Basal Serum Cortisol Concentrations Research Articles

Adrenal response to the low dose ACTH stimulation test and the cortisol-to-adrenocorticotrophic hormone ratio in canine babesiosis

This prospective, interventional, case-controlled study sought to determine the association between adrenocortical function and mortality in dogs with naturally occurring Babesia rossi babesiosis. Sixty-eight dogs with canine babesiosis were studied and fifteen normal dogs were used as controls. Blood samples were obtained from the jugular vein in each dog prior to treatment, at admission to hospital, for the measurement of basal plasma ACTH (adrenocorticotrophic hormone) and serum cortisol concentrations. Immediately thereafter, each dog was injected intravenously with 5 μg/kg of ACTH (tetracosactrin). A second blood sample was taken 1 h later for serum ACTH-stimulated cortisol measurement and the resultant calculation of delta cortisol by subtracting basal from ACTH-stimulated cortisol. Diagnosis of babesiosis was confirmed by polymerase chain reaction (PCR) and reverse line blot (RLB). Three outcomes were defined: hospitalization with subsequent death ( n = 4); hospitalization followed by recovery ( n = 48); and treatment as an outpatient ( n = 16). Basal cortisol, but not ACTH-stimulated cortisol, was significantly higher in patients compared to control dogs. Basal- and ACTH-stimulated serum cortisol concentrations were significantly higher in the dogs that died, compared to hospitalized dogs that survived and compared to dogs treated as outpatients. There was no significant difference in delta cortisol concentrations or cortisol to ACTH ratios across outcome groups in dogs suffering from B. rossi babesiosis However, dogs with delta cortisol concentrations below 83 nmol/l had significantly higher cortisol to ACTH ratios compared to dogs with delta cortisol concentrations above 83 nmol/l. These findings of increased basal- and ACTH-stimulated cortisol and increased cortisol to ACTH ratios confirm the absence of adrenal insufficiency and concur with those in human malaria.

Serum cortisol and thyroxine concentrations as predictors of death in critically ill puppies with parvoviral diarrhea

To evaluate the role of adrenal and thyroid hormones in the prediction of death in a population of critically ill puppies with parvoviral diarrhea by measuring serial daily serum concentrations of cortisol and thyroxine. Prospective case-control study. 57 critically ill puppies with parvoviral diarrhea admitted to the hospital and 17 clinically normal control puppies. Basal serum cortisol and thyroxine concentrations were measured for each dog with parvoviral diarrhea at admission (prior to treatment) and daily until death, euthanasia, or discharge. Median time between admission and death was 48 hours (ie, on day 3). Median serum cortisol concentration on day 1 (admission) in all dogs with parvoviral diarrhea (248 nmol/L) was significantly higher than in control dogs (77 nmol/L). No significant difference was found in the day 1 median serum cortisol concentration of 11 dogs that died (302 nmol/L) and 46 dogs that survived (238 nmol/L). A significantly higher median serum cortisol concentration was, however, found in nonsurvivor group dogs, compared with survivor group dogs, on days 2 and 3. Median serum thyroxine concentration on day 1 in dogs with parvoviral diarrhea was significantly lower than in control dogs (8.12 nmol/L vs 35 nmol/L, respectively). Median serum thyroxine concentration of nonsurvivor group dogs (4.4 nmol/L) was significantly lower than that of survivor group dogs (9.2 nmol/L) at admission and became even lower on days 2 and 3. High serum cortisol and low serum thyroxine concentrations at 24 and 48 hours after admission were associated with death in dogs with parvoviral diarrhea.

Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000–2005)

To determine whether basal serum or plasma cortisol concentration can be used as a screening test to rule out hypoadrenocorticism in dogs. Retrospective case-control study. 110 dogs with nonadrenal gland illnesses and 13 dogs with hypoadrenocorticism. Sensitivity and specificity of basal serum or plasma cortisol concentrations of either <or= 1 microg/dL or <or= 2 microg/dL to detect dogs with hypoadrenocorticism were estimated by use of the ACTH stimulation test as the gold standard. Basal cortisol concentrations of <or= 1 microg/dL had excellent sensitivity (100%) and specificity (98.2%) for detecting dogs with hypoadrenocorticism. For basal cortisol concentrations of <or= 2 microg/dL, sensitivity was 100% but specificity was 78.2%. On the basis of sensitivity and specificity, basal serum or plasma cortisol concentrations had high negative predictive values over a wide range of prevalence rates and can be used to rule out a diagnosis of hypoadrenocorticism. Dogs with basal cortisol concentrations > 2 microg/dL that are not receiving corticosteroids, mitotane, or ketoconazole are highly unlikely to have hypoadrenocorticism. However, if the basal cortisol concentration is <or= 2 microg/dL, little to no information regarding adrenal gland function can be obtained and an ACTH stimulation test should be performed.

