolute eosinophil count was significantly higher in the combined AD and FH groups compared with the group with normal adrenal function (p < 0.05). Forty-six of 104 patients (44.2%) received hydrocortisone; 29 (63%) could be weaned from treatment with vasopressors within 24 h. This beneficial effect of hydrocortisone reached statistical significance in the FH group when compared with untreated patients (p < 0.031); a similar trend was seen in the AD group (p = 0.083). Mortality was also lower in the hydrocortisone-treated AI patients (5 of 23 [21%] vs 5 of 11 [45%] in those not receiving hydrocortisone; p < 0.01).. There is a high incidence of AI among SICU patients > 55 years of age with postoperative hypotension requiring vasopressors. There is also a significant association between hydrocortisone replacement therapy, resolution of vasopressor requirements, and improved survival.

Topics: Adrenal Insufficiency; Aged; Cosyntropin; Critical Illness; Female; Humans; Hydrocortisone; Hypotension; Incidence; Intensive Care Units; Male; Middle Aged; Postoperative Complications; Prospective Studies; Risk Factors; Vasoconstrictor Agents

Whereas the antifungal azole ketoconazole interferes with steroidogenesis and can cause adrenal insufficiency, fluconazole in standard doses is thought to not interfere with cortisol production. The objective was to evaluate the effect of high-dose fluconazole therapy on adrenal function in critically ill patients in an intensive care setting.. Descriptive case reports.. Medical intensive care unit in a university hospital.. Two patients, a 77-yr-old man (case 1) with esophageal cancer and a 66-yr-old woman (case 2) with multiple organ failure developed reversible adrenal insufficiency temporally related to the institution and withdrawal of high-dose fluconazole.. Short cosyntropin (adrenocorticotropic hormone; ACTH) stimulation tests.. Two days after high-dose fluconazole in case 1, the serum ACTH level was 121 pg/mL (normal range is 9-52 pg/mL), and the peak cortisol after ACTH stimulation was 15.5 microg/dL (normal response is >or=18 microg/dL). Eleven days after discontinuation of fluconazole, the peak cortisol level after ACTH stimulation was 43.4 microg/dL. Twenty-four hours after high-dose fluconazole in case 2, an ACTH stimulation test had a low peak serum cortisol of 16.8 microg/dL. Fluconazole was withdrawn, and 5 days later, the peak stimulated cortisol was 20.6 microg/dL.. Although fluconazole is the therapy of choice for patients in the intensive care setting with Candida infections, two patients with multiple organ failure who received high-dose fluconazole appeared to develop adrenal insufficiency. Although preliminary and anecdotal, these data suggest a need to further investigate the possibility that high-dose fluconazole might cause adrenal insufficiency in already compromised critically ill patients.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Antifungal Agents; Candidiasis; Cosyntropin; Critical Care; Critical Illness; Fatal Outcome; Female; Fluconazole; Humans; Hydrocortisone; Male; Multiple Organ Failure; Patient Selection; Time Factors

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.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Cosyntropin; Female; Glucocorticoids; HIV Infections; Humans; Hypoglycemia; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary-Adrenal System

We investigated the renal transport of purine bases (uric acid, hypoxanthine and xanthine) after rapid and continuous ACTH loading tests in a patient with isolated ACTH deficiency, a rare cause of secondary adrenocortical insufficiency. Plasma uric acid concentration and the urinary ratio of uric acid/creatinine did not change in the rapid ACTH test, which did not increase plasma cortisol concentration. In the continuous ACTH loading test, the plasma concentration of uric acid and oxypurines (hypoxanthine and xanthine) decreased, and the urinary excretion and fractional clearance of them increased as well as the plasma concentrations and urinary excretion of cortisol. These findings suggest that glucocorticoid directly affects the common renal transport pathway for uric acid, hypoxanthine, and xanthine.

Topics: Adrenal Cortex; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aldosterone; Cosyntropin; Gonadotropins, Pituitary; Humans; Hypoxanthine; Infusions, Intravenous; Kidney; Male; Middle Aged; Pituitary Hormone-Releasing Hormones; Renin; Uric Acid; Xanthine

Topics: Adrenal Insufficiency; Cosyntropin; Drug Administration Schedule; Humans; Predictive Value of Tests; Stimulation, Chemical

