Evaluating the Low-Dose ACTH Stimulation Test in Neonates: Ideal Times for Cortisol Measurement

2020 ◽  
Vol 105 (12) ◽  
pp. e4543-e4550
Author(s):  
Robyn LeDrew ◽  
Erika Bariciak ◽  
Richard Webster ◽  
Nick Barrowman ◽  
Alexandra Ahmet

Abstract Context Low-dose adrenocorticotropic hormone stimulation testing (LDST) can be used to diagnose central adrenal insufficiency. However, uncertainty remains over optimal times to draw serum cortisol levels. Objective To determine optimal times to draw serum cortisol levels for the LDST in neonates. Design A retrospective chart review of LDSTs performed on neonates from January 1, 2009 to September 30, 2017. Setting Children’s Hospital of Eastern Ontario (CHEO), a tertiary-care outborn pediatric center. Patients Forty-nine patients were included: 23 (46.9%) born at term, 12 (24.5%) born very preterm to late preterm, and 14 (28.6%) born extremely preterm. Intervention Cortisol levels were drawn at baseline and 15, 30, and 60 minutes following administration of Cortrosyn 1 mcg/kg (maximum dose 1 mcg). Main Outcome Measure Timing of peak cortisol level and marginal value of drawing a second and third cortisol sample at 15, 30, or 60 minutes was determined. Results Cortisol peaked at 15-, 30-, and 60-minute sampling times for 4%, 27%, and 69% of patients, respectively. The probability that a failed LDST changes to a pass by adding a 15- or 30-minute sample to the superior 60 minute sample is 5.6% (1% to 25.8%) and 11% (3.1% to 32.6%), respectively, for a cortisol pass threshold of 18.1mcg/dL (500 nmol/L). Conclusions In contrast to studies of older children, we found that the majority of neonatal LDST cortisol peaks occurred at the 60-minute sampling time with the addition of a 30-minute sample providing substantial benefit. It is questionable if a 15-minute sample provides any benefit, making a case to revise LDST protocols to sample cortisol later for neonates.

2019 ◽  
Vol 104 (10) ◽  
pp. 4587-4593 ◽  
Author(s):  
Harpreet Gill ◽  
Nick Barrowman ◽  
Richard Webster ◽  
Alexandra Ahmet

Abstract Context Central adrenal insufficiency (AI) can be diagnosed with the low-dose ACTH stimulation test (LDST). Protocols determining timing of cortisol sampling vary, with 30 minutes after stimulation being most common. Objectives To determine optimal times to draw cortisol levels and factors predicting timing of peak cortisol levels in children undergoing LDST. Design Retrospective chart review of LDSTs between February 2014 and September 2017. Setting The Children’s Hospital of Eastern Ontario. Patients Patients 3 months to 20 years who underwent LDSTs. Intervention LDSTs were performed with cortisol levels at 0, 15, 30, and 60 minutes after 1 μg cosyntropin. Cortisol values <18 μg/dL (500 nmol/L) determined AI. Main Outcome Measures The incremental value of testing cortisol at 15 or 60 minutes, in addition to the standard 30-minute sample, was estimated. Results A total of 221 patients met inclusion criteria. The mean age was 9.7 years, and 32% were female. Peak cortisol levels were 19%, 67%, and 14% at 15, 30, and 60 minutes, respectively. One false positive LDST result would be prevented for every 24 (95% CI, 13 to 46) or 55 (95% CI, 22 to 141) patients tested at 15 or 60 minutes in addition to the standard 30-minute test. Of the 122 patients who passed the LDST, discontinuing the 15- and 60-minute samples would have misdiagnosed 12 patients (9.8%). Glucocorticoid exposure, age, and body mass index z scores were independent predictors of peak cortisol timing. Conclusion Although the majority of patients peak 30 minutes after cosyntropin administration, testing cortisol levels at 15 and 60 minutes reduces the risk of false positive LDSTs.


