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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the responses of plasma CRH, ACTH, cortisol, norepinephrine, epinephrine, and renin activity in 11 patients undergoing parathyroid or thyroid surgery after identical preoperative sedation and during isoflurane (Forane) anesthesia. During surgical exploration, plasma CRH levels [10 +/- 2 (+/- SEM) pg/mL] remained at basal (unstimulated) levels, and plasma ACTH (11.5 +/- 1.4 pg/mL), cortisol (24 +/- 4 micrograms/dL), and epinephrine (35 +/- 10 pg/mL) concentrations remained within their normal morning ranges. The majority of the patients had no evidence of pulsatile ACTH secretion during the operation, but, rather, secreted ACTH and cortisol continuously. There was a small elevation of plasma norepinephrine and PRA which was associated with a small increase in heart rate and decrease in blood pressure. Anesthesia reversal, endotrachial extubation, and the early recovery period were associated with marked mean peak increases in plasma ACTH (173 +/- 45 pg/mL), cortisol (35 +/- 6 micrograms/dL), and epinephrine (220 +/- 56 pg/mL) and the return of plasma norepinephrine and PRA to basal levels. All hormones returned to basal levels by the first post-operative day. The data suggest that with modern anesthetic techniques patients undergoing neck surgery had mildly elevated plasma ACTH, cortisol, and epinephrine levels. Glucocorticoid secretion during the operation was maintained primarily by continuous rather than pulsatile ACTH secretion. The immediate postoperative period was associated with profound elevations of plasma ACTH, cortisol, and epinephrine. The major determinant of ACTH, cortisol, and epinephrine secretion was anesthesia reversal and recovery and not surgical trauma.
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PMID:Responses of the hypothalamic-pituitary-adrenal and renin-angiotensin axes and the sympathetic system during controlled surgical and anesthetic stress. 303 Nov 24

The factors that mediate the hypothalamic-pituitary response to hypoglycemia in man are unknown. To investigate the role of CRH in the plasma ACTH response to hypoglycemia, two different doses of ovine CRH (oCRH) were given to normal men during insulin-induced hypoglycemia. We hypothesized that if the endogenous CRH response to hypoglycemia were less than maximally stimulating, administration of oCRH during hypoglycemia would result in a greater peak plasma immunoreactive (IR) ACTH response. Six normal men were given 1) 0.15 U/kg regular insulin, iv; 2) insulin plus 1 microgram/kg oCRH, iv, 5 min after serum glucose fell to 40 mg/dL or less; and 3) oCRH alone. The degree and duration of hypoglycemia were the same when insulin was given alone or with oCRH. Plasma IR-ACTH after insulin alone and insulin plus oCRH rose at the same rate to similar peaks of 226 +/- 37 (mean +/- SEM) and 213 +/- 53 pg/mL, respectively, both of which were greater (P less than 0.05) than the peak plasma IR-ACTH after oCRH alone (61 +/- 19 pg/mL). The peak plasma IR-cortisol levels after insulin alone (24 +/- 4 micrograms/dL), insulin plus oCRH (27 +/- 3 micrograms/dL), and oCRH alone (18 +/- 2 micrograms/dL) were not significantly different. In a second study, six normal men were given 0.15 U/kg regular insulin, iv; insulin plus 10 micrograms/kg oCRH, iv; and 10 micrograms/kg oCRH alone. Administration of oCRH 5 min after serum glucose fell to 40 mg/dL or less did not affect the degree or duration of hypoglycemia. Plasma IR-ACTH after insulin alone and insulin plus oCRH rose at the same rate to similar peaks of 258 +/- 14 and 290 +/- 33 pg/mL, respectively, both of which were greater (P less than 0.01) than the peak (54 +/- 6 pg/mL) after oCRH alone. After insulin alone, plasma IR-ACTH declined to baseline by 3 h. However, after insulin plus oCRH, plasma IR-ACTH fell gradually until 2 h, rose to a second peak at 2.5-3 h, and remained greater (P less than 0.01) than after insulin or oCRH alone for the 4-h duration of the study. The mean peak plasma IR-cortisol level after insulin plus oCRH (33 +/- 4 micrograms/dL) was similar to that after insulin alone (28 +/- 3 micrograms/dL), but was greater (P less than 0.05) than that after oCRH alone (18 +/- 2 micrograms/dL).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of ovine corticotropin-releasing hormone administered during insulin-induced hypoglycemia on plasma adrenocorticotropin and cortisol. 303 9