Previous studies have shown that the rapid ACTH stimulation test using a low dose of 1 microg is more sensitive than that using 250 microg ACTH for detecting subtle cases of adrenal insufficiency. However, there are controversies for the reproducibility of the 1 microg-test. To evaluate the reproducibility of the 1 microg-test, we assessed both day-to-day and diurnal variations of cortisol responses to 1 microg ACTH injection. In addition, optimum sampling time for the 1 microg-test was also determined.. AND DESIGN Eight healthy volunteers and five patients with secondary adrenal insufficiency were recruited. Healthy subjects were given 1 microg ACTH 3 times in the morning (0800 h) and 2 times in the afternoon (1600 h). Patients with adrenal insufficiency had 2-tests in the morning and 2 in the afternoon. Serum cortisol levels were measured every 10 minutes for 1 h after the injection.. In healthy subjects, basal and peak serum cortisol levels were significantly higher in the morning (P < 0.05), whereas maximum cortisol increments were higher in the afternoon (P < 0.001). In patients with adrenal insufficiency, basal and peak serum cortisol levels in the morning were not different from corresponding values in the afternoon. Intra-individual coefficient of variation (CV) of peak serum cortisol response to 1 microg ACTH ranged from 3.0 to 16.4% in healthy subjects and 10.0-34. 4% in patients. Also, there was a significant correlation between peak morning or afternoon cortisol levels after 1 microg ACTH injection given in different days in both healthy subjects and patients. Twenty-six of the 40 studies in healthy subjects showed peak response at 20 minutes, while nine showed it at 30 minutes Using the data acquired at 20 and 30 minutes, all 40 studies in healthy subjects showed normal results while none of 20 studies in patients was normal.. We conclude that the cortisol response to 1 microg ACTH stimulation was reproducible in both healthy subjects and patients with secondary adrenal insufficiency. In order to assess adrenal function more accurately with the 1 microg ACTH stimulation test, serum cortisol should be measured before and 20 and 30 minutes after ACTH injection.

Topics: Adrenal Cortex Diseases; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adult; Case-Control Studies; Circadian Rhythm; Cosyntropin; Drug Administration Schedule; Female; Humans; Hydrocortisone; Male; Middle Aged; Reproducibility of Results; Time Factors

The short cosyntropin (synthetic ACTH) test is recognized as the best screening manoeuvre in the assessment of adrenocortical insufficiency. Recent data, however, suggest that i.v. administration of 250 microg cosyntropin could be a pharmacological rather than a physiological stimulus, losing sensitivity for detecting adrenocortical failure. Our objective was to compare 10 vs 250 microg cosyntropin in order to find differences in serum cortisol peaks in healthy individuals, the adrenocortical response in a variety of hypothalamic-pituitary-adrenal axis disorders and the highest sensitivity and specificity serum cortisol cut-off point values. The subjects were 83 healthy people and 37 patients, the latter having Addison's disease (11), pituitary adenomas (7), Sheehan's syndrome (9) and recent use of glucocorticoid therapy (10). Forty-six healthy subjects and all patients underwent low- and standard-dose cosyntropin testing. In addition, 37 controls underwent the low-dose test. On comparing low- and standard-dose cosyntropin testing in healthy subjects there were no statistical differences in baseline and peaks of serum cortisol. In the group of patients, 2 out of 11 cases of Addison's disease showed normal cortisol criterion values during the standard test but abnormal during the low-dose test. In our group of patients and controls, the statistical analysis displayed a better sensitivity of the low-dose vs standard-dose ACTH test at 30 and 60 min. In conclusion, these results suggest that the use of 10 microg rather than 250 microg cosyntropin i.v. in the assessment of suspicious adrenocortical dysfunction gives better results.

Topics: Addison Disease; Adenoma; Adrenal Glands; Adrenal Insufficiency; Adult; Aged; Area Under Curve; Cosyntropin; Drug Administration Schedule; Female; Humans; Hydrocortisone; Hypopituitarism; Injections, Intravenous; Male; Middle Aged; Pituitary Neoplasms; Sensitivity and Specificity

Topics: Adrenal Insufficiency; Cosyntropin; Humans; Insulin; Pituitary Diseases

Topics: Acquired Immunodeficiency Syndrome; Adrenal Insufficiency; Adult; Cosyntropin; Humans; Male; Retrospective Studies; Risk Factors; Spain

Adrenal insufficiency (AI) is a well known complication of AIDS. However, the clinical and biochemical features of AI in HIV infected patients have not been extensively studied.. A retrospective clinical study.. We reviewed clinical records of 74 AIDS patients with clinical and/or biochemical indications of AI who underwent Synacthen testing in order to determine adrenocortical function during a 5-year period.. AI was diagnosed when cortisol levels failed to rise above 496 nmol/l at any time during the test. Cortisol was measured by RIA.. Sixteen patients (22%) were diagnosed with AI. Most were young males and all of them had a known risk factor, principally i.v. drug users. The main complaint was fatigue. Hyponatraemia or hyperkalaemia were uncommon. All of them were severely immunosuppressed, with AIDS-defining conditions from at least 6 months before the diagnosis of AI, and had been diagnosed with at least one disease that has been reported to produce AI in AIDS patients. Survival was poor. Thirteen of these patients (81%) died within 6 months. Basal cortisol levels were lower than 275 nmol/l in 75% of patients with AI but in only 2% of the group of 58 patients who had normal adrenal responses to Synacthen.. Adrenal insufficiency features in AIDS patients with advanced disease, without specific findings and with a history of previous opportunistic diseases. Basal cortisol values at 0830 h lower than 275 nmol/l are highly suggestive of adrenal insufficiency in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Insufficiency; Adult; Cosyntropin; Female; Humans; Hydrocortisone; Male; Retrospective Studies; Substance Abuse, Intravenous

