Reproducibility of the cortisol response to stimulation with a low dose of ACTH(1–24): the effect of basal cortisol levels and comparison of low-dose with high-dose secretory dynamics

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

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One microgram is the lowest ACTH dose to cause a maximal cortisol response. There is no diurnal variation of cortisol response to submaximal ACTH stimulation

Acta Endocrinologica ◽

10.1530/eje.0.1370172 ◽

1997 ◽

pp. 172-175 ◽

Cited By ~ 57

Author(s):

G Dickstein ◽

D Spigel ◽

E Arad ◽

C Shechner

Keyword(s):

Diurnal Variation ◽

Cortisol Level ◽

Low Dose ◽

Cortisol Response ◽

Acth Stimulation ◽

Baseline Cortisol ◽

Maximal Stimulation ◽

Basal Cortisol ◽

Basal Cortisol Level ◽

Cortisol Responses

There are many suggestions in the literature that the adrenal gland is more sensitive to ACTH in the evening than in the morning. However, all these studies in humans were conducted when the basal cortisol level was not suppressed, and were based on the observation that, after stimulation, the increases in cortisol differed, though the peak values were the same. To examine this, we established the lowest ACTH dose that caused a maximal cortisol stimulation even when the basal cortisol was suppressed, and used a smaller dose of ACTH for morning and evening stimulation. The lowest ACTH dose to achieve maximal stimulation was found to be 1.0 microgram, with which dose cortisol concentration increased to 607.2 +/- 182 nmol/l, compared with 612.7 +/- 140.8 nmol/l with the 250 micrograms test (P > 0.3). The use of smaller doses of ACTH (0.8 and 0.6 microgram) achieved significantly lower cortisol responses (312 +/- 179.4 and 323 +/- 157.3 nmol/l respectively; both P < 0.01 compared with the 1 microgram test). When a submaximal ACTH dose (0.6 microgram) was used to stimulate the adrenal at 0800 and 1600 h, after pretreatment with dexamethasone, no difference in response was noted at either 15 min (372.6 +/- 116 compared with 394.7 +/- 129.7 nmol/l) or 30 min (397.4 +/- 176.6 compared with 403 +/- 226.3 nmol/l; P > 0.3 for both times). These results show that 1.0 microgram ACTH, used latterly as a low-dose test, is very potent in stimulating the adrenal, even when baseline cortisol is suppressed; smaller doses cause reduction of this potency. Our data show that there is probably no diurnal variation in the response of the adrenal to ACTH, if one eliminates the influence of the basal cortisol level and uses physiologic rather than superphysiologic stimuli.

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Reversible megaoesophagus in a dog with isolated glucocorticoid-deficient hypoadrenocorticism

Veterinary Record Case Reports ◽

10.1136/vetreccr-2019-001055 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001055

Author(s):

Darren Kelly

Keyword(s):

Complete Resolution ◽

Clinical Signs ◽

Serum Cortisol ◽

Cortisol Concentration ◽

Adrenocorticotrophic Hormone ◽

Acth Stimulation ◽

Serum Aldosterone ◽

History Of ◽

Acth Concentration ◽

Serum Cortisol Concentration

An eight-year-old, female, neutered labradoodle was presented for investigation of a three-week history of lethargy and regurgitation. Two sets of conscious thoracic radiographs, performed approximately two weeks apart, revealed the presence of megaoesophagus. Serum cortisol concentration (pre-adrenocorticotrophic hormone (ACTH) and post-ACTH stimulation), serum aldosterone concentration post-ACTH stimulation and plasma endogenous ACTH concentration confirmed the diagnosis of isolated glucocorticoid-deficient hypoadrenocorticism. Following glucocorticoid supplementation, rapid resolution of the clinical signs was reported, and repeated conscious thoracic radiographs one week later showed complete resolution of the megaoesophagus.

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The interpretive contribution of the baseline serum cortisol concentration of the ACTH stimulation test in the diagnosis of pituitary dependent hyperadrenocorticism in dogs

Journal of Veterinary Internal Medicine ◽

10.1111/jvim.15330 ◽

2018 ◽

Vol 32 (6) ◽

pp. 1897-1902 ◽

Cited By ~ 4

Author(s):

Ran Nivy ◽

Kent R. Refsal ◽

Ella Ariel ◽

Sharon Kuzi ◽

Einat Yas-Natan ◽

...