1993 ◽  
Vol 136 (1) ◽  
pp. 167-172 ◽  
Author(s):  
S. Crowley ◽  
P. C. Hindmarsh ◽  
J. W. Honour ◽  
C. G. D. Brook

ABSTRACT We compared the reproducibility and repeatability of the acute adrenal response to low doses (90 and 500 ng/1·73 m2) of Synacthen (ACTH(1–24)) with that of the standard dose (250 μg/1·73 m2). We also examined the effect of basal cortisol levels on peak values achieved after stimulation with a low dose. ACTH(1–24) was given to six male volunteers: 90 ng/1·73 m2 twice at 90-min intervals on day 1, and 90 and 500 ng/1·73 m2 once on day 2 and 250 μg/1·73 m2 once on day 3. The rise in serum cortisol concentration with repeated low doses of ACTH was not attenuated (161 ± 49 (s.d.) nmol/l on initial vs 150 ± 41 nmol/l on repeat stimulation; P = 0·5) and this was reproducible (161 ± 49 nmol/l on day 1 vs 148 ± 15 nmol/l on day 2; P = 0·6). A dose of 500 ng ACTH(1–24)/1·73 m2 produced a maximal adrenal response in that the rise in serum cortisol concentration at 20 min was identical with that produced at the same time by the standard dose of 250 μg/1·73 m2. There was a strong positive correlation between the basal cortisol level and peak cortisol concentration after low-dose ACTH stimulation (r = 0·93, P < 0·001) but not between the basal cortisol level and the incremental rise (r= −0·1, P = 0·69). These results suggest that the cortisol response to low-dose ACTH stimulation is reproducible and not attenuated by repeat stimulation at 90-min intervals. The incremental rise in serum cortisol concentration after ACTH stimulation appears constant in these situations and is not influenced by the basal cortisol level. When there is concern that the standard dose may be excessive and mask subtle but important changes in adrenal function, the low dose (500 ng) of ACTH should be used. Journal of Endocrinology (1993) 136, 167–172


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Vijaykumar Sekar ◽  
Joseph Hughes ◽  
Sugam Gouli

Abstract Background: Osteoporosis in post-menopausal women is usually due to bone loss from estrogen deficiency and/or age. Secondary osteoporosis (SO) is less common. Up to 30% of postmenopausal women and 50% of men with osteoporosis may have an underlying cause. Cushing’s disease (CD) is one cause of SO but rarely the presenting symptoms. The prevalence of osteoporosis (69.6% vs 37.8%) is significantly higher in patients with adrenal rather than pituitary CD. Diagnosing CD remains a challenge to physicians in spite of advances in diagnostic techniques. We report a case of CD in a post-menopausal woman presenting as accelerated osteoporosis. Clinical Case A 63-year-old Caucasian female with a history of hypertension and hysterectomy in her 50s on transdermal estrogen was referred to our Endocrine clinic for evaluation of osteoporosis and incidental finding of bilateral adrenal hyperplasia on CT spine. The patient rapidly developed kyphoscoliosis within the past 2 years. She was debilitated by pain and decreased mobility from compression fractures and spinal stenosis, and underwent thoracic and lumbar fusion surgery. On physical examination, her heart rate was 64 beats per minute, blood pressure 130/92 mmHg, weight 188 lbs. and Height 5.1 ft; a year ago it was 5.5 ft. Her face appeared round but not red. Buffalo hump and supraclavicular pad were noted. No striae or bruises noted. Healing surgical scars over the thoracic and lumbar spine were violaceous. The patient’s urine free cortisol levels, tested a month apart, were 190 mcg and 132 mcg (n 3.5-45 mcg/24h). Midnight salivary cortisol levels taken consecutive nights were 160 ng/dL and 513 ng/dL (n &lt; 100 ng/dL). Morning Serum Cortisol and ACTH were 20.2 ug/dL and 14 pg/mL (n Cortisol 6.0-27.0 ug/dL and ACTH 7.2-63 pg/mL). Following low dose (1mg) dexamethasone suppression testing, her serum cortisol were 12.6 ug/dL, ACTH levels were 32 pg/mL and dexamethasone were 187 ng/dL (n &lt; 30 ng/dL). 25-Hydroxy D total, TSH, Free T4, PTH intact, calcium, renin, aldosterone and SPEP levels were normal. Renal and liver functions were normal except alkaline phosphatase was 142 U/L (n 34-104 U/L). Pituitary MRI with contrast showed pituitary microadenoma. The patient was referred to a neurosurgeon and is planned for an inferior petrosal sinus sampling prior to transsphenoidal resection. Conclusion Cushing’s disease as a cause of osteoporosis is rare. Diagnosis of Cushing’s can be challenging in patients without obvious signs, as in our patient who was referred to an endocrinologist due to incidental finding of bilateral adrenal hyperplasia. A high degree of clinical suspicion is needed when investigating CD, as initial test results can be indecisive. As in our patient, initial ACTH and cortisol levels were normal, the low dose dexamethasone suppression test helped us direct our diagnosis towards CD.


