Differences in thyroid function tests after administration of a single supraphysiological dose of ACTH or a high dose of a synthetic steroid.

OBJECTIVE: Although the suppressive action of synthetic steroids on the hypothalamus-pituitary-thyroid (HPT) axis is established, little is known regarding the effect of the administration of synthetic adrenocorticotropic hormone (ACTH). DESIGN: In the context of a randomized, open label, comparative study assessing the efficacy and safety of ACTH and betamethasone in the treatment of hospitalized patients with acute gout, we compared the effects of these agents on thyroid function tests. METHODS: Serum TSH, total T4 and T3 and cortisol were measured before and at 24 and 48 h after a single intramuscular dose of synthetic ACTH (1 mg) or betamethasone (6 mg), in 38 hospitalized patients with acute gout and normal thyroid function. RESULTS: The final analysis included 32 patients, due to missing data. The ACTH and betamethasone groups did not differ regarding the mean age, gender, severity of gout attack, and baseline thyroid parameters. In the ACTH group TSH and T4 were significantly decreased at 24 and at 48 h compared to baseline, while T3 was decreased at 24 but not at 48 h. In the betamethasone group T3 remained stable; TSH and T4 decreased significantly from baseline levels at 24 h; at 48 h, TSH had returned to and T4 showed a partial rebound towards pre-treatment values. CONCLUSIONS: A single IM administration of 1 mg of synthetic ACTH has more profound and prolonged effects on the HPT axis, lasting for at least 48 h, compared to a single IM dose of 6 mg betamethasone.

Possible adrenal insufficiency among fatigue patients in a psychosomatic medical clinic.

Fatigue is a common symptom in patients visiting the clinic of psychosomatic medicine. A 250-µg synthetic ACTH (1-24) test (rapid ACTH test) and Beck depression inventory (BDI) were performed for 62 patients presenting with fatigue who visited the Department of Psychosomatic Medicine at Fukuoka Tokushukai Hospital. Patients were divided into 3 groups according to the serum cortisol response to the rapid ACTH test; those with a peak serum cortisol level of <15 µg/dL were defined as the adrenal insufficiency (AI) probable group, ≥15 µg/dL and <18 µg/dL as the AI suspected group, and ≥18 µg/dL as the non-AI group. Patients prescribed anti-depressants, had a BDI ≥16, and/or met the full criteria for major depression were diagnosed with depression. Five (8.0%) and 7 patients (11.3%) were assigned to the AI probable and AI suspected groups, respectively. All others were assigned to the non-AI group. Depression was observed in 37 patients (59.6%; 4 in the AI probable group [80.0%], 4 in the AI suspected group [57.1%], and 29 in the non-AI group [58.0%]). Users of exogenous steroids, such as inhaled steroids for bronchial asthma, were seen in the AI probable group (2; 40.0%), the AI suspected group (3; 42.8%), and the non-AI group (7; 14.0%) (χ2 = 4.761, p = 0.0925). In conclusion, probable or suspected AI was observed in about one-fifth of patients presenting with fatigue at the psychosomatic medical clinic. A CRH test and insulin tolerance test (ITT) may help the he mechanism underlying these possible AIs.

International survey on high- and low-dose synacthen test and assessment of accuracy in preparing low-dose synacthen.

OBJECTIVE: The short synacthen test (SST) is widely used to assess patients for adrenal insufficiency, but the frequency and protocols used across different centres for the low-dose test (LDT) are unknown. This study aimed to survey centres and test the accuracy of ten different synacthen preparation strategies used for the LDT. METHODS: Members of 6 international endocrine societies were surveyed regarding diagnostic tests used for adrenal insufficiency, and in particular the SST. Synacthen was diluted for the LDT and concentrations measured using a synacthen ELISA. RESULTS: Survey responses were received from 766 individuals across 60 countries (52% adult, 45% paediatric endocrinologists). The SST is used by 98% of centres: 92% using high-dose (250 µg), 43% low-dose and 37% both. Ten low-dose dilution methods were assessed and variation in synacthen concentration was demonstrated with intramethod coefficients of variation (CV) ranging from 2.1% to 109%. The method using 5% dextrose as a diluent was the least variable (CV of 2.1%). The variation in dilution methods means that the dose of synacthen administered in a LDT may vary between 0.16 and 0.81 µg. CONCLUSIONS: The high-dose SST is the most popular diagnostic test of adrenal insufficiency, but up to 72% of paediatric endocrinologists use a LDT. There is considerable variation observed both within and between low-dose synacthen dilution methods creating considerable risk of inaccurate dosing and thereby invalid results.

