Mean Cortisol Concentrations Research Articles

Fasting suppresses pulsatile luteinizing hormone (LH) secretion and enhances orderliness of LH release in young but not older men.

Pulsatile gonadotropin secretion and sex-steroid concentrations are suppressed reversibly in young fasted or malnourished human subjects. In this study, we investigated the impact of age on the dynamic neuroendocrine mechanisms underlying this stress response in healthy young (age, 28 +/- 3 yr, n = 8) vs. older (age 67 +/- 2 yr, n = 8) men with similar body mass indices (mean, 26 +/- 0.6 vs. 26 +/- 1.3 kg/m2, respectively). Serum LH concentrations were measured by immunoradiometric assay (IRMA) in blood collected at 10-min intervals over 27 h on a control (fed) day and on the third day of a 3.5-day fast (water only) assigned in randomized order. After 24 h of basal sampling, GnRH (10 micrograms i.v. bolus) was administered to test gonadotrope responsiveness. Cortisol, dehydroepiandrosterone sulfate, androstenedione, testosterone, FSH, GH, and PRL were measured in 24-h pooled serum as positive and negative control hormones. Approximate entropy was used to quantitate the orderliness of LH release over 24 h, and a multiple-parameter deconvolution method was applied to quantify pulsatile LH secretion and LH half-life. In the fed state, older men exhibited elevated mean (24-h pooled) serum FSH and cortisol concentrations compared with young controls but equivalent serum LH concentrations and reduced serum GH, free testosterone, androstenedione, and dehydroepiandrosterone sulfate concentrations. Fed older men also manifested a lower frequency and amplitude of 24-h pulsatile LH secretion, and, by approximate entropy calculations, a more disorderly pattern of basal LH release than younger individuals. Three- and one-half days of fasting evoked 40% and 47% increases in mean (24-h) serum cortisol concentrations in young and older men, respectively (P < 0.01 vs. fed, but P = not significant for percentage rise in older vs. young men). Concurrently, fasting induced a 2.1-fold fall in the 24-h endogenous LH production rate in young men (fed 36 +/- 9.7 vs. fasted 17 +/- 2.0 IU/L of distribution volume/day, P < 0.01), but did not significantly affect the daily LH secretion rate in older men (fed 27 +/- 4.5 vs. fasted 21 +/- 3.4 IU/day). The reduced LH production rate in fasting young men was accounted for by a 1.7-fold decline in the mass of LH secreted per burst (fed 2.5 +/- 0.45 vs. fasted 1.5 +/- 0.16 IU/L, P < 0.05), whereas LH burst mass in older men remained unchanged (and low) during fasting. In addition, in young men, during the 3.5-day fast the number of computer-resolved LH secretory bursts per 24 h decreased (fed 15 +/- 0.7 vs. fasted 11 +/- 0.7, P < 0.01), and the interburst interval increased (fed 94 +/- 4.2 vs. fasted 125 +/- 8.7 min, P < 0.05). In contrast, in older men in the fed state, basal LH peak frequency and serum free testosterone concentrations were reduced compared with corresponding values in young men, and did not decline further with fasting. Whereas the orderliness of LH release patterns increased significantly during fasting in the young men, the approximate entropy measure failed to change significantly in unfed older subjects. By cosinor analysis, young men showed lower 24-h mesor (mean of nyctohemeral rhythm of) serum LH concentrations than older volunteers during fasting. Moreover, young but not older men manifested preserved 24-h variations in LH interpulse intervals when fasting. Exogenously stimulated LH release (mean 3-h serum LH concentration or calculated mass of LH secreted) following a single i.v. injection of 10 micrograms GnRH was independent of age and fasting status. We conclude that the metabolic stressor of short-term fasting unmasks specific age-related neuroendocrine contrasts in the stress-responsive control of both the pulsatile and nyctohemeral regulation of the male hypothalamo-pituitary-gonadal-axis.

