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Adrenal Insufficiency (adrenal + insufficiency)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Pediatrics	21%
Dermatology	6%

Selected Abstracts

Adrenal Insufficiency in Critically Ill Emergency Department Patients: A Taiwan Preliminary Study

ACADEMIC EMERGENCY MEDICINE, Issue 7 2001
Shy-Shin Chang MD
Objective: Unrecognized adrenal insufficiency can have serious consequences in critically ill emergency department (ED) patients. This prospective pilot study of adrenal function in patients with severe illness was undertaken to determine the prevalence of adrenal dysfunction and any relation to prior herbal drug use. Methods: In a high-volume urban tertiary care ED, adult patients with sepsis or acute myocardial infarction (AMI) were eligible for the study. Over a two-month period, a convenience sample was enrolled by the authors on arrival to the ED. Inclusion criteria were systemic inflammatory response syndrome (SIRS) criteria plus evidence of at least one organ dysfunction or cardiac marker plus electrocardiogram-proven AMI. Exclusion criteria included known corticosteroid use. Serum cortisol was measured on arrival and for those patients with a level of <15 ,g/dL (<414 nmol/L), an adrenocorticotropic hormone (ACTH) stimulation test was performed. Results: Of the 30 enrolled patients, 23 (77%) were suffering from severe sepsis and the other seven (23%) had an AMI. Thirteen of the 30 patients (43%; 95% CI = 25% to 65%) had serum cortisol levels of <15 ,g/dL, consistent with adrenal insufficiency, nine with severe sepsis and four with an AMI. Eight (62%; 95% CI = 32% to 86%) of the 13 patients with low cortisol levels reported using herbal medications, while only two (12%; 95% CI = 1% to 36%) of the 17 with normal cortisol levels reported taking herb drugs (p = 0.01). Only two (15%; 95% CI = 2% to 45%) of the patients with low cortisol levels failed their corticotropin stimulation test, suggestive of true adrenocortical insufficiency. Both reported using herbal preparations. Conclusions: These results indicate that adrenal dysfunction is common among a group of critically ill patients seen in this Taiwanese ED. Moreover, the use of herbal drugs was high in the patients with low serum cortisols. Further studies are required to both confirm these findings and clarify whether a number of herbal medications contain corticosteroids. [source]

A Case of Human Intramuscular Adrenal Gland Transplantation as a Cure for Chronic Adrenal Insufficiency

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010
E. Grodstein
Intramuscular endocrine gland transplantation has been well described as it pertains to parathyroid autotransplantation; however, transplantation of the adrenal gland is less well characterized. While adrenal autotransplantation in the setting of Cushing's disease has been described, intramuscular adrenal allotransplantation as a cure for adrenal insufficiency to our knowledge has not been previously carried out. Current treatment for adrenal insufficiency leaves patients without diurnal variation in cortisol release and susceptible to the detrimental effects of chronic hypercortisolism. We describe here the case of a 5-year-old girl with renal failure who had adrenal insufficiency following fulminant meningococcemia that led to requirements for both stress-dose steroid and mineralocorticoid replacement. Ten months after the onset of her disease, she received a simultaneous renal and adrenal gland transplant from her mother. The adrenal gland allograft was morselized into 1 mm3 segments and implanted into three 2 cm pockets created in her rectus abdominis muscle. Three years after surgery, her allograft remains fully functional, responding well to adrenocorticotropin hormone stimulation and the patient does not require any steroid or mineralcorticoid supplementation. We believe this case represents the first description of successful functional intramuscular adrenal allograft transplantation with long-term follow up as a cure for adrenal insufficiency. [source]

Antiphospholipid syndrome and endocrine damage: why bilateral adrenal thrombosis?