In order to know the prevalence rate of adrenal insufficiency among patients with renal failure due to amyloidosis; we have performed a stimulation test with synthetic corticotropin hormone (Nuvacthen test) in nine patients diagnosed of renal amyloidosis and in five controls. We also measured ACTH and plasma cortisol levels. In two out of nine patients (22%) a low ACTH, low plasmatic cortisol and an abnormal response to Nuvacthen test were detected being diagnosed of primary adrenal insufficiency. We conclude that adrenal insufficiency is not an infrequent finding in systemic amyloidosis and may be due to secondary amyloidotic infiltration of adrenal or pituitary glands. Though Nuvacthen test is a useful test to diagnose subclinical adrenal insufficiency, in our series patients with an abnormal response also had low levels of basal cortisol and ACTH and no one patient with normal basal levels had an abnormal response to the stimulation test.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Amyloidosis; Cosyntropin; Female; Humans; Hydrocortisone; Kidney Failure, Chronic; Male; Middle Aged; Stimulation, Chemical; Time Factors

Topics: Acquired Immunodeficiency Syndrome; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; AIDS-Related Opportunistic Infections; Aldosterone; Corticotropin-Releasing Hormone; Cosyntropin; Cytomegalovirus Infections; Humans; Hydrocortisone; Hyponatremia; Male; Middle Aged; Tomography, X-Ray Computed

Idiopathic Addison's disease occurs frequently in association with other organ-specific autoimmune diseases, and autoantibodies to adrenal cortex are markers of this condition. A variable asymptomatic period with subtle adrenal dysfunction may precede the onset of clinical manifestations. We studied the pituitary-adrenal axis by measuring plasma ACTH, cortisol, and 17 alpha-hydroxyprogesterone after ovine CRH (100 micrograms as an iv bolus) stimulation in 19 patients with organ-specific autoimmune disease and adrenal autoantibodies, in whom adrenal steroids were normal under baseline conditions and normally responsive to a standard ACTH stimulation test (250 micrograms). In all subjects, oCRH produced a normal increase in plasma ACTH. Plasma cortisol, which was normoresponsive in 11 subjects, showed little or no increase in 8 subjects. Two of these patients developed overt adrenal failure after 1 yr. The 17 alpha-hydroxyprogesterone response to oCRH, tested in 10 of 19 patients, paralleled that of plasma cortisol, excluding a steroidogenic block at the 21-hydroxylase site. Our data demonstrate the existence of a very early phase of Addison's disease in which adrenal function shows an impaired response to ovine CRH-stimulated ACTH.

Topics: 17-alpha-Hydroxyprogesterone; Addison Disease; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aldosterone; Autoantibodies; Autoimmune Diseases; Corticotropin-Releasing Hormone; Cosyntropin; Diabetes Mellitus, Type 1; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Hypothyroidism; Kinetics; Middle Aged; Thyroiditis, Autoimmune

No clear criteria exist to rule out hypoadrenal shock by cosyntropin (alpha 1-24-corticotropin, a synthetic subunit of adrenocorticotropic hormone) testing in persons who have critical nonadrenal illness. Four patients in the surgical intensive care unit with critical multisystem disease and refractory high cardiac output, low vascular resistance shock had significantly diminished or terminated vasopressor requirements after institution of hydrocortisone sodium succinate infusion in doses simulating physiologic stress response (100 to 300 mg of hydrocortisone per day). In each case, cosyntropin testing revealed serum cortisol levels higher than those usually associated with hypoadrenal shock. Positive response was defined as maintenance of blood pressure with a decrease to less than 25% of baseline pressor requirements within 48 hours of treatment. We hypothesize a syndrome of functional hypoadrenalism in patients with multisystem critical illness and refractory shock responsive to glucocorticoid administration in doses simulating physiologic stress response despite cosyntropin stimulation test results that would rule out hypoadrenalism in a normal person.

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Cosyntropin; Critical Illness; Humans; Hydrocortisone; Male; Middle Aged; Shock

A patient with stage D prostatic cancer but in reasonably good general health was discovered to have adrenal failure and tumor destruction of the adrenal glands. Because prostatic cancer is common and compatible with prolonged survival, we surveyed other patients with stage D prostatic cancer. On initial screening with the cosyntropin test, we found that 5 of 14 patients failed to respond with an increase in serum cortisol of 10 micrograms/dL, suggesting an adrenal failure incidence of 36%. Retesting, however, indicated that probably all of these were false-positive results.

