Clinical characteristics and etiological analysis of premature pubarche:A report of 55 cases / 中国实用儿科杂志

OBJECTIVE: To analyse the clinical characteristics,aetiology distribution,and metabolic risk parameters of patients with with premature pubarche(PP). METHODS: A retrospective study was performed in 55 patients affected by PP,who received ACTH stimulation test,and the data were evaluated. Among them 17 cases were detected CYP21 A2 gene,and indicators of lipid metabolism of idiopathic premature adrenarche(IPA,15 cases)and idiopathic premature pubarche(IPP,14 cases)were analyzed. RESULTS: The sample included 55 patients with PP(53 female and 2 male),with a mean pubarche age of(7.2±0.9)years for girls and(7±0.8)years for boys. There was an accelerated bone age(BA/CA ratio>1)(1.20 ± 1.5)in girls. A total of 9 patients were classified as non-classic congenital adrenal hyperplasia(NCCAH,16.4%),15 as IPA(27.3%),14 as IPP(25.4%),16 as HPGA function launch(29.1%)and 1 with exaggerated adrenarche(EA,1.8%). There was no significant difference in the diagnostic rate of NCCAH between ACTH stimulation test and CYP21 A2 gene detection(P=0.596). The sex hormone binding protein(SHBP)of IPA was reduced(P=0.007). CONCLUSION: The etiology of premature pubarche-non-classic congenital adrenal hyperplasia(16.4%)is not uncommon. The ACTH stimulation test is useful for the diagnosis of NCCAH,but the sensitivity is not 100%.

Insuficiência adrenal aguda / Acute adrenal insufficiency

A insuficiência adrenal (IA) consiste em síndrome clínica rara, decorrente da deficiência de glicocorticoides e/ou mineralocorticoides, podendo ser primária. A insuficiência adrenal aguda consiste em emergência endócrina rara, resultante da diminuição súbita do cortisol circulante, ou de aumento significativo da demanda por esse hormônio em pacientes com algum grau de disfunção adrenal, ocorrendo mais frequentemente no contexto da IA primária. O prognóstico da doença depende do reconhecimento e intervenção terapêutica precoces

Adrenal insuficiency (AI) consists of a rare clinical syndrome resulting from glucocorticoids and/or mineralocorticoids deficiency. Adrenal insufficiency may be primary. The acute AI is a rare endocrine emergency resulting from sudden decrease of circulating cortisol or, elevated demand for this hormone in patients with some degree of adrenal disfunction, occuring more frequently in primary AI. The prognosis depends on early recognition and precocious therapeutic intervention

Adrenal insufficiency evaluation by using Iow-dose ACTH stimulation test in critical illness children / 中华急诊医学杂志

Objective To evaluate the validity of original plasma cortisol level and responses to lowdose ACTH stimulation test in assessing the severity of critical illness.Method Original level of cortisol and cortisol concentrations 30 min after administration of a low dose ( 1 μg/1.73m2 ) of cosyntropin were determined within 24 hours after admission to our PICU.Critical illness related cortisol insufficiency was defined by initial level of cortisol ＜ 10 μg/dL or an increment cortisol [ Δmax =Stimulated plasma cortisol level (T1) -initial cortisol level (T0)]≤ 9 μg/dL.Results Ninety-five consecutive patients were admitted to PICU from May 2010 to April 2011.The patients were assigned to severe sepsis group (35/95),major operation group (30/95),and other critical illness group (30/95).Overall mortality was 12.6％ (12/95).The initial and stimulated plasma cortisol levels in three groups were (37.17 ± 47.35 ) μg/dL,(31.52±52.78) μg/dL,(28.61 ±17.45) μg/dL,vs.(50.26±48.21) μg/dL,(58.56±73.21)μg/dL, (42.41 ± 13.56) μg/dL,respectively.There were no significantly differences between above groups ( P ＞ 0.05 ).The incidence of critical illness-related corticosteroid insufficiency (CIRCI) in this study was 55.8％.The incidences of CIRCI were 60％,53.3％,and 53.3％ in severe sepsis,other critical illness and major surgery illness,respectively ( P ＞ 0.05 ).The morbidity of CIRCI and normal response group were 7.5％ and 19％ (P ＞0.05).The levels of T0 and T1 were related to the PCIS (P ＜0.05). Conclusions CIRCI is often seen in children with critical illness. And a low-dose ACTH stimulation test can be used to evaluate the adrenal function in critical illness.However,there is no significant correlation between CIRCI and mortality of critically ill children in this study.