PHARMACOLOGIC VARIABILITY OF EVERY OTHER DAY (QOD) GLUCOCORTICOID THERAPY IN RENAL TRANSPLANT RECIPIENTS (RTR)

287 In order to minimize chronic adverse effects, the use of the lowest effective doses of corticosteroids (prednisone or methylprednisolone-MEPN) are currently recommended in the combination immunosuppressive protocols prescribed in RTR. Therefore, more RTR are receiving steroid-sparing therapy that employ every other day (QOD) glucocorticoid regimens based upon empiric dosing titration. To examine total glucocorticoid exposure during QOD dosing, seven (4 males; 3 females) stable RTR (ranging from 7 months to 7 years post-transplant) stabilized on QOD glucocorticoid doses were evaluated. Patients (mean serum creatinine: 1.4 ± 0.2 mg/dl) were administered their respective oral MEPN dose (dose range: 4 to 14 mg QOD) by intravenous infusion at 8 AM of study. Blood samples were collected at time 0 (0800) and for 24 hours following and analyzed with HPLC for MEPN and cortisol. Significant interpatient variability was noted in the clearance (CL) of MEPN that ranged from 180 to 574 ml/hr/kg. The corresponding half-life(t1/2) ranged from 2.0 to 3.7 h. A defined 24 h cortisol profile was noted an all patients. Cortisol concentrations (mean cortisol at time 0:127± 50 ng/ml) declined concurrent with the serum MEPN. Cortisol rebounded from a mean nadir concentration of 9.2 ± 4.4 ng/ml to 24 hour mean cortisol concentration of 104 ± 39 ng/ml. The total cortisol AUC ranged from 541 to 1438 ng•h/ml and was not correlated with dose or CL of MEPN. No significant correlation was noted between these pharmacologic parameters and patient demographics. These results indicate that pronounced interpatient variability in the pharmacokinetics of MEPN exists during QOD therapy. In addition, the cortisol response during QOD therapy suggests unpredictable recovery rates of the HPA axis. The variation in total glucocorticoid exposure during empiric tapering to QOD therapy suggest that a more objective approach is needed to maintain adequate immunosuppression while also attempting to avoid chronic steroid toxicity. These variations in the MEPN clearance and cortisol recovery may explain why aggressive steroid tapering is complicated by rejection episodes that occur in an unpredictable manner.

Changes in cortisol secretion during shiftwork: implications for tolerance to shiftwork?

The present study was conducted to determine the size of changes and the time point of those changes in biological rhythms during night-shift and whether they are associated with tolerance to shiftwork. The adrenal hormone cortisol has frequently been investigated in the field of shiftwork since it follows a pronounced circadian variation and has been demonstrated to be affected by night-work. However, studies are restricted with respect to sample size, number of measurements or duration of sampling periods. Therefore, a sample of 24 night-shift workers was investigated in a cardiac emergency unit for seven nights. Saliva samples were collected frequently for determination of cortisol. A total of 28 cortisol measurements in each subject were made in order to decide whether the circadian rhythm changed, and if so at which time point. A clear reversal of circadian function could be observed for the total group (mean cortisol concentrations) after the fifth night. However, inspection of individual patterns revealed that six out of 24 subjects did not change in circadian function. These subjects exhibited lower durations of and less consistency in recovery sleep across the following days after night-work. With respect to personality dimensions a pattern associated with neuroticism can be observed in subjects without appropriate changes in cortisol rhythm. However, owing to the small sample size of non-adapters these results are preliminary and should be replicated with larger samples. The overall relationship between neuroticism and low adaptability has been discussed.

PHARMACOLOGIC VARIABILITY OF EVERY OTHER DAY (QOD) GLUCOCORTICOID THERAPY IN RENAL TRANSPLANT RECIPIENTS (RTR)

287 In order to minimize chronic adverse effects, the use of the lowest effective doses of corticosteroids (prednisone or methylprednisolone-MEPN) are currently recommended in the combination immunosuppressive protocols prescribed in RTR. Therefore, more RTR are receiving steroid-sparing therapy that employ every other day (QOD) glucocorticoid regimens based upon empiric dosing titration. To examine total glucocorticoid exposure during QOD dosing, seven (4 males; 3 females) stable RTR (ranging from 7 months to 7 years post-transplant) stabilized on QOD glucocorticoid doses were evaluated. Patients (mean serum creatinine: 1.4 ± 0.2 mg/dl) were administered their respective oral MEPN dose (dose range: 4 to 14 mg QOD) by intravenous infusion at 8 AM of study. Blood samples were collected at time 0 (0800) and for 24 hours following and analyzed with HPLC for MEPN and cortisol. Significant interpatient variability was noted in the clearance (CL) of MEPN that ranged from 180 to 574 ml/hr/kg. The corresponding half-life(t½) ranged from 2.0 to 3.7 h. A defined 24 h cortisol profile was noted an all patients. Cortisol concentrations (mean cortisol at time 0:127 ± 50 ng/ml) declined concurrent with the serum MEPN. Cortisol rebounded from a mean nadir concentration of 9.2 ± 4.4 ng/ml to 24 hour mean cortisol concentration of 104 ± 39 ng/ml. The total cortisol AUC ranged from 541 to 1438 ng·h/ml and was not correlated with dose or CL of MEPN. No significant correlation was noted between these pharmacologic parameters and patient demographics. These results indicate that pronounced interpatient variability in the pharmacokinetics of MEPN exists during QOD therapy. In addition, the cortisol response during QOD therapy suggests unpredictable recovery rates of the HPA axis. The variation in total glucocorticoid exposure during empiric tapering to QOD therapy suggest that a more objective approach is needed to maintain adequate immunosuppression while also attempting to avoid chronic steroid toxicity. These variations in the MEPN clearance and cortisol recovery may explain why aggressive steroid tapering is complicated by rejection episodes that occur in an unpredictable manner.

Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease

The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial because of a lack of placebo-controlled studies. We compared the effect of inhaled fluticasone propionate with placebo in the treatment of patients with COPD. We used a randomised, double-blind, placebo-controlled design. We enrolled from 13 European countries, New Zealand, and South Africa, 281 outpatient current or ex-smokers, aged between 50 and 75 years. They had a forced expiratory volume in 1 s (FEV1) of between 35% and 90% of predicted normal values, a ratio of FEV1 to forced vital capacity of 70% or less and bronchodilator reversibility of less than 15%, as well as a history of chronic bronchitis. Patients were randomly assigned fluticasone propionate 500 microg (n=142) or placebo (n=139) twice daily via a metered-dose inhaler for 6 months. The main outcome measures were the number of patients who had at least one exacerbation by the end of treatment, the number and severity of exacerbations, clinic lung function, diary card symptoms and peak expiratory flow and 6 min walking distance. 51 (37%) patients in the placebo group compared with 45 (32%) in the fluticasone propionate group had had at least one exacerbation by the end of treatment (p=0.449). Significantly more patients had moderate or severe exacerbations in the placebo group than in the fluticasone propionate group (86% vs 60%, p<0.001). Diary-card and clinic morning peak expiratory flows improved significantly in the fluticasone propionate group (p<0.001, p=0.048, respectively), as did clinic FEV1 (p<0.001), forced vital capacity (p<0.001), and mid-expiratory flow (p=0.01). Symptom scores for median daily cough and sputum volume were significantly lower with fluticasone propionate treatment than with placebo (p=0.004 and p=0.016, respectively). At the end of treatment, patients on fluticasone propionate had increased their 6 min walking distance significantly more than those on placebo (p=0.032). Fluticasone propionate was tolerated as well as placebo, with few adverse effects and without a clinically important effect on mean serum cortisol concentration. Fluticasone propionate may be of clinical benefit in patients with COPD over at least 6 months. Inhaled corticosteroids may have an important role in the long-term treatment of COPD.

Characterization of Milk Cortisol Concentrations as a Measure of Short-Term Stress Responses in Lactating Dairy Cows

AbstractThis study compares cortisol concentrations in plasma and milk over a time-span of 1-4h following injection of an adrenocorticotropic hormone (ACTH) or a physiological stressor. Its aim was to characterize the usefulness of milk cortisol concentrations as short-term measures of acute stress.Experiment 1: three groups of lactating cows (Groups B - D; n = 5, each) were injected with ACTH1-24 at 4, 2 and 1h before milking, respectively, so that each experienced a similar period of elevated adrenocortical activity, but presented at milking with varying plasma cortisol concentrations. Another group (Group A; n = 5) was a saline-treated control. Mean plasma cortisol concentrations at milking were 7, 8, 24 and 56ng ml−1 for Groups A, B, C and D, respectively. Mean cortisol concentrations in milk were similar for Groups A and B (1.2 and 0.5 ng ml−1, respectively), higher in Group C (2.4ng ml−1), and greatest in Group D (11.7 ng ml−1; p &lt;0.001).Experiment 2: lactating dairy cows (n = 15) were injected with ACTH, transported by truck, or blood-sampled only (control) during the 2h before milking. Mean plasma cortisol concentrations at milking were 6, 20 and 72 ng ml−1 following control, ACTH and transport treatments, respectively; mean concentrations of cortisol in milk displayed a similar pattern (1.1, 2.4 and 12.0 ng ml−1, respectively; p &lt;0.001).Milk cortisol concentrations were highly correlated with plasma levels at milking, but did not reflect those situations where, following a period of elevation within the previous 4h, plasma cortisol concentrations had returned to basal levels. Concentrations of cortisol in foremilk and composite milk were highly correlated, but the mechanisms of cortisol flux may differ between these two compartments. Milk cortisol concentration can be a useful indicator of responses of lactating cows to acute stressors which act up to 2h before collection of samples.

