The Experts below are selected from a list of 51 Experts worldwide ranked by ideXlab platform
Richard V. Jackson - One of the best experts on this subject based on the ideXlab platform.
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The Insulin Hypoglycemia test: hypoglycemic criteria and reproducibility.
Journal of neuroendocrinology, 2001Co-Authors: E. J. Nye, Jeffrey E. Grice, G. I. Hockings, C. R. Strakosch, G. V. Crosbie, M. M. Walters, David J. Torpy, Richard V. JacksonAbstract:The Insulin Hypoglycemia test (IHT) is widely regarded as the "gold standard" for dynamic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to investigate the temporal relationship between a rapid decrease in plasma glucose and the corresponding rise in plasma adenocorticotropic hormone (ACTH), and to assess the reproducibility of hormone responses to Hypoglycemia in normal humans. Ten normal subjects underwent IHTs, using an Insulin dose of 0.15 U/kg. Of these, eight had a second IHT (IHT2) and three went on to a third test (IHT3). Plasma ACTH and cortisol were measured at 15-min intervals and, additionally, in four IHT2s and the three IHT3s, ACTH was measured at 2.5- or 5-min intervals. Mean glucose nadirs and mean ACTH and cortisol responses were not significantly different between IHT1, IHT2 and IHT3. Combined data from all 21 tests showed the magnitude of the cortisol responses, but not the ACTH responses, correlated significantly with the depth and duration of Hypoglycemia. All subjects achieved glucose concentrations of of < or = 1.6 mmol/l before any detectable rise in ACTH occurred. In the seven tests performed with frequent sampling, an ACTH rise never preceded the glucose nadir, but occurred at the nadir, or up to 15 min after. On repeat testing, peak ACTH levels varied markedly within individuals, whereas peak cortisol levels were more reproducible (mean coefficient of variation 7%). In conclusion, Hypoglycemia of < or = 1.6 mmol/l was sufficient to cause stimulation of the HPA axis in all 21 IHTs conducted in normal subjects. Nonetheless, our data cannot reveal whether higher glucose nadirs would stimulate increased HPA axis activity in all subjects. Overall, the cortisol response to Hypoglycemia is more reproducible than the ACTH response but, in an individual subject, the difference in peak cortisol between two IHTs may exceed 100 nmol/l.
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Comparison of adrenocorticotropin (ACTH) stimulation tests and Insulin Hypoglycemia in normal humans : Low dose, standard high dose, and 8-hour ACTH-(1-24) infusion tests
The Journal of Clinical Endocrinology and Metabolism, 1999Co-Authors: Jeffrey E. Grice, G. I. Hockings, C. R. Strakosch, G. V. Crosbie, M. M. Walters, Richard V. JacksonAbstract:The efficacy of the standard high dose ACTH stimulation test (HDT), using a pharmacological 250-μg dose of synthetic ACTH-(1–24), in the diagnosis of central hypoadrenalism is controversial. The Insulin Hypoglycemia test is widely regarded as the gold standard dynamic stimulation test of the hypothalamo-pituitary-adrenal (HPA) axis that provides the most reliable assessment of HPA axis integrity and reserve. Alternatively, a prolonged infusion of ACTH causes a continuing rise in plasma cortisol levels that may predict the adrenals’ capacity to respond to severe ongoing stress. In nine normal subjects, we compared plasma ACTH and cortisol levels produced by three iv bolus low doses of ACTH-(1–24) (0.1, 0.5, and 1.0μ g/1.73 m2; LDTs) with those stimulated by Hypoglycemia (0.15 U/kg Insulin) and with the cortisol response to a standard 250-μg dose of ACTH-(1–24). The normal cortisol response to an 8-h ACTH-(1–24) infusion (250 μg at a constant rate over 8 h) was determined using three modern cortisol assays:...
