Peak Serum Cortisol Concentrations Research Articles

Endocrine Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

Endocrine dysfunction is common in critically ill children and is manifested by abnormalities in glucose, thyroid hormone, and cortisol metabolism. To develop consensus criteria for endocrine dysfunction in critically ill children by assessing the association of various biomarkers with clinical and functional outcomes. PubMed and Embase were searched from January 1992 to January 2020. We included studies in which researchers evaluated critically ill children with abnormalities in glucose homeostasis, thyroid function and adrenal function, performance characteristics of assessment and/or scoring tools to screen for endocrine dysfunction, and outcomes related to mortality, organ-specific status, and patient-centered outcomes. Studies of adults, premature infants or animals, reviews and/or commentaries, case series with sample size ≤10, and non-English-language studies were excluded. Data extraction and risk-of-bias assessment for each eligible study were performed by 2 independent reviewers. The systematic review supports the following criteria for abnormal glucose homeostasis (blood glucose [BG] concentrations >150 mg/dL [>8.3 mmol/L] and BG concentrations <50 mg/dL [<2.8 mmol/L]), abnormal thyroid function (serum total thyroxine [T4] <4.2 μg/dL [<54 nmol/L]), and abnormal adrenal function (peak serum cortisol concentration <18 μg/dL [500 nmol/L]) and/or an increment in serum cortisol concentration of <9 μg/dL (250 nmol/L) after adrenocorticotropic hormone stimulation. These included variable sampling for BG measurements, limited reporting of free T4 levels, and inconsistent interpretation of adrenal axis testing. We present consensus criteria for endocrine dysfunction in critically ill children that include specific measures of BG, T4, and adrenal axis testing.

Cortisol and Aldosterone Responses to Hypoglycemia and Na Depletion in Women With Non-Classic 21-Hydroxylase Deficiency.

Non-classic 21-hydroxylase deficiency is usually diagnosed in post-pubertal women because of androgen excess. Indication of systematic steroid replacement therapy is controversial because the risk of acute adrenal insufficiency is unknown. In order to specify this risk we evaluated the cortisol and aldosterone secretions in response to appropriate pharmacologic challenges. In this prospective case-control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) >10 ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 age- and body mass index-matched healthy women with 17OHP after Synacthen® <2 ng/mL. Each participant underwent sequentially an insulin tolerance test to evaluate cortisol secretion and a sodium depletion test, obtained by oral administration of 40 mg of furosemide under low sodium diet (<20 mmol during 24 hours), to evaluate renin and aldosterone secretion. The peak serum cortisol concentration after insulin hypoglycemia was lower in patients than in controls (mean difference -47 ng/mL, 90% CI, -66, P = 0.0026). A peak serum cortisol above a cutoff value of 170 ng/mL was obtained in all controls but only in 55% of patients (P = 0.0039). Twenty-four hours after sodium depletion, blood pressure, plasma sodium, potassium, and serum aldosterone concentrations were comparable between the two groups, but patients had higher stimulated renin concentrations than controls (P = 0.0044). Patients with non-classic 21-hydroxylase deficiency frequently display partial cortisol insufficiency and compensated defect in aldosterone secretion. Their clinical management should systematically include assessment of adrenal functions.

Cortisol and Aldosterone Responses to Insulin-Induced Hypoglycemia and Sodium Depletion in Women with Non-Classic 21-Hydroxylase Deficiency