Use of salivary cortisol and cortisone in the high- and low-dose synacthen test.

CONTEXT: Salivary cortisone reflects serum cortisol levels, is more sensitive than salivary cortisol at lower values of serum cortisol and is noninvasive. OBJECTIVE: To investigate the relationship between serum cortisol and salivary cortisol and cortisone following low- and high-dose synacthen. DESIGN AND SETTING: Prospective pharmacodynamic studies in clinical research facilities. PARTICIPANTS AND INTERVENTION: Thirty-five dexamethasone-suppressed, healthy adult males underwent an intravenous synacthen test: N = 23 low-dose (1 mcg), N = 12 high-dose (250 mcg). Paired serum and salivary samples were taken at 15 sampling points over 120 minutes. MAIN OUTCOME MEASURE: Serum cortisol and salivary cortisol and cortisone were analysed for correlations and by a mixed-effects model. RESULTS: At baseline, the correlation between serum cortisol and salivary cortisol was weak with many samples undetectable (r = .45, NS), but there was a strong correlation with salivary cortisone (r = .94, P < .001). Up to 50 minutes following synacthen, the correlation coefficient between serum cortisol and salivary cortisol and cortisone was <0.8, but both had a stronger correlation at 60 minutes (salivary cortisol r = .89, P < .001, salivary cortisone r = .85, P < .001). The relationship was examined excluding samples in the dynamic phase (baseline to 60 minutes). Salivary cortisol and cortisone showed a close relationship to serum cortisol. Salivary cortisone showed the stronger correlation: salivary cortisol r = .82, P < .001, salivary cortisone r = .96, P < .001. CONCLUSION: Following synacthen, both salivary cortisol and cortisone reflect serum cortisol levels, but there is a lag in their rise up to 60 minutes. The results support further research for possible future use of a 60-minute salivary cortisone measurement during the synacthen test.

Different cut-off values of the insulin tolerance test, the high-dose short Synacthen test (250 µg) and the low-dose short Synacthen test (1 µg) in assessing central adrenal insufficiency.

OBJECTIVE: The short Synacthen test (SST) is widely used as alternative test to the insulin tolerance test (ITT) to investigate central adrenal insufficiency (CAI), but the methodology and cut-off values of the SST are controversial. Our aim was to evaluate the cut-off value of the ITT in normal subjects and to assess the different cut-off values of the high-dose SST (250 µg, HDT) and the low-dose SST (1 µg, LDT) in subjects with suspected CAI. SUBJECTS AND METHODS: We conducted ITTs in 208 normal subjects to establish the cut-off value for the ITT, and 28 of those subjects underwent the HDT and LDT. From 1999 to 2007, 182 patients with suspected CAI were recruited and underwent ITTs, LDTs and HDTs to establish cut-off values and compare the diagnostic accuracy between the LDT and HDT. RESULTS: The 95th percentile of the peak cortisol level during the ITT in the normal control subjects was 14·8 µg/dl. Receiver operator characteristics (ROC) analysis revealed that the optimal cut-off values of peak cortisol in the LDT and HDT in patients with suspected CAI were 15·8 and 17·4 µg/dl, respectively. However, the cut-off values from normative data (mean - 2 SD) were 18·3 µg/dl for the LDT and 20·5 µg/dl for the HDT in normal control. CONCLUSIONS: The optimal cut-off values of SSTs needed to be individualized according to the type of SST and tested patient population.