Recent approach of adrenal dysfunction in critical illness / 中国小儿急救医学

There is high incidence of relative adrenal insufficiency (RAI) in critical children. The causes of adrenal insufficiency in patients with severe sepsis and septic shock are the mechanical injury of the hypothalamic-pituitary-adrenal axis, cytokines and other mediators of inflammatory or hormone resistance. There are many symptoms associated with adrenal insufficiency. Diagnosis is often suspected when these patients have hypotension refractory to fluid therapy and to vasoactive drugs. The corticotropin stimulation test is widely used as a method to identify adrenocortical hyporesponsiveness, but controversy exists as to the corticotropin dose to be used. The 250 μg dose is the standard dose. Low doses of corticotropin (1 μg) have recenfly been proposed,suggesting that they may have higher sensitivity and the characteristics of safe and effective.

Mechanism of varied responsiveness to ACTH in patients with polycystic ovary syndrome / 中华内分泌代谢杂志

Objective To explore the potential mechanism of adrenal androgen excess in patients with polycystic ovary syndrome (PCOS), ACTH stimulation test was conducted and the polymorphisms in the promoter region of CYP21 A2 gene were screened to verify the variations related to the responsiveness to ACTH stimulation. Methods 30 healthy women and 101 PCOS patients, matched for age, were recruited from Ruijin hospital. Blood biochemical examinations were taken and sex hormone profiles obtained at baseline. 17 hydroxyprogesterone( 17OHP)was measured at 0 and 60 min in an ACTH stimulation test. The -710 bp -1 bp of the promoter region of CYP21A2 was sequenced in 87 PCOS patients and 30 control subjects. Results According to the post-stimulation 17 OHP levels obtained from 30 healthy women,PCOS patients were allocated into one group with high responsiveness to ACTH ( HR-PCOS, n = 21) and the other with normal responsiveness to ACTH ( NR-PCOS, n = 80). Compared with NR-PCOS subjects, HR-PCOS patients had higher testosterone( P<0.05), basal and post-stimulation 17OHP (both P<0.01)and dehydroepiandrosterone sulfate levels (P<0.05 or P<0.01) .whereas serum cortisol and androstenedione levels were not significantly different before and after ACTH stimulation test. The genotypes of locus -535 were well correlated with post-stimulation 17OHP levels (r = 0. 20,P = 0. 03) in PCOS patients and the control subjects. The genotype T/T or allele T was significantly more frequent in subjects with a higher fertile of post-stimulation 17OHP (P<0.05 or P<0. 01). The odds ratio(OR)for higher responsiveness to ACTH in women with allele T at -535 was 3. 69 (95% CI 1. 69-8. 06,P = 0. 000 7). Conclusions The PCOS patients with higher responsiveness to ACTH are characterized by severe hyperandrogenemia and adrenal androgenexcess,suggesting that adrenal androgen excess in some PCOS patients may be due to higher responsiveness to ACTH. The polymorphism of -535C>T in the promoter region of CYP21 A2 may play a role in regulating 21 hydroxylase gene expression and further influencing 17OHP responsiveness to ACTH.

Diagnostic Value of 1microgram Rapid ACTH Stimulation Test According to the Timing of Sampling of Serum Cortisol in Patients with Suspected Central Adrenal Insufficiency / 대한내분비학회지

