A Comparison Between the Effects of Low (1 μg) and Standard Dose (250 μg) ACTH Stimulation Tests on Adrenal Cortex Functions with Leprosy Patients

OBJECTIVE: Numerous studies have found elevated androgen production by the adrenal glands in patients with polycystic ovary syndrome (PCOS). However, the role and the mechanisms responsible for the adrenal androgen excess in women with PCOS are not well understood. DESIGN: Our aim was to compare 17-hydroxyprogesterone (17-OHP), androstenedione, dehydroepiandrosterone sulfate (DHEAS) and cortisol responses to a low dose (1 microg) ACTH stimulation test (LDT) with the responses to a standard dose (250 microg) ACTH stimulation test (SDT) in patients with PCOS. METHODS: Fifty women with PCOS (mean age 25.4+/-0.7 years) and 20 healthy women (mean age 27.3+/-2.2 years) were included in the study. The patients and controls underwent ACTH stimulation tests with 1 microg and 250 microg synthetic ACTH in the follicular phase of their cycles. Venous blood was drawn at 0, 30 and 60 min for determination of serum cortisol, 17-OHP, androstenedione and DHEAS levels. RESULTS: In PCOS subjects, peak and area under the curve (AUC) 17-OHP (9.3+/-0.3 nmol/l, 378.4+/-61 nmol/lx60 min), androstenedione (15.6+/-0.6 nmol/l, 806.4+/-52 nmol/lx60 min) and DHEAS (7.5+/-0.4 micromol/l, 385.6+/-25.5 micromol/lx60 min) responses to SDT were significantly higher than the levels in healthy women (respectively 5.7+/-0.3 nmol/l and 249.4+/-52.2 nmol/lx60 min for 17-OHP; 9.1+/-0.3 nmol/l and 413.7+/-31.6 nmol/lx60 min for androstenedione; 4.3+/-0.4 micromol/l and 224.9+/-24.5 micromol/lx60 min for DHEAS) (P<0.05). Peak and AUC cortisol responses to SDT were similar in PCOS and control subjects. Peak and AUC cortisol and 17-OHP responses to LDT in women with PCOS were similar to the values obtained in healthy women. Peak androstenedione (12.5+/-0.6 nmol/l) and peak (6.5+/-0.5 nmol/l) and AUC (336.3+/-22.4 micromol/lx60 min) DHEAS responses to LDT were significantly higher in women with PCOS. CONCLUSIONS: These results show that LDT is capable of revealing the adrenal hyperactivity in women with PCOS. Adrenal P450c17alpha enzyme dysregulation in PCOS is revealed by ACTH stimulation at a pharmacological dose (250 microg) but not by a physiological dose (1 microg). LDT is able to demonstrate adrenal hyperactivity characterized by an increase in DHEAS levels.

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EFFECTS OF INCREASING DOSES OF PYROGLUTAMYL-HISTIDYL-PROLINE AMIDE ON SERUM THYROTROPHIN LEVELS IN NORMAL SUBJECTS

Acta Endocrinologica ◽

10.1530/acta.0.0700196 ◽

1972 ◽

Vol 70 (1) ◽

pp. 196-208 ◽

Cited By ~ 12

Author(s):

Bengt Karlberg ◽

Sven Almqvist

Keyword(s):

Normal Saline ◽

Standard Dose ◽

Normal Subjects ◽

Response Curves ◽

Clinical Observations ◽

Trh Stimulation ◽

Stimulation Tests ◽

Serial Measurements ◽

Serum Tsh ◽

Stimulation Of

ABSTRACT The effects of the administration of normal saline in four normal subjects and the single iv injections of synthetic pyroglutamyl-histidyl-proline amide (TRH) in doses of 6.25, 12.5, 25, 50, 100, 200 and 400 μg in 12 healthy subjects were evaluated by clinical observations and serial measurements from −10 to + 360 minutes of serum TSH, PBI, STH, cholesterol, glucose and insulin. Normal saline and TRH 6.25 μg iv did not change the serum TSH level. The minimum iv dose of TRH increasing serum TSH within 10 minutes was 12.5 μg. Nine of 12 subjects gave maximal increases of serum TSH after TRH 100 μg and all after 200 and 400 μg. The time for the peak response varied with the dose from 15 to 60 minutes. The dose-response curves, average and individual, were complex and not linear. This was interpreted as a varying degree of stimulation of both pituitary synthesis and release of TSH by TRH. PBI changes were measured at 2 h and 6 h. Minimum dose for a significant increase of PBI was 12.5 μg and 6.25 μg of TRH for the respective times. No change in basal STH-levels occurred in 53 of 65 TRH-stimulation tests. Nine of the 12 changes in serum STH occurred in four subjects with varying basal STH-levels. No changes were found in serum cholesterol, glucose or insulin. Our results show that 50 μg of TRH can be used as a standard dose for the single iv stimulation of pituitary release of TSH. TRH stimulated both TSH and STH release in 18% of our tests.