We examined the plasma ACTH and cortisol responses to surgery in 25 patients with atherosclerotic heart disease undergoing myocardial revascularization. The patients were all premedicated with diazepam, and general anesthesia was induced with thiopental. They were randomly assigned to one of four groups: I) no dexamethasone (DEX), enflurane anesthesia, II) 40 mg DEX, iv, 45-60 min before sternotomy, enflurane anesthesia, III) no DEX, fentanyl [N-(1-phenethyl-4-piperidyl)propionanilide] anesthesia (50-100 micrograms/kg), and IV) DEX, fentanyl anesthesia. Isokalemic hemodilution of significant magnitude occurred during cardiopulmonary bypass. All groups had significant increases in plasma ACTH during surgery, which returned to control levels 22 h after the bypass. Group I (no DEX, no fentanyl) and group III (no DEX, fentanyl) patients had large similar increases in plasma ACTH, which peaked 2-4 h postbypass [400 +/- 83 (+/- SEM) pg/mL; 88 +/- 18 pmol/L]. The group II (DEX, no fentanyl) patients also had large increases in ACTH which were similar to those in groups I and III, except 2-4 h postbypass (183 +/- 91 pg/mL; 40 +/- 20 pmol/L). The group IV (DEX, fentanyl) patients had a significantly attenuated ACTH response to surgery; the mean plasma ACTH level 2-4 h postbypass was only 54 +/- 21 pg/mL (12 +/- 5 pmol/L). Therefore, although DEX or fentanyl alone had a minimal effect on the ACTH response to surgery, a significant attenuation occurred when DEX and fentanyl were used in combination. We conclude that glucocorticoids and morphine agonists exert interactive inhibitory effects on ACTH release in humans, probably by virtue of their suppression of CRH release from the hypothalamus.
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PMID:Inhibition of the adrenocorticotropin response to surgery in humans: interaction between dexamethasone and fentanyl. 303 3

Plasma CRH was measured in maternal plasma throughout the third trimester of pregnancy, during labor, and postpartum. CRH levels were also measured in arterial and venous umbilical cord plasma samples. In normal pregnant women, plasma CRH increased from 50 +/- 15 (+/- SEM) pg/mL at 28 weeks gestation (n = 41) to 1462 +/- 182 pg/mL at 40 weeks (n = 55) and 1680 +/- 101 pg/mL (n = 65) in labor. Women with pregnancy-induced hypertension (n = 49) had plasma CRH levels significantly elevated above this normal range. Similarly, women who subsequently went into premature labor had raised levels several weeks before the onset of labor. After delivery, plasma CRH returned to normal within 15 h. Total plasma cortisol levels varied little throughout the third trimester, but increased during labor and remained elevated 2-3 days postpartum. There was, therefore, no correlation between plasma cortisol and CRH, implying that this placental CRH is not primarily involved in the control of the maternal hypothalamo-pituitary adrenal axis during pregnancy. The concentrations of CRH in umbilical cord plasma samples were considerably lower than those in the maternal circulation and were close to those in normal nonpregnant adults.
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PMID:Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition. 349 36

