The hypothalamic-pituitary-adrenal axis in preterm infants weighing ≤ 1250 g: association with perinatal data and chronic lung disease

The hypothalamic-pituitary-adrenal axis (HPA) was examined in 34 ventilated preterm infants weighing ≤ 1250 g during the first week of life to evaluate the association between adrenal suppression and subsequent chronic lung disease. The second aim of the study was to detect perinatal and clinical differences between the infants with and without persistent suppression of the HPA after completion of dexamethasone treatment for chronic lung disease. To evaluate the HPA, the corticotropin-releasing hormone stimulation test was performed, and the cortisol and adrenocorticotropic hormone (ACTH) levels were measured by radioimmunoassay. No association could be found between the synthesis of cortisol and ACTH at the end of the first week of life and the development of chronic lung disease. After treatment with dexamethasone, baseline cortisol levels < 138 nmol l^-1 were found in 12 infants (46.2%), 8 of whom (30.8%) had cortisol values below 83 nmol l^-1. The perinatal data of these patients did not differ from infants without HPA suppression. However, the infants with cortisol levels < 83 nmol l^-1 after dexamethasone showed a significantly shorter need for mechanical ventilation and supplemental oxygen ( p < 0:01) and a lower incidence of chronic lung disease ( p < 0:05).     

Suppression of adrenal function in children on inhaled steroids

Inhaled steroid therapy is one of the mainstays of treatment of asthma in children. Side effects, including suppression of the hypothalamic-pituitary-adrenal (HPA) axis, have been noted with high doses of inhaled steroids. Most studies concerning side effects have been done with mechanical nebulization devices or hand-held metered-dose inhalers. The present study attempts to ascertain if dry powder inhalation of beclomethasone dipropionate is associated with any significant suppression of the HPA axis. Fifteen children (10 male and 5 female) between the ages of 4 and 14 years were followed for several years in our outpatient department. They were on inhaled beclomethasone dipropionate at dosages ranging from 6.9 to 25 micrograms/kg per day for 4-24 months. The short adrenocorticotrophic hormone (ACTH) test was used to evaluate function of the HPA axis. Mild suppression of the HPA axis was noted in one of the cases. The study therefore concludes that at therapeutic doses of dry powder beclomethasone dipropionate, suppression of the HPA axis can occur. However, the extent of this complication does not appear to be greater than with hand-held or mechanical nebulization devices.     

Adrenocorticotropin hypersecretion and pituitary microadenoma following bilateral adrenalectomy in a patient with classic 21-hydroxylase deficiency

Bilateral adrenalectomy is an acceptable alternative treatment in salt-wasting 21-hydroxylase deficiency when conventional steroid replacement therapy fails to control hyperandrogenism. Objections to surgical adrenalectomy have been based on surgical risk, possible loss of protective adrenal function, and the risk of ACTH-induced activation of adrenal rest tissue. We report a young female with salt-wasting CAH, who underwent bilateral adrenalectomy and developed severe hyperpigmentation, progressively marked corticotropin hypersecretion to concentrations seen in Nelson's syndrome (5,000-7,000 pg/ml), a pituitary microadenoma 5 years postoperatively, and probable ectopic adrenal rest tissue. Corticotropin concentrations failed to respond to ovine corticotropin-releasing hormone (oCRH) (1 microg/kg given as an i.v. bolus), but did suppress following both hydrocortisone administration (100 mg given as an i.v. bolus) and a low dose (0.5 mg given orally every 6 h for 48 h) dexamethasone suppression test. Patients with CAH have hyperactivity of the hypothalamic-pituitary-adrenal axis and are at risk for pituitary tumor formation.     

A randomized, placebo-controlled trial of effects of dexamethasone on hypothalamic-pituitary-adrenal axis in preterm infants

As part of a blinded, randomized, placebo-controlled study of dexamethasone therapy in 27 preterm infants with bronchopulmonary dysplasia, we investigated the effect of 7 days of high-dose glucocorticoid therapy on the hypothalamic-pituitary-adrenal axis. Before therapy the median basal cortisol concentration in all infants was 8.2 micrograms/dl (226 nmol/L). After stimulation with 1-24 ACTH, the serum cortisol concentration rose in all infants to a median concentration of 23.5 micrograms/dl (649 nmol/L), resulting in a median rise of 13.4 micrograms/dl (37 nmol/L). Immediately after 7 days of glucocorticoid therapy basal and peak cortisol concentrations were significantly decreased in the dexamethasone group. The rise in serum cortisol following 1-24 ACTH, however, remained equivalent in both groups. Ten days after the end of therapy basal and peak cortisol concentrations in the dexamethasone group had returned to levels equivalent to those seen in the placebo group. Weight gain was markedly diminished while the infants were receiving dexamethasone. Weight gains were, however, equivalent 10 days after the end of treatment. These data indicate that 7 days of dexamethasone therapy has significant but short-term effects on cortisol secretion and possibly on weight gain.     