1997 ◽  
Vol 82 (3) ◽  
pp. 856-860
Author(s):  
Samer S. El-Deiry ◽  
Sakkubai Naidu ◽  
Lewis S. Blevins ◽  
Paul W. Ladenson

Abstract Adrenoleukodystrophy (ALD) is an X-linked recessive disorder that destroys the white matter of the brain and is associated with adrenal insufficiency. The prevalence of adrenal dysfunction in 71 women carriers of the X-linked ALD gene was studied. These subjects were identified initially on the basis of being obligate carriers of the X-linked trait by pedigree analysis and were confirmed by plasma very long chain fatty acid levels consistent with a heterozygote status. One subject had well documented overt adrenal insufficiency, diagnosed and treated since age 9 yr. Among the remaining women, the mean serum 0800 h and 1 h post-ACTH cortisol concentrations [16 ± 7 (±sd) and 34 ± 8 μg/dL, respectively] were normal. All subjects had normal ACTH-stimulated serum cortisol levels, i.e. more than 20 μg/dL. However, 4 subjects (6%) had subnormal ACTH-stimulated aldosterone concentrations (mean, 9 ± 6 vs. 42 ± 16 ng/dL for other subjects; P = 0.001, by Mann Whitney rank sum test). Three of these women (75%) were taking nonsteroidal antiinflammatory agents (NSAIDs), whereas only 4 of 67 (6%) subjects with normal aldosterone responsiveness were NSAIDs users (P &lt; 0.01, by Fisher’s exact test). Thus, NSAIDs use was associated with increased risk of hypoaldosteronism (odds ratio, 50.2; 95% confidence interval, 3.3–266; P &lt; 0.002). Three of these four women had symptoms consistent with mineralocorticoid deficiency. Serum sodium and potassium concentrations were normal in all subjects. Basal and metyrapone-stimulated plasma ACTH concentrations were also normal in adequately tested subjects with and without mineralocorticoid insufficiency. Five of eight subjects (63%) who underwent testing with synthetic ovine CRH (oCRH) had abnormalities. Three did not meet the criteria for adequate cortisol stimulation (i.e. &gt;20 μg/dL) and had peak ACTH levels greater than 30 pg/mL. Two other subjects had exaggerated ACTH responses with normal cortisol levels. There were no significant differences in the mean or median levels of very long chain fatty acid, C26:0, C24/22 ratios, or C26/22 ratios among the entire subject group, the subgroup with blunted aldosterone responses to ACTH, and the subgroup with blunted responses to oCRH (P &gt; 0.05, by ANOVA and Kruskall-Wallis test for C26, C24/22 ratio, and C26/22 ratio). We conclude that 1) adrenal cortical insufficiency rarely develops in ALD heterozygotes; 2) isolated mineralocorticoid insufficiency can occur in ALD heterozygotes, as has been previously reported to occur with autoimmune and acquired immunodeficiency syndrome-related adrenal dysfunction; 3) ALD heterozygosity may predispose these individuals to NSAID-related hypoaldosteronism; and 4) a subclinical decrease in glucocorticoid reserve, as measured by oCRH testing, may be present in a majority of these women. Aldosterone levels should be included in the ACTH stimulation testing when seeking evidence of adrenal insufficiency in affected women. NSAIDs should be considered a risk factor for the development of hypoaldosteronism in women heterozygous for ALD.


2000 ◽  
Vol 142 (3) ◽  
pp. 231-235 ◽  
Author(s):  
A Tsatsoulis ◽  
EO Johnson ◽  
CH Kalogera ◽  
K Seferiadis ◽  
O Tsolas