To characterize the short-term ACTH secretion pattern and to investigate factors regulating it, pituitary venous (PV) blood was collected using our nonsurgical method from 8 unperturbed horses every 20 or 30 s for approximately 1 h. In all but 1 horse, sampling occurred during the broad circadian maximum in plasma cortisol concentrations. Concentrations of corticotropin-releasing hormone (CRH; n = 7 horses), arginine vasopressin (AVP), ACTH and cortisol were measured by radioimmunoassay. In all horses, CRH, AVP and ACTH secretion patterns appeared irregular in time and amplitude. The mean (+/- SEM) numbers of peaks per hour detected by the cluster program were 2.8 +/- 1.2, 10.1 +/- 1.9 and 10.2 +/- 1.4 for CRH, AVP and ACTH, respectively. However, when 2- and 5-min sampling frequencies were simulated by meaning consecutive values, significantly fewer peaks were detected in each hormone. There was no correlation between the prevailing cortisol concentration and peak frequencies of CRH, AVP or ACTH. Secretion patterns of ACTH and AVP were closely related in all horses as assessed by cross correlation analysis and coincidence of peaks, although the ratio between PV ACTH and AVP concentrations fluctuated markedly within each horse. In contrast, the relationship between CRH and ACTH secretion was variable. Bivariate spectral analysis showed only a modest degree of underlying periodicity in CRH, AVP and ACTH secretion during the very short term studied. Nevertheless, distinct peaks exceeding the 95% confidence limits of white noise were observed at periods between 2 and 30 min in 5 of 7 CRH, 6 of 8 AVP and 5 of 8 ACTH spectra. Furthermore, the slope of the regression line through each spectrum did not become indistinguishable from zero, i.e. the flat white noise continuum, until mean (+/- SEM) periods of 2.6 +/- 0.8, 1.6 +/- 0.2, and 2.0 +/- 0.2 min, for CRH, AVP and ACTH spectra, respectively. At the ACTH spectral maximum, the coherence coefficient, which is analogous to the squared correlation coefficient, exceeded 0.5 in comparisons of all ACTH and AVP spectra and of 5 of 7 ACTH and CRH spectra.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Short-term secretion patterns of corticotropin-releasing hormone, arginine vasopressin and ACTH as shown by intensive sampling of pituitary venous blood from horses. 796 80

Extremely premature infants manifest clinical features suggestive of adrenal insufficiency. Yet, serum cortisol levels are similar in ill and well preterm infants in a setting where one would expect high stress levels in the ill infants. We investigated the hypothalamic-pituitary-adrenal axis in 17 extremely low birth weight stressed premature infants, mean birth weight 739 g, gestational age, 26.1 weeks, using ovine CRH (oCRH) and ACTH stimulation. oCRH (1 microgram/kg) was administered at 2-7 days of life (mean = 4.1). ACTH rose from a basal value 6.0 +/- 0.8 pmol/L (mean +/- SEM) to 9.6 +/- 1.8 pmol/L (P < 0.01) at 15 min and 9.5 +/- 1.7 pmol/L (P < 0.01) at 60 min. Basal cortisol rose from 349.3 +/- 58.1 nmol/L to 422.3 +/- 57.9 nmol/L (P < 0.01) at 15 min and 568.7 +/- 60.2 nmol/L (P < 0.01) at 60 min. Cortisol values remained significantly (P < 0.05) elevated 24 h after oCRH. An ACTH stimulation test performed 24 h after the oCRH test demonstrated a significant cortisol rise from 603.5 +/- 130.5 nmol/L to 882.7 +/- 136.6 nmol/L (P < 0.05) at 60 min. Plasma CRH immunoactivity was also measured before oCRH testing and was detectable in 10 of 15 infants. The mean CRH immunoactivity was 21.8 +/- 4.4 pmol/L in the infants, significantly higher than 8 adult male controls (P < 0.04). Our results show a normal pituitary response to ovine CRH and a normal adrenal response to ACTH. We hypothesize that cortisol levels are inappropriately low in some ill preterm infants because of the inability of the extremely premature brain to recognize the stress of the illness or because of inadequate hypothalamic secretion of CRH. The significance of the measurable plasma CRH in the first week of life is unknown.
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PMID:Hypothalamic pituitary adrenal function in the extremely low birth weight infant. 838 99