Background: Non-classic 21-hydroxylase deficiency is usually diagnosed in post-pubertal women because of androgen excess. Indication of systematic steroid replacement therapy is controversial because the risk of acute adrenal insufficiency is unknown. In order to specify this risk we evaluated the cortisol and aldosterone secretions in response to appropriate pharmacological challenges. Methods: In this prospective case-control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) >10ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 ageand BMI-matched healthy women with 17OHP after Synacthen® <2ng/mL. Each participant underwent sequentially an insulin tolerance test to evaluate cortisol secretion and a sodium depletion test, obtained by oral administration of 40 mg furosemide under low sodium diet (< 20 mmol during 24 hours), to evaluate renin and aldosterone secretion. Findings: The peak serum cortisol concentration after insulin hypoglycemia was lower in patients than in controls (mean difference -47 ng/mL, 90%CI: -66, p=0.0026). A peak serum cortisol above a cutoff value of 170 ng/mL was obtained in all controls but only in 55% of patients (p=0.0039). 24- hours after sodium depletion, blood pressure, plasma sodium, potassium and serum aldosterone concentrations were comparable between the two groups, but patients had higher stimulated renin concentrations than controls (p=0.0044). Interpretation: Patients with non-classic 21-hydroxylase deficiency frequently display partial cortisol insufficiency and compensated defect in aldosterone secretion. Their clinical management should systematically include assessment of adrenal functions. Trial Registration Number: The trial was registered in ClinicalTrials.gov number NCT01862380. Funding Statement: Institutional grant from APHP AOR11111. Declaration of Interests: The authors state that they have nothing to disclose. Ethics Approval Statement: The study was approved by the local Ethics Committee (Comite de Protection des Personnes Ile de France VII) and the competent authority (ANSM). All subjects gave written informed consent to participate to the study.

L-Dopa Is a Potent Stimulator of Cortisol in Short Children

Aims: In this study, we evaluated the diagnostic usefulness of oral <smlcap>L</smlcap>-dopa as a stimulatory agent for cortisol. Methods: In 27 short children that were evaluated for possible growth hormone deficiency (GHD), the levels of serum GH and cortisol were determined after oral <smlcap>L</smlcap>-dopa administration and after i.m. glucagon administration. We defined cortisol concentrations >18 μg/dl (496 nmol/l) as adequate response. Peak GH concentration <10 ng/ml in both tests defined GHD. Results: Twenty-five out of the 27 children (93%) studied showed a normal cortisol response, i.e. a peak serum cortisol >18 μg/dl in the <smlcap>L</smlcap>-dopa test, whereas 19 children (70%) had a normal cortisol response after stimulation with glucagon. In the children with normal cortisol response in both tests, the mean peak serum cortisol concentration was 28.7 (SD 1.59) after <smlcap>L</smlcap>-dopa and 26.65 (SD 1.26) μg/dl after glucagon administration. There was no statistically significant difference in peak serum cortisol response to <smlcap>L</smlcap>-dopa between GH-deficient and GH-sufficient children [25.90 (SD 4.9) vs. 29.87 (SD 9.9) μg/dl, respectively]. Conclusions: These results clearly suggest that <smlcap>L</smlcap>-dopa administration is a potent stimulus for cortisol secretion at least in short children.

Residual Adrenal Function in Autoimmune Addison's Disease: Improvement After Tetracosactide (ACTH1–24) Treatment

Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy. Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement. This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.

Validation of a low-dose adrenocorticotropic hormone stimulation test in healthy neonatal foals

To determine the lowest ACTH dose that would induce a significant increase in serum cortisol concentration and identify the time to peak cortisol concentration in healthy neonatal foals. Prospective randomized crossover study. 11 healthy neonatal foals. Saline (0.9% NaCl) solution or 1 of 4 doses (0.02, 0.1, 0.25, and 0.5 μg/kg [0.009, 0.045, 0.114, and 0.227 μg/lb]) of cosyntropin (synthetic ACTH) was administered IV. Serum cortisol concentrations were measured before and 10, 20, 30, 60, 90, 120, 180, and 240 minutes after administration of cosyntropin or saline solution; CBCs were performed before and 30, 60, 120, and 240 minutes after administration. Serum cortisol concentration was significantly increased, compared with baseline, by 10 minutes after cosyntropin administration at doses of 0.1, 0.25, and 0.5 μg/kg. Serum cortisol concentration peaked 20 minutes after administration of cosyntropin at doses of 0.02, 0.1, and 0.25 μg/kg, with peak concentrations 1.7, 2.0, and 1.9 times the baseline concentration, respectively. Serum cortisol concentration peaked 30 minutes after cosyntropin administration at a dose of 0.5 μg/kg, with peak concentration 2.2 times the baseline concentration. No significant differences were detected among peak serum cortisol concentrations obtained with cosyntropin administration at doses of 0.25 and 0.5 μg/kg. Cosyntropin administration significantly affected the lymphocyte count and the neutrophil-to-lymphocyte ratio. Results suggested that in healthy neonatal foals, the lowest dose of cosyntropin to result in significant adrenal gland stimulation was 0.25 μg/kg, with peak cortisol concentration 20 minutes after cosyntropin administration.