Topics: Adenocarcinoma; Adrenal Gland Neoplasms; Adrenal Insufficiency; Cosyntropin; False Positive Reactions; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms

Assessment of adrenal reserve and the diagnosis of adrenal insufficiency by acute adrenocortical stimulation with ACTH-(1-24) has been well established. Alternatively, estimation of adrenocortical enzymatic activities by this method for the detection of inherited or acquired biosynthetic abnormalities has been less well characterized. Some of the discrepancies between studies estimating adrenocortical enzymatic activities in different pathological conditions (e.g. hyperandrogenism) may result from the different stimulation protocols used. The objective of this prospective study was to establish the inherent variability of the adrenal response to acute ACTH-(1-24) stimulation and to determine the effect of sampling time, stimulation dose, and subject weight on the same. Forty-one normal female volunteers were recruited (mean age, 29.1 yr), 30 within 90-110% ideal body weight and 11 weighing more than 120% ideal body weight. Three protocols were designed to study 1) the effects of sampling time, ACTH-(1-24) dose, and subject weight on adrenal response; 2) the effect of time of the day on the variability of basal steroid levels and the adrenal response to stimulation; and 3) the long term reproducibility of the adrenal response to ACTH-(1-24). Androstenedione, 17-hydroxyprogesterone, 11-deoxycortisol, dehydroepiandrosterone, and cortisol were measured in serum under basal and stimulated conditions. All subjects had normal basal levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, and PRL. The acute iv administration of 0.10, 0.25, and 1.0 mg ACTH-(1-24) elicited similar and maximal steroid responses, with all steroid levels reaching a plateau 60-90 min poststimulation regardless of subject weight. Sampling of basal steroid levels every 5 min in the morning (AM; beginning 0700-0900 h) or evening (PM; 1500-1700 h) did not reveal any difference in steroid variability. Only the mean basal cortisol level was higher in AM than PM testing (P less than 0.03). Although the mean levels of dehydroepiandrosterone and 17-hydroxyprogesterone 60 min after stimulation were significantly higher in AM than PM studies, these differences were minimal. Ten volunteers underwent an average of four (range, 2-6) adrenal stimulation studies using 1.0 mg ACTH-(1-24) over a 1-yr period. The long term coefficient of variation (CV) for basal steroid levels ranged from 15-28%. Calculations of net adrenal response (delta steroid O-T and area delta steroid O-T) were less

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Glands; Adrenal Insufficiency; Adult; Analysis of Variance; Androstenedione; Body Weight; Circadian Rhythm; Cortodoxone; Cosyntropin; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Menstrual Cycle; Prospective Studies; Reproducibility of Results; Time Factors

Topics: Adrenal Insufficiency; Azathioprine; Cosyntropin; Cyclosporins; Humans; Immunosuppression Therapy; Kidney Transplantation; Prednisone

Thirty-four patients who underwent abdominal or thoracic, or both, operation for injuries were studied. Serum and urinary cortisol levels were elevated perioperatively and returned to normal levels by the fourth postoperative day. Postoperative complication was associated with persistent elevation of levels of serum and urinary cortisol. Baseline serum cortisol levels correlated with Injury Severity Scores. Cosyntropin stimulation produced a significant rise in serum cortisol to a peak level of 47.4 +/- 10.2 (S.D.) micrograms per deciliter in patients after emergent operations for traumatic injury. Use of the cosyntropin stimulation test for the diagnosis of postoperative adrenal insufficiency can be extended to patients who undergo operation for traumatic injury.

Topics: Adrenal Glands; Adrenal Insufficiency; Circadian Rhythm; Cosyntropin; Humans; Hydrocortisone; Injury Severity Score; Postoperative Complications; Wounds and Injuries

Topics: Adrenal Glands; Adrenal Insufficiency; Cosyntropin; Humans; Insulin; Pituitary-Adrenal Function Tests

This case documents scintigraphically that gastric dysmotility associated with hypoadrenalism secondary to hypothalamic-pituitary dysfunction was reversed when the adrenal insufficiency was treated. The patient reported upon received almost immediate relief of symptoms after corticosteroid replacement therapy and improvement of gastric motility, as demonstrated by both liquid and solid phase 99mTc-labeled studies. This experience suggests that glucocorticoids are important permissive hormones for normal gastrointestinal motor function and may have a role in the pathophysiology of gastrointestinal tract disease.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cosyntropin; Gastric Emptying; Humans; Hydrocortisone; Male; Middle Aged; Sarcoidosis

Fifteen consecutive patients with metastatic carcinoma who demonstrated bilateral adrenal metastasis on abdominal computed tomography (CT) were evaluated by the cosyntropin challenge test. Primary sites of tumors included lung, ten; colon, two; gastric, one; ovarian, one; and unknown primary, one. Bilateral adrenal enlargement was defined as greater than 1 cm on CT scan. Adrenal insufficiency was defined as a failure to increase serum cortisol by at least 5 micrograms/100 ml to a minimum of 15 micrograms/100 ml at either 30 or 60 minutes postcosyntropin. No patient had previously been on corticosteroids. All patients were questioned and examined for symptoms/signs of adrenal insufficiency. Five patients (33%) were found to have adrenal insufficiency based on the cosyntropin test. Of the clinical parameters evaluated, all five patients had nausea, anorexia, and orthostatic hypotension. The clinical onset of adrenal insufficiency was insidious; no patient experienced acute adrenal crisis. We conclude that adrenal insufficiency is not a rare occurrence in patients with metastatic cancer and bilateral adrenal involvement on CT scan.

