Failure of cortisone acetate therapy in 21-hydroxylase deficiency in early infancy.

BACKGROUND: Pediatric endocrinologists initially treat congenital adrenal hyperplasia with either cortisone acetate (CA) or hydrocortisone (HC). Despite high doses of CA, we noted that 17-hydroxyprogesterone (17-OHP) and corticotropin were not fully suppressed in serum from neonates with 21-hydroxylase deficiency (21-OHD) until they were 40- to 80-days-old. In contrast, serum concentrations of 17-OHP were suppressed immediately by oral treatment with HC. METHODS: We sought to understand the reason for this discrepancy. Serum cortisol (F), cortisone (E), and 17-OHP were measured by radioimmunoassay or high-performance liquid chromatography in seven neonates with 21-OHD and in 118 normal subjects. From the time of diagnosis, CA was administered to four of the neonates with 21-OHD, while HC was given to the other three. RESULTS: In normal subjects serum E concentrations were greater than F during the first 2 months after birth, whereas F concentrations exceeded E after 2 months of age. Although infants receiving CA initially were given a high dose, serum F concentrations were extremely low, while 17-OHP concentrations were high until about 2 months of age. Then serum F exceeded E, and 17-OHP became fully suppressed even though infants received only a moderate dose of CA. In contrast, HC administration successfully normalized serum 17-OHP in the neonatal period. With temporary switching of neonates from HC to CA, serum F concentrations immediately decreased and 17-OHP concentrations increased. CONCLUSION: Conversion of E to F may be limited during early infancy, adversely affecting treatment with CA. Cortisone acetate may be inappropriate as a glucocorticoid replacement during early infancy in patients with 21-OHD.

Significance of the eosinophil cationic protein/eosinophil count ratio in asthmatic patients: its relationship to disease severity.

BACKGROUND: Serum levels of eosinophil cationic protein (ECP) may reflect the degree of bronchial inflammation in patients with asthma, but its clinical value as a parameter for monitoring asthma remains controversial. OBJECTIVE: We measured the ratios of the serum ECP concentrations to peripheral blood eosinophil counts (ECP/Eo ratio) in patients with asthma and evaluated the correlation between these ratios and individual asthma severity. METHODS: The serum ECP concentrations and peripheral blood eosinophil counts were measured by radioimmunoassay and an autoanalyzer, respectively. Each patient with asthma was in remission at the time the serum specimen was obtained. An overall evaluation of asthma severity for each patient was determined by the frequency and severity of asthma attacks and by clinical scores. RESULTS: The ECP/Eo ratio in patients with severe asthma was significantly higher than in those with mild asthma. However, serum ECP concentrations and peripheral blood eosinophil counts were not different among the patients with mild, moderate, or severe asthma. The ECP/Eo ratios correlated significantly with the monthly average of the clinical scores, but the serum ECP concentrations did not correlate with the monthly average of the clinical scores. The ECP/Eo ratios were also increased in patients with more severe asthma whose serum IgE concentrations and peripheral eosinophil counts were not elevated. CONCLUSIONS: The ECP/Eo ratio may be useful in assessing asthma severity; however, the serum ECP concentration or peripheral blood eosinophil count is not useful.

Morning and afternoon serum levels of cortisone and cortisol in asthmatic patients.

While the diurnal change of serum cortisol in asthmatics has been suggested to influence the occurrence of attacks, this relation remains controversial. Serum concentrations of cortisol, cortisone, and cortisol precursors were measured in the morning and in the afternoon in asthmatic patients by reversed-phase high-performance liquid chromatography. Cortisol and cortisone were detected but their precursors were not. In remission or during attacks, the serum cortisone level in the morning was significantly lower than that in the afternoon, and the serum cortisol level in the morning did not significantly exceed that in the afternoon, which differs from the normal diurnal patterns. In patients with severe asthma in remission, the diurnal pattern of serum cortisone and cortisol was opposite to that seen in normal controls. During the attack, the serum cortisol level showed a lesser increase in the afternoon than in the morning. In patients with persistent asthmatic attacks, the serum cortisone level in the afternoon showed a significant increase as compared with that in remission while their serum cortisol level in the afternoon was equal to that in remission. The diurnal pattern and the duration of asthmatic attacks might be taken into consideration for steroid treatment of asthma.

Plasma concentrations of disodium cromoglycate after various inhalation methods in healthy subjects.

AIMS: To compare the plasma concentrations of disodium cromoglycate (DSCG) following various inhalation procedures in healthy volunteers. METHODS: Nine healthy subjects inhaled 2 mg of aerosol, 20 mg of nebuliser solution only, 20 mg of nebuliser solution mixed with isotonic saline, or 20 mg of nebuliser solution mixed with saline and procaterol, a beta2-adenoceptor agonist, on separate occasions 2-3 weeks apart. Plasma concentrations of DSCG were determined by high-performance liquid chromatography (h.p.l.c.). RESULTS: The peak plasma concentrations of DSCG were 1.5+/-0.7 (range 0.4-2.4) ng ml-1 in the aerosol group, 8.8+/-6.2 (range 5.3-19.9) ng ml-1 in the nebuliser solution only group, 17.2+/-16.3 (range 5.0-38.6) ng ml-1 in the nebuliser solution plus isotonic saline group, and 24.5+/-11. 9 (range 10.2-44.9) ng ml-1 in the nebuliser solution plus saline and procaterol group. Thus subjects who used the nebuliser had markedly higher plasma concentrations of DSCG than subjects who used the aerosol inhaler. CONCLUSIONS: These findings may have important implications for the evaluation of inhalation treatment with DSCG for bronchial asthma.