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2003
Kaspar Berneis
Abstract: We describe a rare case of bilateral hemorrhagic infarction of the adrenal glands diagnosed in the context of positive antiphospholipid antibodies (aPL). The patient presented atypical clinical symptoms of adrenal insufficiency. Laboratory investigation showed complete adrenal failure and increased aPL, both manifestations persisted 1 yr after the initial event. MR imaging at baseline was compatible with bilateral hemorrhagic infarction and showed almost complete loss of viable adrenal tissue 1 yr later. Although no direct causal effect can be proved, the sequence of events and the exclusion of other common causes of bilateral adrenal hemorrhage (e.g. tuberculosis, severe coagulation disorder) support an association between aPL and adrenal hemorrhagic infarction. A unique link between particular anatomical characteristics of the adrenal fascicular zone and a novel, previously described, explanation model of aPL-thrombosis is hypothesized. It is based on the properties of late endosomes, which are important organelles participating in cholesterol trafficking and protein sorting within cells and express epitopes recognized by aPL. It would be interesting to investigate adrenal tissue for presence of late endosomes and their aPL relevant epitopes for proof of this tempting hypothesis. Focal accumulation of aPL and isolated, simultaneous, bilateral adrenal infarctions could thus be explained. [source]

Adrenal Insufficiency in Critically Ill Emergency Department Patients: A Taiwan Preliminary Study

Preclinical Cushing's syndrome: Report of seven cases and a review of the literature

INTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2000
Masaaki Morioka
Abstract Background: Adrenal adenomas showing autonomous cortisol secretion without specific endocrine symptoms are sometimes discovered in patients with adrenal incidentalomas. This entity has been described as subclinical or preclinical Cushing's syndrome (PCS), but the endocrine data of reported cases have varied and the diagnostic criteria of PCS have been uncertain. Methods: We report seven Japanese cases of PCS due to a unilateral, solitary adrenal adenoma with examination of the endocrine data of these patients. The diagnostic parameters of subtle hypercortisolism and the risk of postoperative adrenal insufficiency and surgical indications are discussed and reviewed. Results: In the present cases, the most frequently found biochemical parameters of autonomous cortisol secretion were a low adrenocorticotropic hormone (ACTH) level (100%) and insufficient suppression of cortisol by low-dose dexamethasone (85.7%). Unilateral accumulation of radiopharmaceuticals in tumors was also frequently observed (100%). A postoperative hydrocortisone supplement was given to six of the seven patients for 5,122 days. It was not given to case 4, because a moderate response of 11-deoxycortisol to metyrapone was identified. Plasma ACTH levels and the diurnal rhythm of plasma cortisol rapidly recovered within 3 weeks postoperatively in six of the seven cases. Conclusion: This entity is heterogeneous and various degrees of cortisol excess have been observed. It should be diagnosed in the wide spectrum and the risk of adrenal insufficiency after surgery should be evaluated by dynamic tests such as the corticotropin-releasing hormone (CRH) test. Based on the results of the present study and a review of the literature, PCS patients may not require hydrocortisone supplement therapy for a long period. [source]

Primary adrenal insufficiency in childhood and adolescence: Advances in diagnosis and management

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 11 2004
PJ Simm
Objectives: Primary adrenal insufficiency occurring in childhood and adolescence is due to abnormalities of gland development, gland responsiveness, and steroid biosynthesis or target organ response. Causes include autoimmune Addison's disease, tuberculosis, HIV, adrenoleukodystrophy, adrenal hypoplasia congenita and syndromes including triple A and IMAGe. We aimed to define the causes of adrenal insufficiency for a cohort of children in Melbourne. Methods: We reviewed the frequency and variety of presentation of primary adrenal insufficiency to the Royal Children's Hospital over the past 10 years through an audit of patient records, collating demographic information, presentation and investigations. Results: Sixteen cases (13 male, 3 female) of primary adrenal insufficiency were diagnosed at this hospital between January 1993 and July 2003. Median age at presentation was 7.7 years (range: birth to 14.8 years). Symptoms at presentation included weakness, increased pigmentation, abdominal pain, nausea, developmental delay or a reduction in school performance. Four patients presented with adrenal crisis. Median adrenocorticotrophic hormone (ACTH) at diagnosis was 246 pmol/L (range 30,969 pmol/L). Autoantibodies were positive in five patients. Five patients had elevation of very long chain fatty acids. Five patients were diagnosed with autoimmune adrenal insufficiency, five with adrenal hypoplasia congenita, five with adrenoleukodystrophy and one with IMAGe syndrome. Conclusions: A high index of suspicion results in earlier detection and possible prevention of adrenal crisis with a reduction in associated morbidities. Definitive diagnosis is now possible for almost all cases of primary adrenal insufficiency using technologies for screening autoimmunity, adrenoleukodystrophy (ALD) and genetic screening. [source]