Keyword(s):

Serum Cortisol ◽

Cortisol Concentration ◽

Stimulation Test ◽

Acth Stimulation Test ◽

Acth Stimulation ◽

Baseline Serum ◽

Serum Cortisol Concentration

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THE FREQUENCY OF ADRENAL INSUFFICIENCY IN ADOLESCENTS AND YOUNG ADULTS WITH THALASSEMIA MAJOR VERSUS THALASSEMIA INTERMEDIA IN IRAN

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2015.005 ◽

2014 ◽

Vol 7 ◽

pp. e2015005 ◽

Cited By ~ 4

Author(s):

Sara Matin ◽

Masoud Ghanei Jahromi ◽

Zohreh Karemizadeh ◽

Sezaneh Haghpanah ◽

Vincenzo De Sanctis ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Standard Dose ◽

Serum Cortisol ◽

Thalassemia Major ◽

Cross Sectional Study ◽

Cortisol Response ◽

Acth Stimulation ◽

Cross Sectional ◽

Basal Cortisol ◽

The Mean

Background: Endocrine dysfunction is not uncommon complication in patients with transfusion dependent thalassemia and is thought to occur as a consequence of excessive iron overload. The main objective of this study is to determine the frequency of adrenal insufficiency in patients with thalassemia major and thalassemia intermediate. Methods: This cross-sectional study was done at the Shiraz University of Medical Sciences, Shiraz, Southern Iran, in 2013. One hundred and ninety patients were divided into two groups; thalassemia major(TM) and thalassemia intermediate (TI) groups. We measured 8 AM serum cortisol, ACTH and ferritin concentrations in all patients. Results: The mean age of the TM and TI group were 22.5±5.7 and 23.8±6 years, respectively. 90 patients (47.4%) were splenectomized, 34 (36.2%) with TM and 56 (58.2%) with TI (p : 0.001). The mean serum ferritin levels were 3056.5±2306 and 666.2±616.5 in TM and TI respectively (p: 0.001). Three patients with TM (1.6%) had low basal cortisol and ACTH levels. However their cortisol response to ACTH stimulation was normal. Conclusions: Low basal concentrations of cortisol and ACTH occurred in 1.6% of our adolescents young adult patients with TM suggesting a central defect of cortisol secretion at the basal state. However, cortisol response to standard – dose ACTH was normal in all patients with TM and TI.

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Evaluation of thymus morphology and serum cortisol concentration as indirect biomarkers to detect low-dose dexamethasone illegal treatment in beef cattle

BMC Veterinary Research ◽

10.1186/1746-6148-8-129 ◽

2012 ◽

Vol 8 (1) ◽

pp. 129 ◽

Cited By ~ 14

Author(s):

Marta Vascellari ◽

Katia Capello ◽

Annalisa Stefani ◽

Giancarlo Biancotto ◽

Letizia Moro ◽

...

Keyword(s):

Beef Cattle ◽

Low Dose ◽

Serum Cortisol ◽

Cortisol Concentration ◽

Serum Cortisol Concentration

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Gender difference in adrenal sensitivity to ACTH is abolished in type 2 diabetes

Endocrine Connections ◽

10.1530/ec-15-0003 ◽

2015 ◽

Vol 4 (2) ◽

pp. 92-99 ◽

Cited By ~ 4

Author(s):

Lisa Arnetz ◽

Neda Rajamand Ekberg ◽

Kerstin Brismar ◽

Michael Alvarsson

Keyword(s):

Type 2 Diabetes ◽

Gender Differences ◽

Hpa Axis ◽

Serum Cortisol ◽

Cortisol Concentration ◽

Clinical Implications ◽

Healthy Men ◽

Adrenal Response ◽

Serum Cortisol Concentration

ObjectiveDysfunction of the hypothalamus–pituitary–adrenal (HPA) axis has been implicated in type 2 diabetes (T2D). The aim of this study was to investigate the impact of T2D and gender on the HPA axis.MethodsSynthetic ACTH (1 μg) was administered to 21 subjects with T2D (age 62 (54–70) years, 11 men/ten women, HbA1c 49±2 mmol/mol, treated with diet or oral antidiabetic drugs) and 38 controls (age 58 (41–67) years, 20 men/18 women). Fasting basal B-glucose, serum cortisol, insulin, IGF1 and IGFBP1 concentrations were measured, and sampling for all but IGF1 was repeated 30, 60, and 90 min after ACTH injection. Patients took 0.25 mg dexamethasone at 2200–2300 h and returned the next morning for the measurement of serum cortisol concentration.DesignCross-sectional study.ResultsPatients with T2D had similar fasting serum cortisol, IGF1 and IGFBP1 concentrations; however, serum cortisol concentration after administration of dexamethasone did not differ between the groups. Healthy women exhibited higher peak cortisol levels compared with healthy men (675±26 vs 582±21 nmol/l, P=0.014), while the peak levels were equally high in men and women with T2D, resulting in a higher peak level in men with T2D compared with healthy men (691±42 vs 582±21 nmol/l, P=0.024). Serum cortisol concentration after administration of dexamethasone did not differ between the groups, nor did IGF1 and IGFBP1.Novelty of the findingsSome studies have previously indicated disturbed regulation of the hypothalamus–pituitary–adrenal (HPA) axis in subjects with type 2 diabetes (T2D); however, much remains unknown in this area. To the best of our knowledge, this is the first study to show that the gender difference in the adrenal response to ACTH (with greater reactivity in women) is abolished in T2D. While the clinical implications cannot be determined by this paper, it is known that gender differences exist in the pathogenesis and complications of T2D. Thus, our findings suggest that further research into gender differences in the HPA axis is warranted.ConclusionsGender differences in adrenal response to ACTH were abolished in T2D. Men with T2D had a higher peak cortisol compared with controls. Further studies are needed to elucidate the clinical implications.