Prevalence of hypothalamic-pituitary-adrenal axis suppression in children treated for asthma with inhaled corticosteroid

OBJECTIVE:

To determine the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression in asthmatic children on inhaled corticosteroids (ICS).

METHODS:

Clinical and demographic variables were recorded on preconstructed, standardized forms. HPA axis suppression was measured by morning serum cortisol levels and confirmed by low-dose adrenocorticotropic hormone stimulation testing.

RESULTS:

In total, 214 children participated. Twenty children (9.3%, 95% CI 5.3% to 13.4%) had HPA axis suppression. Odds of HPA axis suppression increased with ICS dose (OR 1.005, 95% CI 1.003 to 1.009, P<0.001). All children with HPA axis suppression were on a medium or lower dose of ICS for their age (200 μg/day to 500 μg/day). HPA axis suppression was not predicted by drug type, dose duration, concomitant use of long-acting beta-agonist or nasal steroid, or clinical features.

CONCLUSION:

Laboratory evidence of HPA axis suppression exists in children taking ICS for asthma. Children should be regularly screened for the presence of HPA axis suppression when treated with high-dose ICS (>500 μg/day). Consideration should be given to screening children on medium-dose ICS.     

Changes in serum leptin concentration after corticosteroid treatment in preterm infants

The aim of this study was to investigate the effect of postnatal systemic dexamethasone on serum leptin, insulin and hormones of the hypothalamic-pituitary-adrenal (HPA) axis in preterm, very low birthweight (VLBW) infants. Nineteen VLBW infants who received a 3 wk dose tapering course of dexamethasone for treatment of bronchopulmonary dysplasia were prospectively enrolled. Blood for hormone assays was collected immediately before the start of the dexamethasone course (T(d-per)), 3 wk after commencement of the drug (T(d-end)) and 2 wk after dexamethasone treatment had been stopped (T(d-post)). In addition, 28 VLBW infants who participated in a concurrent longitudinal leptin study within the same period but did not receive corticosteroid had their serum leptin and insulin concentrations serially monitored. Blood specimens for the latter group of infants were obtained at 2 (T(wk-2)), 5 (T(wk-5)) and 7 (T(wk-7)) wk of postnatal age. Serum leptin and insulin at T(d-end) were significantly increased, whereas plasma ACTH and serum cortisol were significantly suppressed compared with the pretreatment (T(d-pre)) levels in the corticosteroid group (p < 0.0001 for leptin and insulin; p < 0.05 and p < 0.001 for ACTH and cortisol, respectively). In contrast, serum leptin and insulin at weeks 5 (T(wk-5)) and 7 (T(wk-7)) did not differ significantly from their respective levels at week 2 (T(wk-2)) in the non-treatment group. CONCLUSION: The administration of systemic corticosteroid resulted in significant increases in serum leptin and insulin, but marked suppression of hormones of the HPA axis. The effect of dexamethasone on the "adipoinsular" and HPA axes was transient and reversible. The adipoinsular axis in preterm infants is likely to be functional and active at an early stage of human development, and leptin may regulate energy balance in VLBW infants in the early postnatal period. Corticosteroids may, through the adipoinsular axis or its associated pathways, mediate in the regulation of body weight in preterm neonates.     

The hypothalamic-pituitary-adrenal and the hypothalamic- pituitary-gonadal axes interplay

Vertebrates respond to stress with activation of the hypothalamic-pituitary-adrenal (HPA) axis, the adrenergic and the autonomic nervous systems. The principal central nervous system regulators of the HPA axis are corticotropin releasing hormone (CRH) and antidiuretic hormone (AVP). Apart from in the central nervous system, CRH has been found in the adrenal medulla, ovaries, myometrium, endometrium, placenta, testis and elsewhere. The activation of the HPA axis during stress affects all body systems. The reproductive axis is inhibited by the HPA axis for the sake of saving energy. The changes to the hypothalamic-pituitary-gonadal (HPG) axis during stress are species-specific, and depend on the type and duration of the stimulus. Several conditions may be associated with altered regulation of the HPA axis. Polycystic ovary syndrome, anorexia nervosa and pregnancy in the third trimester are all characterized by HPA axis activation. In contrast, during the postpartum period, HPA axis suppression is implicated in the "postpartum blues". The actions of CRH are also essential in fetal development and neonatal survival.     

