幼年型粒单核细胞白血病单倍体相合造血干细胞移植1例

目的探讨单倍体相合造血干细胞移植治疗幼年型粒单核细胞白血病(JMML)的可行性。方法 1岁6个月JMML患儿,行单倍体相合造血干细胞移植。采用Bu/Cy+Flu+ALG方案预处理及CSA+MMF+MTX方案预防移植物抗宿主病(GVHD)。结果于移植+10 d粒系植入成功(1.2×109/L),移植+14 d血小板植入成功(260×109/L),造血初步恢复。移植+21 d查植入证据为100%嵌合。患儿移植后反复出现Ⅰ～Ⅱ度GVHD(皮肤型),给予免疫抑制剂治疗后好转。至今已生存14个月,未见复发。结论单倍体相合造血干细胞移植可能是治愈JMML的可行方法。     

Impaired adrenal function after glucocorticoid therapy in children with acute lymphoblastic leukemia

BACKGROUND: Glucocorticoids are commonly used in the treatment of childhood acute lymphoblastic leukemia (ALL). The purpose of this study was to assess the incidence of adrenal insufficiency and the time for children with ALL to recover after treatment with the glucorticoids prednisolone or dexamethasone. PROCEDURE: Seventeen children, 2-15 years, with ALL were studied after receiving prednisolone (60 mg/m(2)/day, n = 10) for 5 weeks during remission induction therapy or dexamethasone (10 mg/m(2)/day, n = 7) for 3 weeks during reinduction therapy. Both drugs were tapered over 9 days. The adrenal function was assessed by an ACTH stimulation test within 2 weeks after discontinuing glucocorticoid therapy. In case of adrenal insufficiency, the ACTH test was repeated at 3-5 weeks interval, and patients were put on hydrocortisone substitution therapy. RESULTS: Three out of ten patients had a normal adrenal function within the first 2 weeks after prednisolone therapy. Another three patients recovered within 7 weeks, whereas the remaining four patients still showed adrenal insufficiency at the end of follow-up after 2.5-4 months. For dexamethasone, two out of seven patients showed a normal adrenal function within the first 2 weeks. Of the remaining patients, two recovered within 7 weeks, whereas three patients still had a demonstrated adrenal insufficiency at the end of follow-up after 4-8 months. CONCLUSIONS: Adrenal insufficiency occurs and may persist for several months in children with ALL after treatment with high doses of prednisolone or dexamethasone.     

Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia

Background A 4‐week course of high‐dose glucocorticoids may cause prolonged adrenal suppression even after a 9‐day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high‐dose prednisone (PDN) or dexamethasone (DXM). Procedures Sixty‐four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD‐ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1–2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period. Results All patients had normal basal cortisol values at diagnosis. Twenty‐four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD‐ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7–14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression. Conclusions High‐dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated. Pediatr Blood Cancer 2008;50:537–541. © 2007 Wiley‐Liss, Inc.     

Management of advanced‐stage neuroblastoma in a patient with 21‐hydroxalase deficiency

A 2‐year‐old boy presented with a 21‐hydroxylase deficiency, associated with advanced‐stage neuroblastoma primarily occurring in the left adrenal gland. He required intensive chemotherapy with polypharmacy, followed by cord blood stem cell transplantation to treat the neuroblastoma. The precise adjustment of cortisol levels was crucial in this patient to prevent adrenal crisis. We administered hydrocortisone by continuous infusion while monitoring blood cortisol levels. As there are no published reports on the target cortisol levels for children, we used two control infants with advanced‐stage neuroblastoma, also undergoing chemotherapy and cord blood stem cell transplantation, to guide the continuous hydrocortisone therapy. The daily dose of hydrocortisone during chemotherapy required about threefold the normal treatment to avoid adrenal insufficiency. Continuous hydrocortisone therapy is feasible for preventing adrenal crisis and this report may provide an effective management for hydrocortisone replacement in 21‐hydroxylase‐deficient patients undergoing chemotherapy and hematopoietic stem cell transplantation.     