BACKGROUND: Traditional testing of the hypothalamic-pituitary-adrenal axis function has essentially relied upon the insulin tolerance test or the metyrapone test(both tests are not only uncomfortable, but are also dangerous). The standard ACTH stimulation test uses an extremely supra-physiologic amount(250f microgram) of ACTH to evaluate a physiological response, which may result in a false normal response. The 1microgram rapid ACTH stimulation test is more physiological and more sensitive than the standard test, but there exist much controversy about when the serum cortisol should be measured or what the most appropriate cut-off point is for normality or whether the 1microgram ACTH commercial solution is needed. The aims of this study were to investigate 1) whether 1microgram of ACTH is an appropriate amount to stimulate the adrenal gland of patients that have suspected central adrenal insufficiency compared with insulin tolerance test(ITT) and 2) the diagnostic value of the 1microgram rapid ACTH stimulation test according to timing of sampling of serum cortisol. METHODS: In order to evaluate the dose-response relationship between ACTH and cortisol, we performed the ITT in 77 patients with suspected central adrenal insufficiency with serial measurements of serum cortisol and plasma ACTH. We drew the blood samples in 10 min intervals between 10 and 60 min after the administration of 1microgram ACTH in 39 patients with central adrenal insufficiency and in 38 pituitary control patients with pituitary. ITT was used to confirm the diseases for the patients of central adrenal insufficiency, but for pituitary control patients, the ITT indicated normality in the patients. Also, all subjects underwent the 250microgram rapid ACTH stimulation test, and we compared the diagnostic value of the 1microgram ACTH stimulation test with the 250microgram test. RESULTS: 1) The plasma ACTH level after the 1microgram ACTH stimulation test, even if it was be assumed as approximately 300pg/mL, was expected to be sufficient enough to stimulate the adrenal cortex normally(serum cortisol levels >18microgram/dL) compared to the plasma ACTH level in the ITT. 2) The sensitivity and specificity of the 1microgram rapid ACTH stimulation test was highest with 92.3% and 84.2%, respectively, when serum cortisol levels were measured at 20, 30, and 40 min after the ACTH injection. The 1microgram rapid ACTH stimulation test was more sensitive than the 250microgram ACTH test(sensitivity: 92.3%, specificity: 71.8%). CONCLUSION: The 1microgram rapid ACTH stimulation test was more sensitive test in patients with suspected central adrenal insufficiency, and blood samples for cortisol levels should be drawn at 20, 30, and 40 min after ACTH administration.

The Maternal and Fetal Adrenal Effect of 1 cycle Dexamethasone on women with Preterm Labor / 대한산부인과학회잡지

OBJECTIVE: The aim of this study was to determine whether 1 cycle of dexamethasone administration to women at risk of preterm delivery causes adrenal suppression METHODS: Nonpregnant ten control subjects were checked baseline cortisol and stimulated cortisol level after low-dose (1 microgram) ACTH stimulation test. Ten women at risk of preterm delivery had two weekly low-dose (1 microgram) ACTH stimulation tests with the first one at admission. Immediately after the first ACTH stimulation test, we gave each women a 5 mg dexamethasone dose intramuscularly and repeated it 12 hours later for two days. Serum cortisol levels were measured before (baseline) and 30 minutes after ACTH administration. RESULTS: All ten subjects had normal baseline and stimulated cortisol levels for the first ACTH stimulation test. The adrenal suppressed Group was composed of 5 patients. But the remainders was not suppressed. Mean baseline serum cortisol levels decreased from 38.52 microgram/dL (before dexamethasone) to 33.26 microgram/dL (1 week after 1 cycle of dexamethasone) in adrenal suppressed Group. The mean stimulated cortisol levels also decreased from 46.40 microgram/dL (before dexamethasone) to 45.02 microgram/dL (1 week after 1 cycle of dexamethasone) in adrenal suppressed Group. CONCLUSIONS: Antenatal administration of 1 cycle dexamethasone produced slightly adrenal suppression, but no adrenal insufficiency, in some women at risk of preterm delivery and may be harmless to maternal and fetal adrenal function.

Usefullness of Urinary Free Cortisol Measurement in Diagnosis of Iatrogenic Cushing Syndrome / 대한내분비학회지