Effects of chronic maternal dexamethasone treatment on the hormones of the hypothalamo-pituitary-adrenal axis in the rat fetus

Different hormones of the hypothalamo-pituitary-adrenal axis (corticotropin-releasing factor, adrenocorticotropic hormone, corticosterone) were measured in brain pieces (stalk, median eminence, hypothalamus), hypophyses, adrenals and plasma of 21-day-old rat fetuses from mothers which were given either plain tap water or water containing dexamethasone acetate (10 micrograms/ml) from day 15 to 21 of gestation. Dexamethasone induced drastic reduction of body weight (-66% vs. controls), severe atrophy of the adrenals (-83%) and a sharp drop in their corticosterone content (-74%). Fetal plasma corticosterone levels were below the lower limit of detection of the competitive corticosteroid-binding globulin (CBG) radioassay (less than 0.01 microgram/ml). Both atrophy and severe reduction of the adrenal activity in fetuses from dexamethasone-treated females were in good correlation with a drastic decrease in plasma adrenocorticotropic hormone (ACTH) levels which were below the lower limit of detection of the radioimmunoassay (RIA) used (less than 10 pg/ml) and a significant reduction in pituitary ACTH content (-93%). The low corticostimulating activity of the fetal hypophyses was associated with a drop in both corticotropin-releasing factor (CRF) hypothalamic content (-57%) and concentration (-67%). The effects of dexamethasone on plasma and pituitary ACTH concentrations in 21-day-old fetuses were compared to those, previously reported, of encephalectomy and decapitation performed on day 16 of gestation. The reported data were consistent with the present results, suggesting both pituitary and hypothalamic sites for the in vivo inhibiting action of dexamethasone on the rat hypothalamic-pituitary-adrenal axis in late gestation.     

Hypothalamic-pituitary-adrenal axis function in very low birth weight infants treated with dexamethasone

The effect of dexamethasone therapy on hypothalamic-pituitary-adrenal axis function was prospectively investigated in very low birth weight infants with bronchopulmonary dysplasia. Ten infants (mean +/- SD birth weight 825 +/- 265 g, gestation 25.8 +/- 1.9 weeks, postnatal age 33.1 +/- 17.7 days) initially received intravenous dexamethasone, 0.5 mg/kg per day for 3 days, and then were weaned over a period of 45 +/- 19.0 days to a replacement dose, followed by a metyrapone test. Morning plasma cortisol and 11-deoxycortisol levels were measured before and after an oral metyrapone dose given at midnight. Five infants (group A: birth weight 876 +/- 313 g, gestation 26.2 +/- 1.3 weeks, age of entry 31.8 +/- 22.8 days) had normal metyrapone test results, and five infants (group B: 778 +/- 234 g, 25.4 +/- 2.5 weeks, 34.4 +/- 13.4 days) had suppressed test results. Group A infants, in comparison with group B infants, had higher basal cortisol plasma levels (14.52 +/- 12.53 and 3.00 +/- 1.38 micrograms/dL, P = .047), higher postmetyrapone 11-deoxycortisol plasma levels (3.11 +/- 3.93 and 0.55 +/- 0.51 micrograms/dL, P = .028), larger differences between basal and postmetyrapone cortisol levels (7.10 +/- 4.67 and 2.12 +/- 1.31 micrograms/dL, P = .047), and larger differences between basal and postmetyrapone 11-deoxycortisol levels (2.99 +/- 3.93 and 0.29 +/- 0.25 micrograms/dL, P = .009). The hypothalamic-pituitary-adrenal axis function in group B infants eventually returned to normal when they continued to receive low-dose dexamethasone therapy after a period of 36.8 +/- 16.6 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Overt glucocorticoid excess due to inhaled corticosteroid therapy