促肾上腺皮质激素刺激对脓毒症及脓毒性休克患儿肾上腺功能评估的意义

目的 探讨小剂量(1μg/1.73 m2)促肾上腺皮质激素(ACTH)刺激实验评估儿童脓毒症和脓毒性休克肾上腺功能状态的价值.方法 患儿入院24h内完成基础皮质醇(T0)测定,静脉注射1μg/1.73m2 ACTH,30 min后测定血液皮质醇(T1),根据T0和皮质醇增值(△max=T1-T0)判断肾上腺功能,以△max≤90μg/L为肾上腺功能障碍(AI)指标.结果 62例中,脓毒症53例,脓毒性休克9例,病死率为27.4%(17/62).肾上腺功能障碍(adrenal insufficiency,AI)发生率40.3%(25/62),其中脓毒症和脓毒性休克患儿AI发生率分别是39.6%和44.4%,差异无显著统计学意义(P>0.05).两组脓毒症和脓毒性休克平均T0和T1分别是(318.6±230.4)μg/L、(452.3±230.7)μg/L和(454.7±212.7)μg/L、(579.3±231.9)μg/L,差异无统计学意义(P>0.05).存活组和死亡组患儿T0、T1分别是(320.5±223.9)μg/L、(462.3±212.0)μg/L和(384.3±258.3)μg/L、(500.7±470.6)μg/L,两组AI发生率分别是37.8%和47.1%,差异无统计学意义(P>0.05).T0和T1水平与儿童危重病例评分(PCIS)有关(P<0.05),AI发生率与PCIS、PRISMⅢ和器官功能障碍数目无关(P>0.05).结论 儿童脓毒症和脓毒性休克患儿AI发生率较高.小剂量ACTH刺激实验可以判断严重感染患者肾上腺功能,可为激素治疗提供依据.     

What is the rationale for hydrocortisone treatment in children with infection-related adrenal insufficiency and septic shock?

Recent studies show that children who die from fulminant meningococcaemia have very low cortisol:adrenocorticotrophic hormone (ACTH) ratios within the first 8 h of presentation to emergency facilities compared with survivors. This observation supports the possibility that adrenal insufficiency may contribute to rapid cardiovascular collapse in these children. In recent years, the use of hydrocortisone treatment has become increasingly popular in the care of adult and paediatric patients with septic shock. In this review, the classical adrenal insufficiency literature is presented and the existing rationale for using titrated hydrocortisone treatment (2-50 mg/kg/day) to reverse catecholamine-resistant shock in children who have absolute adrenal insufficiency (defined by peak cortisol level <18 microg/dl after ACTH challenge) or pituitary, hypothalamic or adrenal axis insufficiency is provided. In addition, the concept of relative adrenal insufficiency (basal cortisol >18 microg/dl but a peak response to ACTH <9 microg/dl) is reviewed. Although there is a good rationale supporting the use of 7 days of low-dose hydrocortisone treatment (about 5 mg/kg/day) in adults with this condition and catecholamine resistant septic shock, the paediatric literature suggests that it is prudent to conduct more studies before recommending this approach in children.     

Adrenal responsiveness in children with steroid responsive idiopathic nephrotic syndrome

Impaired adrenal cortical responsiveness to ACTH has been reported in children with steroid responsive nephrotic syndrome. Plasma cortisol levels at 8 AM and 2 hours post ACTH stimulation were measured on 42 occasions in 33 children with steroid-responsive nephrotic syndrome. Twenty-two of 42 fasting 8 AM plasma cortisol and 39 of 42 post-ACTH plasma cortisol values were subnormal. Plasma cortisol values were similar in children evaluated prior to, immediately following or 2-24 moths after prednisone therapy. No relationship was observed between 8 AM or post-ACTH plasma cortisol values and serum albumin concentration or the presence of edema. Impaired adrenal responsiveness to ACTH was not helpful in predicting the length of clinical remission. Hydrocortisone replacement therapy given to five children with impaired ACTH-responsiveness did not alter the rate of relapses observed prior to this treatment.     