Echocardiographic features, mortality, and adrenal function in patients with cirrhosis and septic shock

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2008
S. THIERRY
Objectives: 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. Design: Prospective single-center cohort study. Patients and methods: 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. Results: Patients with cirrhosis had higher values for the CI (3.69±1.0 vs. 2.86±0.8 l/min/m2; P=0.02), SI (37.5±8 vs. 32.4±7 ml/m2; 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). Conclusion: 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. [source]

HPA-suppressive effects of aqueous clobetasol propionate in the treatment of patients with oral lichen planus

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 9 2010
MA Gonzalez-Moles
Abstract Background, Oral topical corticosteroids have potential to produce inhibition of the hypothalamus,pituitary,adrenal (HPA) axis. Objective, To assess whether clobetasol propionate (CP) in aqueous solution causes HPA inhibition. Patients and methods, Sixty-two patients with oral lichen planus or oral lichenoid lesions presenting with severe lesions were treated with topical oral 0.05% CP plus 100 000 IU/cm3 nystatin in aqueous solution. Initial treatment of three 5-min mouthwashes (10 mL) daily was reduced, when the response was deemed complete or excellent, to a maintenance treatment of one 5-min mouthwash on alternate days for 6 months; treatment was then withdrawn and patients were followed up for 1 year. HPA function was assessed by plasma cortisol measurement and adrenocorticotropin (ACTH) stimulation at the end of the initial and maintenance treatment regimens. Results, The HPA axis was more frequently inhibited during initial (53/62; 85.5%) vs. maintenance (2/49; 4%) regimens of aqueous CP. Limitations, In patients with morning plasma cortisol levels between 3 and 18 ,g/dL, a normal result for the ACTH stimulation test only moderately reduces the possibility that a patient has secondary adrenal insufficiency. This can be considered a minor limitation in our study, as only three patients required additional assessment with the ACTH stimulation test. Conclusions, Hypothalamus,pituitary,adrenal inhibition is substantial during initial treatment with aqueous CP three times daily. [source]

Withdrawal of corticosteroids in inflammatory bowel disease patients after dependency periods ranging from 2 to 45 years: a proposed method

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009
S. J. MURPHY
Summary Background, Even in the biologic era, corticosteroid dependency in IBD patients is common and causes a lot of morbidity, but methods of withdrawal are not well described. Aim, To assess the effectiveness of a corticosteroid withdrawal method. Methods, Twelve patients (10 men, 2 women; 6 ulcerative colitis, 6 Crohn's disease), median age 53.5 years (range 29,75) were included. IBD patients with quiescent disease refractory to conventional weaning were transitioned to oral dexamethasone, educated about symptoms of the corticosteroid withdrawal syndrome (CWS) and weaned under the supervision of an endocrinologist. When patients failed to wean despite a slow weaning pace and their IBD remaining quiescent, low dose synthetic ACTH stimulation testing was performed to assess for adrenal insufficiency. Multivariate analysis was performed to assess predictors of a slow wean. Results, Median durations for disease and corticosteroid dependency were 21 (range 3,45) and 14 (range 2,45) years respectively. Ten patients (83%) were successfully weaned after a median follow-up from final wean of 38 months (range 5,73). Disease flares occurred in two patients, CWS in five and ACTH testing was performed in 10. Multivariate analysis showed that longer duration of corticosteroid use appeared to be associated with a slower wean (P = 0.056). Conclusions, Corticosteroid withdrawal using this protocol had a high success rate and durable effect and was effective in patients with long-standing (up to 45 years) dependency. As symptoms of CWS mimic symptoms of IBD disease flares, gastroenterologists may have difficulty distinguishing them, which may be a contributory factor to the frequency of corticosteroid dependency in IBD patients. [source]