Reproductive Seasonality in Female Platypuses, Ornithorhynchus anatinus, in the Upper Barnard River, New South Wales.

Progesterone concentrations were determined in samples of blood, urine and faeces collected from female platypuses which were captured in the Upper Barnard River, NSW, from February to November, 1996. Mean concentrations in blood plasma were higher in July, August and September than in other months with the highest concentrations being in August. Progesterone concentrations in dried urine and faeces were highly correlated with values for blood plasma (r = 0.61, P&amp;lt;0.05 and 0.7 1, P&amp;lt;O.OI, respectively), and the coefficient of variation for progesterone determinations was lower for samples of urine and faeces than blood. There was a seasonal change in mean concentration of cortisol in blood (being elevated in May-August), but the concentrations of progesterone and cortisol in blood were not significantly correlated.

Adrenal response to corticotrophin and testosterone during long-term therapy with itraconazole in patients with chromoblastomycosis

In order to establish whether long-term itraconazole therapy can affect adrenal or testicular function, the adrenal response to corticotrophin and testosterone was evaluated by radioimmunoassay in 15 patients undergoing treatment for chromoblastomycosis. Mean cortisol and testosterone concentrations were 12.4 microg/dL and 454 ng/dL respectively at baseline and 15.4 microg/dL and 480 ng/dL respectively after 12.4+/-5.2 months of treatment with itraconazole (200-400 mg daily). Results were analysed using Student's t-test. There was no clinical or laboratory evidence of steroidogenic or androgenic impairment.

Atorvastatin, a New HMG-CoA Reductase Inhibitor, Does Not Affect Glucocorticoid Hormones in Patients With Hypercholesterolemia.

BACKGROUND: Atorvastatin calcium (Lipitor) is a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. The present study was conducted to examine the effect of pronounced cholesterol lowering on adrenal function in patients with severe hypercholesterolemia. METHODS AND RESULTS: Adrenal function was examined under basal conditions and following adrenal corticotropin hormone stimulation in 40 patients (36 with heterogeneous familial and 4 with polygenic hypercholesterolemia). The study was part of a larger study comparing the efficacy and safety of atorvastatin, colestipol, atorvastatin + colestipol, and simvastatin + colestipol treatment over a 1-year period. Maximum doses of all agents were studied: 80 mg atorvastatin once daily, 40 mg simvastatin once daily, and 20 g/day colestipol. At the end of the 1-year treatment period, reductions in low-density lipoprotein cholesterol were 57%, 54%, and 49% for the atorvastatin, colestipol + atorvastatin, and colestipol + simvastatin groups, respectively. No clinically significant changes in basal serum cortisol levels were seen in any treatment group during the 1-year treatment period. Mean serum cortisol concentrations and area under the curve for cortisol concentration versus time data following adrenal corticotropin hormone stimulation were not clinically different during treatment compared with values obtained at baseline for any of the treatment groups. CONCLUSIONS: Treatment with maximum doses of atorvastatin for 1-year did not have any adverse effects on adrenal function under basal conditions or during maximum stimulation. Similarly, colestipol therapy alone and in combination with either atorvastatin or simvastatin did not appear to affect adrenal function.

Diel and annual variation in plasma cortisol concentrations among wild and captive harbor seals (Phoca vitulina)

Annual and diel changes in plasma cortisol concentrations were investigated among wild and captive harbor seals (Phoca vitulina) of various sex and age classes. No significant effects of age, sex, or season were found in captive animals. However, significant inter-individual differences between two juvenile males were noted during both the breeding/molt (p = 0.041) and postbreeding/postmolt (p = 0.001) seasons. Seasonal and sex- and age-related differences were found among wild harbor seals. Across all sex and age categories, mean cortisol concentrations during the postbreeding and prebreeding seasons were significantly different from those measured during the breeding season (p = 0.014 and p = 0.038, respectively), but did not differ from each other. When each sex and age group was examined separately, seasonal effects were significant for mature females (p = 0.009) and mature males (p = 0.048). Differences in plasma cortisol concentration between captive and wild animals of the same sex during the same seasons were highly significant, particularly in mature animals (between p &lt; 0.0001 and p = 0.035). There was a diel pattern of plasma cortisol concentrations in samples collected from captive animals over a 24-h period. Mean concentrations differed between samples collected during the hours of light and dark, being highest at night (p = 0.009), peaking around 01:00, and dropping again at around 13:00. Annual and diel patterns of plasma cortisol concentrations occur in harbor seals, and seasonal differences may relate to important physiological and behavioral phases in the harbor seals' annual cycle.