呼吸衰竭新生儿肾上腺皮质功能状态分析

目的 研究呼吸衰竭新生儿(新生儿呼吸窘迫综合征、肺炎和重症湿肺)肾上腺皮质功能变化、肾上腺皮质功能不全(AI)的发生率及其与病情的关系.方法 研究对象为人住我院的呼吸衰竭新生儿55例(其中早产儿33例,足月儿22例),分别检测清晨血清基础皮质醇和促肾上腺皮质激素(ACTH)浓度,及小剂量ACTH刺激试验30 min后血清皮质醇峰值.血清皮质醇峰值浓度＜200 μg/L为合并AI.结果 呼吸衰竭早产儿基础皮质醇浓度较足月儿高[(139.2±85.4)μg/L vs(92.1±75.0)μg/L,P=0.040 7],而小剂量ACTH刺激试验前后皮质醇差值及ACTH浓度则较足月儿低[(122.3±56.4)μg/L vs(198.2±77.9)μg/L,P=0.000 1;(5.22±2.40)ng/L vs(8.66±5.41)ng/L.P=0.008 4].呼吸衰竭新生儿合并AJ的发生率为20.0%(11/55),其中早产儿组为21.2%(7/33),足月儿组为18.2%(4/22).需机械通气呼吸衰竭新生儿AI的发生率(29.4%)高于非机械通气新生儿(4.8%).AI新生儿中无死亡病例.结论 呼吸衰竭早产儿肾上腺皮质和垂体功能较足月儿差.呼吸衰竭新生儿合并AJ的发生率较高.需机械通气的呼吸衰竭新生儿AJ的发生率高于机械通气者.未发现AJ与病死率相关.小剂量ACTH刺激试验可较好地评估新生儿肾上腺皮质功能.     

Busulfan and cyclophosphamide as a conditioning regimen for pediatric acute lymphoblastic leukemia patients undergoing bone marrow transplantation

Bone marrow transplantation (BMT) has become the standard therapy for children with relapsed acute lymphoblastic leukemia. The authors report their experience with histocompatible BMT for 52 children with acute lymphoblastic leukemia conditioned with a non-total body irradiation (TBI) regimen using busulfan and cyclophosphamide (Bu/Cy). The efficacy and long-term toxicity of the Bu/Cy regimen were determined. Overall survival was 35%. One-year, 3-year, and 7-year event-free survival rates were 54%, 33%, and 23%, respectively. Of the 52 BMT recipients, 26 relapsed. Thirteen of the relapsed patients received a second BMT and three were surviving as of this writing. The most frequent cause of death was leukemia relapse. An initial remission duration of less than 18 months was a factor in decreasing the event-free survival. The Bu/Cy regimen was well tolerated, with minimal transplant-related mortality. Neurocognitive function was tested before BMT and 1 year after BMT. When 1-year posttransplant neurocognitive test scores were compared with pretransplant scores, there was no decrease. However, there was a significant decrease in the pretransplant neurocognitive test scores in BMT recipients compared with their normal siblings. The use of Bu/Cy as a conditioning regimen for BMT does not appear to affect posttransplant neurocognitive function. Other long-term side effects, such as endocrinopathies and secondary malignancies, were also minimal. These data show that the Bu/Cy regimen is well tolerated, but the overall survival rate remains low.     

