Serum androgens in intensive-care patients: correlations with clinical findings

Serum androgen levels were studied in 100 patients (50 male) with varying degrees of severe illness, determined by Acute Physiological and Chronic Health Evaluation (APACHE). Comparison with normal subjects revealed the following changes: (1) Basal dehydroepiandrosterone sulphate (DHEAS) values were decreased in the ill female patients (P less than 0.001) as well as in the ill males (two groups, P less than 0.01; P less than 0.05). Androstenedione values did not differ from the controls in patients of either sex. Basal testosterone levels were decreased in ill male patients (P less than 0.001), but not in females. (2) The low testosterone concentrations in the severely ill male patients correlated inversely with the APACHE score; additionally, a dependence on diagnostic categories could be demonstrated in men, since the lowest values were found in patients suffering from sepsis or liver cirrhosis. Acutely ill males had a moderately decreased testosterone, whereas chronically ill males showed a marked reduction of testosterone compared to the controls. Lowered DHEAS and androstenedione levels could be measured in chronically ill males but not in ill females. (3) 17 alpha-OH-progesterone and 17 alpha-OH-pregnenolone levels in subgroups of the patients suggested a probable enzymatic block in the delta 5-pathway of androgen biosynthesis in severe illness. The ratio of 17 alpha-OH-pregnenolone to DHEAS was significantly higher in male patients and tended to be high in ill females, whereas the ratio of 17 alpha-OH-progesterone to androstenedione showed no difference between healthy and ill subjects.     

老年重症患者血清皮质醇和促肾上腺皮质激素浓度检测的临床意义

目的 探讨血清皮质醇（corticosteroids,COR）和促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）浓度与老年重症患者病情严重程度及预后的关系,为老年重症患者临床病情评估、治疗和判断预后提供参考依据.方法 采用回顾分析的方法,收集2010年2月至2013年11月在广东省人民医院老年医学研究所危重症监护三区收治并进行COR和ACTH检测的70例老年重症患者的病历资料,分别检测4个时间点的血清COR浓度和两个时间点的血清ACTH浓度,用急性生理学与慢性健康状况评分系统（acute physiology and chronic health evaluationscoringsystem,APACHE）Ⅱ评估患者的病情严重程度.按照病情严重程度分为感染性休克组和对照组,分析两组血清COR和ACTH浓度与病情及预后的关系,并计算感染性休克组患者相对性肾上腺皮质功能不全（RAI）的发生率.按照年龄分为老年组和老老年组,分析年龄对血清COR及ACTH浓度的影响.结果 老年重症患者4个时间点血清COR浓度相近,昼高夜低的分泌节律消失.感染性休克组老年患者血清COR浓度显著高于对照组,差异有统计学意义（P＜0.05）;感染性休克组ACTH浓度高于对照组,但差异无统计学意义（P＞0.05）;感染性休克组28 d内病死率高于对照组,差异有统计学意义（41.94％ vs.5.13％,P=0.000 11）;感染性休克组肾上腺皮质功能不全的发生率为68.5％.不同年龄组的血清COR和ACTH浓度比较,差异无统计学意义（P＞0.05）.结论 持续的应激反应导致老年重症患者血清COR分泌节律消失,老年重症患者血清COR浓度随着病情危重程度加重而升高.年龄可能不是影响老年重症患者血清COR和ACTH浓度的首要因素.     

Serum cortisol and cortisone levels in newborns with congenital adrenal hyperplasia before the start of therapy

Sodium loss in infants with salt wasting (SW) congenital adrenal hyperplasia (CAH) does usually not occur within the first week of life. We hypothesized that sufficient mineralocorticoid activity might by temporarily maintained by still appropriate concentrations of cortisol. Plasma samples were obtained from 15 infants with SW-CAH before the onset of sodium loss, 17 patients with simple virilizing (SV)-CAH and 28 healthy infants under 14 days of age. Plasma aldosterone concentrations were significantly lower in SW-CAH infants than in SV-CAH patients and in healthy neonates. Plasma cortisol levels and cortisol/cortisone (F/E) ratios in SW-CAH patients were almost the same as in the SV-CAH and control group. While declining plasma aldosterone levels precede the onset of SW in CAH patients, plasma cortisol concentrations are kept normal in SW-CAH infants, temporarily maintaining sufficient mineralocorticoid activity.     