CRH regulates POMC gene expression and subsequent ACTH biosynthesis and release. In sheep, the preterm rise in fetal plasma ACTH commences at approximately 125 days gestation (dGA; 147 dGA = term), preceding the initiation of adrenocortical steroidogenesis. We hypothesized that an increase in CRH expression in the hypothalamic paraventricular nucleus (PVN) and POMC expression in the anterior pituitary in the late gestation sheep fetus may precede adrenal cortex maturation. Fetal sheep were obtained at 105-107 (n = 4), 128-130 (n = 5), and 138-140 (n = 4) dGA. Hypothalami were cryosectioned and subjected to in situ hybridization for ovine CRH mRNA. In all dGA groups, expression of CRH mRNA was observed throughout the rostrocaudal extent of the fetal PVN. The midrostral region of the fetal PVN where the dorsal and ventral divisions of the rostral PVN merge to form a single structure was selected for quantification. The number of copies of CRH probe hybridized per micron 3 were determined to estimate the quantity of hybridized CRH mRNA; the mean estimated CRH mRNA copy number per micron 3 midrostral PVN were 0.064 +/- 0.012 (105-107 dGA), 0.237 +/- 0.048 (128-130 dGA), and 0.108 +/- 0.034 (138-140 dGA; mean +/- SEM copies per micron 3 PVN). CRH mRNA signal significantly increased between 105-107 and 128-130 dGA (P < or = 0.05); 138-140 dGA levels of mRNA were not different from either 105-107 or 128-140 dGA levels. Regional variation in CRH mRNA levels were observed within the midrostral PVN between groups; at 138-140 dGA, a population of lateral midrostral PVN neurons maintain CRH mRNA levels greater than 105-107 dGA (P < 0.05), similar to those at 128-130 dGA. Fetal anterior pituitary RNA was subjected to Northern analysis for POMC mRNA. POMC mRNA levels in fetal anterior pituitaries were 14.1 +/- 2.2 (105-107 dGA), 28.9 +/- 10.9 (128-130 dGA), and 43.2 +/- 6 (138-140 dGA; mean +/- SEM arbitrary units). A significant increase (P < or = 0.05) was observed at 138-140 dGA compared to levels at 105-107 dGA. We conclude CRH mRNA levels in the fetal PVN increase coincident with increased POMC gene expression and the late gestation rise in fetal plasma ACTH. We speculate that a neuroendocrine stimulus at the fetal PVN may precipitate increased levels of CRH mRNA, initiating the maturation of the fetal hypothalamic-hypophyseal-adrenal axis, thus inducing the events of labor and delivery in sheep.
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PMID:Levels of corticotropin-releasing hormone messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus and proopiomelanocortin mRNA in the anterior pituitary during late gestation in fetal sheep. 838 7

"Steroid burst therapy" is commonly used for various acute medical conditions, but its suppressive effect on hypothalamic-pituitary-adrenocortical (HPA) function and the time period for recovery of HPA function is not fully known. We therefore evaluated the HPA function in 10 normal adults before and after a short burst of Prednisone (40 mg/three times daily for 3 days, then tapered over the next 4 days). HPA function was evaluated by iv administration of 100 micrograms of ovine CRH (oCRH) and blood samples for ACTH and cortisol assay were obtained at -30,0,10,15,30,60,90, and 120 min. On another day, 250 micrograms synthetic ACTH (Cosyntropin) were given iv and blood samples for cortisol were obtained at 0,30,60, and 90 min. Basal and peak levels of ACTH and cortisol before and 1,2, and 3 weeks after discontinuation of prednisone in response to oCRH iv are shown below (see Table 1). All values are mean (SEM). Peak levels of cortisol after iv administration of Cosyntropin at week 0 were 922(56.8), week 1 899(63.7), week 2 861(70.9), and week 3 855(53.0). There was no significant difference noted in the levels of ACTH and cortisol in response to oCRH before and after prednisone treatment. Pre- and posttreatment responses of cortisol to Cosyntropin administration were also similar. In addition, cumulative responses (area under the curve) and the change from baseline (delta) before and after administration of prednisone were similar for ACTH and cortisol. We conclude that HPA function is normal 1 week after discontinuation of a short burst of prednisone. These findings suggest that administration of additional steroids may not be required during periods of "stress" for those patients who have previously received similar steroid burst therapy, if at least 1 week has elapsed after such treatment was given.
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PMID:Hypothalamic-pituitary-adrenal function one week after a short burst of steroid therapy. 838 1