OBJECTIVE: Variations in thyroid function are known to be associated with changes in adrenocortical activity. Previous studies in animals have suggested that long-standing hyperthyroidism may be associated with diminished adrenal functional reserve despite a continuing hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. In humans, there has been no direct assessment of adrenal secretory reserve in clinical thyrotoxicosis. This study aimed to assess adrenocortical reserve in response to low-dose ACTH, following dexamethasone suppression, in patients with severe thyrotoxicosis. DESIGN AND METHODS: Ten patients (four men and six women, 30-45 years) with severe long-standing thyrotoxicosis due to Graves' disease (n=6) or toxic nodular goitre (n=4) were studied at diagnosis and again when in a stable euthyroid state following drug therapy for 8-12 months. All patients underwent ACTH stimulation tests at 0800h with ACTH(1-24) (Cortrosyn; 0.1microg/kg body weight, i.v.) following overnight suppression of the HPA axis with dexamethasone (1mg per os at 2300h). Serum cortisol was assayed at -15, 0, 15, 30, 60 and 90min after the administration of ACTH. RESULTS: The mean (+/-s.d.) peak and delta cortisol responses to ACTH (634.5+/-164nmol/l and 618+/- 196nmol/l respectively), as well as the net area under the response curve (36769+/-12188nmol/lx min) in the hyperthyroid patients were significantly lower compared with the values when the same patients were euthyroid (911+/-157nmol/l, 905+/-160nmol/l and 57652+/-10128nmol/lxmin respectively; P<0.005). Subnormal peak cortisol responses (<500nmol/l) were observed in two severely toxic patients. The findings were independent of the cause of thyrotoxicosis. CONCLUSION: In patients with severe thyrotoxicosis, cortisol secretion in response to low-dose ACTH stimulation, following dexamethasone suppression, is lower in the hyperthyroid than in the euthyroid state. It appears that thyrotoxicosis is associated with subtle impairment of adrenocortical reserve.


1991 ◽  
Vol 19 (01) ◽  
pp. 9-15 ◽  
Author(s):  
J. H. Lin ◽  
H. L. Su ◽  
S. H. Chang ◽  
Y. S. Shien ◽  
L. S. Wu

This study was conducted to evaluate the effectiveness of electroacupuncture (EA) on the recovery of adrenocortical function from Iatrogenic Cushings Syndrome (ICS) in dogs. Experiment I: Selection of the most effective Acupuncture point to treat ICS — Six healthy adult female dogs were treated bilaterally with EA for 15 minutes at loci BL22 + BL23 + BL24, ST36, or a non-locus control point on M. brachialis. Each dog was tested at all three sites in rotation. Blood samples were collected before and 0, 15 and 60 minutes after EA, and the serum cortisol levels were measured by radioimmunoassay. The data showed that EA at ST 36 resulted in the highest response of serum cortisol levels among the three treatments. Experiment II: Evaluation of the effectiveness of EA ST36 in the treatment of ICS in dogs - Eight healthy adult female dogs were given prednisolone acetate 2mg/kg/day IM for 3 weeks. They were then randomly divided into ST36 and control groups of 4 dogs each. In the ST36 group, ST36 was treated bilaterally with EA for 30 minutes, 3 times per week, for 3 consecutive weeks. For the control, a non-locus point on M. brachialis was treated bilaterally with the same protocol. After the first week of EA, the serum cortisol levels of the ST36 and control groups were 0.9±0.1 and 0.5 ± 0.1 μg/dl ( P < 0.005) baseline and 2.5±0.2 and 1.4 ±0.4 μg/dl ( p < 0.05) and after ACTH stimulation test, respectively. After the third week of EA treatment, the results were 1.0±0.1 and 0.6±0.2 μg/dl ( p < 0.05) baseline and 4.0±0.5 and 1.7±0.5 μg/dl ( p < 0.001) after ACTH stimulation respectively. These data indicated that EA at ST36 could restore the adrenocortical hypofunction resulting from ICS in dogs.


Medicina ◽  
2020 ◽  
Vol 56 (1) ◽  
pp. 23
Author(s):  
Worapaka Manosroi ◽  
Mattabhorn Phimphilai ◽  
Jiraporn Khorana ◽  
Pichitchai Atthakomol ◽  
Tanyong Pipanmekaporn

Background and Objectives: To diagnose adrenal insufficiency (AI), adrenocorticotropic hormone (ACTH) stimulation tests may need to be performed, but those tests may not be available in some institutions. In addition, they may not be necessary for some patients. The objective of this study was to identify clinical and biochemical factors that could facilitate AI diagnosis in outpatient departments and decrease the number of unnecessary dynamic tests. Materials and Methods: This seven-year retrospective study was performed in a tertiary care medical center. A total of 517 patients who had undergone ACTH stimulation tests in the outpatient department were identified. AI was described as a peak serum cortisol level of <18 µg/dL at 30 or 60 min after stimulation. The associations between clinical factors, biochemical factors, and AI were analyzed using the Poisson regression model and reported by the risk ratio (RR). Results: AI was identified in 128 patients (24.7%). Significant predictive factors for the diagnosis of AI were chronic kidney disease (RR = 2.52, p < 0.001), Cushingoid appearance (RR = 3.44, p < 0.001), nausea and/or vomiting (RR = 1.84, p = 0.003), fatigue (RR = 1.23, p < 0.001), serum basal cortisol <9 µg/dL (RR = 3.36, p < 0.001), serum cholesterol <150 mg/dL (RR = 1.26, p < 0.001), and serum sodium <135 mEq/L (RR = 1.09, p = 0.001). The predictive ability of the model was 83% based on the area under the curve. Conclusion: The easy-to-obtain clinical and biochemical factors identified may facilitate AI diagnosis and help identify patients with suspected AI. Using these factors in clinical practice may also reduce the number of nonessential dynamic tests for AI.