Oxygen consumption rates of tilapia in fresh water, sea water, and hypersaline sea water

Whole animal oxygen consumption rates and plasma constituents were determined in the tilapia O. mossambicus, acclimated for 1 month in fresh water, sea water, and 1·6 × sea water. Oxygen consumption rates for the three water salinities were: 177·2 ± 16·86, 78·6 ± 2·32, and 195·4 ± 15·39 mg O2 kg−1 h−1 (means ± 1 s.e.), respectively. Plasma prolactin (tPRL188) concentration was significantly lower in 1·6 × sea water compared to fresh and sea water. There were no significant differences among mean plasma cortisol concentration and lysozyme activity. Ventilation was significantly higher in fish in sea water compared to the fish in fresh and 1·6 × sea water. The lowest oxygen consumption rates were found in fish acclimated to sea water. That salinity is probably closest to the brackish waters from which they were captured in the wild, and this agreement likely reflects the selection for optimal morphological and physiological characteristics to live in that environment.

Oxygen consumption rates of tilapia in fresh water, sea water, and hypersaline sea water

Whole animal oxygen consumption rates and plasma constituents were determined in the tilapia O. mossambicus, acclimated for 1 month in fresh water, sea water, and 1·6 × sea water. Oxygen consumption rates for the three water salinities were: 177·2 ± 16·86, 78·6 ± 2·32, and 195·4 ± 15·39 mg O2 kg−1 h−1 (means ± 1 s.e.), respectively. Plasma prolactin (tPRL188) concentration was significantly lower in 1·6 × sea water compared to fresh and sea water. There were no significant differences among mean plasma cortisol concentration and lysozyme activity. Ventilation was significantly higher in fish in sea water compared to the fish in fresh and 1·6 × sea water. The lowest oxygen consumption rates were found in fish acclimated to sea water. That salinity is probably closest to the brackish waters from which they were captured in the wild, and this agreement likely reflects the selection for optimal morphological and physiological characteristics to live in that environment.

Twenty-Four Hour Cortisol Release Profiles in Patients With Alzheimer’s and Parkinson’s Disease Compared to Normal Controls: Ultradian Secretory Pulsatility and Diurnal Variation

Endocrine abnormalities of the hypothalamic-pituitary-adrenal (HPA) system in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD) have been described repeatedly. However, no data are available on the diurnal cortisol secretory pattern in these major neurodegenerative disorders. Therefore, we studied 24-h pulsatile cortisol secretion in 12 patients with AD and 12 patients with PD compared to 10 normal community- and age-matched volunteers (NV). Twenty-four hour blood sampling was performed from 1800 h to 1800 h at 15-min intervals. Cortisol half-life, number of cortisol secretory bursts/24-h, interpulse interval, mass of cortisol secreted per burst, amplitude of cortisol secretory bursts, pulsatile cortisol production rate, 24-h mean, and integral cortisol concentrations were calculated by applying deconvolution analysis. Furthermore, the relative diurnal variation and the quiescent period were determined. Patients with AD and PD were found to have significantly higher total plasma cortisol concentrations (24-h pulsatile cortisol production rate: AD + 56%; PD + 52%/24-h integrated cortisol: AD + 37%; PD + 29%) compared to NV. This sustained hypercortisolism is due to a higher mass of cortisol secreted per burst (AD + 62%; PD + 79%), but not to increased cortisol half-life or secretory pulse frequency or amplitude. Despite these similarities between AD and PD patients, relative diurnal variation of cortisol secretion was significantly decreased in patients with PD (−22%), whereas the pattern of secretory curves was not different between NV and AD patients. This observation was indirectly supported by a reduction of the quiescent period in patients with PD (−74 min) compared to the NV and AD group. Based on these results and recently published animal data, we hypothesize that decreased expression of hippocampal mineralocorticoid receptors (MR) may account for the flattened diurnal cortisol secretory curve observed in PD patients, whereas the intact diurnal profile in AD patients may be due to a relative increase in MR compensating for the hippocampal neuronal loss commonly occurring in this disorder.

Cortisol concentrations in post competition horse urine: a French and British survey.

