AIM: 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. METHOD: 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. RESULTS: 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%. CONCLUSION: 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. (+info)
Effect of multiple courses of antenatal corticosteroids on pituitary-adrenal function in preterm infants.
AIM: To evaluate the pituitary-adrenal function of preterm infants whose mothers received multiple courses (8 or more doses) of antenatal dexamethasone. METHODS: The pituitary-adrenal function of 14 preterm infants whose mothers received eight or more doses of antenatal dexamethasone were assessed using the human corticotrophin releasing hormone (hCRH) stimulation test when 7 days (n = 14) and 14 days old (n = 12). During each test, blood samples were taken at 0 (baseline), 15, 30 and 60 minutes after an intravenous bolus dose of hCRH (1 microg/kg). The corresponding hormone concentrations were compared between days 7 and 14, and with various associated factors. RESULTS: The baseline (0 min) plasma adrenocorticotrophic hormone concentration was significantly higher at day 14 than at day 7 (p = 0.036). None of the corresponding poststimulation (15, 30, and 60 min) hormone concentrations was significantly different between the two time epochs. When the association between the hormone concentrations and the number of antenatal dexamethasone doses received by the mothers was assessed, a significant negative correlation was observed in serum cortisol concentrations at 15 and 30 min on day 14 (r = -0.59, p = 0.04 and r = -0.60, p = 0.039, respectively). CONCLUSIONS: The absence of a significant difference in poststimulation hormone concentrations between days 7 and 14 in this cohort of infants, and the similarity of their hormone responses with those of older children and adults, suggests that no severe pituitary-adrenal suppression had occurred. None the less there was evidence of mild adrenal suppression in some of the treated infants. Vigilance in monitoring blood pressure, electrolytes and signs of adrenal suppression in infants whose mothers receive multiple courses (8 or more doses) of antenatal dexamethasone is required, as some of them might have diminished adrenal reserve. (+info)
Adrenal insufficiency in septic shock.
BACKGROUND: Functional adrenal insufficiency has been documented in critically ill adults. OBJECTIVE: To document the incidence of adrenal insufficiency in children with septic shock, and to evaluate its effect on catecholamine requirements, duration of intensive care, and mortality. SETTING: Sixteen-bed paediatric intensive care unit in a university hospital. METHODS: Thirty three children with septic shock were enrolled. Adrenal function was assessed by the maximum cortisol response after synthetic adrenocorticotropin stimulation (short Synacthen test). Insufficiency was defined as a post-Synacthen cortisol increment < 200 nmol/l. RESULTS: Overall mortality was 33%. The incidence of adrenal insufficiency was 52% and children with adrenal insufficiency were significantly older and tended to have higher paediatric risk of mortality scores. They also required higher dose vasopressors for haemodynamic stability. In the survivor group, those with adrenal insufficiency needed a longer period of inotropic support than those with normal function (median, 3 v 2 days), but there was no significant difference in duration of ventilation (median, 4 days for each group) or length of stay (median, 5 v 4 days). Mortality was not significantly greater in children with adrenal insufficiency than in those with adequate adrenal function (6 of 17 v 5 of 16, respectively). CONCLUSION: Adrenal insufficiency is common in children with septic shock. It is associated with an increased vasopressor requirement and duration of shock. (+info)
Expression of adrenocorticotropin receptor gene in adrenocortical adenomas from patients with Cushing syndrome: possible contribution for the autonomous production of cortisol.