The Treatment of Acute Adrenocortical Insufficiency in the Dog

JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 1 2001
DACVECC, DACVIM, Michael Schaer DVM
Summary Acute hypoadrenocorticism in the dog is a true medical emergency that requires a prompt and accurate diagnosis and appropriate treatment in order to provide for the most optimal outcome. Because the signs of adrenal insufficiency mimic those caused by other more common clinical conditions such as renal failure, intoxications, and various gastrointestinal disorders, it behooves the emergency clinician to always include this condition in the list of differential diagnoses. This paper will review the main elements of this hypoendocrinopathy in order to provide the emergency clinician with the essentials that will be required for appropriate diagnosis and treatment. J Vet emerg Crit Care 2001; 11(1):7,14 [source]

Oral budesonide for maintenance of remission of Crohn's disease: a pooled safety analysis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009
G. R. LICHTENSTEIN
Summary Background, Budesonide exhibits similar efficacy to systemic glucocorticosteroids (GCSs) in Crohn's disease (CD), but with fewer adverse events (AEs). Aim, To evaluate budesonide's safety profile in CD patients, in particular, incidences of clinically important AEs known to be associated with systemic GCSs. Methods, Five 1-year, double-blind, placebo-controlled trials evaluating budesonide for mild-to-moderate CD were pooled for analysis. Results, The highest incidence rates of AEs were gastrointestinal- and endocrine systems-related in both groups (budesonide 6 mg/day, n = 208; placebo, n = 209). Incidence rates were similar, except for higher incidence of endocrine disorders in budesonide versus placebo patients (P = 0.0042) caused by a higher overall occurrence of cutaneous GCS symptoms (P = 0.0036) in the budesonide group; differences in individual symptoms were nonsignificant. Percentage of patients with normal adrenal function was significantly lower at 13 weeks (three of five studies), but not at 52 weeks (two studies) in the budesonide versus placebo groups. Occurrence of clinically important or serious AEs associated with systemic GCSs, including sepsis, cataracts, adrenal insufficiency was rare and similar between groups. Conclusions, Budesonide treatment for up to 1 year is well-tolerated in CD patients, with an AE profile similar to placebo and only rare occurrences of clinically important AEs associated with systemic GCSs. [source]

Cardiac failure and multiple organ dysfunction syndrome in a patient with endocrine adenomatosis

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2002
M. W. Dünser
In this case report, we present the successful therapy of severe cardiac failure in pituitary adrenal insufficiency. A previously healthy 56-year-old-man in pituitary coma due to an atypical variant of multiple endocrine adenomatosis (pituitary adenoma and pheochromocytoma) suffered from cardiac failure resistant to catecholamine and standard hydrocortisone therapy. After two bolus injections of dexamethasone (2 × 24 mg) mean arterial pressure and cardiac function dramatically improved, probably due to restoration of permissive effects on catecholamine action and reversal of pathophysiological mechanisms of cardiac failure. We conclude that in patients with severe cardiovascular failure in pituitary coma the administration of potent glucocorticoids may be more effective in reversing cardiovascular failure than standard dosages of hydrocortisone. [source]

Therapeutic doses of glucocorticoids: implications for oral medicine

ORAL DISEASES, Issue 5 2006
SK Baid
Glucocorticoids can cause adverse systemic side-effects ranging from iatrogenic Cushing's syndrome during treatment, to hypothalamic,pituitary,adrenal axis suppression and clinically significant adrenal insufficiency when the agents are discontinued. While the oral route of administration is most often implicated, it is now becoming more apparent that inhaled and topical administration also can cause these effects. Given the high therapeutic value of glucocorticoids, the ability to prescribe these agents while maintaining a low risk-to-benefit ratio for patients is critical. The aim of this review is to provide oral healthcare practitioners with a practical guide to commonly used glucocorticoids, their adverse effects, and perioperative use. [source]