Deconvolution analysis of 24‐h serum cortisol profiles informs the amount and distribution of hydrocortisone replacement therapy

Hydrocortisone therapy is based on a dosing regimen derived from estimates of cortisol secretion, but little is known of how the dose should be distributed throughout the 24 h. We have used deconvolution analysis of 24-h serum cortisol profiles to determine 24-h cortisol secretion and distribution to inform hydrocortisone dosing schedules in young children and older adults. Twenty four hour serum cortisol profiles from 80 adults (41 men, aged 60-74 years) and 29 children (24 boys, aged 5-9 years) were subject to deconvolution analysis using an 80-min half-life to ascertain total cortisol secretion and distribution throughout the 24-h period. Mean daily cortisol secretion was similar between adults (6.3 mg/m(2) body surface area/day, range 5.1-9.3) and children (8.0 mg/m(2) body surface area/day, range 5.3-12.0). Peak serum cortisol concentration was higher in children compared with adults, whereas nadir serum cortisol concentrations were similar. Timing of the peak serum cortisol concentration was similar (07.05-07.25), whereas that of the nadir concentration occurred later in adults (midnight) compared with children (22.48) (P = 0.003). Children had the highest percentage of cortisol secretion between 06.00 and 12.00 (38.4%), whereas in adults this took place between midnight and 06.00 (45.2%). These observations suggest that the daily hydrocortisone replacement dose should be equivalent on average to 6.3 mg/m(2) body surface area/day in adults and 8.0 mg/m(2) body surface area/day in children. Differences in distribution of the total daily dose between older adults and young children need to be taken into account when using a three or four times per day dosing regimen.

Technical note: Comparison of salivary and serum cortisol concentrations after adrenocorticotropic hormone challenge in ewes1,2

An ACTH challenge was conducted to determine if salivary cortisol concentration reflects serum cortisol concentration in ewes. Twelve yearling ewes (64.0 +/- 1.2 kg) were administered ACTH (100 IU, intravenously) or saline. Serum and salivary samples were collected at 30-min intervals for 2 h before ACTH administration, at 15-min intervals for 2 h after treatment, and at 30-min intervals for an additional 3 h, and cortisol concentration was determined by RIA. Although ewes responded to ACTH and saline, cortisol concentration was greater (P < 0.001) in ACTH-treated ewes from 15 to 120 min and tended to be greater (P = 0.054) at 150 min after challenge in serum. In saliva, cortisol concentration was greater (P < 0.001) in ACTH-treated ewes from 30 to 120 min and tended to be greater (P = 0.092) at 15 min after challenge. No difference was observed between ACTH-treated ewes and controls for time to peak serum cortisol concentration (P = 0.126) and time to peak salivary cortisol concentration (P = 0.109), or between saliva and serum for time to peak cortisol concentration (P = 0.220) and return to baseline cortisol concentration (P = 0.341). The serum (P = 0.009) and salivary (P = 0.050) cortisol areas under the curve between 0 and 150 min were greater for ACTH-treated ewes than controls, and serum (P = 0.002) and salivary (P < 0.001) cortisol return to baseline concentration was longer for ACTH-treated ewes. The correlation coefficient between serum and salivary cortisol concentrations was 0.88 (P < 0.001). These data indicate that salivary cortisol concentration is closely related to serum cortisol concentration and that the former may represent a suitable noninvasive alternative to blood collection for measurement of cortisol in sheep.