OBJECTIVE: To examine whether inhibition of endogenous adrenocorticotropin (ACTH) secretion in patients with Cushing syndrome affects the expression of the ACTH receptor (ACTH-R) gene in adrenocortical adenoma and attached atrophic normal gland. SUMMARY BACKGROUND DATA: ACTH increases adrenal cell growth and steroidogenesis by means of ACTH-R. In vivo and in vitro studies have shown that expression of ACTH-R is upregulated by its own ligand ACTH in several species. In patients with Cushing syndrome resulting from adrenocortical adenoma, there is autonomous production of cortisol from the adenoma. This strongly inhibits endogenous ACTH secretion, giving rise to the speculation that the expression of the ACTH-R gene in these patients is also suppressed. However, previous studies have shown that administration of exogenous ACTH to these patients leads to a further increase in the production of cortisol, suggesting the expression of functional ACTH-R in the adenoma. The authors, therefore, examined the expression of the ACTH-R gene in these patients. METHODS: Fourteen patients with Cushing syndrome were studied. Glucocorticoid excess resulting from autonomous production from the adenomas was ascertained, and unilateral adrenalectomy was performed. The levels of ACTH-R and cytochrome P450 side chain cleavage enzyme (P450scc) mRNAs were determined by Northern blot analysis. The entire coding region of the ACTH-R gene in these patients was sequenced. RESULTS: ACTH-R mRNA abundance in the attached atrophic normal adrenals was suppressed and invariably less than that in the normal gland obtained from a patient with renal cancer. However, the expression of ACTH-R mRNA was not suppressed in any of the adenomas. Expression of ACTH-R mRNA in the adenomas was four- to sixfold greater than that in the attached atrophic gland. No mutation in the coding sequence of the ACTH-R gene in the adenoma was detected in any of the patients. The mRNA in the adenomas appeared to be translated into functionally active receptor because intramuscular administration of ACTH resulted in significant increases in plasma cortisol before surgery but not 3 months after surgery. In addition, there was a positive linear correlation between the expressions of ACTH-R and P450scc mRNAs in the adenoma tissue. CONCLUSIONS: Suppressed ACTH secretion in patients with Cushing syndrome results in reduction of the ACTH-R mRNA expression in nonneoplastic adrenocortical cells. However, the regulatory mechanism of ACTH-R expression might be different in adenoma. Persistent expression in the adenoma of ACTH-R alone, even in the absence of ACTH, might result in increased basal adenyl cyclase activity, as observed in the case of thyroid-stimulating hormone receptor, and thereby might play a role in the autonomous production of cortisol. (+info)
Effect on adrenal function of topically applied clobetasol propionate (Dermovate).
Thirty-nine patients (15 outpatients and 24 inpatients) with a variety of skin diseases affecting variable areas of the body surface were treated with clobetasol propionate ointment (Dermovate). Before and after treatment the adrenal response to an intramuscular injection of tetracosactrin was rested and additional 9 am plasma cortisol levels were measured at intervals during treatment. A satisfactory initial therapeutic response was achieved in almost all cases during the trial period. When more than 50 g of ointment a week was used a significant number of patients developed adrenal suppression. WHen less than 50 g per week was used any suppression tended to be transtion. These cysts may be the cause of this condition, producing abnormal amounts of ovarian steroids which modify the pituitary response. Futher studies are needed, however, to determine this possibility. (+info)
Evaluation and management of adrenal masses.
BACKGROUND: The widespread use of abdominal imaging has led to increased detection of adrenal tumors. The significance of these masses, as well as the optimal management approach to treatment, has generated some controversy regarding further evaluation and therapy. METHODS: The authors reviewed the literature regarding the evaluation and management of these masses, particularly adrenal incidentalomas. Based on their institutional experience, they propose a diagnostic, evaluation, and management algorithm for treating adrenal masses. RESULTS: Appearance and clinical history should indicate how to perform the biochemical evaluation, keeping in mind that the presence of pheochromocytomas must be ruled out. Radiological evaluation by CT or MRI provides useful parameters to identify malignant lesions. Surgery is indicated for masses that are larger than 5 cm in diameter or suspected of malignancy. Fine-needle aspiration biopsy should be used when other extra-adrenal malignancies are suspected and after pheochromocytoma has been ruled out. CONCLUSIONS: Careful analysis of each adrenal mass is essential to effectively avoid potential problems. Guidelines to manage patients with adrenal masses are needed. (+info)
Evaluation of low dose ACTH stimulation test in suspected secondary adrenocortical insufficiency.
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. (+info)
Prospective examination of adrenocortical function in advanced AIDS patients.
In human immunodeficiency virus infected individuals, human cytomegalovirus (CMV) remains a significant pathogen. The adrenal gland is a preferential site of CMV disease in acquired immunodeficiency syndrome (AIDS) patients. However, glucocorticoid replacement is often not selected because of the risk of exacerbating underlying infection. To evaluate the need for glucocorticoid replacement in these patients, we performed a prospective study to investigate the adrenal function in 60 advanced AIDS patients. Their adrenal function including rapid ACTH test (RAT), basal plasma ACTH level, and daily urinary free cortisol level was evaluated. Approximately 25% of the patients turned out to be abnormal in this evaluation. Almost 60% of the patients could be followed up for one year or until their death. Using the follow-up data, we calculated sensitivity, specificity, positive predictive value and negative predictive value. Excretion of urinary free cortisol with normal RAT was comparable to normal controls, whereas patients with abnormal RAT excreted significantly lower urinary free cortisol. During hospitalization, 14 patients with normal RAT had febrile episode. During the febrile period the concentration of the urinary free cortisol level increased by 2.2 times. This study suggests that glucocorticoid replacement is necessary for AIDS patients suspected as clinically adrenal insufficiency, and that the dose of glucocorticoid replacement might be increased during sick days in AIDS patients with abnormal adrenal function. (+info)