Inhaled corticosteroids have become an important therapeutic option in the treatment of childhood asthma. The preparations currently available for pediatric use (beclomethasone dipropionate and triamcinolone acetonide) do not, in general, cause significant hypothalamic-pituitary-adrenal axis suppression and physical signs of glucocorticoid excess have not been described with their use. We report an 8-year-old girl with asthma in whom obesity, hirsutism, and growth retardation developed during treatment with inhaled triamcinolone acetonide alone. Laboratory studies showed suppression of endogenous cortisol production but did not demonstrate suppression of the hypothalamic-pituitary-adrenal axis. Cessation of inhaled triamcinolone acetonide therapy resulted in resolution of obesity and hirsutism, resumption of normal growth, and a return to normal of serum cortisol levels and urinary 17-hydroxycorticosteroid excretion. Careful monitoring of growth velocity and (if clinically indicated) morning serum cortisol levels in asthmatic children using inhaled corticosteroids will detect the rare instance of glucocorticoid excess resulting from systemic absorption of these drugs.     

Pituitary-adrenal responses to acute hypoxemia during and after maternal dexamethasone treatment in sheep

The effects of maternal dexamethasone treatment on hypothalamic-pituitary-adrenal axis function were determined during basal and hypoxemic conditions in maternal and fetal sheep. Under halothane, ewes and their fetuses were catheterized at 117 d gestation (term = 145 d). Starting at 124 d, the ewes received i.m. injections of two doses of either dexamethasone (12 mg) or saline at 24-h intervals. All animals experienced one episode of hypoxemia when the dexamethasone was present in the maternal and fetal circulations [125 +/- 1 d (H1)] and a second episode of hypoxemia when the steroid was no longer detectable in either the maternal or fetal circulations [128 +/- 1 d (H2)]. The fall in partial pressure of oxygen in arterial blood in response to hypoxia was similar in the two episodes in both the fetal and the maternal blood. Maternal dexamethasone treatment diminished maternal and fetal basal plasma cortisol but not ACTH during the normoxic period of H1 but not H2. In control animals, hypoxemia induced increases in fetal but not maternal ACTH and cortisol concentrations. In dexamethasone-treated animals, maternal ACTH and cortisol concentrations also remained unchanged from baseline in both H1 and H2. In contrast, fetal plasma ACTH and cortisol responses to hypoxemia were significantly suppressed during H1 but not H2. Correlation of fetal plasma ACTH and cortisol concentrations suggested diminished cortisol output without a change in adrenocortical responsiveness in dexamethasone-treated fetuses during H1 but not H2. Maternal treatment with dexamethasone transiently suppressed maternal and fetal basal hypothalamic-pituitary-adrenal axis function and the fetal plasma ACTH and cortisol responses to acute hypoxemia in sheep.     

Duration of adrenal insufficiency during treatment for childhood acute lymphoblastic leukemia

Children with acute lymphoblastic leukemia (ALL) recive high doses of glucocorticosteroid as part of their treatment. This may lead to suppression of the hypothalamic-pituitary-adrenal axis, acute adrenal insufficiency, and ultimately to life-threatening conditions. This study explores the adrenal function in 96 children with ALL treated according to common protocols. After cessation of induction glucocorticosteroid therapy, they received hydrocortisone substitution therapy (10 mg/m/24 h) until an adrenocorticotropic hormone test (250 μg tetracosatide) showed a sufficient adrenal response [plasma (p)-cortisol ≥500 nM]. At the first adrenocorticotropic hormone test, 67% of the patients had adrenal insufficiency. When including these patients in a multivariate model, not adjusting for risk factors, the mean elapsed time between end of induction therapy and adrenal sufficiency was 8.5 months (95% confidence interval: 6.3;10.7). Low 0-minute p-cortisol (P=0.02) and low rise in p-cortisol (P<0.0001) at first test caused a longer time of adrenal insufficiency. In addition, patients with B-cell precursor leukemia reached adrenal sufficiency later than those with T-cell leukemia (P=0.067). As adrenal insufficiency is frequent in children treated for ALL and as they often experience infections and other stressors, the adrenal response should be determined and hydrocortisone substitution therapy should be considered during such episodes in patients with adrenal insufficiency.     

