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.     

Rectal hydrocortisone during stress in patients with adrenal insufficiency

OBJECTIVE—Patients with glucocorticoid deficiency need lifelong glucocorticoid replacement treatment. During acute stressful events, steroid dosage must be increased several times, which is often problematical in children. This study investigated the reliability of rectal hydrocortisone administration as an alternative to the intramuscular route.
STUDY DESIGN—Serum cortisol was assessed during stress in normal children to determine the concentration that should be achieved after rectal hydrocortisone. Subsequently, serum cortisol concentrations were measured three hours after administering a suppository containing hydrocortisone 100 mg/m² to 57 patients with adrenocortical insufficiency. In eight patients, the time dependency of the cortisol rise after rectal administration was established.
RESULTS—In 51 previously healthy children admitted to hospital with an acute stressful condition, the mean serum cortisol concentration was 1092 nmol/l. Rectal hydrocortisone in patients with adrenocortical insufficiency resulted in a mean serum cortisol concentration of 1212 nmol/l three hours after insertion of the suppository containing hydrocortisone. In 14 of 57 children, serum cortisol was < 1000 nmol/l and in eight children it was below 600 nmol/l. One hour after administration, the mean cortisol concentration had reached 1000 nmol/l. This was sustained for more than four hours.
CONCLUSION—Rectal hydrocortisone is a safe alternative to parenteral administration in the self management of Addisonian prone conditions. However, because eight of 57 children did not achieve concentrations > 600 nmol/l, its use is recommended only after previously documenting an adequate serum cortisol concentration three hours after receiving a test dose.

     

Corticosteroids in the treatment of the acute phase of Kawasaki disease.

OBJECTIVES: Corticosteroids are considered to be contraindicated during the acute phase of Kawasaki disease (KD) based on unfavorable results in early studies. In our hospital, however, corticosteroids have been used in some cases of KD with satisfactory results. We analyzed outcomes of patients with KD treated with or without corticosteroids. STUDY DESIGN: Medical records of 299 children with KD treated with one of the 4 regimens were reviewed retrospectively. Regimen 1 consisted of aspirin, dipyridamole, and propranolol; regimen 2 was regimen 1 plus prednisolone, 2 mg/kg/d, for 1 week, followed by tapering over 2 weeks; regimen 3 was regimen 1 plus intravenous gamma-globulin (IVGG), 200 or 400 mg/kg/d, for 5 consecutive days; and regimen 4 was regimen 1 plus both prednisolone and IVGG. RESULTS: Although patients treated with regimens 2 and 4 were more ill at presentation than those treated with regimens 1 and 3, respectively, the duration of fever was shorter in the former patient groups (P =.0013). Coronary aneurysms developed least frequently in patients treated with regimen 4 and less frequently with regimen 2 than with regimen 1 (P =.0730). Multiple regression analysis showed significant reductions of fever and coronary aneurysm incidence with prednisolone (P <.0001 and P =.0307, respectively). CONCLUSION: Our data suggest a possible role of corticosteroids in the treatment of the acute phase of KD.     

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.     

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 μg) 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.     

Primary adrenal insufficiency in a child after busulfan and cyclophosphamide-based conditioning for hematopoietic stem cell transplantation

High rates of skeletal complications, growth disturbances, thyroid and gonadal dysfunction have been described in children undergoing stem cell transplantation. Although secondary adrenal insufficiency has been diagnosed, no primary adrenal insufficiency has been reported after busulfan and cyclophosphamide (Bu/Cy)-based conditioning regimens for stem cell transplantation in children. A 9-year-old girl with myelodysplastic syndrome was treated with stem cell transplantation of allogeneic origin. She received myeloablative conditioning chemotherapy, Bu and Cy. Her serum cortisol level was normal before stem cell transplantation. Then, 17 months after stem cell transplantation, chronic graft-versus-host disease developed and was treated with methyl prednisolone for 3 months. The control endocrinological investigation revealed low serum cortisol and high serum adrenocorticotropin (ACTH) levels 6 months after completion of methyl prednisolone treatment. The ACTH stimulation test demonstrated primary adrenal insufficiency, and the other etiologies of primary adrenal insufficiency were excluded. The patient received oral prednisolone replacement therapy. She was followed-up for 44 months and required increases in steroid doses during stress periods. Primary adrenal insufficiency which was observed in our patient after Bu/Cy-based conditioning regimen for stem cell transplantation has not been reported in children and adrenal function should be closely monitored in these patients both before stem cell transplantation and after stem cell transplantation.     