Salivary cortisol estimation to assess adrenal status in children with fluid unresponsive septic shock

We evaluated the adrenal status by estimating baseline and ACTH stimulated salivary cortisol in 51 children with fluid unresponsive septic shock at 30 and 60 minutes, and basal salivary cortisol (9–11 am) in 79 healthy children. The baseline salivary cortisol (median, IQR) among patients (19.8, 7.2–42.4 nmol/L) was higher than healthy children (2.6, 1.3–7.6 nmol/L) (P=0.001). Non-survivors and those with catecholamine refractory shock had higher baseline cortisol level, though difference was statistically insignificant. Absolute adrenal insufficiency (baseline salivary cortisol <1.3nmol/L) was diagnosed in 8 (15.7%) patients. Relative adrenal insufficiency (rise in cortisol level above baseline value after stimulation <25nmol/L) was observed in 68.6% of all patients; 71.9% among non-survivors, and in 71.4% patients with catecholamine refractory shock. Salivary cortisol estimation appears to be feasible in children with septic shock. Relative adrenal insufficiency is common in these children.     

Low-dose adrenocorticotropic hormone stimulation testing in term infants

BACKGROUND: Low-dose adrenocorticotropic hormone (ACTH) stimulation testing is a commonly accepted way to evaluate adrenal function in children. However, there are no published data on the use of this test in term infants less than 12 months of age outside the newborn period. METHODS: We identified 14 infants at our center who were full term and had one or more ACTH tests at less than 12 months of age to evaluate for secondary adrenal insufficiency (AI). We retrospectively assessed peak cortisol response in these infants to determine whether a cut-off of 20 microg/dl is appropriate to distinguish normal from abnormal adrenal function in this age group. RESULTS: Five infants had peak cortisol > or =20 microg/dl on their first ACTH test and had a clinical picture consistent with normal adrenal function. Nine infants had peak cortisol <20 microg/dl on their first ACTH test. When retested later in infancy, four of these patients achieved peak cortisol > or =20 microg/dl. CONCLUSIONS: In term infants, the low-dose ACTH stimulation test is useful for demonstrating normal adrenal function but is of limited value in diagnosing secondary AI. For infants with peak cortisol <20 microg/dl, clinical observation and repeat ACTH testing later in infancy clarified diagnosis.     

Adrenal response in children receiving high doses of ketoconazole for systemic coccidioidomycosis

The effect of ketoconazole on adrenal cortical function was studied in 10 prepubertal children receiving long-term (3 to 52 months) high-dose (10 to 23 mg/kg/d) orally administered ketoconazole treatment because of systemic coccidioidomycosis. Four hours after the once daily morning dose of ketoconazole, the patients had significantly elevated baseline desoxycorticosterone (DOC) and precursor/product ratios, and blunted cortisol and aldosterone responses to ACTH stimulation. Twenty-four hours after ketoconazole ingestion, both DOC and DOC/corticosterone ratio were approaching normal; the cortisol response to ACTH was normal in all but two of the 10 study patients, and these two had significantly improved response compared with their own 4-hour values. There appeared to be no differential adrenal response related to either duration of treatment (greater than 12 vs less than 12 months) or dose of medication per kilogram (greater than 18 or less than 18 mg/kg/d). Our data suggest that ketoconazole impairs production of cortisol and aldosterone by imposing a partial and temporary block at the 11-beta-hydroxylase step of steroid hormone synthesis. None of the patients required adrenal steroid replacement therapy in times of acute illness or surgery, and none had clinical evidence of adrenal insufficiency.     

Clinical and molecular genetic findings in a 6-year-old Bosnian boy with triple A syndrome

The triple A syndrome is a rare autosomal recessive disease that is characterised by the triad of adrenocorticotropin (ACTH)-resistant adrenal insufficiency, achalasia and alacrima. In most patients, neurological and dermatological abnormalities are associated features. We report on the first Bosnian patient with triple A syndrome. Endocrine investigation confirmed primary adrenal insufficiency at the age of 5.8 years. Two months lather, achalasia was diagnosed, and in the presence of alacrima, the patient satisfies the diagnostic criteria of triple A syndrome. In addition, a large number of associated neurological and dermatological features were present in this patient. Moreover, he has dysmorphic facial features, which have not been previously described in triple A syndrome. Triple A syndrome was confirmed by molecular analysis, revealing a nonsense mutation p.W84X in the AAAS gene. The parents are both heterozygous carriers of the mutation. The affected twin brother unfortunately died from hypoglycaemic shock, despite a normal cortisol rise in an ACTH stimulation test. Further, triple A syndrome patients carrying the identical homozygous p.W84X mutation have to be studied to assess a genotype–phenotype relationship for this mutation. Publication of these pictures was granted by the parents of the patient.     