In vivo evidence of cortisol secretion by aldosterone-producing adenomas

This study was done to confirm that aldosterone-producing adenomas secrete cortisol in vivo. Plasma cortisol and aldosterone concentrations were measured in samples obtained by selective adrenal-vein sampling in 8 patients with primary aldosteronism due to unilateral adenoma. All cases revealed higher adrenal-vein plasma cortisol concentrations on the adenoma side than the opposite, irrespective of adenoma location. These concentrations correlated significantly with plasma aldosterone concentrations (r = 0.972, P less than 0.001) in effluents from the adenoma side, but not from the opposite. Plasma concentrations also correlated significantly with estimated adenoma volume (r = 0.918, P less than 0.05). These findings strongly suggest that aldosterone-producing adenomas secrete cortisol in vivo. In a second study, we used metyrapone to test 6 patients with adenomas. Their responsiveness to cortisol and corticotrophin was found to be the same as that in normal subjects, suggesting that adenoma-secreted cortisol did not disturb the relationship between corticotrophin and cortisol. We thus concluded that cortisol is secreted concomitantly with aldosterone from aldosterone-producing adenomas under corticotrophin influence.     

Dehydroepiandrosterone sulphate in critical illness: effect of dopamine

OBJECTIVE As part of a study on the effect of dopamine therapy on pituitary dependent hormone secretion in critical illness, we documented the impact of this inotropic and vasoactive catecholamine on the serum concentrations of dehydroepiandrosterone sulphate (DHEAS). Concomitantly, serum levels of PRL and cortisol were determined. PATIENTS AND DESIGN In a prospective, randomized, controlled, open-labelled clinical study, 20 critically ill, adult polytrauma patients receiving dopamine treatment (5 μg/kg/ml i.v. for a median 109 hours (range 21–296 hours), were studied to evaluate the effect of dopamine withdrawal on serum concentrations of DHEAS, PRL and cortisol. The median age of the studied patients was 37 years (range 18–83 years) MEASUREMENTS Serum DHEAS and cortisol concentrations were measured by RIA and PRL by IRMA. The assessed serum samples were obtained at 0300h on each of two consecutive study nights. RESULTS Withdrawal of dopamine infusion was found to elicit a median 25% Increase of serum DHEAS concentrations within 24 hours whereas no significant change in DHEAS levels was observed when dopamine infusion was continued throughout both study nights (P= 0.01 continued vs interrupted dopamine). Prolactin levels were undetectable as long as dopamine was infused, and increased to a median of 317 IU/I after 24 hours of dopamine withdrawal (P = 0.0007). Elevated serum cortisol levels remained comparable with continued and interrupted dopamine infusion. CONCLUSIONS Dopamine infusion appears to suppress serum DHEAS concentrations in critically ill patients without affecting their elevated serum cortisol levels, suggesting a differential regulation of DHEAS and cortisol metabolism in critical illness. The lowering effect of dopamine on DHEAS levels could be linked to the concomitant suppression of circulating PRL. The simultaneous suppression of circulating PRL and DHEAS by dopamine infusion may be an iatrogenic factor maintaining or aggravating the anergic state of prolonged severe illness.     

STUDIES OF DIURNAL CHANGES IN PLASMA RENIN ACTIVITY, AND PLASMA NORADRENALINE, ALDOSTERONE AND CORTISOL CONCENTRATIONS IN MAN

Diurnal studies were performed on ten normal volunteers taking a normal sodium diet. Half-hourly blood samples were taken throughout 25 h and assayed for plasma renin activity (PRA) and the plasma concentrations of noradrenaline, aldosterone and cortisol. Sleep was recorded polygraphically and scored by standard criteria. Circadian rhythms were demonstrated for plasma cortisol, aldosterone and noradrenaline concentrations, but not for plasma renin activity. The nadir of the rhythm for the noradrenaline concentration appeared to be related to sleep itself rather than to any chronological index. Only PRA was effected by the stage of sleep, falling sharply during periods of REM sleep. Plasma cortisol and aldosterone concentrations showed a positive correlation over the 24 h. There was, however, no correlation between PRA and plasma aldosterone concentrations, except when the subjects arose after their night's recumbency. Plasma noradrenaline concentration did not correlate with the concentration of any of the other hormones measured.     