Topics: Adrenal Gland Neoplasms; Adrenal Insufficiency; Aged; Aged, 80 and over; Cosyntropin; Female; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Tomography, X-Ray Computed

Adrenocortical function was assessed by the intravenous short synacthen test in 22 control subjects and 68 patients admitted to hospital with acute severe asthma. The cortisol increment was subnormal in 19 of the 68 asthmatics. This included 11 of the 14 patients on continuous oral steroids, seven of the 29 patients who had had occasional courses of oral steroids, one of the seven on inhaled steroids only, and none of the 18 who had had no steroids. Adrenal suppression was greatest in those patients taking oral steroids in divided daily doses. Nineteen of 43 patients were on or had taken oral steroids in this fashion. Of those 19 patients with low cortisol increments only one half had received supplementary steroids in the 24 hours preceding admission. Based on the synacthen test, serum DHEA-SO4 values were not a good discriminant of adrenocortical function. Adrenal insufficiency may be an important cause of death in acute severe asthma in New Zealand.

Topics: Acute Disease; Adolescent; Adrenal Cortex; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Aged; Asthma; Cosyntropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Hydrocortisone; Male; Middle Aged

Disseminated infections with cytomegalovirus have become an increasingly important cause of morbidity and mortality in patients with the acquired immune deficiency syndrome. Herein we describe a male homosexual with the acquired immune deficiency syndrome who became severely hyponatremic during bowel preparation for colonoscopy. Biochemical evidence of adrenal insufficiency and clinical evidence for cytomegalovirus colitis was found. We propose that the patient had clinically significant cytomegalovirus adrenalitis. A random urinary sodium concentration is suggested as a potential screening test before bowel preparation in such patients.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Gland Diseases; Adrenal Insufficiency; Adult; Bisacodyl; Colonoscopy; Cosyntropin; Cytomegalovirus Infections; Diet; Enema; Homosexuality; Humans; Hyponatremia; Inflammation; Male

A 37 year old black female presented with congestive cardiac failure, 2 months postpartum. She developed spontaneous hypoglycaemia and symptoms of acute adrenal crisis (hypotension, nausea, abdominal pain and tachycardia with small thready pulse), which responded to i.v. dextrose, sodium chloride and hydrocortisone. Biochemical investigations revealed low serum cortisol and plasma adrenocorticotrophic hormone (ACTH) levels. The patient initially showed an impaired cortisol response to intramuscular aqueous tetracosactrin, but an exuberant response after priming with intramuscular tetracosactrin depot. These findings, together with the normal remaining pituitary function, led us to conclude that this patient had isolated ACTH deficiency associated with congestive cardiac failure and acute adrenal crisis.

Topics: Acute Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Heart Failure; Humans; Hydrocortisone

Plasma cortisol was measured in 18 patients undergoing gynecological procedures under etomidate or methohexital and nitrous oxide anesthesia. Plasma ACTH was also measured in three patients in each group. The mean plasma cortisol concentration before anesthesia was comparable in both groups. Plasma cortisol increased in patients anesthetized with methohexital, while none of the patients anesthetized with etomidate had an increase in plasma cortisol. The increase in plasma ACTH was equivalent in the two groups. Therefore, etomidate is a potent inhibitor of the adrenal response to surgery. The absence of clinical consequences associated with the blunted response suggests that a major increase in adrenal hormone production may not be necessary during surgery.

Topics: Adrenal Cortex; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Anesthetics; Cosyntropin; Etomidate; Female; Genital Diseases, Female; Growth Hormone; Humans; Hydrocortisone; Imidazoles; Methohexital; Pituitary Gland, Anterior; Postoperative Complications; Prolactin; Stress, Physiological

To investigate the mechanism of adrenal suppression by high-dose MPA, we performed direct and indirect stimulation tests in postmenopausal women with disseminated breast cancer who were receiving MPA and in a postmenopausal breast cancer control group. A partial adrenal insufficiency was found during Synacthen stimulation, confirmed by a slight increase of 11-desoxycortisol after metyrapone, despite a sufficient rise in ACTH levels. Peak levels of androstenedione and 17-OH progesterone after Synacthen correlated with those after metyrapone. Peak cortisol levels after Synacthen also correlated with the sum of cortisol and 11-desoxycortisol values after metyrapone, indicating the presence of a maximum adrenal response and a sufficient rise of endogenous ACTH after metyrapone. As the peak levels of cortisol and androstenedione were highly correlated with baseline values, a short Synacthen stimulation test may give a good indication as to whether adrenal suppression by MPA is adequate. The adrenal androgen androstenedione is the precursor of the main postmenopausal oestrogen, oestrone. In this way, adrenal suppression may constitute an important therapeutic effect of high-dose MPA.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Insufficiency; Aged; Androstenedione; Breast Neoplasms; Cosyntropin; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Medroxyprogesterone; Medroxyprogesterone Acetate; Metyrapone; Middle Aged