BACKGROUND: Although insulin induced hypoglycemia test is a standard diagnostic method in assessment of hypothalamo-pituitary-adrenal axis, rapid ACTH stimulation test using 250microgram has been used as a first line diagnostic test especially in secondary adrenal insufficiency due to iatrogenic Cushing syndrome because it is easy and safe. However, it was suggested that a maximal cortisol response can be achieved with a much lower ACTH dose and 1microgram ACTH enhances the sensitivity without decreasing specificity of test. Also recently, there was a report that midnight to morning urine cortisol increment is more accurate, noninvasive method can be used for measurement of hypothalmo-pituitary-adrenal axis. In this study, we compared the 1microgram ACTH stimulation test with midnight to morning urinary free cortisol increment in secondary adrenal insufficiency due to iatrogenic Cushing syndrome to study the agreement of two test and accuracy of increment of urinary free cortisol in diagnosis of adrenal insufficiency. METHODS: Double voided urine sample were collected at midnight and 8 A.M. in 12 patients who have Cushing-like feature and history of taking glucocorticoids and in 12 normal controls. Urinary free cortisol was measured and cortisol increment was defined as the morning urine free cortisol minus the midnight urine free cortisol. The 1microgram ACTH stimulation test was performed in 12 iatrogenic Cushing syndrome patients at the same day and compard with the result of cortisol increment. RESULTS: Using the results of 12 controls, normal urine free cortisol increment was defined as greater than 165.5nmol/L(6.0microgram/dL). Subnormal cortisol response in 1microgram ACTH stimulation test was noted in 8 out of 12 patients group and urinary free cortisol increment was not observed in 7 out of 8 subnormal response group. Normal cortisol response in 1microgram ACTH stimulation test was noted in 4 out of 12 patients group and urinary free cortisol increment was observed in 3 out of 4 normal response group. So 83% of concordance rate between 1microgram ACTH stimulation test and urine free cortisol increment was recorded. CONCLUSION: Urinary free cortisol increment has high concordance rate with 1microgram ACTH stimulation test and simple, easy test in diagnosing secondary adrenal insufficiency due to iatrogenic Cushing syndrome. Further study including more patients will be helpful to know the adequacy and reliability of test in evaluation of hypothalamo-pituitary-adrenal axis.

The Effect of Low Dose and High Dose ACTH in the Evaluation of Adrenal Function / 대한내분비학회지

BACKGROUND: Pharmacological ACTH test provide information only about the ability of the adrenal gland to respond to unusual stimuli and may not reflect the daily cortisol secretion. There were some controversies in the diagnosis of mild adrenal insufficiency by using a pharmacological dose of ACTH. The purpose of the present study was to assess and compare the effect of low dose 1 pg ACTH and high dose 249 pg ACTH in the evaluation of adrenal function. The intravenous injection of a pharmacological dose(250 pg) of ACTH has been used as a standard test in the initial assessment of adrenal function. So we low dose ACTH to evaluate the adrenal function and compare the result of high dose ACTH. METHOD: Basal serum cortisol sampling was done at 2:00 p.m.. And after 1 pg ACTH iv bolus injection, cortisol sampling was done at 20, 30, 45 and 60 min respectively. On the next day same procedure was repeated at same time, but 249 mg ACTH was given instead of the low dose. Normal adrenal function was diagnosed with the criteria of stimulated serum cortisol concentration over 20 mg/dL. Total 65 patients took part in this study. Three hypopituitarism patients and one Addisons disease were included. Sixty-one patients had the history of glucocorticoid ingestion or had physical findings of cushingoid features with symptoms suggest the adrenal insufficiency. RESULTS: Sixteen patients showed normal response to both low dose and high dose ACTH. Thirty-six patients were not stimulated to both low dose and high dose ACTH. The remaining thirteen patients revealed normal response to high dose ACTH, but not to low dose ACTH. CONCLUSION: It appears that low dose ACTH stimulation test is more sensitive and specific than high dose ACTH and is capable of revealing mild adrenal insufficiency.

The Diagnostic Value of a Low Dose (1ug) Rapid ACTH Stimulation Test to Assess the Adrenocortical Function / 대한내분비학회지