Disodium cromoglycate use in children and adolescents with asthma: correlation between plasma concentrations and protective effects for various inhalation methods.

BACKGROUND: Few studies have addressed the association between the plasma concentration of disodium cromoglycate and its protective effects on patients with bronchial asthma. OBJECTIVE: We measured plasma concentrations of disodium cromoglycate for various asthmatic treatments in children and adolescents and estimated plasma concentrations and protective effects. METHOD: Disodium cromoglycate as a 2-mg aerosol (n = 12), 4-mg aerosol (n = 5), or 20-mg nebulizer solution (n = 13) was inhaled by patients in remission. RESULTS: The plasma concentrations of disodium cromoglycate after 5 minutes of inhalation were 3.04 +/- 2.72 ng/mL in the 2-mg aerosol group, 2.95 +/- 0.86 ng/mL in the 4-mg aerosol group, and 7.72 +/- 4.65 ng/mL in the nebulizer solution group. Subjects who used the nebulizer exhibited markedly higher plasma concentrations of disodium cromoglycate. There was a significant correlation between the concentration of disodium cromoglycate at 5 minutes and the protective effect determined by a ratio of the difference in the asthma score between baseline and treatment periods to the baseline asthma score. CONCLUSION: When the plasma concentration of disodium cromoglycate is low, administration of larger aerosol dose or nebulization might be necessary.

Serum concentrations of cortisone and cortisol in premature infants.

To determine the relationship between biological active cortisol and its inert metabolite cortisone accurately in premature infants, serum cortisone and cortisol concentrations were measured by reversed-phase high-performance liquid chromatography (HPLC) in a group of 232 premature infants and in a control group of 127 children and 88 adults. In the control group, serum cortisone concentrations were greater than serum cortisol levels during the first 2 months after birth; cortisol levels were higher than cortisone levels after 2 months of age. However, in premature infants, serum cortisone concentrations were greater than serum cortisol levels even after the first 2 months, and total concentrations of cortisone and cortisol were equal to those in controls. Results were then analyzed according to the equivalent gestational age of premature infants. Cortisone was predominant in premature infants older than 32 weeks of equivalent gestational age, but cortisol was higher than cortisone from equivalent gestational age 24 to 31 weeks. These findings suggest that the ability of premature infants to secrete glucocorticoids resembled that of normal controls. Also, the fetal zone of the cortex, which is associated with a predominance of cortisone, remained functional in premature infants for a longer time than in control infants. Our findings that in premature infants cortisone was predominant compared with cortisol and the sum of cortisone and cortisol was equal to that in the controls indicate that cortisone cannot be disregarded whenever the cortisol level is estimated, although cortisone itself is recognized to be biologically inactive. Simultaneous measurement of serum cortisone and cortisol concentrations is important when adrenocortical function is being determined, especially in premature infants.

Adrenocortical function in asthmatic children: low levels of adrenocortical hormones in children with persistent attacks.

UNLABELLED: The existence of adrenal dysfunction in asthmatic patients remains controversial. Assessing adrenal function in these patients is difficult because of varying severity and duration of attacks and large fluctuations in the secretion of adrenocortical hormones. Total and free (unbound) levels of serum cortisol and cortisone were measured in asthmatic children and healthy controls using reversed-phase high performance liquid chromatography. The results were correlated with the severity and duration of asthma attacks. In asthmatic patients in remission, total and free concentrations of cortisol and cortisone did not differ significantly from those in healthy controls. During attacks, levels increased in proportion to the severity of the attack. These values decreased to control levels after 24 h. However, in children with attacks lasting for more than 5 days, values remained significantly decreased with no relation to the severity of the attack. CONCLUSION: During an asthma attack, adrenocortical hormone concentrations increase in proportion to the severity of the attack but subsequently decrease with time. It is speculated that the inability to sustain an elevated cortisol level may lead to the persistent asthma attacks.

Circadian rhythms in plasma cortisone and cortisol and the cortisone/cortisol ratio.

We evaluated the circadian rhythms in the plasma concentrations of cortisol, cortisone and their free forms, and in the cortisone/cortisol ratios by means of reversed-phase high performance liquid chromatography in normal adult subjects. Plasma concentrations of cortisone, as well as cortisol, exhibited a circadian rhythm. The ratios of cortisone/cortisol remained almost constant during the waking hours of normal subjects. Changes in the cortisone/cortisol ratios previously reported in patients with various diseases exceeded the diurnal changes detected in the present study. Thus, the determination of the cortisone/cortisol ratio provides information that is useful in assessing the adrenal function of patients with various diseases.

Clinical significance of cortisone and cortisone/cortisol ratio in evaluating children with adrenal diseases.

Cortisone is derived from the peripheral metabolism of cortisol and lacks biological activity. The rapid interconversion between cortisol and cortisone has been well established. The altered equilibrium between these steroids may regulate glucocorticoid activity in various tissues. We evaluated the serum levels of cortisol and cortisone, and the cortisone/cortisol ratio in ten children with adrenal diseases using reversed-phase high performance liquid chromatography. Children with hypoadrenalism exhibited a greater decrease in cortisol as compared with cortisone. Cortisone levels were higher than cortisol levels, and the cortisone/ cortisol ratio exceeded 1.0. Children with adrenal cancer exhibited normal or high values of cortisol, whereas cortisone levels were decreased and the cortisone/cortisol ratio was decreased to nearly zero. The ratio returned to normal after the excision of adrenal tumors. The simultaneous evaluation of cortisol, cortisone, and cortisone/cortisol ratio provides a clinical clue of adrenal diseases.