Adrenal function testing in pediatric cancer survivors

PEDIATRIC BLOOD & CANCER, Issue 7 2009
Briana C. Patterson MD
Abstract Background Central adrenal insufficiency is observed after cranial radiation therapy for cancer. Screening at risk patients is recommended, but the best screening strategy is unknown. Methods A retrospective review of pediatric cancer survivors who underwent hypothalamic/pituitary/adrenal axis testing was conducted. Data included: cancer diagnosis, radiotherapy dose, other endocrinopathies, and adrenal function testing. Adrenal testing included sequential low-dose corticotropin test (LDCT) and standard-dose corticotropin test (SDCT). 8 a.m. serum cortisol levels were compared to LDCT results. LDCT results were compared by radiotheroapy dose and according to the presence of endocrine comorbidities. Results Seventy-eight subjects (56% male, mean age at diagnosis 6.5 years) underwent testing. 67.9% had been treated with radiotherapy to the hypothalamus/pituitary. Mean time to diagnosis of adrenal insufficiency was 6.8 years after cancer diagnosis. Adequate adrenal function was found in 65% of patients by LDCT and 89% by SDCT. Only 21% of patients had basal serum cortisols collected at 8 a.m. Agreement between 8 a.m. baseline cortisol and LDCT was fair. Agreement between random baseline cortisol and LDCT was poor. Prevalence of central adrenal insufficiency diagnosed by LDCT increased with radiotherapy dose (8% for 10,19.9,Gy; 83% for ,40,Gy) and the number of endocrine comorbidities. Conclusions In pediatric cancer survivors, central adrenal insufficiency was common even in patients receiving <40,Gy to the hypothalamus/pituitary. We recommend use of LDCT, not 8 a.m. serum cortisol to screen patients who received >30,Gy of radiotherapy and those with other central endocrinopathies. Pediatr Blood Cancer 2009; 53:1302,1307. © 2009 Wiley-Liss, Inc. [source]

Anti-inflammatory treatment for recurrent wheezing in the first five years of life

PEDIATRIC PULMONOLOGY, Issue 4 2003
Athanasios G. Kaditis MD
Abstract Medications identified for the treatment of recurrent wheezing in preschool children by the Expert Panel Report of the NHLBI Guidelines for the Diagnosis and Management of Asthma include inhaled corticosteroids, chromones, theophylline, and leukotriene pathway modifiers. However, these various agents differ in their mechanism, extent of action on the airway inflammatory process, and degree of clinical efficacy. Inhaled corticosteroids can control symptoms in many young children with even severe persistent wheezing, but data on their long-term safety when administered in preschool-age children are scarce. There is some information on the uninterrupted use of inhaled corticosteroids in school-age children and the absence of an adverse effect on ultimate adult height. Despite laboratory evidence of adrenal suppression in some studies, few pediatric cases of clinical adrenal insufficiency have been reported. Low-dose inhaled corticosteroid (<400 mcg/day for beclomethasone), which is adequate for controlling mild persistent symptoms, is generally safe. Chromones have a remarkable safety profile, but they are most effective for symptoms of mild severity. Promising data have been published on the efficacy and safety of leukotriene pathway modifiers when used in young children with persistent symptoms. It is uncertain whether early introduction and long-term administration of inhaled corticosteroids prevent development of irreversible airway obstruction. Nevertheless, they may be especially useful for patients with moderate to severe disease in whom other agents (chromones or leukotriene pathway modifiers) will most likely fail to control symptoms. Pediatr Pulmonol. 2003; 35:241,252. © 2003 Wiley-Liss, Inc. [source]

A Case of Human Intramuscular Adrenal Gland Transplantation as a Cure for Chronic Adrenal Insufficiency

Topical treatment of uveitis resulting in adrenal insufficiency

ACTA PAEDIATRICA, Issue 3 2009
Liisa Kröger
Abstract The adverse effects of corticosteroids are well-known and occur more frequently when corticosteroids are used perorally or intravenously. The management of uveitis, which normally consists of topical corticosteroids and mydriates, can be challenging. We report a case in which continuous use of topical corticosteroids resulted in adrenal insufficiency and obesity. Conclusion: When topical corticosteroids are used over longer periods, hypophysis-pituitary-adrenal (HPA) function should be carefully monitored. [source]