Dissociation of adrenal androgen and cortisol secretion in Cushing's syndrome

OBJECTIVES While ACTH may modulate adrenal androgen production, there is evidence that other factors are required. Cushing's disease and ectopic ACTH secretion provide a little utilized opportunity to examine adrenal androgen levels in conditions of ACTH excess. We have compared plasma cortisol values with plasma levels of androstenedione, dehydroeplandrosterone (DHEA), DHEA-sulphate (DHEAS), testosterone and an Index of free testosterone, the testosterone/sex hormone binding globulin ratio, prior to treatment in patients with Cushing's syndrome. PATIENTS AND MEASUREMENTS Plasma from 15 adult patients with Cushing's disease and three adults with the ectopic ACTH syndrome was obtained prior to treatment and submitted to specific immunoassays for the measurement of the above steroids. RESULTS Plasma cortisol values of 15 patients with Cushing's disease (range 326–1140 nmol/l, normal range 190–690 nmol/l) were elevated in 9; In contrast, plasma androstenedione (4·1–11·3 nmol/l, normal range, men 2·1–7·7, women 3·3–9·9 nmol/l) was elevated in only two patients, plasma DHEAS (3·3–17·8 μmol/l, normal range, men 4·5–18·4, women 3·5–11·8 μmol/l) was elevated in only 4 patients and plasma DHEA (4·8–45·2 nmol/l, normal range 11–48 nmol/l) was normal or low in all 15 patients. Plasma androstenedione was markedly elevated (74 nmol/l) in one of three patients with ectopic ACTH syndrome, moderately elevated in another, and normal in the third patient. In contrast, plasma DHEA and DHEAS levels were suppressed in the patient with the highest androstenedione level and low or normal in the other two patients. CONCLUSIONS These data suggest that ACTH alone does not control adrenal androgen Secretion. The data also suggest that variability in the processing of proopiomelanocortin (the precursor of ACTH and related peptides) occurring in Cushing's disease and ectopic ACTH syndrome may account for differences in the relation of cortisol to androgens observed between the disorders and when compared to that in normal subjects.     

Familial cortisol resistance: differential diagnostic and therapeutic aspects

A 26-yr-old woman presented with hirsutism, male pattern scalp baldness ("geheimratsecken"), and menstrual irregularities. She had no hypertension or other signs and symptoms of Cushing's syndrome. Plasma cortisol levels were greatly elevated and did not suppress normally in response to dexamethasone. Cortisol binding to transcortin was normal. Plasma androstenedione and testosterone levels were also increased, but 17-hydroxyprogesterone and aldosterone levels were normal. Further studies revealed an increased cortisol production rate, increased 24-h urinary cortisol excretion, increased plasma ACTH levels, a normal diurnal rhythm of cortisol at an elevated level, and normal increments of plasma ACTH, cortisol, GH, and PRL in response to insulin-induced hypoglycemia. The father and two brothers also had increased plasma cortisol levels, which did not suppress normally in response to dexamethasone. Chronic therapy with dexamethasone (at first 1 and later 0.5 mg, three times daily) for more than 30 weeks resulted in decreased hirsutism, normalization of scalp hair and menstrual cyclicity, and normal plasma testosterone and androstenedione levels. No signs or symptoms of Cushing's syndrome developed, and the central regulation of secretion of ACTH, cortisol, GH, and PRL (insulin test, diurnal rhythm) remained qualitatively normal at a lower set-point. We conclude that this patient had autosomal dominantly inherited hereditary (partial) cortisol insensitivity, which had resulted in increased adrenocortical cortisol and androgen secretion. The latter had not resulted in clinical symptoms in the three afflicted male members of the family, but had in the propositus. The results also indicate the potential usefulness of the insulin test in distinguishing this disorder from Cushing's disease.     