Endocrine and Immunologic Effects of Inhaled Fluticasone Propionate in Healthy Dogs

Inhaled glucocorticoids reduce airway inflammation while minimizing systemic effects in several species. Inhaled fluticasone suppresses the hypothalamic-pituitary-adrenal axis (HPAA), modifies immune function, and induces clinical signs to a lesser extent than PO-administered prednisone in dogs. Seven healthy adult pet dogs. Dogs were randomized to 1 of 3 treatment groups in a crossover design: fluticasone propionate (220 mug actuation of a metered dose inhaler delivered via a spacer and mask, q12h), placebo (spacer and mask alone, q12h), or prednisone (1 mg/kg PO q24h). Each treatment was administered for 3 weeks followed by a 4-week washout. Appetite, attitude, and water consumption were recorded during the last week of each treatment period. Urine cortisol : creatinine ratios, ACTH stimulation tests, white blood cell counts, lymphocyte phenotype, and serum IgM and IgA concentrations were recorded at each baseline and after the last day of each treatment. Clinical observations were expressed descriptively. Friedman's test was applied to all data comparisons. Pairwise comparisons were made with a mixed model analysis when data were normally distributed, whereas signed rank tests were used otherwise (significance P-value <.01). Appetite and water consumption increased during prednisone treatment. Peak serum cortisol concentrations post-ACTH were significantly decreased in prednisone- and fluticasone-treated dogs compared with placebo (prednisone > fluticasone). Serum IgM concentrations were significantly decreased in dogs treated with prednisone. As used, fluticasone suppresses the HPAA to a lesser extent than prednisone and may avert systemic signs associated with PO-administered glucocorticoids in dogs.

Effect of low doses of cosyntropin on serum cortisol concentrations in clinically normal dogs

To determine the lowest of 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, or 0.01 microg/kg) administered IV that stimulates maximal cortisol secretion in clinically normal dogs. 10 clinically normal dogs. 5 dose-response experiments were performed in each of the dogs. Each dog received 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, and 0.01 microg/kg) IV in random order (2-week interval between each dose). Serum samples for determination of cortisol concentrations were obtained before (baseline) and at 10, 20, 30, 40, 50, 60, 120, and 240 minutes after cosyntropin administration. Compared with baseline values, mean serum cortisol concentration in the study dogs increased significantly after administration of each of the 5 cosyntropin doses. Mean peak serum cortisol concentration was significantly lower after administration of 0.01, 0.05, and 0.1 microg of cosyntropin/kg, compared with findings after administration of 0.5 and 1.0 microg of cosyntropin/kg. After administration of 0.5 and 1.0 microg of cosyntropin/kg, mean peak serum cortisol concentration did not differ significantly; higher doses of cosyntropin resulted in more sustained increases in serum cortisol concentration, and peak response developed after a longer interval. Administration of cosyntropin IV at a dose of 0.5 microg/kg induced maximal cortisol secretion in healthy dogs. Serum cortisol concentration was reliably increased in all dogs after the administration of each of the 5 doses of cosyntropin. These data should be useful in subsequent studies to evaluate the hypothalamic-pituitary-adrenal axis in healthy and critically ill dogs.

Synthetic Adrenocorticotropic Hormone Stimulation Tests in Healthy Neonatal Foals

Background:Cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation tests are used to evaluate adrenal function. Low‐dose ACTH stimulation tests are the most accurate method for diagnosing relative adrenal insufficiency in critically ill humans but have not been evaluated in foals.Hypothesis:Peak serum cortisol concentrations in healthy foals will not be significantly different after intravenous administration of 1, 10, 100, and 250 μg of cosyntropin.Animals:14 healthy neonatal foals, 3–4 days of age.Methods:A randomized cross‐over model was used in which cosyntropin (1, 10, 100, or 250 μg) was administered intravenously on days 3 and 4 of life. Blood samples were collected before and 30, 60, 90, 120, and 150 minutes after administration of cosyntropin for determination of serum cortisol concentration.Results:Serum cortisol concentrations did not significantly increase after administration of 1 μg of cosyntropin. Cortisol concentration peaked 30 minutes after administration of 10 μg of cosyntropin and 90 minutes after 100 and 250 μg of cosyntropin. There was no relationship between cosyntropin dose and serum cortisol concentration at 30 minutes. Compared with the 10‐μg dose, 100 and 250 μg of cosyntropin induced significantly greater cortisol concentrations at 90 minutes, at which point the 10‐μg cosyntropin‐dose cortisol values were indistinguishable from baseline. There was no significant difference in the area under the cortisol concentration curve between the 100‐and 250‐μg doses. No effect of day of testing or foal weight on peak cortisol concentration was detected.Conclusions and Clinical Importance: The results of this study suggest that 10‐and 100‐μg doses of cosyntropin would be appropriate for evaluating adrenal function in neonatal foals.