Aldosterone secretion in patients with septic shock: a prospective study.

OBJECTIVE: To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS: In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS: Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS: Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

Aldosterone secretion in patients with septic shock: a prospective study / Secreção de aldosterona em pacientes com choque séptico: estudo prospectivo

OBJECTIVE: To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS: In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS: Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS: Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

OBJETIVO: Avaliar os níveis séricos dos principais fatores que regulam a ativação da zona glomerulosa e a produção de aldosterona em pacientes com choque séptico, assim como sua resposta ao teste de cortrosina em alta dose (250 µg). SUJEITOS E MÉTODOS: Em 27 portadores de choque séptico, foram aferidos níveis basais de aldosterona, cortisol, ACTH, renina, sódio, potássio e lactato, bem como realizado teste de cortrosina. RESULTADOS: Renina se correlacionou com níveis basais de aldosterona e sua variação após teste de cortrosina. Cortisol basal e sua variação não se correlacionaram com ACTH. Apenas três pacientes apresentaram disfunção concomitante da secreção de aldosterona e cortisol. CONCLUSÕES: Ativação das zonas fasciculada e glomerulosa são independentes. Secreção de aldosterona é dependente da integridade do sistema renina-angiotensina-aldosterona, enquanto secreção de cortisol não parece predominantemente dependente do eixo hipotálamo-hipófise-adrenal. Esses resultados sugerem que a ativação da adrenal em pacientes críticos ocorre por múltiplos mecanismos.

Evaluation of serum concentrations of cortisol and sex hormones of adrenal gland origin after stimulation with two synthetic ACTH preparations in clinically normal dogs.

OBJECTIVE: To compare the adrenocortical response of healthy dogs to a commonly used dose of a nonadsorbed tetracosactide product (tetracosactide) with responses to 2 doses of a depot formulation of tetracosactide (depot tetracosactide). ANIMALS: 14 dogs. PROCEDURES: Dogs were randomly assigned to receive tetracosactide (5 mg/kg, IV) or depot tetracosactide (250 µg, IM, or 5 µg/kg, IM). Dogs received each treatment once with a 2-week interval between treatments. Blood samples were assayed for cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, and estradiol concentrations. RESULTS: Serum cortisol concentrations were significantly higher than the preadministration (baseline) concentrations for all treatments 60 minutes after administration of ACTH. Peak cortisol concentration was detected 180 minutes after IM administration of 250 µg of the depot tetracosactide. Serum concentrations of progesterone, 17-hydroxyprogesterone, and androstenedione did not differ significantly from baseline concentrations after stimulation with the 5 µg/kg dose of depot tetracosactide. Adrenal gland progesterone response was significantly higher than baseline concentrations at 60 minutes after administration of the 250-µg dose of depot tetracosactide, and the 17-hydroxyprogesterone and androstenedione responses were significantly higher than baseline concentrations at 120 minutes. Compared with the response to tetracosactide, adrenocortical response was higher and more sustained following administration of the depot tetracosactide, except for androstenedione concentration, which had a nonsignificant response. CONCLUSIONS AND CLINICAL RELEVANCE: Except for androstenedione concentrations, a high dose of the depot tetracosactide (250 µg, IM) induced an adrenocortical response similar to that after administration of tetracosactide. Thus, depot tetracosactide may represent an alternative to the nonadsorbed tetracosactide product.

Normal cortisol response to high-dose synacthen and insulin tolerance test in children and adults with Prader-Willi syndrome.