Topics: 17-Hydroxycorticosteroids; Adrenal Insufficiency; Cortodoxone; Cosyntropin; Humans; Hydrocortisone; Ketoconazole; Male; Metyrapone; Middle Aged

A 81-year-old man presented with bilateral adrenal masses found pathologically to be a large cell, non-follicular center, non-Hodgkin's lymphoma. His clinical course was remarkable for the lack of macroscopic extra-adrenal tumor and for adrenal insufficiency in response to stress and cosyntropin stimulation. This is believed to be the first reported case of a non-Hodgkin's lymphoma limited to the adrenal glands with associated adrenal insufficiency.

Topics: Adrenal Gland Neoplasms; Adrenal Insufficiency; Aged; Cosyntropin; Hormones; Humans; Lymphoma; Male; Tomography, X-Ray Computed

The adrenocortical response to a short tetracosactrin (Synacthen) test was studied in 11 patients receiving either etomidate infusion or thiopentone infusion used to maintain anaesthesia for abdominal hysterectomy. Pethidine was used as the narcotic component. The results showed that etomidate infusion (median 28.5 ug/kg/min) completely blocked the adrenocortical response to corticotropin stimulation for at least 24 h after surgery. No suppression was found in patients receiving thiopentone infusion. It is concluded that etomidate cannot be recommended for routine induction and maintenance of anaesthesia.

Topics: Adrenal Cortex; Adrenal Insufficiency; Anesthetics; Cosyntropin; Drug Tolerance; Etomidate; Female; Fentanyl; Humans; Hydrocortisone; Hysterectomy; Imidazoles; Postoperative Complications; Thiopental

The reliability of the beta 1-24 corticotropin test, which is both cheap and safe, in the assessment of the hypothalamic-pituitary-adrenocortical function was re-evaluated by comparing its results with those of the metyrapone test in 71 subjects: 30 controls and 51 patients with suspected pituitary-adrenal dysfunction. Response to a 500 micrograms intramuscular injection of beta 1-24 corticotropin was evaluated by measuring the 60 min plasma cortisol levels; 4.5 g of metyrapone divided into 6 doses were then administered orally and response was evaluated by measuring plasma 11-desoxycortisol levels. A highly significant correlation (r = 0.79; p less than 0.001) was observed between plasma cortisol and plasma 11-desoxycortisol levels. The results were best interpreted by expressing the values obtained as plasma cortisol concentrations which, in normal subjects are at least 21 micrograms/100 ml. The rapid beta 1-24 corticotropin test was found to be very reliable (sensitivity 90%, specificity 100%) to detect adrenal insufficiency, irrespective of the organs affected on the hypothalamic-adrenocortical axis.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Cortodoxone; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metyrapone; Middle Aged; Pituitary-Adrenal System; Time Factors

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cosyntropin; Humans; Hydrocortisone; Probability

Eighteen renal transplant patients were studied to identify predictors of steroid-induced adrenal suppression. A cosyntropin adrenal stimulation test was administered to each patient and the response was correlated with the past transplant course and their subsequent prognosis. Eight (44%) of the 18 patients studied had a suppressed cosyntropin stimulation test. The suppressed adrenal response could not be predicted accurately by any one factor, although a history of a total prednisone dose greater than 25 g or a duration of steroid therapy of more than 12 months occurred more often among the suppressed patients. Four of the five deaths occurred among the suppressed patients. These deaths occurred despite maintenance of steroid administration. The cosyntropin stimulation test can be easily performed to identify renal transplant patients at risk of steroid-induced adrenal suppression when rapid steroid tapering is desired. An unsuppressed response gives assurance that steroid withdrawal is safe.

Topics: Adolescent; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Child; Cosyntropin; Dose-Response Relationship, Drug; Female; Humans; Kidney Transplantation; Male; Middle Aged; Prednisone

A normal plasma cortisol response to exogenous corticotropin has been advanced as a reliable indication of adequate hypothalamic-pituitary-adrenal function in patients suspected of having secondary adrenal failure. We have examined the validity of this diagnostic strategy in five patients who had undergone hypophysectomy and 27 patients recently treated with glucocorticoids. Eleven of the patients had normal adrenal responses to cosyntropin but had subnormal responses when the entire hypothalamic-pituitary-adrenal axis was examined using metyrapone; no patient who responded normally to metyrapone failed to respond to cosyntropin. Inducing hypoglycemia with insulin yielded results concordant with the results induced by metyrapone in four patients tested. A normal cortisol response to corticotropin alone should not be relied on to exclude secondary adrenal insufficiency. To do this it is necessary to demonstrate normal activity of the entire hypothalamic-pituitary-adrenal axis, which can be conveniently examined using metyrapone.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone; Hypophysectomy; Hypothalamo-Hypophyseal System; Insulin; Metyrapone; Pituitary-Adrenal System