Adverse effect of phenytoin on glucocorticoid replacement in a child with adrenal insufficiency

Chronic administration of antiepileptic agents such as phenytoin can increase clearance rates of cortisol and synthetic glucocorticoids through hepatic microsomal enzyme induction. However, data concerning an adverse interaction between antiepileptic and steroid drugs are scarce. We herein report an adolescent boy with primary adrenal insufficiency that developed glucocorticoid deficiency after added phenytoin treatment. The patient had an increased requirement for hydrocortisone replacement, and two episodes of vomiting, hyponatremia and mild hypoglycemia. His ACTH levels were markedly elevated. Fifteen days after stopping phenytoin, his serum ACTH concentration returned to normal range. Even though the hydrocortisone dose was gradually decreased, hyponatremia and vomiting have not recurred. In conclusion, we suggest that drugs such as phenytoin affecting hepatic clearance of synthetic glucocorticoids and mineralocorticoids should not be preferred for therapy in patients with adrenal insufficiency. If their use is vital, one should be aware of increased replacement requirements for steroid drugs, and patients should be closely monitored.     

Long-term treatment with corticosteroids/ACTH in asthmatic children. II. Hypothalamic-pituitary-adrenal function

Hypothalamic-pituitary-adrenal (HPA) function was studied in 23 children with severe bronchial asthma during and after long-term treatment with prednisolone and/or ACTH1-24 depot tetracosactrin) by means of ACTH stimulation test and insulin tolerance test. In the 14 children primarily treated with depot tetracosactrin, the cortisol levels in insulin tests were within normal limits both during and after treatment. An enhanced response to ACTH stimulation was found during the treatment period. During treatment with prednisolone a marked impairment of the adrenocortical function was found, with low basal plasma cortisol levels and subnormal response to ACTH stimulation, more marked the lower the age at the start of treatment and the higher the dose per kg body weight. After substitution with depot tetracosactrin the HPA-function was restituted, with plasma cortisol levels within normal limits. Growth hormone levels after insulin induced hypoglycemia were greater than or equal to 7 ng/ml during and after treatment with depot tetracosactrin. As long-term treatment with depot tetracosactrin has little side-effects in terms of suppression of the HPA-axis it is a useful alternative to oral prednisolone in severe asthma in children.     

Adrenal function in children with severe asthma treated with high-dose inhaled glucocorticoids: recommended screening tests in outpatient conditions

BACKGROUND: A number of previous studies have suggested that adrenal suppression occurs in asthmatic children treated with high-doses of inhaled glucocorticoids (IGC). This study was designed to determine the frequency of adrenal suppression in children with severe asthma treated with recommended doses of IGC: namely 500-1,000 microg/day of fluticasone propionate or the equivalent of budesonide (1,000-2,000 microg/day) for a period of at least 12 months. METHODS: Early morning cortisol (F) and ACTH serum levels were measured in 27 severe asthmatics aged 6-16 years old. The children underwent a low dose ACTH test (1 microg/1.73 m2) with a parallel glucose measurement. Twenty-four hour urine collection was performed before examination for free F (UfF) and creatinine levels. There were no clinical manifestations of adrenal hypofunction in the analyzed children. RESULTS: Of the 27 patients, 22 had normal basal and post-stimulatory levels of F and normal UfF, and the other five (18.5%) had basal serum F levels of <400 nmol/l. Four of the five also had normal post-stimulatory levels of F and normal UfF. One child had a subnormal peak F value of 484 nmol/l during the ACTH test. None of the patients had a suppressed serum ACTH level, but an elevated ACTH level was found in four children. This study provided biochemical evidence of suboptimal adrenal function in one child in the examined group (3.7%) and a good response to stimulation in all the others, even in those with slightly reduced basal cortisol levels. CONCLUSION: This study showed that the use of fluticasone in doses of up to 1,000 microg/day (or the equivalent of budesonide) as long-term treatment of children with severe asthma did not substantially affect their adrenal function.     