CONTEXT: Prader-Willi syndrome (PWS) is a genetic disease associated with hypogonadism and partial GH insufficiency, possibly explained in part by a hypothalamic dysfunction. Partial insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis has recently been suggested. OBJECTIVE: The objective of the study was to further explore the HPA axis in PWS by use of routine tests. DESIGN: Nonselected PWS patients were examined with a standard high-dose synacthen test or the insulin tolerance test (ITT). A random serum (s) cortisol was measured in case of acute illness. SETTING: The study was conducted at university hospitals in Denmark and Sweden. PATIENTS: Sixty-five PWS patients with a confirmed genetic diagnosis participated in the study. MAIN OUTCOME MEASURES: A s-cortisol value above 500 nmol/liter as well as an increase of 250 nmol/liter or greater was considered a normal response. RESULTS: Fifty-seven PWS patients (median age 22 yr, total range 0.5-48 yr) were examined with the high-dose synacthen test. The median s-cortisol at the time of 30 min was 699 (474-1578) nmol/liter. Only one patient had a s-cortisol level below 500 nmol/liter but an increase of 359 nmol/liter. This patient subsequently showed a normal ITT response. Two patients had increases less than 250 nmol/liter but a time of 30-min s-cortisol values of 600 nmol/liter or greater. These three patients were interpreted as normal responders. Eight patients [aged 26 (16-36) yr] examined with the ITT had a median peak s-cortisol of 668 (502-822) nmol/liter. Four children admitted for acute illnesses had s-cortisol values ranging from 680 to 1372 nmol/liter. CONCLUSION: In this PWS cohort, the function of the HPA axis was normal, suggesting that clinically significant adrenal insufficiency in PWS is rare.

[Frequency and risk factors of biological adrenal insufficiency screened by the 250 microg Synacthene stimulation test after a prolonged course of systemic glucocorticoid therapy. A study of 100 patients]. / Fréquence et déterminants de l'insuffisance surrénalienne biologique dépistée par le test au Synacthène à 250mug lors du sevrage d'une corticothérapie prolongée. Etude chez 100 patients.

PURPOSE: The frequency of adrenal insufficiency after a prolonged, continuous course of oral high-dose corticosteroids is poorly documented. We evaluated it retrospectively in our internal medicine department. METHODS: The patients were included between February 2000 and June 2007 and were administered a Synacthene 250 microg test (ST250) before tapering prednisone dose below 5mg per day. A non-responsive test was defined by a cortisol increase below 18 microg/dL, 60 min after stimulation. We also studied the risk factors associated with biological adrenal insufficiency by a multivariate logistic regression analysis. RESULTS: Hundred patients were included (mean age: 61.5+/-16.3 years). Mean initial dose of corticosteroids was 65.5+/-112 mg/d. Forty-five patients failed to respond to the ST250. A normal ST250 was negatively associated with a duration of corticosteroids therapy longer than 19.5 months (OR=0.38 [0.15-0.94]; p=0.04) and positively with an age over 63.5 years (OR=2.5 [1.1-6.4]; p=0.05). Two patients experienced a clinical adrenal insufficiency crisis. CONCLUSION: Biological adrenal insufficiency is very common after a prolonged course of oral high-dose corticosteroids. The risk does not seem to increase with age. The clinical benefit of a systematic ST250 at the time of corticosteroids withdrawal followed by hydrocortisone substitution if the test is non responsive remains unknown, and this practice is still a matter of debate.

Mapping of hormones and cortisol responses in patients after Lyme neuroborreliosis.

BACKGROUND: Persistent symptoms after treatment for neuroborreliosis are common for reasons mainly unknown. These symptoms are often unspecific and could be caused by dysfunctions in endocrine systems, an issue that has not been previously addressed systematically. We therefore mapped hormone levels in patients with previous confirmed Lyme neuroborreliosis of different outcomes and compared them with a healthy control group. METHODS: Twenty patients of a retrospective cohort of patients treated for definite Lyme neuroborreliosis were recruited 2.3 to 3.7 years (median 2.7) after diagnosis, together with 23 healthy controls. Lyme neuroborreliosis patients were stratified into two groups according to a symptom/sign score. All participants underwent anthropometric and physiological investigation as well as an extensive biochemical endocrine investigation including a short high-dose adrenocorticotropic hormone stimulation (Synacthen) test. In addition to hormonal status, we also examined electrolytes, 25-hydroxy-vitamin D and interleukin-6. RESULTS: Eight patients (40%) had pronounced symptoms 2-3 years after treatment. This group had a higher cortisol response to synacthen as compared with both controls and the Lyme neuroborreliosis patients without remaining symptoms (p < 0.001 for both comparisons). No other significant differences in the various baseline biochemical parameters, anthropometric or physiological data could be detected across groups. CONCLUSIONS: Apart from a positive association between the occurrence of long-lasting complaints after Lyme neuroborreliosis and cortisol response to synacthen, no corticotropic insufficiency or other serious hormonal dysfunction was found to be associated with remaining symptoms after treatment for Lyme neuroborreliosis.