The purpose of the present report was to estimate the population parameters of cortisol concentrations in urine, an endogenous hormone used as a 'doping' agent and for which an international threshold (1.0 micrograms/ml) has been proposed. Two data bases (French and UK) corresponding to 112 and 142 samples, respectively were considered. Urine was collected under specific post competition conditions. Cortisol concentrations were obtained by validated methods (HPLC for the French samples, and GC-MS for UK samples). No difference was observed between the 2 data sets and statistical analyses were carried out on the two merged files. The overall geometric mean cortisol concentration was 48 ng/ml. Distribution was not Gaussian. A log-normal distribution was not rejected (for P > 0.05). Using the log-normal distribution, it was calculated that the probability of exceeding a cortisol concentration in urine of 1.0 micrograms/ml was 1.1 x 10(-4). It was concluded that the actual international threshold is specific i.e. robust with regard to the risk of erroneously declaring an unmedicated horse as positive.

Cortisol in human tissues at different stages of life.

Aim of the work was to measure the cortisol level in human tissues at different stages of life, by means of radioimmunoassay and by chromatography. Viable samples of 13 different tissues were obtained during surgical intervention from 30 to 70 years old patients of either sex. Mean tissue cortisol concentration was 78 +/- 35 ng/g, ranging from 20 +/- 10 ng/g in the thyroid to 124 +/- 76 ng/g in the kidney. Similar values were measured in the corresponding tissues from not decayed corpses, so that paired values could be mediated. However the pancreas, and corrupted autopsy tissues, gave nil or exceedingly high cortisol concentration values; in some cases, opposite extreme values were measured in different organs of the same body. Cortisol concentration was also measured in 11 sound different tissues of spontaneously aborted or stillbirth fetuses, between 16 and 36 weeks of gestation. Mean value was 63 +/- 27 ng/g, ranging from 30 +/- 25 ng/g in the liver to 104 +/- 52 ng/g in the lungs. Also in fetuses nil or exceedingly high cortisol values occurred in altered tissues. One hundred and fourteen samples of limbs and carcasses of 7 to 12 gestational weeks embryos, obtained from voluntary abortions, were also examined: 20% gave nil result, in the remaining mean cortisol concentration was 32 ng/g. In 33 samples of embryos' mixed viscera, RIA and chromatography gave unreliable exceedingly high values. The nil and the exceedingly high values measured in the altered autoptic tissue specimens were inconsistent with the cortisol blood level measured in the patients, as were those measured in embryonic tissues with the acknowledged blood and adrenals cortisol levels at that stage of life. Thus cortisol may be measured by RIA and by chromatography in sound tissues, while the values obtained in the pancreas, in corrupted tissues, and in embryonal viscera do not represent the hormonal milieu, but are likely artifacts due to impeachment of the diagnostic system.

PLASMA CORTISOL CONCENTRATIONS AND LUNG DISEASE IN PREMATURE INFANTS.† 1934

Plasma cortisol concentrations are known to be relatively low at birth in premature infants and to be suppressed by antenatal betamethasone therapy. It has been suggested that low cortisol levels in the newborn period reflect adrenal insufficiency and are associated with respiratory disease. To further examine this relationship we determined plasma cortisol levels during the first 2 weeks of life in infants ≤32 wk gestation enrolled in an ongoing, blinded multi-center trial of antenatal thyrotropin releasing hormone (TRH). Women in premature labor at ≤30 wk gestation received betamethasone and either TRH or placebo and clinical data were obtained on the infants. Blood was collected at birth (cord) and postnatally from 145 infants ≤32 wk gestation at 8 participating sites and cortisol was assayed by immunoassay using enhanced chemiluminescence (Nichols Inst.). Natural log values for the data were used to evaluate correlations with lung disease. The geometric mean cortisol concentration in cord blood was 2.4 μg/dl (2.3 and 2.8 μg/dl for male and female infants, respectively), and there was a significant positive correlation with gestational age. Cortisol levels increased after birth with levels of 6.5, 11.2, 8.5, 8.2 and 6.4 μg/dl at 2 h and 1, 3, 7, and 14 days of age, respectively. Cortisol concentrations were significantly higher in infants with RDS at 2 h, 1 day and 3 days but not in cord blood(maximal levels on day 1, mean 13.6 vs 7.6 μg/dl, p=0.003). Levels were not significantly different at all time points for infants with and without chronic lung disease (CLD) at 28 days (ongoing requirement for oxygen or ventilator), CLD at 36 wk postconceptional age, or adverse outcome (death or CLD) at 36 wk postconceptional age. We conclude that very low birth weight infants exposed to betamethasone treatment in utero increase their plasma cortisol after birth and in response to the stress of RDS; low postnatal cortisol concentrations do not appear to be a predictor of CLD.

Fasting as a metabolic stress paradigm selectively amplifies cortisol secretory burst mass and delays the time of maximal nyctohemeral cortisol concentrations in healthy men.