Growth hormone and insulin-like growth factor-I therapy promote protein deposition and growth in dexamethasone-treated piglets

BACKGROUND: Dexamethasone treatment facilitates the weaning of premature infants from mechanical ventilation but impairs protein homeostasis, lean tissue deposition, and growth. The current study was conducted to investigate whether dexamethasone mediates these effects by reducing protein synthesis or elevating protein breakdown, and whether adjuvant growth hormone+/-insulin-like growth factor-I therapy can attenuate such effects. METHODS: Piglets (n = 24) were randomized to placebo, a tapered course of dexamethasone (0.5, 0.3, 0.2 mg/kg per day for 5, 5 and 4 days each, respectively), dexamethasone + growth hormone 0.1 mg/kg per day, or dexamethasone + growth hormone + insulin-like growth factor-I 0.1 mg/kg per day for 14 days. On day 13, 15N-glycine was administered as a single oral dose, and urine was collected at timed intervals during the subsequent 48 hours. RESULTS: Total urinary N and cumulative 15N excretion were higher in all dexamethasone groups than in control subjects. Protein synthesis was suppressed, whereas protein breakdown was unaltered by dexamethasone. Adjunctive growth hormone+/-insulin-like growth factor-I therapy enhanced protein synthesis, but only combined therapy improved net protein gain compared with dexamethasone alone. Higher circulating insulin-like growth factor-I may have mediated the greater net protein gain. Blood urea nitrogen was elevated in all dexamethasone-treated groups at days 6 and 11 but was normalized by day 15 with adjunctive growth hormone+/-insulin-like growth factor-I. From a functional perspective, both adjunctive growth hormone and growth hormone+/-insulin-like growth factor-I partially attenuated the dexamethasone-induced reduction in weight and length gain but not in whole body lean and fat mass. Conclusion: Adjunctive growth hormone+/-insulin-like growth factor-I therapy partially reverses the dexamethasone-induced reduction in protein synthesis, resulting in improved growth when given concurrently with a low tapering dose of dexamethasone.     

Effect of multiple courses of antenatal corticosteroids on pituitary-adrenal function in preterm infants

AIM: To evaluate the pituitary-adrenal function of preterm infants whose mothers received multiple courses (8 or more doses) of antenatal dexamethasone. METHODS: The pituitary-adrenal function of 14 preterm infants whose mothers received eight or more doses of antenatal dexamethasone were assessed using the human corticotrophin releasing hormone (hCRH) stimulation test when 7 days (n = 14) and 14 days old (n = 12). During each test, blood samples were taken at 0 (baseline), 15, 30 and 60 minutes after an intravenous bolus dose of hCRH (1 microg/kg). The corresponding hormone concentrations were compared between days 7 and 14, and with various associated factors. RESULTS: The baseline (0 min) plasma adrenocorticotrophic hormone concentration was significantly higher at day 14 than at day 7 (p = 0.036). None of the corresponding poststimulation (15, 30, and 60 min) hormone concentrations was significantly different between the two time epochs. When the association between the hormone concentrations and the number of antenatal dexamethasone doses received by the mothers was assessed, a significant negative correlation was observed in serum cortisol concentrations at 15 and 30 min on day 14 (r = -0.59, p = 0.04 and r = -0.60, p = 0.039, respectively). CONCLUSIONS: The absence of a significant difference in poststimulation hormone concentrations between days 7 and 14 in this cohort of infants, and the similarity of their hormone responses with those of older children and adults, suggests that no severe pituitary-adrenal suppression had occurred. None the less there was evidence of mild adrenal suppression in some of the treated infants. Vigilance in monitoring blood pressure, electrolytes and signs of adrenal suppression in infants whose mothers receive multiple courses (8 or more doses) of antenatal dexamethasone is required, as some of them might have diminished adrenal reserve.     

Adrenal function in premature infants during inhaled beclomethasone therapy.

OBJECTIVE: We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia does not cause adrenal suppression. STUDY DESIGN: Infants receiving ventilatory support with birth weights 相似文献   

Decreased growth during therapy with selective serotonin reuptake inhibitors

BACKGROUND: There is no information on the effects of selective serotonin reuptake inhibitors (SSRIs) on growth and puberty in children. We examined growth and growth hormone secretion in 4 children treated with SSRIs for various psychiatric disorders. DESIGN: Case study. PARTICIPANTS: Four children (3 boys) aged 11.6 to 13.7 years with obsessive-compulsive disorder or Tourette syndrome. MAIN OUTCOME MEASURES: Growth, pubertal progression, and hypothalamic pituitary function. METHODS: The patients were treated with SSRIs for 6 months to 5 years (dosage, 20-100 mg/d). All were regularly examined for changes in height and bone age and for pubertal progression. They also underwent evaluation of somatotrophic axis and hypothalamic-pituitary axis function. RESULTS: All 4 patients had growth attenuation. Three of them exhibited growth retardation at a pubertal stage when a growth spurt was anticipated. Three had a decreased growth hormone response to clonidine hydrochloride stimulation and 2 to both clonidine and glucagon stimulation, and 1 had decreased 24-hour secretion of growth hormone that normalized when therapy was stopped. The rest of the endocrine evaluations were within reference ranges in all patients. At follow-up, 2 patients were being treated with somatropin while continuing SSRI therapy, and the other 2 resumed normal growth after discontinuation of therapy. CONCLUSIONS: A decrease in growth rate, possibly secondary to suppression of growth hormone secretion, may occur during SSRI therapy. As the use of this group of drugs is expected to increase in the young age groups, larger studies are warranted to investigate their effect on growth and growth hormone secretion.     

