Using the high-dose corticotropin test to diagnose relative adrenal insufficiency in vasopressor-dependent septic shock.
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BACKGROUND: Several studies in the last few years have shown that the standard 250 micro g dose used in ACTH stimulation test may be very high and have suggested that a dose of 1 micro g may be sufficient for evaluating hypothalamo-pituitary adrenal (HPA) axis. AIMS: To evaluate the role of low dose ACTH stimulation test in patients with suspected Secondary Adrenal Insufficiency (SAI). SUBJECTS AND METHODS: Thirty-one patients of suspected SAI with a documented pituitary lesion and seven normal healthy controls were included in the study. All the subjects underwent ACTH stimulation test with standard high dose (HD= 250 microg) and low dose (LD= 1 microg) ACTH. Insulin Induced Hypoglycaemia (IIH) test was done in 7 out of 9 patients in whom the results of the two tests were discordant. The cut off for normal HD stimulation test was taken as peak cortisol response > 18 microg/dl and for LD test, either a cortisol response of > 18 microg/dl or an increment of more than 7 micro g/dl over the basal value at any time during the test, on the basis of response observed in controls. RESULTS: 22/31 patients (74%) in SAI group showed concordant results with both tests, whereas nine patients had discordant results. These nine patients showed AI with LD ACTH, but HD ACTH test showed a normal response. In 7 of these 9 patients who underwent IIH, AI was confirmed in 6. CONCLUSION: The LD ACTH stimulation test seems to be better than HD ACTH stimulation test for evaluating HPA axis in patients with suspected SAI. When basal cortisol is normal, LD ACTH stimulation test detects subtle SAI.
Tuberculosis is a major public health problem in Pakistan and adrenal involvement in long-standing tuberculosis has been found to be common. A multi-center study was conducted to assess the adrenal function using short Synacthen test in one hundred patients with tuberculosis of more than 6 months duration at three hospitals of Rawalpindi and Islamabad. Forty patients demonstrated impaired response to Synacthen test. In 21 (52.5%) the increment from basal level was less than 300 nmol/L with a peak level increasing to over 600 mmol/L in 15 (37.5%) patients, the increment from basal level was less than 300 nmol/L as well as the peak level was also less than 600 nmol/L. In 4 (10%) patients the increment was more than 300 nmol/L but they were not able to obtain a peak level of 600 nmol/L. No significant difference was found between the patients with normal response and the impaired response with regards to their clinical features, duration of illness, body mass index (BMI), blood pressure variation and routine biochemical profile. It is concluded that adrenal dysfunction is common in patients with long-standing tuberculosis. Diagnosis of hypoadrenalism is not possible on clinical grounds and routine biochemical examinations. Synacthen stimulation test is necessary for its diagnosis.
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BACKGROUND: Premature ovarian failure is a rare syndrome characterized by cessation of menstruation before 35 years of age associated with an elevated gonadotropin level (serum follicle stimulating hormone > 40 IU/L) and oestrogen deficiency. Premature ovarian failure is often the result of an autoimmune process and involvement of other endocrine glands has been reported but available studies are hampered by a lack of uniformity in diagnostic criteria. METHODS: The endocrine profile of 37 north Indian women with premature ovarian failure was studied. The investigations included measurement of serum follicle stimulating hormone, luteinizing hormone, oestradiol, prolactin, total thyroxine, total triiodothyronine and thyroid stimulating hormone. To assess adrenocortical reserve, adrenocorticotropic hormone stimulated plasma cortisol levels were estimated. RESULTS: Eighteen (49%) patients had extraovarian endocrine abnormalities. Eight (22%) had abnormal thyroid function tests and 12 of 29 (41%) patients tested for adrenocortical reserve showed impaired response of plasma cortisol to adrenocorticotropic hormone stimulation. CONCLUSION: Extraovarian endocrine (especially adrenocortical) involvement is frequent in patients with premature ovarian failure. Because none of the patients had overt clinical evidence of thyroid or adrenocortical disease, we suggest that tests for thyroid and adrenal function be performed routinely in females presenting with premature ovarian failure.