Evidence for adrenocortical adaptation to severe illness

During serious illness, there are characteristic increases in serum cortisol concentrations and urinary cortisol excretion. In the present studies, we investigated these changes in glucocorticoid metabolism in relation to adrenal androgen metabolism, as measured by RIA of dehydroepiandrosterone (DHA) and DHA sulfate (DHAS). A group of 23 seriously ill men with various disorders, ill for a week or longer, was age-matched to a control group of 25 men, and the following changes were found: 1) basal serum cortisol concentrations were elevated in the ill group (P less than 0.001), 2) basal serum DHA and DHAS concentrations tended to be lower in the ill group (P less than 0.1); 3) basal serum DHA to cortisol and DHAS to cortisol ratios were decreased in the ill group by 80.3% and 77.2%, respectively (P less than 0.001); 4) ACTH-stimulated serum cortisol concentrations increased by the same absolute amount in both groups, whereas the increase in stimulated DHA concentrations in the ill group was 57.2% less (P less than 0.05), indicating a defect in ACTH-stimulated DHA reserve in serious illness; 5) basal daily unconjugated DHA excretion was lower in the ill group (P less than 0.05); (6) basal daily cortisol excretion was higher in the ill group (P less than 0.05); and 7) the basal daily urinary unconjugated DHA to cortisol ratio was 85.4% lower in the ill group (P less than 0.001). Recently, Zipser et al. described the entity of hyperreninemic hypoaldosteronism in the seriously ill. Their findings combined with our own indicate a relative shift in the metabolism of adrenal pregnenolone in serious illness away from mineralocorticoids and adrenal androgens and toward glucocorticoids. The cause of this change is unknown. We speculate that this shift of relative biochemical pathway predominance may be a factor necessary for survival during chronic severe stress.     

Steroids in the plasma of the gray seal,Halichoerus grypus

Cortisol, cortisone, corticosterone, aldosterone, 11-deoxycorticosterone, and testosterone were identified and quantified by a double isotope derivative method in the peripheral plasma of adult male gray seals Halichoerus grypus. Plasma from two seals sampled in late January had cortisol and testosterone levels of 33.0, 35.4 and 7.45, 3.39 μg/100 ml, respectively. Plasma from one seal sampled in late August of the same year had cortisol and testosterone levels of 3.60 and 0.31 μg 100 ml, respectively. The cortisol/corticosterone ratios were 7.14 and 4.32 in the January seals and 0.73 in the August seal. The concentrations of aldosterone were high (0.14–0.33 μg/100 ml) and did not reflect marked differences as was shown for cortisol and testosterone in the seals sampled.     

Renal clearance and daily excretion of cortisol and adrenal androgens in patients with rheumatoid arthritis and systemic lupus erythematosus

BACKGROUND: In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), patients demonstrate low levels of adrenal hormones. OBJECTIVE: To investigate whether increased renal clearance and daily excretion contribute to this phenomenon. METHODS: Thirty patients with RA, 32 with SLE, and 54 healthy subjects (HS) participated. Serum and urinary levels of cortisol, cortisone, 17-hydroxyprogesterone (17OHP), androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulphate (DHEAS) were measured. RESULTS: Clearance of DHEAS and DHEA was lower in patients than in HS, and clearance of androstenedione was somewhat higher in patients than in HS, but daily excretion of this latter hormone was low. Clearance of cortisol, cortisone, and 17OHP was similar between the groups. The total molar amount per hour of excreted DHEA, DHEAS, and androstenedione was lower in patients than HS (but similar for cortisol). Serum DHEAS levels correlated with urinary DHEAS levels in HS and patients, whereby HS excreted 5-10 times more of this hormone than excreted by patients. Low serum levels of adrenal androgens and cortisol in patients as compared with HS were confirmed, and proteinuria was not associated with changes of measured renal parameters. CONCLUSIONS: This study in patients with RA and SLE demonstrates that low serum levels of adrenal androgens and cortisol are not due to increased renal clearance and daily loss of these hormones. Decreased adrenal production or increased conversion or conjugation to downstream hormones are the most likely causes of inadequately low serum levels of adrenal hormones in RA and SLE.     