Adrenocortical suppression increases the risk of relapse in nephrotic syndrome.

OBJECTIVE: Children with nephrotic syndrome (NS) are usually treated with long-term low dose alternate day prednisolone with or without glucocorticoid sparing therapy, such as levamisole or ciclosporin, to maintain remission. The degree of hypothalamic-pituitary-adrenal axis (HPA) suppression with such therapeutic strategies has not been studied systematically. HPA suppression could cause a relapse or adrenal crisis. STUDY DESIGN: To study the risks of HPA suppression, a modified low dose synacthen test (0.5 mug) was administered to 32 patients (22 male,10 female) with a mean age of 9.7 years (range 3.8-17.6 years) with NS receiving long-term alternate day prednisolone for over 12 months. Twelve patients received alternate day prednisolone, 11 alternate prednisolone+levamisole and nine alternate prednisolone+ciclosporin. All patients were followed up for 3 years and the relapse rate noted. RESULTS: 20/32 (62.5%) patients had a peak serum cortisol concentration of <500 nmol/l, which suggested suboptimal cortisol secretion and possible HPA suppression. 10/12 children in the prednisolone group and 8/11 in the levamisole group had a suboptimal cortisol response compared with 2/9 in the ciclosporin group. During follow-up, the 20 children who had a suboptimal cortisol response had significantly more relapses (95 relapses) compared to the 12 children with a normal cortisol response who had 24 relapses (p = 0.01). CONCLUSIONS: Children with NS receiving long-term alternate day prednisolone therapy are at risk of developing HPA suppression and should be evaluated using the modified synacthen test. Children with evidence of HPA suppression are at a greater risk of relapse.     

Adrenal status in children with septic shock using low-dose stimulation test.

OBJECTIVES: 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. DESIGN: Cross-sectional study. SETTING: Pediatric intensive care unit in a tertiary care hospital in northern India. PATIENTS: Children with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: Relative adrenal insufficiency is common in children with septic shock and is associated with catecholamine refractory shock.     

Assessing adrenal function in primary care settings with a single sample subcutaneous glucagon test

OBJECTIVE: To test the efficacy of the low-dose glucagon test in assessing adrenal gland function. STUDY DESIGN: Subcutaneous glucagon was used to assess the hypothalamo-pituitary-adrenal gland (HPA) axis in 215 healthy children. Concordance of this test with the low-dose intravenous ACTH test was established for 42 children. Glucagon testing was conducted for 150 minutes after subcutaneous glucagon administration and for 30 minutes after 1 microg intravenous ACTH. RESULTS: Mean peak serum cortisol concentrations were 22.4 +/- 0.6 microg/dL (SEM) after subcutaneous glucagon and 20.0 +/- 0.6 microg/dL after intravenous ACTH. Specificity of 95% was found at peak cortisol concentrations of 9.5 and 12.5 microg/dL for the glucagon and ACTH tests, respectively. Concordance between the glucagon and ACTH tests was 90.5%. CONCLUSIONS: The glucagon test was found to be as good a test of the HPA axis as the ACTH test and had a 90.5% concordance with it. The ease of performing the glucagon test, namely, obtaining a single sample of blood 150 minutes after the subcutaneous administration of glucagon, makes it a useful method of assessing the HPA axis in primary care settings.     

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.