We report here on a patient who was unilaterally adrenalectomized for Cushing's syndrome, and who developed antibodies to 1-24 ACTH. A 49-year-old nurse had undergone right adrenalectomy for adrenal adenoma. After surgery, she was treated with 0.5 mg of 1-24 ACTH-Z together with glucocorticoid replacement therapy for 40 days. Thereafter she was given 0.25-0.5 mg of ACTH-Z every other day for 4 months. ACTH-Z was then stopped for a year but glucocorticoid therapy was continued. About one year prior to this admission, 1 mg of ACTH-Z was again initiated 1 to 2 times a week. Glucocorticoid therapy was not withdrawn during the four years after adrenalectomy. She was admitted for the purpose of withdrawal of glucocorticoids. Her serum was found to bind labeled ACTH. This labeled ACTH was competitively displaced from binding by unlabeled hormones. Finally, reaction with specific antihuman Ig demonstrated an antibody of the IgG class. The titer of the antibodies gradually decreased after the discontinuation of ACTH-Z, but it is still present in measurable quantity in her serum. The clinical significance of the circulating anti-ACTH antibody in her serum is discussed.

Topics: Adrenal Insufficiency; Adrenalectomy; Adrenocorticotropic Hormone; Antibodies; Cosyntropin; Cushing Syndrome; Female; Humans; Middle Aged; Postoperative Complications

Topics: Acute Disease; Adrenal Gland Diseases; Adrenal Insufficiency; Age Factors; Cosyntropin; Diagnosis, Differential; Hemorrhage; Hemorrhagic Disorders; Humans; Male; Middle Aged; Pulmonary Embolism; Spleen; Splenectomy; Subphrenic Abscess; Tomography, X-Ray Computed

In 22 patients undergoing elective surgery, adrenal function was assessed before and on the day of surgery. Patients receiving corticosteroid therapy but with a normal cortisol response to a corticotropin stimulation test (group II, n = 8) were not given hydrocortisone on the day of operation. Their cortisol concentration increased in a manner similar to patients (group I, n = 8) who had never had corticosteroid treatment. The plasma cortisol concentrations in these two groups were less than in subjects (group III), n = 6) with an impaired cortisol response to corticotropin stimulation, who were given hydrocortisone 25 mg at the induction of anaesthesia followed by a continuous infusion of hydrocortisone 100 mg during the next 24 h. There were no clinical signs of circulatory insufficiency in any group. The low-dose hydrocortisone therapy regimen is sufficient for substitution of adrenal function during surgery and in the early postoperative phase. It could lead to mild oversubstitution in patients with impaired adrenal insufficiency undergoing major surgery.

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Aged; Aldosterone; Anesthesia, General; Cosyntropin; Humans; Hydrocortisone; Long-Term Care; Middle Aged; Preoperative Care; Surgical Procedures, Operative

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Cosyntropin; Humans; Hyperaldosteronism; Hypertension; Membrane Potentials; Pituitary-Adrenal Function Tests; Potassium; Spironolactone

In 30 resting normal persons, 5 ambulant normal persons and 3 patients with disorders of the pituitary-adrenal-system before and 30 minutes after intravenous injection of 0,25 mg synthetic adrenocorticotrophin (tetracosactid, Synacthen) plasma cortisol and aldosterone levels were evaluated. The evaluation of the corticoids was continued over 240 minutes in intervals of 30 minutes. The basal cortisol and aldosterone levels of the resting normal persons and ambulant persons ordinarily doubled 30 minutes after ACTH application. The plasma cortisol level of a steroid-treated patient with lupus erythematodes disseminatus rose subnormally but his aldosterone level increased normally. 2 patients with untreated hypopituitarism had subnormal plasma cortisol and normal aldosterone responses after ACTH administration. In contrast with patients with primary adrenal insufficiency, whose plasma aldosterone levels fail to rise, patients with secondary adrenal insufficiency had normal corticotrophin-stimulated aldosterone increments. Thus the extended ACTH test can be useful in differential diagnosis of primary and secondary adrenal insufficiency.