Adrenocortical suppression increases the risk of relapse in nephrotic syndrome

Objective: Children with nephrotic syndrome (NS) are usually treated with long-term low dose alternate day prednisolone with or without glucocorticoid sparing therapy, such as levamisole or ciclosporin, to maintain remission....

Assessing adrenal function in primary care settings with a single sample subcutaneous glucagon test

To test the efficacy of the low-dose glucagon test in assessing adrenal gland function. Subcutaneous glucagon was used to assess the hypothalamo-pituitary-adrenal gland (HPA) axis in 215 healthy children. Concordance of this test with the low-dose intravenous ACTH test was established for 42 children. Glucagon testing was conducted for 150 minutes after subcutaneous glucagon administration and for 30 minutes after 1 microg intravenous ACTH. Mean peak serum cortisol concentrations were 22.4 +/- 0.6 microg/dL (SEM) after subcutaneous glucagon and 20.0 +/- 0.6 microg/dL after intravenous ACTH. Specificity of 95% was found at peak cortisol concentrations of 9.5 and 12.5 microg/dL for the glucagon and ACTH tests, respectively. Concordance between the glucagon and ACTH tests was 90.5%. The glucagon test was found to be as good a test of the HPA axis as the ACTH test and had a 90.5% concordance with it. The ease of performing the glucagon test, namely, obtaining a single sample of blood 150 minutes after the subcutaneous administration of glucagon, makes it a useful method of assessing the HPA axis in primary care settings.

Cytokine Response to Surgical Stress: Comparison of Pure Laparoscopic, Hand-Assisted Laparoscopic, and Open Nephrectomy

Laparoscopic surgery has been shown to induce less immune suppression than open surgery, presumably because there is less tissue trauma, a factor that may impact oncologic-disease control. The objective of this study was to compare the cytokine and stress response associated with pure laparoscopic, hand-assisted laparoscopic (HAL), and open nephrectomy. Fifteen female farm pigs (45-50 kg) underwent transperitoneal laparoscopic, handassisted (HAL), or open nephrectomy (N = 5 in each group). At 1, 4, 24, and 48 hours post-nephrectomy, blood and peritoneal fluid samples were collected for measurement of tumor necrosis factor (TNF) alpha, interleukin (IL)-1beta, and IL-6 using enzyme-linked immunosorbent assay (ELISA) techniques. Body temperature and serum glucose and cortisol were also measured. No evidence of perioperative infection was detected in any animal through temperature and glucose monitoring. Operating time and blood loss were comparable among the three groups. Peak serum cortisol concentrations were significantly higher in the HAL group than in the pure laparoscopic group at 24 hours (P = 0.02). Serum TFNalpha concentrations were significantly lower in the pure laparoscopy group (40 +/- 6 pg/mL) than in the HAL and open-nephrectomy groups (81 +/- 6 pg/mL and 83 +/- 17 pg/mL, respectively; P < 0.05), although no differences between groups were found in the serum IL-1beta and IL-6 concentrations. Peritoneal IL-1beta was significantly higher in the HAL than in the open-nephrectomy group (2993 +/- 507 pg/mL and 733 +/- 185 pg/mL, respectively; P = 0.05). Peritoneal IL-6 was significantly lower in the pure laparoscopy group (694 +/- 234 pg/mL) than in the open-surgery group (1668 +/- 312 pg/mL) (P = 0.04). Pure laparoscopic surgery in pigs elicits a less-robust cytokine response than HAL or open nephrectomy with respect to serum TNFalpha and peritoneal IL-6 concentrations, perhaps reflecting less impairment of the immune system. Clinical confirmation is required, and the implications with regard to oncologic tumor surveillance in humans require further study.