The water-loading test (Robinson's test) has been used since 1941 to evaluate the adrenocortical function. Due to this technique, impaired water excretion has become a classical feature of adrenal deficiency. The purpose of this study was to assess the reliability of this test when compared with modern procedures for adrenal exploration. Water excretion was decreased in 23 cortisol-deficient patients but also in 16 out of 58 subjects (27%) with normal adrenal biological tests. We consider that this simple test, although old-fashioned, remains useful since normal diuresis after 2 hours is sufficient to rule out a cortisol deficiency.
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Basal plasma cortisol levels and adrenal responses to stimulation by endogenous and exogenous ACTH were compared between a group of controls and a group of patients with corticotrophic insufficiency. In addition, the adrenal response to the administration of exogenous ACTH was compared in each of these groups in relation to the timing of the test. There was a clear parallel between respective adrenal responses to exogenous ACTH and endogenous ACTH. Adrenal stimulation by exogenous ACTH may be used to investigate the residual secretion of endogenous ACTH and in the diagnosis or corticotrophic insufficiency, when a lesion interrupting functional hypothalamo-pituitary connections has been excluded. In the opposing case, use of a short test with metopirone is essential in order to confirm corticotrophic insufficiency. This test is better tolerated than the classical test and is not subject to sources of error due to urine collections.
OBJECTIVE: To describe the clinicopathologic characteristics of dogs with hyperadrenocorticism and concurrent pituitary and adrenal tumors. DESIGN: Retrospective study. ANIMALS: 17 client-owned dogs. PROCEDURE: Signalment, response to treatment, and results of CBC, serum biochemical analysis, urinalysis, endocrine testing, and histologic examinations were obtained from medical records of dogs with hyperadrenocorticism and concurrent adrenal and chromophobe pituitary tumors. RESULTS: On the basis of results of adrenal function tests and histologic examination of tissue specimens collected during surgery and necropsy, concurrent pituitary and adrenal tumors were identified in 17 of approximately 1,500 dogs with hyperadrenocorticism. Twelve were neutered females, 5 were males (3 sexually intact, 2 neutered); and median age was 12 years (range, 7 to 16 years). Hyperadrenocorticism had been diagnosed by use of low-dose dexamethasone suppression tests and ACTH stimulation tests. During high-dose dexamethasone suppression testing of 16 dogs, serum cortisol concentrations remained high in 11 dogs but decreased in 5 dogs. Plasma concentrations of endogenous ACTH were either high or within the higher limits of the reference range (12/16 dogs), within the lower limits of the reference range (2/16), or low (2/16). Adrenal lesions identified by histologic examination included unilateral cortical adenoma with contralateral hyperplasia (10/17), bilateral cortical adenomas (4/17), and unilateral carcinoma with contralateral hyperplasia (3/17). Pituitary lesions included a chromophobe microadenoma (12/17), macroadenoma (4/17), and carcinoma (1/17). CLINICAL IMPLICATIONS: Pituitary and adrenal tumors can coexist in dogs with hyperadrenocorticism, resulting in a confusing mixture of test results that may complicate diagnosis and treatment of hyperadrenocorticism.