Plasma immunoreactive proopiolipomelanocortin-derived peptides in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism

Immunoreactive plasma levels of the proopiolipomelanocortin-derived peptides, ACTH, beta-endorphin-lipotropin, and gamma 3MSH, were measured in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism. Plasma peptide concentrations in patient groups were not different from those in normal controls. Removal of aldosterone-producing adenomas in three patients and of an aldosterone-producing adrenocortical carcinoma in one patient did not affect plasma peptide concentrations. Furthermore, infusion of the opiate antagonist naloxone (0.2 mg/min) in one patient with bilateral adrenal hyperplasia had no effect on either plasma aldosterone or cortisol. These results suggest that the proopiolipomelanocortin-derived peptides are not overproduced in states of hyperaldosteronism.     

The dissociation of renin and aldosterone during critical illness

A syndrome of elevated PRA accompanied by inappropriately low plasma aldosterone (ALDO) levels has been identified in some critically ill patients. To determine whether this phenomenon is due to a disturbance in factors that stimulate ALDO, we measured PRA, angiotensin II (AII), potassium (K+), and ACTH levels in 83 patients admitted to an intensive care unit. In 59 patients, PRA was greater than 2.0 ng/ml X h. Of these, 24 had an ALDO to PRA ratio (ALDO/PRA) below 2 (group I), and 35 had an ALDO/PRA ratio of 2 or more (group II). An ALDO/PRA ratio below 2 was deemed inappropriately low. Despite markedly elevated PRA [34 +/- 12 (+/- SE) ng/ml X h], the group I patients had inappropriately low ALDO levels (19 +/- 5 ng/dL). Patients in group II had significantly higher ALDO levels (48 +/- 6 ng/dL) despite lower PRA (9 +/- 1 ng/ml X h). AII levels were appropriately elevated in group I (39 +/- 26 pg/mL) and significantly greater (P less than 0.5) than those in group II. PRA correlated well with AII in both groups. There were no differences in plasma ACTH or K+ in these 2 groups, and plasma cortisol levels were similarly elevated in both groups of patients. Of 66 consecutively studied patients, 14 (21%) had inappropriate ALDO (group I). Mortality was significantly greater in group I (75%) than in group II (46%; P less than 0.001). In summary, a significant subset (21%) of seriously ill patients have inappropriately low ALDO levels despite elevated PRA. This dissociation is not due to an impairment of AII production or changes in plasma ACTH or K+. This phenomenon is associated with a higher mortality during critical illness. In light of evidence of decreased adrenal androgen secretion during severe illness, this dissociation of renin and aldosterone may represent an additional adrenal adaptation designed to promote cortisol production in critically ill patients.     

Hyperreninemic hypoaldosteronism in the critically ill: a new entity

To define the changes in adrenal gland function during critical illness, we evaluated 28 severely ill patients with persistent hypotension who were hospitalized in a medical intensive care unit. The patients had increased plasma cortisol (mean +/- SE, 40.1 +/- 10.1 micrograms/dl). PRA was increased in all subjects (21.6 +/- 7.2 ng/ml.h); however, the plasma aldosterone concentration was inappropriately low in 18 of the subjects, with values ranging from 1-9 ng/dl, despite normal serum potassium concentrations (4.3 +/- 0.1 meq/liter) and increased concentrations of the aldosterone percursor, 18-hydroxycorticosterone. These 18 patients had hypotension associated with major infections and a high mortality rate (78%). Infusions of ACTH or angiotensin II were associated with a normal aldosterone response in only 2 of the 14 patients tested, also suggesting that the defect was probably at the level of the zone glomerulosa cell. Although infection was a common underlying illness, no other factors, such as dopamine administration, decreased angiotensin-converting enzyme activity, or increased aldosterone clearance, could be implicated as the cause of the phenomena. Thus, selective hypoaldosteronism in the presence of high renin levels exists in a substantial percentage of hypotensive critically ill patients.     