Disturbed Adrenal Function in Adolescents with Chronic Fatigue Syndrome

To investigate adrenal function in children and adolescents with chronic fatigue syndrome (CFS) compared with age-matched controls. Case-control study of low dose (500 ng/m2) synacthen tests (LDST) in 23 adolescents with CFS and 17 age-matched controls. Serum cortisol concentrations were measured at 5-min intervals from 10 to 45 minutes. Peak serum cortisol concentration, time to peak, rise in cortisol and area under the curve (AUC) were derived. Patients with CFS had significantly lower mean cortisol levels during the LDST (p <0.001), lower peak cortisol (p <0.025), reduced cortisol AUC (p <0.005) and longer time to peak cortisol (p <0.05). Abnormalities were seen in both sexes but were more pronounced in females. Unstimulated adrenal androgen and 17-hydroxyprogesterone concentrations were normal. Adolescents with CFS have subtle alterations in adrenal function suggesting a reduction in central stimulation of the adrenal glands. The more pronounced effects in females may reflect differential central effects of stress on hypothalamic-pituitary-adrenal axis regulation between the sexes.

Hydrocortisone levels in the urine and blood of horses treated with ACTH.

An investigation was undertaken to demonstrate whether therapeutic treatment with ACTH raises hydrocortisone (cortisol) levels in horse urine above the limit (1000 ng/ml) established by the International Conference of Racing Authorities with the aim of controlling the abuse of cortisol and ACTH in equine sports. ACTH (200 iu) was administered i.m. to 3 Thoroughbred horses; urine and blood samples were collected at intervals afterwards and analysed by an immunoenzymatic system (ELISA) and HPLC-MS. To ascertain post exercise cortisol levels in untreated horses, 101 urine and 103 serum samples were taken from horses immediately after racing and analysed by ELISA. The peak urine level of cortisol, detected 8 h after ACTH administration, was around 600 ng/ml using either ELISA or HPLC-MS. The peak serum cortisol concentration was found to be around 250 ng/ml by ELISA, but consistently less by HPLC-MS. Mean cortisol levels in post race horses were 135.1+/-72.1 ng/ml in urine and 90.1+/-41.7 ng/ml in serum. High levels of the metabolite 20beta-dihydrocortisol in urine and the cortisol precursor 11beta-desoxycortisol in serum were found. The latter showed high cross-reactivity with cortisol on ELISA. In our experiment, treatment with ACTH 200 iu i.m. did not raise urinary cortisol levels above the 1000 ng/ml threshold proposed by the ICRA.

Adrenal function in the cat: comparison of the effects of cosyntropin (synthetic ACTH) and corticotropin gel stimulation

The serum cortisol responses of 10 normal cats to natural adrenocorticotrophic hormone (ACTH) gel and synthetic ACTH (cosyntropin) were evaluated and compared. Following administration of either ACTH gel or cosyntropin, mean serum cortisol concentrations increased significantly (P less than 0.05) within 30 minutes and reached a maximal response (2.5 to 10 times basal values) at 90 minutes. The time to reach peak serum cortisol concentrations was variable, however, and occurred sooner after cosyntropin (30 to 60 minutes) than after ACTH gel administration (90 to 180 minutes). While ACTH gel tended to produce a prolonged cortisol response, the effects of cosyntropin were more transient, with serum cortisol concentrations returning to normal range within three hours after injection. Results of this study indicate that the administration of either ACTH gel or cosyntropin consistently produces an adequate adrenocortical response in the cat. Based on the time response studies, post ACTH cortisol samples should be collected 60 to 90 minutes after cosyntropin or 90 to 120 minutes after ACTH gel injection to ensure detection of peak adrenocortical response with either ACTH preparation.