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It is commonly thought that patients receiving exogenous glucocorticoids have suppression of the hypothalamic-pituitary-adrenal axis and need high supplemental doses of exogenous glucocorticoids (so-called stress steroids) to meet the demands of operative stress. Several reports have suggested that clinically important suppression of the hypothalamic-pituitary-adrenal axis is extremely uncommon and that the levels of glucocorticoids required for stress are much lower than previously believed. A prospective study of twenty-eight patients who had thirty-five major orthopaedic operations was conducted. No patient received stress steroids; they were given only the baseline immunosuppressive doses of glucocorticoids (mean dose, ten milligrams of prednisone). Clinical information (based on regular physical examinations for signs and symptoms of hypotension, myalgia, arthralgia, ileus, and fever) and laboratory data (serum sodium levels, eosinophil count, and twenty-four-hour urinary free-cortisol levels, determined at perioperative and non-stress postoperative time-periods) were obtained to document any evidence of adrenocortical insufficiency. There was no such evidence in any of the patients, who were monitored during their entire hospitalization. The levels of twenty-four-hour urinary free cortisol showed that all patients had endogenous adrenocortical function and, when this information was considered together with the clinical outcome, it was concluded that this level of function was sufficient to meet the demands of operative stress. Adrenocortical insufficiency in patients who have orthopaedic operations without receiving supplemental stress steroids appears to be much less common than previously thought. While biochemical testing of the function of the hypothalamic-pituitary-adrenal axis may sometimes reveal evidence of adrenal insufficiency, these tests do not predict the clinical outcome and may be too sensitive to guide decisions regarding treatment. Supplemental exogenous stress glucocorticoids may not be needed to meet the demands of operative stress in these patients.
BACKGROUND: Adrenal insufficiency impacts on the haemodynamic management of patients in intensive care. Very little is known about the incidence of adrenal insufficiency in the first 10 days after traumatic brain injury. METHODS: We retrospectively reviewed the charts of 113 traumatic brain injury patients within 10 days of their injury. They all had a high-dose corticotropin stimulation test performed because of haemodynamic instability. Blood cortisol concentrations were measured at baseline, 30 and 60 min after the administration of high-dose corticotropin. The incidence of adrenal insufficiency was determined according to various definitions used in the literature. RESULTS: The baseline cortisol concentration was <414 nmol litre(-1) (15 microg dl(-1)) in 78% of patients and <690 nmol litre(-1) (25 microg dl(-1)) in all patients. The cortisol concentration did not rise above 500 nmol litre(-1) (18 microg dl(-1)) at 30 and 60 min in 49 and 22% of patients, respectively. The cortisol concentration did not rise by 250 nmol litre(-1) (9 microg dl(-1)) at 30 and 60 min in 48 and 25% of patients respectively. Primary adrenal insufficiency defined by an abnormal baseline cortisol concentration and an abnormal response to the high-dose corticotropin stimulation test was present in 13-28% of patients according to the cut-off values used. CONCLUSIONS: The incidence of adrenal insufficiency varies from 25 to 100% in the first 10 days after traumatic brain injury. The range of incidences reported illustrates the need for standardization of the definition of adrenal insufficiency. This has a direct impact on treatment. Sampling at 60 min after the high-dose corticotropin stimulation test seems to correlate better with the maximum secreting capacity of the adrenal glands.
BACKGROUND: POEMS syndrome is a multisystem disorder. It usually presents as severe polyneuropathy and monoclonal gammapathy associated with endocrinopathies, organomegaly, skin hyperpigmentation. CASE REPORT: A patient with POEMS syndrome developed primary adrenocortical deficiency revelated by asthenia and hyperpigmentation. Hydrocortisone replacement therapy produced a rapidly beneficial effect on asthenia and hyperpigmentation. DISCUSSION: Although asthenia and skin pigmentation are common in POEMS syndrome, adrenocortical deficiency is seldom reported. This endocrinopathy might be underestimated in POEMS patients. We suggest systematic screening with a rapid ACTH test in all POEMS patients in order to detect underlying adrenal deficiency.