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Adrenocorticotropin Stimulation Test: Effects of Basal Cortisol Level, Time of Day, and Suggested New Sensitive Low Dose Test*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem-72-4-773 ◽

1991 ◽

Vol 72 (4) ◽

pp. 773-778 ◽

Cited By ~ 284

Author(s):

GABRIEL DICKSTEIN ◽

CARMELA SHECHNER ◽

WENDELL E. NICHOLSON ◽

ITZHAK ROSNER ◽

ZILA SHEN-ORR ◽

...

Keyword(s):

Cortisol Level ◽

Low Dose ◽

Time Of Day ◽

Stimulation Test ◽

Basal Cortisol ◽

Basal Cortisol Level

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Evaluation of adrenal reserve in patients with differential thyroid cancer receiving thyroid hormone suppression therapy- case-control comparative study

10.21203/rs.3.rs-1043425/v1 ◽

2021 ◽

Author(s):

Muhammet Cuneyt Bilginer ◽

Abbas Ali Tam ◽

Sevgul Faki ◽

Nagihan Bestepe ◽

Fatma Dilek Dellal ◽

...

Keyword(s):

Thyroid Cancer ◽

Adrenal Insufficiency ◽

Patient Group ◽

Standard Dose ◽

Serum Cortisol ◽

Control Group ◽

Cortisol Response ◽

Acth Stimulation ◽

Tsh Suppression ◽

Basal Cortisol

Abstract Background Patients with differentiated thyroid cancer (DTC) are exposed to subclinical exogenous hyperthyroidism for the suppression of thyroid-stimulating hormone (TSH). In this study, we aimed to evaluate the adrenal reserve in DTC patients receiving suppression therapy. Materials and Methods The study included 55 DTC patients on suppression therapy and 32 healthy volunteers. Basal serum cortisol of all participants and adrenocorticotropic hormone (ACTH) of the patient group were measured. A standard-dose ACTH test (0.25 mg) was performed in patients with a basal cortisol < 14.5 mcg/dL. Results In the patient group, TSH was lower, free thyroxine (fT4) was higher, and free triiodothyronine (fT3) was similar to those of the control group (p < 0.01, p < 0.01, p = 0.140, respectively). The serum cortisol of the patient group was significantly lower than the control group (12.14 ± 5.12 mcg/dL vs 18.00 ± 5.56 mcg/dL, p < 0.001). 34 (61.8%) patients with DTC had a basal cortisol < 14.5 mcg/dL. Prolonged TSH suppression (≥ 5 years vs < 5 years) was associated with lower basal cortisol (7.46 ± 2.63 mcg/dL vs 9.48 ± 2.65 mcg/dL, p = 0.022). The ACTH stimulation test showed that 2 (5.8%) patients had a cortisol response < 18 mcg/dL. The rate of adrenal insufficiency was 3.6% in DTC patients. A moderate negative correlation was found between ACTH and fT3 of patients with low basal cortisol (r = − 0.358, p = 0.038) Conclusion Patients with DTC receiving TSH suppression therapy are at risk for adrenal insufficiency. The duration and severity of suppression might increase this possibility. Dynamic testing with synthetic ACTH can be used to reveal insufficient cortisol response in case of clinical suspicion.

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Platelet Function in Surgical Stress

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660146 ◽

1985 ◽

Vol 54 (04) ◽

pp. 849-852 ◽

Cited By ~ 36

Author(s):

O Naesh ◽

J T Friis ◽

I Hindberg ◽

K Winther

Keyword(s):

Stress Response ◽

Negative Correlation ◽

Surgical Stress ◽

Plasma Concentrations ◽

Serum Cortisol ◽

Cortisol Concentration ◽

Pulmonary Dysfunction ◽

Arterial Po2 ◽

Elective Cholecystectomy ◽

Serum Cortisol Concentration

SummaryTen patients for elective cholecystectomy were studied pre-, per- and postoperatively. All had neurolept anesthesia. Plasma concentrations of β-TG, TXB2 and 5-HT and intraplatelet 5-HT were measured. Aggregation to ADP was recorded.Serum cortisol concentration was used as index of the stress response, showing peroperative increase and postoperative decrease. Closely related to this we observed a significant increase in P-β-TG and P-TXB2 with postoperative normalization in 6 patients without complications. P-5-HT had a peak peropera-tively and remained elevated postoperatively. A negative correlation between P--5-HT and decreasing intraplatelet 5-HT postoperatively was observed.High postoperative levels of P--5-HT seem to be related to low arterial Po2 and pulmonary dysfunction. In 3 patients with complications a second increase in P-β-TG, P-TXB2 and partly in P--5-HT was found. Platelets were temporarily refractory to ADP immediately following surgery and showed increased aggregabil-ity postoperatively. We conclude that platelets are activated in surgical stress.

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