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PROPERTIES OF RAT ADRENAL ZONA RETICULARIS CELLS: PRODUCTION AND STIMULATION OF CERTAIN STEROIDS

Journal of Endocrinology ◽

10.1677/joe.0.0830435 ◽

1979 ◽

Vol 83 (3) ◽

pp. 435-447 ◽

Cited By ~ 18

Author(s):

J. B. G. BELL ◽

R. P. GOULD ◽

P. J. HYATT ◽

J. F. TAIT ◽

S. A. S. TAIT

Keyword(s):

Adrenal Cortex ◽

Significant Role ◽

Zona Fasciculata ◽

Cell Type ◽

Acth Stimulation ◽

Specific Stimulus ◽

Zona Reticularis ◽

Cell Pool ◽

Stimulation Of

The outputs of corticosterone, deoxycorticosterone and androstenedione from dispersed, purified rat adrenal zona reticularis and zona fasciculata cells have been measured by radioimmunoassay. Preferential production of deoxycorticosterone by zona reticularis cells was demonstrated by their higher basal deoxycorticosterone: corticosterone ratio when compared with zona fasciculata cells. Adrenocorticotrophin (ACTH) stimulated corticosterone output by all cell pools prepared by unit gravity (1 g) sedimentation, zona fasciculata cells being stimulated 130-fold compared with 20-fold for the zona reticularis cells in relation to their basal corticosterone output. In every cell pool, ACTH stimulated the output of corticosterone more than it stimulated the output of deoxycorticosterone. In parallel cell preparations, it was shown that ACTH increased the conversion of tracer amounts of radioactive deoxycorticosterone to corticosterone and decreased the conversion of radioactive corticosterone to 11-dehydrocorticosterone. Adrenocorticotrophin did not increase the conversion of radioactive deoxycorticosterone to total 11-oxygenated steroids (corticosterone+ 11-dehydrocorticosterone). It is unlikely therefore that ACTH stimulates 11 β-hydroxylation. Data indicate that the ratio of deoxycorticosterone to total 11-oxygenated steroids (corticosterone +11-dehydrocorticosterone) is characteristic for each cell type, and that this ratio will be relatively independent of ACTH stimulation or the amount of pregnenolone substrate available. Basal androstenedione outputs were similar for both types of cell, and ACTH stimulation was very small, being slightly greater for zona fasciculata than for zona reticularis cells. The contribution of the zona reticularis cells to the basal output of any steroid by the cells of the inner two zones of the adrenal cortex of the rat was relatively small (20% for deoxycorticosterone and 10% for corticosterone) and was even less after stimulation by ACTH. Unless a specific stimulus can be found, therefore, a significant role for the zona reticularis cannot yet be established.

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Effect of method of blood sample collection on adrenal activity in farmed red deer and sheep following administration of ACTH

Animal Science ◽

10.1017/s1357729800009899 ◽

1998 ◽

Vol 67 (1) ◽

pp. 157-164 ◽

Cited By ~ 8

Author(s):

I. Ferre ◽

P. J. Goddard ◽

A. J. Macdonald ◽

C. A. Littlewood ◽

E. I. Duff

Keyword(s):

Blood Sample ◽

Plasma Cortisol ◽

Sampling Method ◽

Red Deer ◽

Blood Sampling ◽

Domestic Sheep ◽

Sample Collection ◽

Acth Stimulation ◽

Treatment Groups ◽

Stimulation Tests

AbstractThe effect of method of blood sample collection (automatic blood sampling equipment (ABSE) v. manual) on cortisol and progesterone concentrations was investigated in 20 farmed red deer hinds and 20 domestic sheep ewes following dexamethasone and exogenous ACTH administration. Ten animals were subjected to either automatic sampling or manual sampling via jugular venipuncture in 1 week, with the treatment groups reversed in the 2nd week. The ABSE was programmed to collect a blood sample, then deliver 2 mg dexamethasone, collect a further blood sample 120 min later and then inject 100 fig ACTH. Thereafter, samples were collected at 15-min intervals during a 2·5 h period (12 samples in total). In the manual injection and sampling treatment, four samples were collected: (1) before dexamethasone administration, (2) before ACTH administration, (3) 60 min after ACTH administration, and (4) 150 min after ACTH administration. The success rate of blood sampling with ABSE was 80%. The overall mean packed cell volume (PCV) from samples collected by ABSE from both hinds and ewes was significantly lower than that from samples collected manually (P < 0·01) and PCV declined with time in manually sampled animals (P < 0·01). Plasma cortisol concentrations peaked at 45 min after ACTH administration in sheep and deer. In sheep, there was a marked fluctuation in the plasma cortisol concentrations with time. Both deer and sheep showed a reduced cortisol response to ACTH during week 2 irrespective of sampling method suggesting down-regulation of the response to ACTH. Maximum mean plasma progesterone concentration was reached at 15 to 30 min after ACTH administration. No significant differences in cortisol and progesterone responses due to blood sampling method were found in animals receiving prior dexamethasone treatment. This demonstrates that the ABSE has the ability to be used to effectively conduct ACTH stimulation tests without the need to handle the animals during the test.

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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

Journal of Endocrinology ◽

10.1677/joe.0.1360167 ◽

1993 ◽

Vol 136 (1) ◽

pp. 167-172 ◽

Cited By ~ 61

Author(s):

S. Crowley ◽

P. C. Hindmarsh ◽

J. W. Honour ◽

C. G. D. Brook

Keyword(s):

Cortisol Level ◽

Low Dose ◽

Standard Dose ◽

Serum Cortisol ◽

Cortisol Concentration ◽

Acth Stimulation ◽

Basal Cortisol ◽

Basal Cortisol Level ◽

Adrenal Response ◽

Serum Cortisol Concentration

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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Use of ACTH stimulation tests to monitor the treatment of canine hyperadrenocorticism

Veterinary Record ◽

10.1136/vr.137.7.161 ◽

1995 ◽

Vol 137 (7) ◽

pp. 161-165 ◽

Cited By ~ 17

Author(s):

K. Dunn ◽

M. Herrtage ◽

J. Dunn

Keyword(s):

Acth Stimulation ◽

Stimulation Tests

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