OBJECTIVE: To review the criteria for diagnosing and treating adrenal insufficiency in patients with septic shock. SOURCE OF DATA: Articles published in Brazilian and foreign journals selected through these publicationś websites and Medline, as well as references cited in key articles. SUMMARY OF THE FINDINGS: The literature reports a range betwen 17 and 54% for the finding of adrenal insufficiency in patients with septic shock. There is no consensus for diagnosing adrenal insufficiency in patients suffering from critical diseases, particularly in patients with septic shock. The presence of volume-refractory and catecholamine-resistant septic shock suggests this condition, while basal cortisol under 25 micro g/dl is a diagnostic criterion indicating adrenal insufficiency. The adrenal stimulation test is a useful resource for identifying patients with relative adrenal insufficiency. Our testing option for adrenal stimulation in children is the use of corticotropin in low doses (0.5 micro g/1,73 m(2)). An increase of less than 9 micro g/dl in the value of postcorticotropin-stimulated cortisol suggests the presence of occult (relative) adrenal insufficiency. In patients with septic shock presenting adrenal insufficiency, either suspected or confirmed, the administration of hydrocortisone in shock or stress doses can be vital for a favorable clinical outcome. CONCLUSIONS: The existing data, although controversial, already provides a basis to determine when to begin hormone replacement therapy, the serum level of cortisol accepted as adequate, and the choice of corticotropin doses for performing the adrenal stimulation test and diagnosing occult or relative adrenal insufficiency in patients with septic shock.
The increase of plasma cortisol (F), androstenedione (A), 17 alpha-hydroxy-progesterone (17-OH-P) and testosterone (T) was measured after iv administration of ACTH in heterozygotes for CAH and in controls under two different conditions: Test 1: ACTH stimulation was performed without any particular preparation. Test 2: 1.5 mg of dexamethasone (dex.) was given the evening before the ACTH stimulation. Plasma F, A, 17-OH-P and T were measured by specific radioimmunoassays (RIA). Following ACTH stimulation, the increase of 17-OH-P was significantly higher in CAH-heterozygotes than in controls in both tests (P less than 0.0005). Heterozygotes were characterized by a 17-OH-P increase after ACTH stimulation exceeding the + 2 SD limit of the 17-OH-P increase found in controls. The detection of female heterozygotes was considerably improved by the administration of dex. before testing (test 2). In males, however, a better identification of heterozygotes was obtained without previous administration of dex. (test 1). By these tests, 100% of female (test 2) and 79% of male (test 1) CAH heterozygotes could be correctly identified. There were no significant differences in the levels of F, A and T between heterozygotes and controls except for decreased T levels in test 1 (2P less than 0.01) in most male heterozygotes after ACTH stimulation.
BACKGROUND: The short Synacthen test, the overnight metyrapone test and the insulin tolerance test are frequently used in the evaluation of patients suspected of adrenal insufficiency. in the present study, we established reference values for these diagnostic tests, as well as for baseline morning plasma cortisol and adrenocorticotrophic hormone (ACTH). METHODS: We studied 50 subjects recruited from the general population, equally distributed according to sex and age between 20 and 69 years. A short ACTH stimulation test (250 microg Synacthen iv), an overnight metyrapone test (2.0, 2.5, or 3.0 g given orally depending on body weight at 23.30 hours) and an insulin tolerance test (0.15 U/kg actrapid iv) were performed. Reference intervals are given as the means +/- 2SD of observed hormone concentrations after logarithmic transformation. RESULTS: The following reference values were established: 09.00 hr plasma cortisol 150 to 802 nmol/l, 09.00 hr plasma ACTH 8 to 93 ng/l, peak plasma cortisol after Synacthen 591 to 1,113 nmol/l, peak plasma cortisol after insulin-induced hypoglycaemia 557 to 1,015 nmol/l, and plasma 11-deoxycortisol after metyrapone 197 to 759 nmol/l. CONCLUSION: We established reference values for diagnostic tests that are useful in the evaluation of patients suspected of primary or secondary/tertiary adrenal insufficiency.
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Adrenocortical disease is a frequent problem affecting pet ferrets in the United States. This article describes the typical history, signs, and diagnostic test results to be expected in ferrets with this disease. Treatment options are discussed. A newly developed diagnostic technique is also described.