Repeatability of the low-dose ACTH test in asthmatic children on inhaled corticosteroids.

AIM: To assess the repeatability of low-dose Synacthen test (LDST) in asthmatic children receiving high-dose fluticasone propionate (FP). METHODS: Low-dose Synacthen test was performed on 18 children with stable chronic asthma treated with FP at a constant daily dose of > or =500 microg and repeated 1 month later. Repeatability was assessed using the Kappa statistic for categorical variables. RESULTS: Fifteen patients had consistent results (either two normal or two abnormal responses) and three patients had inconsistent results (one normal and one abnormal response). The Kappa statistic was 0.56 indicating fair to good agreement between the tests. CONCLUSION: The results of adrenal function testing in patients on inhaled steroids can have major implications for patient management, making it important to use a test with excellent repeatability. The LDST conducted using our protocol does not fulfil this criterion.

Low-dose and high-dose synacthen tests and the hemodynamic response to hydrocortisone in acute traumatic brain injury.

INTRODUCTION: In order to identify whether low-dose (1 microg) tetracosactide (Synacthen) testing may be preferable to high-dose (250 microg) testing in the diagnosis of adrenal insufficiency in traumatic brain injury (TBI), as suggested by studies in other forms of critical illness. METHODS: We retrospectively reviewed the results of modified tetracosactide tests (involving administration of both low-dose and high-dose tetracosactide) conducted for clinical indications in patients in a neurocritical care unit within 10 days of TBI. Sixty-three modified tests were included and cortisol concentrations before and after administration of tetracosactide were extracted from the hospital records. Data were also extracted regarding hemodynamic response to empirical corticosteroid therapy, based on rapid weaning from vasoactive drugs. RESULTS: Cortisol increments at 30 and 60 min following tetracosactide correlated well in the low-dose test (r(2) = 0.875, P < 0.0001). The mean cortisol concentration was 581 nmol/l at 30 min and 556 nmol/l at 60 min in the low-dose test. Cortisol increments following low-dose and high-dose testing correlated well overall (r(2) = 0.839, P < 0.0001), but results were discordant in 27 of 63 cases (43%) when the same diagnostic threshold was used. ROC curve analysis showed that both tests performed poorly in identifying hemodynamic steroid responsiveness (AUC 0.553 and 0.502, respectively). CONCLUSIONS: In the low-dose tetracosactide test, it is sufficient to determine cortisol concentrations at baseline and at 30 min. Low-dose and high-dose tests give discordant results in a significant proportion of cases when using the same diagnostic threshold. Neither test can be used to guide the initiation of corticosteroid therapy in acute TBI.

Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary disease: comparison between serum and salivary cortisol during the high-dose short synacthen test.