Klinefelter's syndrome: a study of its hormonal plasma pattern

Plasma testosterone (T), dihydrotestosterone (DHT), 17 beta-estradiol (E2), 17-hydroxyprogesterone (17-OHP), androstenedione (delta), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 5-androstene-3 beta-17 beta-diol (A-diol) and cortisol (F) have been measured in a group of normal males and in a group of patients with Klinefelter's syndrome (KS) before and after hCG stimulation. Significantly lower baseline levels of T and DHT and significantly higher baseline levels of E2 were found in patients with KS. No significant differences were found between baseline levels of 17-OHP, delta, DHEA, DHEAS, A-diol, and F. After hCG stimulation between T, DHT, E2 and 17-OHP levels showed a significant increase in the two groups of subjects. The percentage variation of T and DHT, however, was much less important in Klinefeiter patients, while E2 and 17-OHP did not show a significantly different pattern from that of normal controls, hCG administration did not produce any significant variation of delta, DHEA, DHEAS, and F in the two groups of subjects, while A-diol levels increased significantly in normal subjects, but not in Klinefelter patients. Our data may be consistent with the hypothesis that testicular steroidogenesis in Klinefelter patients is impaired below the 21-C-steriod level not only at delta 4 but also at the delta 5 pathway.     

The plasma levels of dehydroepiandrosterone sulfate are decreased in patients with chronic heart failure in proportion to the severity

Dehydroepiandrosterone sulfate (DHEAS) is the major secretory steroid of the human adrenal glands. The secretion of DHEAS decreases with aging. The incidence of heart failure also rises in the elderly population. We measured the plasma levels of DHEAS and cortisol in 49 patients with chronic heart failure (CHF) and 32 age-matched controls and assessed its relation to plasma levels of A-type natriuretic peptide and B-type natriuretic peptide, biochemical markers of heart failure. Plasma levels of DHEAS were significantly lower in patients with CHF than in controls, whereas there was no significant difference in plasma levels of cortisol between the two groups. In stepwise regression analysis, the plasma level of DHEAS was significantly and independently correlated with age (beta = -0.451; P < 0.0001) and the plasma level of B-type natriuretic peptide (beta = -0.338; P < 0.001), and the plasma cortisol/DHEAS ratio was significantly and independently correlated with the plasma levels of A-type natriuretic peptide (beta = 0.598; P < 0.0001) and thiobarbituric acid-reactive substances (a marker of oxidative stress; beta = 0.252; P < 0.01) and age (beta = 0.171; P < 0.05). These results indicate that the plasma levels of DHEAS are decreased in patients with CHF in proportion to its severity and that oxidative stress is associated with decreased levels of DHEAS in patients with CHF.     

Association of hypotension with hyperreninemic hypoaldosteronism in the critically ill patient

Paradoxical suppression of plasma aldosterone (PA) despite increased plasma renin activity (PRA) has recently been noted in some critically ill patients. To determine the prevalence of this entity and to identify possible etiologic factors, we studied 100 consecutive patients admitted to a medical intensive care unit (ICU). Twenty-two of 100 ICU patients had hyperreninemia and inappropriately reduced PA concentrations, with a PA to PRA ratio less than the 98th percentile of the control population. Comparison of clinical data of these 22 patients with the other hyperreninemic ICU patients revealed no differences in electrolyte concentrations, nutrition, medications, or survival. However, persistent hypotension was much more frequent (91% v 53%). Thus, impaired aldosterone response to hyperreninemia has a high prevalence among critically ill patients and may be related to adrenal damage from persistent hypotension.     

Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6

OBJECTIVE: To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. METHODS: Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and clinical and laboratory measures of disease activity such as C-reactive protein and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8 patients with recent onset PMR not treated with glucocorticoid in comparison to controls after challenge with ovine corticotropin releasing hormone (oCRH) test. In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were evaluated after stimulation with low dose (1 microg) intravenous ACTH. RESULTS: Serum cortisol and ASD levels of all PMR patients at baseline did not differ from controls. During followup, cortisol levels dipped at one and 3 months. Serum DHEAS levels in all patients were significantly lower than in controls at baseline. In female PMR patients a significant correlation was found at baseline between cortisol levels and duration of disease. Serum concentrations of IL-6 at baseline were significantly higher in PMR patients than in controls. During 12 months of glucocorticoid treatment IL-6 levels dropped significantly at one month; thereafter they remained stable and did not increase again despite tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol response was found in patients and controls. After ACTH administration, a significant cortisol peak was detected in patients and controls, whereas no significant difference in cortisol area-under-the-curve (AUC) was found between the groups. In contrast, ACTH induced a significantly higher (p < 0.05) peak of 17-OHP and AUC in PMR patients than in controls. CONCLUSION: This study found reduced production of adrenal hormones (cortisol, DHEAS) at baseline in patients with active and untreated PMR. The defect seems mainly related to altered adrenal responsiveness to the ACTH stimulation (i.e., increased 17-OHP), at least in untreated patients. The 12 month glucocorticoid treatment of patients reduced the production of inflammatory mediators (i.e., IL-6) in a stable manner that persisted after glucocorticoids were tapered.     

Copeptin and arginine vasopressin concentrations in critically ill patients

CONTEXT: Determination of arginine vasopressin (AVP) concentrations may be helpful to guide therapy in critically ill patients. A new assay analyzing copeptin, a stable peptide derived from the AVP precursor, has been introduced. OBJECTIVE: Our objective was to determine plasma copeptin concentrations. DESIGN: We conducted a post hoc analysis of plasma samples and data from a prospective study. SETTING: The setting was a 12-bed general and surgical intensive care unit (ICU) in a tertiary university teaching hospital. PATIENTS: Our subjects were 70 healthy volunteers and 157 ICU patients with sepsis, with systemic inflammatory response syndrome (SIRS), and after cardiac surgery. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Copeptin plasma concentrations, demographic data, AVP plasma concentrations, and a multiple organ dysfunction syndrome score were documented 24 h after ICU admission. RESULTS: AVP (P < 0.001) and copeptin (P < 0.001) concentrations were significantly higher in ICU patients than in controls. Patients after cardiac surgery had higher AVP (P = 0.003) and copeptin (P = 0.003) concentrations than patients with sepsis or SIRS. Independent of critical illness, copeptin and AVP correlated highly significantly with each other. Critically ill patients with sepsis and SIRS exhibited a significantly higher ratio of copeptin/AVP plasma concentrations than patients after cardiac surgery (P = 0.012). The American Society of Anesthesiologists' classification (P = 0.046) and C-reactive protein concentrations (P = 0.006) were significantly correlated with the copeptin/AVP ratio. CONCLUSIONS: Plasma concentrations of copeptin and AVP in healthy volunteers and critically ill patients correlate significantly with each other. The ratio of copeptin/AVP plasma concentrations is increased in patients with sepsis and SIRS, suggesting that copeptin may overestimate AVP plasma concentrations in these patients.     

Chronobiological study of factors affecting plasma aldosterone concentration in cirrhosis

We studied the mechanisms leading to derangement of aldosterone secretion in cirrhosis. The circadian patterns of plasma renin activity (PRA), aldosterone, cortisol, sodium, and potassium were studied in 16 nonazotemic cirrhotics (group 1 without ascites, 7 cases; group 2 with ascites, 9 cases) and 7 healthy controls. Group 1 did not differ from controls in aldosterone, sodium, and potassium mean daily levels (mesors), but had reduced PRA mesor (p less than 0.05). Moreover, minor derangements in circadian patterns of PRA, aldosterone, and potassium were also found. Group 2 not only showed an increased mesor of PRA (p less than 0.05), aldosterone (p less than 0.001), and reduced sodium (p less than 0.005), but also achronia in daily fluctuations of PRA, aldosterone, and potassium. In all groups the mesors of PRA and aldosterone were correlated (r greater than or equal to 0.82; p less than 0.01 or less), but the regression line slopes of patients were steeper than those of controls (group 1, p less than 0.05; group 2, p less than 0.01). Moreover, although in controls and some group 1 patients aldosterone paralleled cortisol rhythmicity, most group 2 patients had aldosterone daily patterns correlated with those of PRA. Finally, no relationships between plasma potassium and aldosterone concentrations were found in patients, whereas they were strictly related in controls. These results suggest that the renin-angiotensin system is the prevalent determinant of aldosterone secretion in cirrhosis.