Rectal hydrocortisone during stress in patients with adrenal insufficiency

OBJECTIVE: Patients with glucocorticoid deficiency need lifelong glucocorticoid replacement treatment. During acute stressful events, steroid dosage must be increased several times, which is often problematical in children. This study investigated the reliability of rectal hydrocortisone administration as an alternative to the intramuscular route. STUDY DESIGN: Serum cortisol was assessed during stress in normal children to determine the concentration that should be achieved after rectal hydrocortisone. Subsequently, serum cortisol concentrations were measured three hours after administering a suppository containing hydrocortisone 100 mg/m2 to 57 patients with adrenocortical insufficiency. In eight patients, the time dependency of the cortisol rise after rectal administration was established. RESULTS: In 51 previously healthy children admitted to hospital with an acute stressful condition, the mean serum cortisol concentration was 1092 nmol/l. Rectal hydrocortisone in patients with adrenocortical insufficiency resulted in a mean serum cortisol concentration of 1212 nmol/l three hours after insertion of the suppository containing hydrocortisone. In 14 of 57 children, serum cortisol was < 1000 nmol/l and in eight children it was below 600 nmol/l. One hour after administration, the mean cortisol concentration had reached 1000 nmol/l. This was sustained for more than four hours. CONCLUSION: Rectal hydrocortisone is a safe alternative to parenteral administration in the self management of Addisonian prone conditions. However, because eight of 57 children did not achieve concentrations > 600 nmol/l, its use is recommended only after previously documenting an adequate serum cortisol concentration three hours after receiving a test dose.     

Adrenal Cortical Function in Children on Steroids

Adrenal cortical function was assessed in 20 children receiving 2·5 to 10 mg. prednisolone daily, by measuring plasma cortisol levels before and after the administration of the synthetic polypeptide β^1-24, tetracosactrin (Synacthen). 18 of the children were asthmatics, one had nephrosis, and one had dermatomyositis.Adrenal function was classified as (a) abnormal response to tetracosactrin, where basal plasma cortisol and post-tetracosactrin levels did not exceed 6 μg./100 ml.; (b) partial response, where there was a rise of 5-10 μg./100 ml. in plasma cortisol following tetracosactrin but the basal levels (< 10 μg./100 ml.) were below or only slightly above the lower normal limit; (c) normal response, where there was usually at least a doubling of the basal value and an incremental increase of at least 10 μg./100 ml. in the plasma cortisol concentrations following tetracosactrin.All 6 children receiving the higher dosage of 10 mg. prednisolone daily had abnormal adrenal function. 4 receiving the lower dosage of 2·5 mg./day had satisfactory adrenal reserve. Of the 10 children receiving the intermediate dosage of 5 mg. prednisolone daily, 2 had frankly abnormal adrenocortical function, 3 had poor adrenal reserve, and 5 produced good incremental values, though their baseline cortisol levels were low. At the 5 mg. prednisolone dose adrenocortical suppression was not correlated either with duration of therapy or with age.     

Cushing's syndrome in childhood and adolescence

Objective: To review the diagnosis, management and outcome of Cushing's syndrome in children and adolescents.
Methods: We conducted a retrospective review of nine cases treated between 1976 and 1996 at the Royal Children's Hospital, Melbourne, Australia.
Results: Six children with Cushing's disease and three with primary adrenal disease were identified. Mean age at diagnosis in the Cushing's disease patients was 11.3 years and in the children with primary adrenal disease 9.5 years. The most common presenting symptoms were weight gain and delayed growth. Two children had the unusual presenting symptoms of an eating disorder and hemihypertrophy, respectively. Laboratory diagnosis of Cushing's syndrome was established by demonstration of elevated urine free cortisol, loss of normal diurnal variation of serum cortisol, and loss of suppressibility of cortisol secretion by low dose dexamethasone. Investigations used to determine the aetiology of hypercortisolism included serum adrenocorticotropic hormone (ACTH) levels, high dose dexamethasone suppression tests, imaging studies, and inferior petrosal sinus sampling. Four patients with Cushing's disease had successful transphenoidal adenomectomies. Two patients with bilateral primary pigmented nodular adrenocortical dysplasia underwent bilateral adrenalectomies. One child with an adrenal adenoma was treated by left adrenalectomy.
Conclusions: Cushing's syndrome in children and adolescents remains a diagnostic challenge. Successful treatment often requires the use of multiple tests to achieve the correct diagnosis, appropriate surgery and a good long-term outcome.     