BACKGROUND: Insulin induced hypoglycemia has been used to assess the adrenocortical function, but may be hazardous. The standard rapid ACTH stimulation test has been advocated as a substitute but is sometimes insensitive. In this study, low dose (1ug) rapid ACTH stimulation test was compared to insulin induced hypoglycemia and standard dose (250ug) rapid ACTH stimulation. METHODS: 27 patients (14 men and 13 women) with pituitary disease and definite adrenocortical dysfunction (14 patients were confirmed by insulin induced hypoglycemia) and 23 controls (pituitary control: 3 men and 7 women, confirmed by insulin induced hypoglycemia, normal control: 8 men and 5 women) were studied. All subjects underwent rapid ACTH stimulation test with 2 different level of stimulation (1 and 250ug). Serum cortisol levels were measured at 0, 30 and 60 min after each dose of ACTH injection. A normal response was defined as a peak cortisol value of 497nrnol/L (18ug/dL) or above, RESULTS: During rapid ACTH stimulation study in controls, the peak serum cortisol level was significantly lower (690+-25lnmol/L (25.0+-9.1ug/dL) vs. 933+-257nmol/L (33.8+-9.3ug/dL); p0.1). None of these 27 patients showed normal response to low dose stimulation, but 2 of 27 did to standard dose. In controls, 19 of 23 showed normal response to low dose, and all of 23 did to standard dose (sensitivity 100% vs 92.5%, specificity 82.5% vs 100%). The results of low and high dose stimulation test agreed with those of insulin induced hypoglycemia (Kendalls g= 0.50 vs 0.92, p<0.01 vs 0.001). CONCLUSIONS: The results of a low dose (1ug) rapid ACTH stimulation test showed good correlation with those of the standard dose (250ug) rapid ACTH stimulation test and insulin induced hypoglycemia. Thus it may be used in screening for the diagnosis of adrenal insufficiency.

The Role of Low-dose ACTH Stimulation Test in the Diagnosis of Adrenal Insufficiency / 대한내분비학회지

BACKGROUND: Rapid adrenocorticotropin (ACTH) stimulation test using 250ug of ACTH (1-24) has been used as a standard test in the initial assessment of adrenal function. However, it has recently been suggested that a rnaximal cortisol response can be achieved with a much lower ACTH dose, and reducing the dose might further enhance the sensitivity of the test in the detection of mild adrenal insufficiency. This study was performed to evaluate the role of low-dose (lug) ACTH stimulation test in the assessment of adrenal function and the diagnosis of subtle adrenal insufficiency. METHODS: Twenty-two subjects with suspected adrenal insufficiency due to long-term corticosteroid use were included in this study. The correlations between clinical features and the serum cortisol responses to low dose (lug) and high dose (250 ug) ACTH stimulation were evaluated. RESULTS: In high dose test, 10 (67%) out of 15 subjects with clinical features of adrenal insufficiency showed decreased serum cortisol response (peak cortisol level 18ug/dL). On the other hand, 14 (93%) subjects with clinical features of adrenal insufficiency showed decreased serum cortisol response in low dose test, while only one showed normal response. In 7 subjects without clinical features of adrenal insufficiency, 5 subject (71%) showed normal response, and 2 subjects (29%) showed decreased response in both low and high dose tests. CONCLUSION: These results suggest that the 1-ug low dose ACTH stimulation test might be more sensitive than conventional 250-ug test in the detection of mild adrenal insufficiency. Further studies are needed to determine the optimal dose of ACTH and the criteria for normal response to ACTH stimulation.

Prenatal diagnosis of a heterozygote of salt wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency by genetic linkage analysis

For the purpose of prenatal diagnosis of CAH, genetic linkage analysis by HLA genotyping with lymphocytes and cultured amniotic cells were performed in a family at risk in which two consecutive children had been affected with SW CAH. In addition, the response of serum 17-OHP to intravenous ACTH was determined in obligate carrier parents, and 17-OHP concentration of amniotic fluid was also measured at 16 weeks of gestation. As might be expected, the baseline levels of 17-OHP in obligate parents were significantly higher than that of normal control. Although the post stimulation response of 17-OHP to ACTH in the mother (I-2) was significantly higher than that of normal control, the post stimulation levels of 17-OHP were in normal range in the father (I-1). The 17-OHP level (5.7 ng/ml) in the amniotic fluid showed intermediate value compared to Pang's report (normal less than 30 ng/ml, CAH greater than 12.0 ng/ml) suggesting heterozygote of the fetus. Genetic linkage analysis by HLA genotyping with cultured amniotic cells revealed heterozygote in their fetus (II-3) who has received one chromosome No,6 containing HLA haplotype A24, B40, Cw3 (normal allele for 21-OH) from the father and the other chromosome No,6 containing HLA haplotype A2, Bw62, Cw4 (mutant allele for 21-OH D) from the mother. In conclusion, attempts to detect heterozygote for 21-OH deficiency by ACTH stimulation test were partially successful and prenatal diagnosis of CAH by the hormone studies in ammiotic fluid requires reliable values in normal, heterozygotes and patients group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)