Ariel L Barkan - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the integrity of the hypothalamic pituitary adrenal axis by Insulin Hypoglycemia test
The Journal of Clinical Endocrinology and Metabolism, 1998Co-Authors: Erdinc Erturk, Craig A. Jaffe, Ariel L BarkanAbstract:We retrospectively reviewed dynamic ACTH and cortisol responses to Insulin Hypoglycemia in 193 subjects with suspected ACTH deficiency to ascertain the predictive values of various diagnostic criteria. Based on the achievement of a peak cortisol level of 18 micrograms/dL or above, 133 subjects were classified as having an intact hypothalamic-pituitary-adrenal (HPA) axis, and 60 subjects were determined to have ACTH deficiency. Baseline and peak cortisol concentrations were strongly correlated (r = 0.63; P < 0.0001). Peak cortisol increased in parallel to ACTH increments, but plateaued at approximately 22 micrograms/dL at peak ACTH levels above approximately 75 pg/mL (r = 0.61; P < 0.0001). Basal cortisol values above 17 micrograms/dL or below 4 micrograms/dL were highly predictive of an intact or impaired HPA axis, respectively, but intermediate values had only limited sensitivity and specificity. The criteria of HPA axis integrity, defined as an increment in plasma cortisol of more than 7 micrograms/dL above the baseline or as a doubling of the baseline cortisol value, were associated with high false positive and false negative rates. We conclude that 1) the baseline morning serum cortisol concentration has very limited predictive power in differentiating between normal and impaired HPA function; 2) the use of criteria based on incremental changes in serum cortisol from baseline leads to unacceptably high false positive and false negative rates; and 3) Insulin Hypoglycemia is still the best indicator of the integrity of the response of the HPA axis to stress.
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Evaluation of the Integrity of the Hypothalamic-Pituitary-Adrenal Axis by Insulin Hypoglycemia Test
The Journal of clinical endocrinology and metabolism, 1998Co-Authors: Erdinc Erturk, Craig A. Jaffe, Ariel L BarkanAbstract:We retrospectively reviewed dynamic ACTH and cortisol responses to Insulin Hypoglycemia in 193 subjects with suspected ACTH deficiency to ascertain the predictive values of various diagnostic criteria. Based on the achievement of a peak cortisol level of 18 μg/dL or above, 133 subjects were classified as having an intact hypothalamic-pituitary-adrenal (HPA) axis, and 60 subjects were determined to have ACTH deficiency. Baseline and peak cortisol concentrations were strongly correlated (r = 0.63; P < 0.0001). Peak cortisol increased in parallel to ACTH increments, but plateaued at approximately 22 μg/dL at peak ACTH levels above approximately 75 pg/mL (r = 0.61; P < 0.0001). Basal cortisol values above 17μ g/dL or below 4 μg/dL were highly predictive of an intact or impaired HPA axis, respectively, but intermediate values had only limited sensitivity and specificity. The criteria of HPA axis integrity, defined as an increment in plasma cortisol of more than 7μ g/dL above the baseline or as a doubling of th...
A. Brew Atkinson - One of the best experts on this subject based on the ideXlab platform.
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Low- and standard-dose corticotropin and Insulin Hypoglycemia testing in the assessment of hypothalamic-pituitary-adrenal function after pituitary surgery.
The Journal of clinical endocrinology and metabolism, 2004Co-Authors: C. Hamish Courtney, Andrew S. Mcallister, Patrick M. Bell, David R. Mccance, H. Leslie, Brian Sheridan, A. Brew AtkinsonAbstract:The optimal means of assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis after pituitary surgery remains controversial. We compared low-dose (1 micro g iv) and standard-dose (250 micro g im) corticotropin tests performed 1 and 4-6 wk after pituitary surgery with an Insulin Hypoglycemia test performed at 4-6 wk. Forty-one patients (21 male and 20 female; median age, 52 yr; range, 23-73 yr) who had undergone pituitary surgery were studied (Cushing's disease excluded). Twenty-two of the 41 patients had normal cortisol responses to all tests both at 1 and 4-6 wk after surgery. Eight patients had subnormal cortisol responses to all tests. Of the 11 patients with discrepant results, seven had subnormal responses only after the low-dose corticotropin test; the remaining four patients had borderline responses to one or more tests. At 4-6 wk after surgery, subjects with a 30-min serum cortisol after standard-dose corticotropin of less than 350 nmol/liter (12.7 micro g/dl) consistently had a subnormal response to Hypoglycemia, and those with a serum cortisol greater than 650 nmol/liter (23.6 micro g/dl) had a normal response to Hypoglycemia. Definitive testing of the HPA axis using the standard-dose corticotropin test can be carried out provided it is performed at least 4 wk after pituitary surgery. A 30-min cortisol level greater than 650 nmol/liter (23.6 micro g/dl) indicates adequacy of the HPA axis, and a level of less than 350 nmol/liter (12.7 micro g/dl) indicates ACTH deficiency. No further testing is then required. An intermediate level of 350-650 nmol/liter (12.7-23.6 micro g/dl) warrants further assessment using the Insulin Hypoglycemia test.