Serum cortisol concentrations are increased in fasted or malnourished human subjects. The dynamic mechanisms underlying this adaptive response have been investigated in eight normal men by analyzing serum cortisol concentrations measured in blood obtained at 5-min intervals over 24 h on a control (fed) day and on the fifth day of a fast (water only) assigned in randomized order. A multiple parameter deconvolution method was used to simultaneously resolve endogenous cortisol secretion and half-life. Five days of fasting induced a 1.8-fold increase in the 24-h endogenous cortisol production rate (fed, 2504 +/- 308; fasted, 4528 +/- 488 nmol/L distribution volume; P < 0.006). This enhanced cortisol production rate was accounted for by a 1.6-fold increase in the mass of cortisol secreted per burst (fed, 115 +/- 12.1; fasted, 183 +/- 17.3 nmol/L; P < 0.02). Cortisol secretory event amplitudes (maximal rates of cortisol release attained within a burst) increased in seven of eight men, and mean secretory burst durations remained unchanged by fasting. Moreover, the number of computer-resolved cortisol secretory bursts per 24 h (fed, 22 +/- 1.4; fasted, 25 +/- 2.0; P = NS) and the interburst interval (fed, 65 +/- 4.0; fasted, 57 +/- 4.4 min) did not change significantly during a 5-day fast. The calculated half-life of endogenous cortisol was not significantly altered by fasting (fed, 108 +/- 9.7; fasted, 129 +/- 11 min). There was no significant change in the nyctohemeral pattern of varying adrenocortical secretory burst frequency in response to fasting. However, the mean (mesor) mass of glucocorticoid secreted per burst over 24 h rose significantly in response to fasting. In addition, by cosinor analysis, maximal serum cortisol concentrations occurred (95% confidence intervals) between 0930-1334 h in the fed state and between 1116-1612 h in the fasted state (P < 0.04). Fasting augmented the mesor (average value about which the diurnal rhythm oscillates; P < 0.0008 compared with fed state) and the amplitude (P < 0.04) of the 24-h serum cortisol concentration profile. Linear regression analysis disclosed a significant inverse relationship between mean serum cortisol and GH concentrations in fasted men (r = -0.76; P < 0.02). In conclusion, the present data indicate that starvation-induced enhancement of cortisol secretion in young healthy men is mediated by an increased glucocorticoid secretory burst mass, rather than changes in secretory burst frequency or duration or in cortisol half-life. In addition, fasting modifies the diurnal secretory pattern of cortisol by delaying maximal serum concentrations to the early afternoon. The inverse relationship between serum cortisol and GH responses to fasting suggests differential regulation of the corticotropic and somatotropic axis by the metabolic stress of fasting and/or feedback interactions between these two axes when they are both activated.

Effects of disease on the results of diagnostic tests for use in detecting hyperadrenocorticism in dogs

Summary The purpose of the study reported here was to assess 3 commonly used screening tests for hyperadrenocorticism (low-dose dexamethasone suppression test, acth stimulation test, and urinary cortisol:creatinine ratio) in dogs with various diseases other than those of the adrenal glands (nonadrenal diseases). A group of 100 dogs was studied: 59 dogs with nonadrenal disease, 21 clinically normal dogs, and 20 dogs with pituitary-dependent hyperadrenocorticism. Of 59 dogs with nonadrenal disease, 20 (34%) had high baseline cortisol concentration (greater than reference range limits), and 22 (38%) and 33 (56%) had inadequate serum cortisol suppression at 4 and 8 hours, respectively, after administration of a low dose of dexamethasone. Compared with clinically normal dogs, dogs with nonadrenal disease had significantly (P &lt; 0.05) higher mean serum cortisol concentration at 4 and 8 hours after administration of a low dose of dexamethasone; however, significant differences were not detected between the mean cortisol concentration at 8 hours after administration for dogs with nonadrenal disease and for dogs with hyperadrenocorticism. After acth stimulation, only 8 of 59 (14%) dogs with nonadrenal disease had high serum cortisol concentrations. Significant differences did not exist after acth stimulation between mean cortisol concentration of clinically normal dogs and that of dogs with nonadrenal disease. Of 59 dogs with nonadrenal disease, 45 (76%) had a high urinary cortisol:creatinine ratio. When compared with clinically normal dogs, dogs with nonadrenal disease had a significantly higher mean urinary cortisol:creatinine ratio, but significant differences did not exist between the mean urinary cortisol:creatinine ratio of dogs with nonadrenal disease and that of dogs with hyperadrenocorticism. The calculated sensitivity for each diagnostic test used on the 20 dogs with hyperadrenocorticism in this study ranged from 0.70 to 1.0, with the acth stimulation test having the lowest sensitivity and the low-dose dexamethasone suppression test having the highest sensitivity. In dogs with nonadrenal disease, the acth stimulation test had the highest specificity (0.86) and efficiency (0.85), whereas the specificity of the low-dose dexamethasone suppression test (0.44) and urinary cortisol:creatinine ratio (0.24) were lower. The acth stimulation test also had the highest positive predictive value (0.67), whereas this value was lower for the low-dose dexamethasone suppression test (0.38) and urinary cortisol:creatinine ratio (0.25). Analysis of results of this study indicated that many dogs with nonadrenal disease have false-positive test results for hyperadrenocorticism when tested with the commonly used pituitary-adrenal function tests. Because false-positive test results were observed for all of the commonly used screening tests, a definitive diagnosis of hyperadrenocorticism should never be made solely on the basis of results of 1 or more of these screening tests, especially in dogs without classic clinical signs of hyperadrenocorticism or in dogs known to have nonadrenal disease.