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.     

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.     

Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate.

AIMS: To assess adrenal function in asthmatic children treated with inhaled fluticasone propionate for up to 16 weeks. METHODS: Children with asthma and bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled fluticasone 250-750 microg/day via Volumatic spacer. The insulin tolerance test (ITT) was performed to assess adrenal function. RESULTS: Eighteen asthmatic patients (10 boys, 8 girls), aged 7-17 years received inhaled fluticasone therapy at a median dose of 477 microg/m2 per day for 5-16 weeks. Adrenal suppression, defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18 children. Following the ITT, the median basal and 60 minute serum cortisol concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively; the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l. Repeat ITT in the suppressed group 2-3 months after discontinuation of fluticasone revealed that all patients had a 60 minute serum cortisol greater than 500 nmol/l. CONCLUSION: After therapy for asthma with inhaled fluticasone at approximately 500 microg daily for up to 16 weeks, half the children had evidence of adrenal suppression.     

Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate

Aims: To assess adrenal function in asthmatic children treated with inhaled fluticasone propionate for up to 16 weeks. Methods: Children with asthma and bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled fluticasone 250–750 µg/day via Volumatic spacer. The insulin tolerance test (ITT) was performed to assess adrenal function. Results: Eighteen asthmatic patients (10 boys, 8 girls), aged 7–17 years received inhaled fluticasone therapy at a median dose of 477 µg/m² per day for 5–16 weeks. Adrenal suppression, defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18 children. Following the ITT, the median basal and 60 minute serum cortisol concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively; the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l. Repeat ITT in the suppressed group 2–3 months after discontinuation of fluticasone revealed that all patients had a 60 minute serum cortisol greater than 500 nmol/l. Conclusion: After therapy for asthma with inhaled fluticasone at approximately 500 µg daily for up to 16 weeks, half the children had evidence of adrenal suppression.     

Long-term Treatment with Corticosteroids/ACTH in Asthmatic Children

Hypothalamic-pituitary-adrenal (HPA) function was studied in 23 children with severe bronchial asthma during and after long-term treatment with prednisolone and/or ACTH_1-24 (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 ±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.     

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.     

Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease

Objectives: Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are <5 years old. Intravenous immunoglobulin (IVIG) is the standard therapy for KD. However, many patients with KD still show poor response to initial IVIG treatment. This study was conducted to investigate the risk factors for initial IVIG treatment failure in KD. Methods: Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients were divided into IVIG‐responsive and IVIG‐resistant groups. Initial laboratory data before IVIG treatment were collected for analysis. Results: A total of 131 patients were enrolled during the study period. At 48 h after completion of initial IVIG treatment, 20 patients (15.3%) had an elevated body temperature. Univariate analysis showed that patients who had initial findings of high neutrophil count, abnormal liver function, low serum albumin level (≤2.9 g/dL) and pericardial effusion were at risk for IVIG treatment failure. Multivariate analysis with a logistic regression procedure showed that serum albumin level was considered the independent predicting factor of IVIG resistance in patients with KD (p = 0.006, OR = 40, 95% CI: 52.8–562). There was no significant correlation between age, gender, fever duration before IVIG treatment, haemoglobin level, total leucocyte and platelet counts, C‐reactive protein level, or sterile pyuria and initial IVIG treatment failure. The specificity and sensitivity for prediction of IVIG treatment failure in this study were 96% and 34%, respectively. Conclusion: Pre‐IVIG treatment serum albumin levels are a useful predictor of IVIG resistance in patients with KD.     

A case of incomplete Kawasaki disease with extremely high serum ferritin and interleukin-18 levels

Background

The clinical features and laboratory parameters of patients with Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (sJIA) occasionally overlap. Therefore, serum levels of cytokine and ferritin are used as markers to distinguish between KD and sJIA. KD patients have a high level of interleukin (IL)-6, low level of IL-18, and no elevation of the level of serum ferritin. Conversely, sJIA patients have a low level of IL-6 and high levels of IL-18 and ferritin in the serum. However, to the best of our knowledge, no case report of KD with a low serum level of IL-6 and extremely high levels of IL-18 and ferritin is found.