Craig A. Jaffe - One of the best experts on this subject based on the ideXlab platform.
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Insulin Hypoglycemia and growth hormone secretion in sheep: a paradox revisited
The American journal of physiology, 1999Co-Authors: Craig A. Jaffe, Bryan W. Huffman, Roberta Demott-fribergAbstract:Although Insulin-induced Hypoglycemia is a potent stimulus for growth hormone (GH) secretion in humans, Hypoglycemia was reported to suppress GH in sheep. We investigated whether GH suppression in sheep during Insulin Hypoglycemia resulted from the dose of Insulin administered or the fed state of the animal. Saline or Insulin (0.05, 0.2, 1.0, or 5.0 U/kg) intravenous boluses were administered to eight fasted ewes in a crossover experiment. In another experiment, four sheep were fed 2 h before intravenous administrations of either 0.2 or 5 U/kg of Insulin. All doses of Insulin resulted in comparable Hypoglycemia, although the duration of Hypoglycemia increased directly with Insulin dose. Hypoglycemia in fasted animals stimulated GH secretion. The GH rise above baseline was inversely related to the Insulin dose, and the Insulin doses of 1 and 5 U/kg resulted in late suppression of GH below baseline concentrations. Insulin administration to fed animals caused an identical degree of Hypoglycemia but no increase in GH. Insulin-Hypoglycemia stimulates GH secretion in sheep in a manner similar to humans, and the response is dependent on both fed state and Insulin dose.
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evaluation of the integrity of the hypothalamic pituitary adrenal axis by Insulin Hypoglycemia test
The Journal of Clinical Endocrinology and Metabolism, 1998Co-Authors: Erdinc Erturk, Craig A. Jaffe, Ariel L BarkanAbstract:We retrospectively reviewed dynamic ACTH and cortisol responses to Insulin Hypoglycemia in 193 subjects with suspected ACTH deficiency to ascertain the predictive values of various diagnostic criteria. Based on the achievement of a peak cortisol level of 18 micrograms/dL or above, 133 subjects were classified as having an intact hypothalamic-pituitary-adrenal (HPA) axis, and 60 subjects were determined to have ACTH deficiency. Baseline and peak cortisol concentrations were strongly correlated (r = 0.63; P < 0.0001). Peak cortisol increased in parallel to ACTH increments, but plateaued at approximately 22 micrograms/dL at peak ACTH levels above approximately 75 pg/mL (r = 0.61; P < 0.0001). Basal cortisol values above 17 micrograms/dL or below 4 micrograms/dL were highly predictive of an intact or impaired HPA axis, respectively, but intermediate values had only limited sensitivity and specificity. The criteria of HPA axis integrity, defined as an increment in plasma cortisol of more than 7 micrograms/dL above the baseline or as a doubling of the baseline cortisol value, were associated with high false positive and false negative rates. We conclude that 1) the baseline morning serum cortisol concentration has very limited predictive power in differentiating between normal and impaired HPA function; 2) the use of criteria based on incremental changes in serum cortisol from baseline leads to unacceptably high false positive and false negative rates; and 3) Insulin Hypoglycemia is still the best indicator of the integrity of the response of the HPA axis to stress.
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Evaluation of the Integrity of the Hypothalamic-Pituitary-Adrenal Axis by Insulin Hypoglycemia Test
The Journal of clinical endocrinology and metabolism, 1998Co-Authors: Erdinc Erturk, Craig A. Jaffe, Ariel L BarkanAbstract:We retrospectively reviewed dynamic ACTH and cortisol responses to Insulin Hypoglycemia in 193 subjects with suspected ACTH deficiency to ascertain the predictive values of various diagnostic criteria. Based on the achievement of a peak cortisol level of 18 μg/dL or above, 133 subjects were classified as having an intact hypothalamic-pituitary-adrenal (HPA) axis, and 60 subjects were determined to have ACTH deficiency. Baseline and peak cortisol concentrations were strongly correlated (r = 0.63; P < 0.0001). Peak cortisol increased in parallel to ACTH increments, but plateaued at approximately 22 μg/dL at peak ACTH levels above approximately 75 pg/mL (r = 0.61; P < 0.0001). Basal cortisol values above 17μ g/dL or below 4 μg/dL were highly predictive of an intact or impaired HPA axis, respectively, but intermediate values had only limited sensitivity and specificity. The criteria of HPA axis integrity, defined as an increment in plasma cortisol of more than 7μ g/dL above the baseline or as a doubling of th...