Cushing's syndrome caused by Ewing's sarcoma secreting corticotropin releasing factor-like peptide.

Procedures were carried out in a 12-year-old girl to relate Ewing's sarcoma of the left tibia with Cushing's syndrome. Computed tomography revealed a normal pituitary and hypothalamus but bilateral adrenal hyperplasia without focal enlargement, thus readily excluding hypothalamic-pituitary-adrenal tumor. Negative results from a high-dose dexamethasone suppression test do not support pituitary-dependent Cushing's disease. Ewing's sarcoma was diagnosed on tibial biopsy. The regression of the physical and biochemical findings of Cushing's syndrome subsequent to amputation of the left lower leg strongly suggests ectopic Cushing's syndrome caused by Ewing's sarcoma. Immunohistochemical studies of the resected bone were negative for corticotropin but positive for corticotropin releasing factor-like peptide. We conclude that this is the first reported case of ectopic Cushing's syndrome in a child that is caused by Ewing's sarcoma secreting corticotropin releasing factor-like peptide.     

Evaluation of hypothalamic-pituitary-adrenal axis suppression by low-dose (0.5 microg) and standard-dose (250 microg) adrenocorticotropic hormone (ACTH) tests in asthmatic children treated with inhaled corticosteroid

The aim of this study was to compare the results of low-dose (LDT) and standard-dose (SDT) ACTH tests in the assessment of adrenal function in 30 asthmatic children (mean age 9.35 +/- 1.9 years, 19 boys) who were treated with budesonide Turbohaler at conventional 400 microg or 600 microg daily doses for 8 weeks by a prospective, randomized, and open parallel study. Budesonide did not lead to any significant suppression of the hypothalamic-pituitary-adrenal (HPA) axis in either treatment group. However, when individual patient values were examined at the end point, peak cortisol concentrations after LDT were below 2 SDs of the pretreatment values in four patients (13.3%). Also, the increment in cortisol values was <200 nmol/l in all four patients. Decreased 24-hour urinary free cortisol excretion provided further evidence for HPA axis suppression in these patients. Two of these four poor responders to LDT showed normal stimulation with SDT. In conclusion, even with moderate doses and short-term use, adrenal suppression may occur in certain susceptible patients. The low-dose ACTH test is more reliable than SDT for the evaluation of such patients.     

Partial glucocorticoid resistance in obese children detected by very low dose dexamethasone suppression test

The effects of glucocorticoids (GC) are mediated by the activation of specific receptors that can be quantified in vitro by several laboratory tests. In vivo, other tests to determine GC sensitivity have been described, but only employing pharmacological doses. In this study, we used a very low dose of dexamethasone, an in vivo model to assess individual GC sensitivity. Fifty-five obese children and adolescents and 17 controls were studied. The patients were submitted to four 12-h urine collections, starting at 22:00 h; dexamethasone was administered orally at the end of the second urine sample. Patients were divided in the following groups: group Ob75 (n = 29) and the control group (n = 17) received dexamethasone 75 microg/m2, and group Ob150 (n = 26) received dexamethasone 150 microg/m2. Urinary cortisol was determined by RIA and expressed as microg/m2/12 h. All patients and controls showed a circadian rhythm before GC, which was maintained after dexamethasone only in controls. In the obese patients the circadian rhythm was abolished following both doses of dexamethasone, but more prominently with the dose of 150 microg/m2. In the obese group given 75 microg/m2, urinary cortisol inhibition was only observed in the first 12 h after dexamethasone, suggesting a partial and shorter suppression of the hypothalamic-pituitary axis. In both control and obese patients, the very low dose of dexamethasone was able to create a gradient of cortisol suppression that could be useful to identify an individual's sensitivity to glucocorticoids.