Case presentation

A 6-year-old boy presented with a history of fever for 9?days and a rash that appeared 7?days from the onset. He was diagnosed with incomplete KD because of fever, skin rash, oral cavity erythematous changes, and erythema and edema of the hands with laboratory findings of serum albumin level?<?3.0?g/dL, elevated alanine aminotransferase level and leukocyturia. Intravenous immunoglobulin and prednisolone and oral aspirin were introduced on the 10th day. Fever subsided 1?day after initiating the treatment, but arthritis of both knees appeared in addition to hepatosplenomegaly. We suspected sJIA, as the serum level of ferritin was 19,740?ng/mL, IL-6 was <?3?pg/mL, and IL-18 was 132,000?pg/mL. Skin desquamation of the fingertips was observed 18?days from the onset; thus, he was finally diagnosed with incomplete KD with arthritis. At 32?days from the onset, we stopped the prednisolone therapy and no symptoms of relapse were observed afterwards. In the follow-up at 16?months from the onset, he had neither signs of active joint or skin involvement, nor cardiac involvement.

Conclusions

Although patients with sJIA generally have high serum levels of IL-18 and ferritin, this was a case of incomplete KD with extremely high serum levels of IL-18 and ferritin. Serum cytokine and ferritin are often used for the differential diagnosis of KD and sJIA. We need to recognize the existence of KD with high serum levels of IL-18 and ferritin.

     

Comparison of low‐dose and high‐dose cosyntropin stimulation testing in children

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

Monitoring growth in asthmatic children treated with high dose inhaled glucocorticoids does not predict adrenal suppression.

AIMS: To determine whether routine outpatient monitoring of growth predicts adrenal suppression in prepubertal children treated with high dose inhaled glucocorticoid. METHODS: Observational study of 35 prepubertal children (aged 4-10 years) treated with at least 1000 microg/day of inhaled budesonide or equivalent potency glucocorticoid for at least six months. Main outcome measures were: changes in HtSDS over 6 and 12 month periods preceding adrenal function testing, and increment and peak cortisol after stimulation by low dose tetracosactrin test. Adrenal suppression was defined as a peak cortisol < or =500 nmol/l. RESULTS: The areas under the receiver operator characteristic curves for a decrease in HtSDS as a predictor of adrenal insufficiency 6 and 12 months prior to adrenal testing were 0.50 (SE 0.10) and 0.59 (SE 0.10). Prediction values of an HtSDS change of -0.5 for adrenal insufficiency at 12 months prior to testing were: sensitivity 13%, specificity 95%, and positive likelihood ratio of 2.4. Peak cortisol reached correlated poorly with change in HtSDS (rho = 0.23, p = 0.19 at 6 months; rho = 0.33, p = 0.06 at 12 months). CONCLUSIONS: Monitoring growth does not enable prediction of which children treated with high dose inhaled glucocorticoids are at risk of potentially serious adrenal suppression. Both growth and adrenal function should be monitored in patients on high dose inhaled glucocorticoids. Further research is required to determine the optimal frequency of monitoring adrenal function.     

Thiamphenicol in treatment of Haemophilus influenzae meningitis.

17 infants and children with pyogenic meningitis (14 Haemophilus influenzae, 2 Diplococcus pneumoniae, 1 Neisseria meningitidis) were treated with thiamphenicol, 100 mg/kg body weight/day in 4 doses i.v., as single drug. In the H. influenzae group 10 patients were cured, 4 had relapses of meningitis, 3 with documented subdural effusions. This group is compared with 14 children matched for age, initial leucocyte and CSF cell count treated with ampicillin: all of these were cured, 1 had a subdural effusion. Thiamphenicol concentrations were determined in the serum and CSF 2 h after administration. The mean serum levels were between 10-12 mcg/ml, the mean CSF levels varied from 5.4 mcg/ml at the beginning to 1-1.9 mcg/ml at the end of meningitis. The MIC of H. influenzae was 0.6-12 mcg/ml. A significant, acute, and dose related bone marrow toxicity of thiamphenicol could be documented, but was always rapidly fully reversible. We conclude that thiamphenicol cannot replace chloramphenicol in the treatment of pyogenic meningitis as single systemic antibiotic. Special indications for thiamphenicol in this disease are discussed.