Plasma ACTH and cortisol concentrations are frequently elevated in patients in intensive care units (ICU). To examine the functional integrity of the hypothalamic-pituitary-adrenal axis during critical illness, we evaluated prospectively 53 ICU patients in a general medical ICU. Thirty-one patients and 7 normal controls underwent an overnight dexamethasone suppression test (3 mg dexamethasone, orally, at 2300 h). Plasma ACTH and serum cortisol were measured at 0900 h. In a separate experiment, 22 patients and 7 control subjects underwent a CRH stimulation test [100 micrograms human (h) CRH, iv]. ACTH and cortisol concentrations were determined from -15 to 120 min. Compared to normal controls, plasma ACTH and serum cortisol concentrations were not fully suppressible by dexamethasone [mean +/- SEM: plasma ACTH, 21 +/- 4 vs. 3 +/- 0.5 pg/mL (4.7 +/- 0.9 vs. 0.7 +/- 0.1 pmol/L); serum cortisol, 13.9 +/- 1.9 vs. 1.5 +/- 0.3 micrograms/dL (390 +/- 50 vs. 40 +/- 10 nmol/L); P = 0.0001], demonstrating an altered glucocorticoid feedback in the ICU patients. Patients undergoing hCRH stimulation had clearly elevated mean baseline plasma ACTH and serum cortisol concentrations [ACTH, 78 +/- 20 pg/mL vs. 15 +/- 3 in controls (17.2 +/- 4.4 vs. 3.4 +/- 0.7 pmol/L; P = 0.007); cortisol, 36.8 +/- 3.4 micrograms/dL vs. 9.6 +/- 1.2 (1020 +/- 80 vs. 260 +/- 30 nmol/L; P = 0.0001)]. Despite elevated baseline glucocorticoid concentrations, stimulation with hCRH resulted in significantly higher peak plasma ACTH concentrations 15 min after hCRH than in controls [134 +/- 31 vs. 48 +/- 9 pg/mL (29.5 +/- 6.8 vs. 10.6 +/- 2.0 pmol/L); P < 0.05]. Serum cortisol concentrations in ICU patients were significantly elevated throughout the test period (P = 0.0001) and rose to a peak of 43.9 +/- 3.5 micrograms/dL compared to 18.2 +/- 2.0 micrograms/dL in controls (1210 +/- 70 vs. 500 +/- 60 nmol/L). We conclude that ICU patients have a markedly altered responsiveness of their pituitary corticotroph to suppression with dexamethasone and stimulation with hCRH. These findings may be explained by altered pituitary glucocorticoid feedback and/or hypersecretion of peptides with CRH-like activity (vasopressin and cytokines) during critical illness.
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PMID:The hypothalamic-pituitary-adrenal axis in critical illness: response to dexamethasone and corticotropin-releasing hormone. 839 81

During human pregnancy, plasma CRH immunoreactivity (CRH-IR) rises progressively, peaking during labor and falling after delivery. Among animal species, only higher primates have elevated CRH-IR during pregnancy. This study examines whether changes in plasma CRH-IR in the baboon (Papio hamadryas) are similar to those in the human. CRH-IR was determined by RIA in 16 baboons at different stages of gestation (44 samples) and in 3 males. Assays were performed on Vycor extracts of plasma and CRH-IR diluted in parallel to synthetic human (h) CRH-41 standard. Reverse phase high pressure liquid chromatography and size-exclusion chromatography with Sephadex G-50 showed that baboon CRH-IR eluted in a position similar to that of hCRH-41. Regression analysis revealed a cubic association between plasma CRH-IR and gestational age, with peak concentrations occurring at 60 days gestation (term = 182 days). Although greatly elevated concentrations persisted throughout pregnancy, concentrations in the first half (1-91 days) were significantly higher (mean +/- SEM, 1.9 +/- 0.3 nM/L; n = 27) than in the second half (92-182 days; 1.0 +/- 0.2 nM/L; n = 11; P < 0.003 by t test). CRH-IR fell to low levels by day 1 postpartum. The concentration of total cortisol in nonpregnant animals was 1370.9 +/- 134.9 nM/L (n = 5), which was similar to pregnancy levels (1346.3 +/- 356.1 nM/L; n = 28); there was no gestational age-related pattern evident. Plasma corticosteroid-binding globulin was estimated by RIA, and plasma free cortisol was calculated to be 73 +/- 14 nM/L in pregnant animals and showed no gestational age-related changes. The mean progesterone concentration in the pregnant baboon was 12.5 +/- 2.2 nM/L (7-169 days; n = 27). There was no significant change in progesterone levels during the period of gestation studied; however, they were higher than nonpregnant levels. Baboon and human plasma (0.1 mL each) were incubated with [125I]Tyr-hCRH in Tris-HCl buffer (pH 7.5) and chromatographed with Sephadex G-75, using the same buffer. The radioactivity of fractions was determined, and no CRH-binding protein was identified in baboon plasma. This study indicates that gestational changes in CRH-IR in the baboon are different from those observed in humans. There is a dissociation between maternal plasma CRH and cortisol. The apparent lack of bioactivity of baboon plasma CRH is not due to a circulating binding protein, which is absent in this species.
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PMID:Corticotropin-releasing hormone in baboon pregnancy. 847 82


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