Adrenocortical function in neonatal and weanling Beagle pups

Abstract Adrenocortical function was assessed in 27 Beagle pups at 2, 4, 6, 8, 10, and 12 weeks of age by determination of plasma sodium, potassium, and chloride concentrations; serum aldosterone and cortisol concentrations; and plasma ACTH concentrations. Serum cortisol concentration was measured before and 1 and 2 hours after IM administration of 2.2 IU of acth/kg of body weight. Serum progesterone concentration also was determined for all pups at 2, 4, and 6 weeks of age. Mean baseline cortisol concentration was lower for pups 8 weeks old or younger than for mature dogs. Nevertheless, mean serum ACIH-stimulated cortisol concentration in dogs of all age groups increased into the adult reference range after administration of acth. For pups 4 weeks old or younger, increase in cortisol concentration was maximal at 2 hours after acth administration. However, in pups between 6 and 12 weeks of age, the increase in cortisol concentration was maximal 1 hour after acth administration in about a third of the pups, whereas the remaining pups had peak values at 2 hours. Mean plasma sodium, potassium, and chloride concentrations for each age group were within the reference ranges established for mature dogs, with the exception of lower mean plasma sodium and chloride concentrations in pups 4 weeks old or younger. Mean serum aldosterone concentration in pups of each age group was substantially higher than the range of aldosterone concentrations for clinically normal mature dogs. Median progesterone concentration was uniformly less than 0.2 ng/ml for all pups 6 weeks old or younger. The normal endogenous acth concentration and adequate cortisol responses to exogenous acth seen in our pups would support functional pituitary gland and adrenal cortex for cortisol production. The low baseline cortisol concentration observed in the pups of this study may be related to reduced binding of cortisol to plasma proteins, as exists in human infants. The hyponatremia and increased aldosterone concentration may be explained by reduced renal tubular response to aldosterone, as also evidenced in the human infant kidney.

A retrospective study of increased plasma progestagen concentrations in compromised neonatal foals.

Plasma progestagen concentrations were measured daily by radioimmunoassay (RIA) in 35 sick foals for the duration of their illness. The foals were divided into three groups on the basis of time to stand after birth. Foals were given intensive care treatment according to the severity of their illness. Plasma and urine concentrations of pregnenolone (P5) and pregnenediol (P5 beta beta) were measured by gas chromatography--mass spectrometry; plasma cortisol concentrations were measured by RIA and the foals' renal and respiratory status were assessed by creatinine clearance ratios and arterial oxygen concentrations respectively. Five patterns of plasma progestagen concentrations were identified; in general, values increased when the foal's clinical condition deteriorated and decreased as the foal improved. Median progestagen concentrations decreased over the first three days post partum in Group 1 foals but remained elevated in foals from Groups 2 and 3. Similar changes were observed in plasma P5 and P5 beta beta concentrations. Plasma cortisol concentrations were highest in foals from Groups 2 and 3 (P < 0.01) compared with foals from Group 1. Regardless of foal group, mean cortisol concentrations were highest (P < 0.001) in those foals treated with adrenocorticotrophic hormone compared with those treated with dexamethasone or with neither drug. There was no relationship (r2 = 0.21) between plasma cortisol and progestagen concentrations. Results from renal clearance, steroid conjugation and respiratory status suggest that these factors did not play a significant role in elevating progestagen concentrations in sick foals. It is hypothesized that there may be a relationship between adrenal stimulation and an enzyme block resulting in overproduction of P5 and P5 beta beta in the sick neonatal foal.