Iatrogenic adrenal insufficiency associated with calcipotriol,betamethasone topical combination in psoriasis

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2010
M. Giannitelli
No abstract is available for this article. [source]

Allgrove syndrome with features of familial dysautonomia: A novel mutation in the AAAS gene

ACTA PAEDIATRICA, Issue 9 2006
Essam A. Ismail
Abstract Allgrove syndrome (or triple-A syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, adrenal insufficiency (glucocorticoid in the majority of cases) and autonomic/neurological abnormalities. This disease is now known to be caused by mutation in the AAAS gene located on chromosome 12q13. Diagnosis should be readily available when the full-blown features are there, but it becomes less apparent when presentation is atypical or in the evolving process. We present a brother and sister (12 and 19 y old, respectively) born to consanguineous parents of Palestinian origin with Allgrove syndrome. The index patient was erroneously diagnosed to be a case of familial dysautonomia before the diagnosis of adrenal insufficiency was made at the age of 7.5 y, while his elder sister had only alacrima from birth and developed achalasia at the age of 15 y. She started to develop early evidence of adrenal disease at the age of 19 y. Both of them had neuroautonomic dysfunction. The diagnosis of Allgrove syndrome was confirmed in these two patients by studying the gene mutation in the family. The sequencing of the AAAS gene in the two patients identified a novel homozygous mutation within intron 5 (IVS5+1(G),A). Both parents as well as all three other children were heterozygous for the same mutation. Conclusion: These two cases illustrate the heterogenous nature and the intrafamilial phenotypic variability of Allgrove syndrome. [source]

Modified-release hydrocortisone for circadian therapy: a proof-of-principle study in dexamethasone-suppressed normal volunteers

CLINICAL ENDOCRINOLOGY, Issue 1 2008
J. Newell-Price
Summary Background All existing long-term glucocorticoid replacement therapy is suboptimal as the normal nocturnal rise and waking morning peak of serum cortisol is not reproduced. Aim To test whether it is possible to reproduce the normal overnight rise and morning peak in serum cortisol using an oral delayed and sustained release preparation of hydrocortisone (Cortisolds). Subjects and methods Six healthy normal male volunteers attended on two occasions, in a single-dose, open-label, nonrandomized study. Endogenous cortisol secretion was suppressed by administration of dexamethasone. Cortisolds (formulation A or B) was administered at 2200 h on day 1. Blood samples for measurement of cortisol were taken from 2200 h every 30 min until 0700 h, then hourly until 2200 h on day 2. Fifteen body mass index (BMI)-matched control subjects had serum cortisol levels measured at 20-min intervals for 24 h. Serum cortisol profiles and pharmacokinetics after Cortisolds were compared with those in controls. Results Formulations A and B were associated with delayed drug release (by 2 h and 4 h, respectively), with median peak cortisol concentrations at 4·5 h (0245 h) and 10 h (0800 h), respectively, thereby reproducing the normal early morning rise in serum cortisol. Total cortisol exposure was not different from controls. Conclusions For the first time we have shown that it is possible to mimic the normal circadian rhythm of circulating cortisol with an oral modified-release formulation of hydrocortisone, providing the basis for development of physiological circadian replacement therapy in patients with adrenal insufficiency. [source]

Novel polymorphisms and lack of mutations in the ACD gene in patients with ACTH resistance syndromes