OBJECTIVE: Accurate assessment of adrenal function is essential in patients with hypothalamic-pituitary-adrenal (HPA) disease. The measurement of salivary cortisol (SaC) instead of serum cortisol (SeC) offers several advantages, such as the determination of the free hormone. We evaluated the diagnostic value of SeC and SaC both unstimulated and during a high-dose short synacthen test (HDT) in comparison to the insulin tolerance test (ITT). DESIGN: Comparative study between 2005 and 2007. METHODS: Fifty-five patients with HPA impairment and 21 healthy controls were enrolled. Samples were collected in the early morning and over 120 min during the HDT. Receiver operating characteristic analysis revealed individual thresholds for four HDT periods (0-30, 0-60, 0-90, and 0-120 min). RESULTS: The ITT identified 30 subjects as adrenal insufficient. With respect to the four HDT periods, sensitivity and specificity were 67-79% and 71-88% for SeC, compared with 63-72% and 72-86% for SaC. If upper and lower thresholds (with specificities >95%) were applied, patients were diagnosed in 40-45% by SeC and in 25-31% by SaC. The combination of basal cortisol and HDT allowed a diagnosis in 47-49% (SeC) and in 42-45% (SaC) respectively. CONCLUSION: We suggest the determination of basal SeC or SaC as first-line test. In comparison to the ITT, the HDT has only limited value in screening for alterations of the HPA axis. If the HDT is performed, sampling may be limited to 30 min post-synacthen, using either SeC or SaC. Due to the ease of collection and the independence of binding proteins, SaC may be preferable.

The effect of synacthen on acute necrotizing pancreatitis in rats.

OBJECTIVES: This study investigates the hypothesis that an adrenocorticotropic hormone-analog therapy may ameliorate relative adrenal insufficiency in the early phase of acute necrotizing pancreatitis (NP) by boosting endogenous glucocorticoid production. METHODS: Forty Wistar rats with taurocholate-induced NP were divided into 5 groups: the first group received low-dose Synacthen (0.5 mg/kg); the second, high-dose Synacthen (5mg/kg); the third,low-dose cortisol (10 mg/kg); the fourth, high-dose cortisol (100 mg/kg); and the fifth, the control group, received no treatment. All animals were killed after 6 hours: concentrations of plasma corticosterone, interleukin 1 (IL-1), IL-6, IL-10, tumor necrosis factor alpha, amylase, and lipase in ascites, myeloperoxidase activity in the pancreas, and a histological score were evaluated. RESULTS: Corticosterone increased neither in the low-dose nor in the high-dose Synacthen group. Synacthen did not improve the early course of NP in terms of laboratory and histological results. A reduction of pancreatic necrosis and inflammation was observed in the low-dose cortisol group. CONCLUSIONS: Endogenous glucocorticoid release seemed to be at its maximum during the early stage of NP and could not be further increased by Synacthen. Low-dose exogenous cortisol ameliorated the disease. These findings support the existence of relative adrenal insufficiency in the early phase of acute NP.

Assessment of adrenal suppression in children with asthma treated with inhaled corticosteroids: use of dehydroepiandrosterone sulfate as a screening test.

BACKGROUND: Inhaled corticosteroids (ICs) are considered first-line therapy for persistent asthma. At medium to high doses, ICs can suppress the hypothalamic-pituitary-adrenal (HPA) axis. Various provocative stimuli have been used to evaluate HPA axis function, but they are labor intensive and time-consuming. Dehydroepiandrosterone sulfate (DHEA-S) is a corticotropin-dependent adrenal androgen precursor that is suppressible in patients treated with ICs. OBJECTIVES: To evaluate DHEA-S as a possible marker for HPA axis dysfunction in children treated with ICs. METHODS: Children with moderate-to-severe persistent asthma and a history of medium- to high-dose IC exposure for at least 6 months were evaluated using low-dose and standard high-dose cosyntropin stimulation testing to assess adrenal function, and DHEA-S levels were compared with the results. RESULTS: Thirteen (59%) of 22 patients exhibited an abnormal cortisol response to cosyntropin. Age- and sex-specific mean DHEA-S z scores were significantly lower in cosyntropin abnormal responders (-1.2822) compared with normal responders (0.2964) (P = .008). The receiver operating characteristic curve for DHEA-S z scores had an area of 0.786 (95% confidence interval, 0.584-0.989), reaching 100% sensitivity with a DHEA-S z score of -1.5966 or less and 100% specificity with a DHEA-S z score greater than 0.0225. CONCLUSIONS: Most children develop biochemical evidence of adrenal suppression after treatment with medium to high doses of ICs. The presence of low DHEA-S levels can be used as a screening test to identify the child who needs more formal testing of the HPA axis.