Jeffrey E. Grice - One of the best experts on this subject based on the ideXlab platform.
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The Insulin Hypoglycemia test: hypoglycemic criteria and reproducibility.
Journal of neuroendocrinology, 2001Co-Authors: E. J. Nye, Jeffrey E. Grice, G. I. Hockings, C. R. Strakosch, G. V. Crosbie, M. M. Walters, David J. Torpy, Richard V. JacksonAbstract:The Insulin Hypoglycemia test (IHT) is widely regarded as the "gold standard" for dynamic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to investigate the temporal relationship between a rapid decrease in plasma glucose and the corresponding rise in plasma adenocorticotropic hormone (ACTH), and to assess the reproducibility of hormone responses to Hypoglycemia in normal humans. Ten normal subjects underwent IHTs, using an Insulin dose of 0.15 U/kg. Of these, eight had a second IHT (IHT2) and three went on to a third test (IHT3). Plasma ACTH and cortisol were measured at 15-min intervals and, additionally, in four IHT2s and the three IHT3s, ACTH was measured at 2.5- or 5-min intervals. Mean glucose nadirs and mean ACTH and cortisol responses were not significantly different between IHT1, IHT2 and IHT3. Combined data from all 21 tests showed the magnitude of the cortisol responses, but not the ACTH responses, correlated significantly with the depth and duration of Hypoglycemia. All subjects achieved glucose concentrations of of < or = 1.6 mmol/l before any detectable rise in ACTH occurred. In the seven tests performed with frequent sampling, an ACTH rise never preceded the glucose nadir, but occurred at the nadir, or up to 15 min after. On repeat testing, peak ACTH levels varied markedly within individuals, whereas peak cortisol levels were more reproducible (mean coefficient of variation 7%). In conclusion, Hypoglycemia of < or = 1.6 mmol/l was sufficient to cause stimulation of the HPA axis in all 21 IHTs conducted in normal subjects. Nonetheless, our data cannot reveal whether higher glucose nadirs would stimulate increased HPA axis activity in all subjects. Overall, the cortisol response to Hypoglycemia is more reproducible than the ACTH response but, in an individual subject, the difference in peak cortisol between two IHTs may exceed 100 nmol/l.
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Comparison of adrenocorticotropin (ACTH) stimulation tests and Insulin Hypoglycemia in normal humans : Low dose, standard high dose, and 8-hour ACTH-(1-24) infusion tests
The Journal of Clinical Endocrinology and Metabolism, 1999Co-Authors: Jeffrey E. Grice, G. I. Hockings, C. R. Strakosch, G. V. Crosbie, M. M. Walters, Richard V. JacksonAbstract:The efficacy of the standard high dose ACTH stimulation test (HDT), using a pharmacological 250-μg dose of synthetic ACTH-(1–24), in the diagnosis of central hypoadrenalism is controversial. The Insulin Hypoglycemia test is widely regarded as the gold standard dynamic stimulation test of the hypothalamo-pituitary-adrenal (HPA) axis that provides the most reliable assessment of HPA axis integrity and reserve. Alternatively, a prolonged infusion of ACTH causes a continuing rise in plasma cortisol levels that may predict the adrenals’ capacity to respond to severe ongoing stress. In nine normal subjects, we compared plasma ACTH and cortisol levels produced by three iv bolus low doses of ACTH-(1–24) (0.1, 0.5, and 1.0μ g/1.73 m2; LDTs) with those stimulated by Hypoglycemia (0.15 U/kg Insulin) and with the cortisol response to a standard 250-μg dose of ACTH-(1–24). The normal cortisol response to an 8-h ACTH-(1–24) infusion (250 μg at a constant rate over 8 h) was determined using three modern cortisol assays:...