Topics: Addison Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aldosterone; Cosyntropin; Diagnosis, Differential; Humans; Hydrocortisone; Hypopituitarism; Time Factors

A 13-year-old girl who had been well previously was admitted with fulminant meningococcemic purpura. Her plasma cortisol level was only 3 micrograms/dL and failed to rise after cosyntropin administration. Maintenance doses of corticosteroid were administered. As her infection cleared her adrenal glands were restimulated and shown to have near normal response. Replacement doses of corticosteroids should be given to patients with fulminant meningococcemia until adrenal cortical insufficiency can be excluded because of the high incidence of adrenal failure in these patients and the possibility that excessive adrenal stimulation might contribute to adrenal abnormality.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenal Insufficiency; Cosyntropin; Female; Humans; Hydrocortisone; Meningitis, Meningococcal; Neisseria meningitidis; Remission, Spontaneous

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aldosterone; Chronic Disease; Cosyntropin; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Time Factors; Zinc

Parallel fluctuations of potential difference (P.D.) across oral and rectal mucosa are probably related to the activity of autonomic nerves rather than adrenal steroids. Unlike rectal mucosa, oral mucosa does not respond to exogenous or endogenous aldosterone. Therefore subtraction of oral P.D. from rectal P.D. gives a closer indication of mineralocorticoid activity than does rectal P.D. alone. In normal subjects plasma-aldosterone correlated well with subtraction P.D. (r = 0.74; P is less than 0.001). A subtraction P.D. higher than 26 mV in subjects on a normal sodium intake indicated primary or secondary hyperaldosteronism; if the level was lower than 11 mV four hours after intramuscular injection of 0.25 mg tetracosactrin this suggested mineralocorticoid deficiency. Measurement of oral and rectal P.D. permits rapid and inexpensive diagnosis of aldosterone excess and deficiency. The method may also be used in study of the mineralocorticoid effect of other adrenal steroids: as assessed with this bioassay, the plasma 18-OH-deoxycorticosterone, which is raised in some patients with essential hypertension, lacked any in vivo mineralocorticoid activity.

Topics: Action Potentials; Adrenal Insufficiency; Aldosterone; Circadian Rhythm; Cosyntropin; Desoxycorticosterone; Female; Humans; Hydrocortisone; Hyperaldosteronism; Intestinal Mucosa; Male; Mouth Mucosa; Potassium; Rectum; Sodium; Stimulation, Chemical

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Arthritis, Rheumatoid; Cosyntropin; Humans

Tetracosactrin (Synacthen) tests were performed on 19 elderly women who had leucocyte ascorbic acid (LAA) levels of less than 15 microgram/108 WBC. 9 were then given a daily dose of 200 mg ascorbic acid orally for 2 weeks while the other 10 were left untreated. Following this, tetracosactrin tests were repeated in both groups. All initial plasm cortisol responses to tetracosactrin were within normal limits. Treatment with ascorbic acid produced no changes in these. This suggests that the low LAA levels often found in old people do not result in adrenal insufficiency.

Topics: Adrenal Glands; Adrenal Insufficiency; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Cosyntropin; Female; Humans; Hydrocortisone

Thirty-five of 41 asthmatic patients, who had been taking oral corticosteroids regularly for between one and 12 years, recovered their adrenal function after courses of depot tetracosactrin, even those with apparently complete adrenal suppression. They all showed benefit by transfer to depot tetracosactrin, though steroid withdrawal symptoms could be troublesome. Skin pigmentation in three, and two severe reactions to tetracosactrin were encountered. We believe that it is advisable to give depot tetracosactrin when converting severe asthmatics to the use of beclomethasone dipropionate aerosols who have previously been treated by long-term steroids with consequent adrenal suppression.

Topics: Adolescent; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Asthma; Child; Cosyntropin; Humans; Hydrocortisone; Prednisolone; Prednisone

The cortisol secretion rate was determined in 18 children according to a modified and simplified method. In 7 cases the determination was repeated after stimulation with synthetic ACTH. 12 of these children suffered from diseases which may affect glucocorticoidsteroid production and the remaining 6 children served as normal controls. In some cases the plasma 11-hydrocorticoid level and urinary excretion of 17-ketogenic steroids were additionally determined. Differences in adrenal function were noted in 2 patients with congenital adrenal hyperplasia (one of the salt-losing type, the other nonsalt-losing type) and 5 patients with adrenal insufficiency. A normal cortisol secretion rate was found in 3 children with diverse disturbances of carbohydrate metabolism, as well as in a child with subtotal adrenalectomy. The clinical value of the determination of the cortisol secretion rate is discussed and was found to be a more reliable indicator of glucocorticoid activity than other parameters.

Topics: 11-Hydroxycorticosteroids; 17-Ketosteroids; Adolescent; Adrenal Cortex; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenalectomy; Adult; Child; Cosyntropin; Diabetes Mellitus, Type 1; Female; Humans; Hydrocortisone; Secretory Rate; Stimulation, Chemical

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Insufficiency; Adrenocorticotropic Hormone; Blood; Cosyntropin; Drug Therapy; Hydrocortisone; Peptides; Pharmacology

Topics: 17-Ketosteroids; Addison Disease; Adolescent; Adrenal Cortex; Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenalectomy; Adrenocorticotropic Hormone; Cosyntropin; Cushing Syndrome; Hypertrichosis; Hypoadrenocorticism, Familial; Pituitary-Adrenal Function Tests; Urine