The low-dose (1 microg) adrenocorticotropin stimulation test in kidney and kidney-pancreas transplant patients: a potential guideline for steroid withdrawal.

Chronic steroid treatment is known to impair the hypothalamic-pituitary adrenal axis (HPA) but the need to assess HPA function prior to withdrawal of steroid therapy in post-transplant patients has not been uniformly accepted. We evaluated the status of the HPA axis in 48 kidney or kidney-pancreas transplant patients who were considered for possible discontinuation of glucocorticoid therapy using a recently validated dynamic test of HPA integrity, the low-dose (1 microg) adrenocorticotropin (ACTH) test. HPA suppression was detected in 29 (60%) of the patients, four of which had severe hypoadrenalism prohibitive of steroid withdrawal. Neither the duration of steroid treatment nor 8:00 am serum cortisol was a useful marker of hypoadrenalism. 8:00 am cortisol in subjects with normal HPA reserve and subjects with partial hypoadrenalism overlapped considerably but levels <5 microg/dL were indicative of severe hypoadrenalism. Pre-withdrawal diagnosis of partial hypoadrenalism allowed the identification of subjects requiring no further steroid replacement under regular daily circumstances. However glucocorticoid supplementation was prescribed in the event of stress such as infection, exceptional effort, trauma or surgery. Individuals with partial HPA impairment, but not patients with severe HPA suppression, improved upon retesting 3 months later. Patients exhibiting normal response to 1 mcg ACTH enjoyed an uneventful course following steroid withdrawal. Since hypoadrenalism is extremely common in post-transplant patients, we recommend the use of the low-dose ACTH test as a convenient method to identify patients with various degrees of hypoadrenalism prior to steroid withdrawal.

Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone.

BACKGROUND AND AIMS: Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose. METHODS: Children recorded as prescribed FP > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l). RESULTS: A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6-19.3 years) were successfully tested. Of 194 receiving FP > or = 500 microg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of > or = 1000 microg/day. CONCLUSION: Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.

Elevated intraocular pressure associated with steroid treatment for infantile spasms.

PURPOSE: To evaluate the ocular changes and medical and surgical therapy after high-dose systemic steroid treatment in babies with infantile spasm and hypsarrhythmia. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: In 5 of the 9 (55%) babies with infantile spasm exposed to systemic corticosteroid treatment, an increase in intraocular pressure (IOP) and optic disc cupping was observed. INTERVENTION: Ophthalmic examination under mild sedation was conducted 3 to 4 weeks after initiation of systemic therapy. Antiglaucoma treatment was given to the patients found to have high IOPs and cup-to-disc ratio changes. Routine follow-up was continued until systemic therapy was completed. MAIN OUTCOME MEASURES: Controlled IOP with a decrease in cupping damage after antiglaucoma therapy. RESULTS: Five patients required antiglaucoma treatment; one also underwent augmented trabeculectomy. Mean IOP decreased in this subgroup from 30.1 +/- 9.5 mmHg to 15.4 +/- 4.2 mmHg in the right eye (P = 0.043) and from 32.6 +/- 7.4 mmHg to 15.2 +/- 1.8 mmHg in the left eye (P = 0.043). Mean cup-to-disc ratio improved from 0.53 +/- 0.2 to 0.37 +/- 0.04 in the right eye (P = 0.06) and from 0.57 +/- 0.12 to 0.35 +/- 0.05 in the left eye (P = 0.042). CONCLUSIONS: The rapid onset of IOP and cup-to-disc ratio changes in patients with infantile spasm and hypsarrhythmia treated by high-dose corticosteroids necessitates early and intensive monitoring to prevent anatomic ocular damage and visual impairment in the future.