CLINICAL ENDOCRINOLOGY, Issue 2 2007
Catherine E. Keegan
Summary Objective ACTH resistance is a feature of several human syndromes with known genetic causes, including familial glucocorticoid deficiency (types 1 and 2) and triple A syndrome. However, many patients with ACTH resistance lack an identifiable genetic aetiology. The human homolog of the Acd gene, mutated in a mouse model of adrenal insufficiency, was sequenced in 25 patients with a clinical diagnosis of familial glucocorticoid deficiency or triple A syndrome. Design A 3·4 kilobase genomic fragment containing the entire ACD gene was analysed for mutations in all 25 patients. Setting Samples were obtained by three investigators from different institutions. Patients The primary cohort consisted of 25 unrelated patients, primarily of European or Middle Eastern descent, with a clinical diagnosis of either familial glucocorticoid deficiency (FGD) or triple A syndrome. Patients lacked mutations in other genes known to cause ACTH resistance, including AAAS for patients diagnosed with triple A syndrome and MC2R and MRAP for patients diagnosed with familial glucocorticoid deficiency. Thirty-five additional patients with adrenal disease phenotypes were added to form an expanded cohort of 60 patients. Measurements Identification of DNA sequence changes in the ACD gene in the primary cohort and analysis of putative ACD haplotypes in the expanded cohort. Results No disease-causing mutations were found, but several novel single nucleotide polymorphisms (SNPs) and two putative haplotypes were identified. The overall frequency of SNPs in ACD is low compared to other gene families. Conclusions No mutations were identified in ACD in this collection of patients with ACTH resistance phenotypes. However, the newly identified SNPs in ACD should be more closely examined for possible links to disease. [source]

Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers

CLINICAL ENDOCRINOLOGY, Issue 3 2006
P. Alía
Objective, 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 µg) (HDT) and low-dose test (1 µg) (LDT) in healthy subjects in order to provide a deeper knowledge about the relationship between stimulus and response. Design and patients, ACTH tests were performed in 10 healthy volunteers (five men, five women) with at least 1 week of difference. Measurements, 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. Results, 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). Conclusions, 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. [source]

Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency

CLINICAL ENDOCRINOLOGY, Issue 3 2004
Peak M. Mah
Summary objective, The objective of this study was to examine the variables determining hydrocortisone (HC) disposition in patients with adrenal insufficiency and to develop practical protocols for individualized prescribing and monitoring of HC treatment. design and patients, Serum cortisol profiles were measured in 20 cortisol-insufficient patients (09·00 h cortisol < 50 nmol/l) given oral HC as either a fixed or ,body surface area-adjusted' dose in the fasted or fed state. Endogenous cortisol levels were measured in healthy subjects. Pharmacokinetic analysis was performed using P-Pharm software, and computer simulations were used to assess the likely population distribution of the data. results, Body weight was the most important predictor of HC clearance. A fixed 10-mg HC dose overexposed patients to cortisol by 6·3%, whereas weight-adjusted dosing decreased interpatient variability in maximum cortisol concentration from 31 to 7%, decreased area under the curve (AUC) from 50 to 22% (P < 0·05), and reduced overexposure to < 5%. Food taken before HC delayed its absorption. Serum cortisol measured 4 h after HC predicted cortisol AUC (r2 = 0·78; P < 0·001). conclusions, We recommend weight-adjusted HC dosing, thrice daily before food, monitored with a single serum cortisol measurement using a nomogram. This regimen was prospectively examined in 40 cortisol-insufficient patients, 85% of whom opted to remain on the new thrice-daily treatment regimen. [source]

Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient

ACTA PAEDIATRICA, Issue 9 2002
KM Main
Treatment of allergic bronchopulmonary aspergillosis with itraconazole is becoming more widespread in chronic lung diseases. A considerable number of patients is concomitantly treated with topical or systemic glucocorticoids for anti-inflammatory effect. As azole compounds inhibit cytochrome P450 enzymes such as CYP3A isoforms, they may compromise the metabolic clearance of glucocorticoids, thereby causing serious adverse effects. A patient with cystic fibrosis is reported who developed iatrogenic Cushing's syndrome after long-term treatment with daily doses of 800 mg itraconazole and 1600 ,g budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total suppression of spontaneous and stimulated plasma cortisol and adrenocorticotropin. Discontinuation of both drugs led to an improvement in clinical symptoms and recovery of the pituitary-adrenal axis after 3 mo. Conclusion: This observation suggests that the metabolic clearance of budesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge. [source]