2007 ◽  
pp. 449-454 ◽  
Author(s):  
K Šimůnková ◽  
R Hampl ◽  
M Hill ◽  
J Doucha ◽  
L Stárka ◽  
...  

To date, a single report has appeared on the use of salivary cortisol for adrenal function testing with a low dose ACTH, although 1 microg has become preferred as a more physiological stimulus than the commonly used 250 microg ACTH test. Our present study was aimed to obtain physiological data on changes of free salivary cortisol after 1 microg ACTH stimulation. This approach was compared with the common method based on the changes of total serum cortisol. Intravenous, low-dose ACTH test was performed in 15 healthy women (aged 22-40 years) with normal body weight, not using hormonal contraceptives, in the follicular phase of the menstrual cycle. Blood and saliva for determination of cortisol were collected before ACTH administration and 30 and 60 min after ACTH administration. Basal concentration of salivary cortisol (mean +/- S.E.M., 15.9+/-1.96 nmol/l) increased after 1 microg ACTH to 29.1+/-2.01 nmol/l after 30 min, and to 27.4+/-2.15 nmol/l after 60 min. The differences between basal and stimulated values were highly significant (p<0.0001). The values of salivary cortisol displayed very little interindividual variability (p<0.04) in contrast to total serum cortisol values (p<0.0001) A comparison of areas under the curve (AUC) related to initial values indicated significantly higher AUC values for salivary cortisol than for total serum cortisol (1.89+/-0.88 vs. 1.22+/-0.19, p<0.01). Correlation analysis of serum and salivary cortisol levels showed a borderline relationship between basal levels (r=0.5183, p=0.0525); correlations after stimulation were not significant. Low-dose ACTH administration appeared as a sufficient stimulus for increasing salivary cortisol to a range considered as a normal adrenal functional reserve.


Author(s):  
Stefan Fischli ◽  
Viktor von Wyl ◽  
Walter Wuillemin ◽  
Roland von Känel ◽  
Philipp Schütz ◽  
...  

Abstract Context Glucocorticoids regulate hemostatic and endothelial function and are critical for adaptive functions during surgery. No data regarding the impact of adrenal function on hemostasis and endothelial function in the perioperative setting is available. Objective We assessed the association of adrenal response to adrenocorticotropic hormone (ACTH) and markers of endothelial/hemostatic function in surgical patients. Design Prospective observational study. Setting Single center study, tertiary care hospital. Patients 60 patients (35 male/25 female) undergoing abdominal surgery. Main Outcome Measures Adrenal function was evaluated by low-dose ACTH-stimulation test on the day before, during and the day after surgery. According to their stimulated cortisol level (cut-off ≥500nmol/L) patients were classified having normal HPA-axis function (nHPA) or deficient HPA-axis function (dHPA). Parameters of endothelial function (soluble vascular cell adhesion molecule-1 [sVCAM-1], thrombomodulin [TM]) and hemostasis (fibrinogen, von Willebrand factor-antigen [vWF], factor VIII [FVIII]) were measured during surgery. Results 21 had dHPA and 39 had nHPA. Compared to nHPA, Patients with dHPA had significantly lower peak cortisol before (median 568 vs. 425 nmol/L, p &lt;0.001) and during (693 vs. 544 nmol/L, p &lt;0.001) surgery and lower postoperative hemoglobin levels (116 g/L vs. 105 g/L, p=0.049). FVIII was significantly reduced in patients with dHPA in uni- and multivariable analyses, other factors displayed no significant differences. Coagulation factors/endothelial markers changed progressively in relation to stimulated cortisol levels and showed a turning point at cortisol levels between 500-600 nmol/L. Conclusions Patients with dHPA undergoing abdominal surgery demonstrate impaired hemostasis which can translate into excessive blood loss.


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