The response of the pituitary-adrenal and pituitary-thyroidal axes to the plasma glucose perturbations in Babesia canis rossi babesiosis

This prospective, cross-sectional, interventional study was designed to determine the association between the hormones of the pituitary-adrenal and pituitary-thyroid axes and other clinical parameters with the blood glucose perturbations in dogs with naturally occurring Babesia canis rossi babesiosis. Thirty-six dogs with canine babesiosis were studied. Blood samples were obtained from the jugular vein in each dog prior to treatment at admission to hospital and serum endogenous adrenocorticotrophic hormone (ACTH), pre-ACTH cortisol, thyroxine, free thyroxine and TSH concentrations were measured. Immediately thereafter each dog was injected intravenously with 5 microg/kg of ACTH (tetracosactrin). A 2nd blood sample was taken 1 hour later for serum post-ACTH cortisol measurement. Three patient groups were recruited: hypoglycaemic dogs (glucose < 3.3 mmol/l, n = 12); normoglycaemic dogs (glucose 3.3-5.5 mmol/l, n = 12); hyperglycaemic dogs (glucose > 5.5 mmol/l, n = 12). Basal and post-ACTH serum cortisol concentrations were significantly higher in hypoglycaemic dogs, whereas body temperature, serum thyroxine and free thyroxine were significantly lower in hypoglycaemic dogs. Haematocrit was significantly lower in both hypo-and hyperglycaemic dogs compared with normoglycaemic dogs. Low blood glucose concentrations were significantly associated with high basal and post-ACTH cortisol concentrations and with low serum thyroxine and free thyroxine concentrations in dogs suffering from B. canis rossi babesiosis.

Relative Adrenal Insufficiency in Dogs with Sepsis

A syndrome of relative adrenal insufficiency has been identified in septic humans, and is associated with hypotension and death. Relative adrenal insufficiency is generally associated with basal serum cortisol concentration within or above the reference range and a blunted cortisol response to adrenocorticotropic hormone administration. It is unknown whether relative adrenal insufficiency occurs in septic dogs. That relative adrenal insufficiency occurs in septic dogs, and that relative adrenal insufficiency is associated with hypotension and mortality. Thirty-three septic dogs admitted to a small animal intensive care unit. Dogs were included in the study if they had a known or suspected infectious disease and had systemic inflammatory response syndrome. Dogs were excluded if they had disease or medication history expected to affect the hypothalamic-pituitary-adrenal axis. Serum cortisol and endogenous plasma adrenocorticotropic hormone concentrations were measured before, and serum cortisol concentration measured 1 hour after, intramuscular administration of 250 microg of cosyntropin/dog. The change in cortisol concentration (delta-cortisol) before and after cosyntropin administration was determined in each dog. Hypotension was associated with lower delta-cortisol values (OR 1.3; CI 1.0-1.9; P = .029). delta-Cortisol cutoff of 3.0 microg/dL was most accurate for predicting hypotension, survival to discharge, and 28-day survival. The rate of death in dogs with delta-cortisol < or = 3 microg/dL was 4.1 times that of dogs with delta-cortisol > 3 microg/dL (RR 4.1; CI 1.5-12.3; P = .01). Delta-cortisol < or = 3 microg/dL after adrenocorticotropic hormone administration is associated with systemic hypotension and decreased survival in septic dogs.

Value of basal serum cortisol to detect corticosteroid-induced adrenal insufficiency in elite cyclists

The frequent use of glucocorticoids by athletes necessitates testing for adrenal insufficiency because of the risk of death in cases of associated severe stress (trauma, infection). During the 2001 and 2002 sporting seasons, we assessed the value of measuring baseline serum cortisol concentrations and the frequency of corticosteroid use during compulsory medical tests carried out by the French Cycling Federation on 659 elite cyclists (585 men and 74 women); the risk of adrenal insufficiency is negatively correlated with the basal serum cortisol level. Adrenal insufficiency was suspected in 34 cyclists (5.2%; 22 in 2001 and 12 in 2002) on the basis of below normal cortisol concentrations and in three cyclists (in 2001) because they had received corticosteroid treatment. In 2001, 10 of the 25 cyclists convoked underwent baseline follow-up serum cortisol determinations and 15 underwent dynamic exploration of adrenal function with the short ACTH test. Adrenal function was found to be deficient in four of these cyclists, at the limits of the normal range in four and normal in seven. Based on these results, the FFC sent a questionnaire in 2002 to all the cyclists to assess the use of corticosteroid in this population. This survey revealed that 85 of 538 cyclists (15.8%) had received corticosteroid treatment in the previous 3 months. Moreover, 11 of the 12 cyclists (92%) with low basal serum cortisol concentrations had received corticosteroid therapy. These results show that basal serum cortisol is relevant to detect adrenal insufficiency in sportsmen, in particular in cases of values below the normal range. The high frequency of corticosteroid use among elite cyclists, and in particular road cyclists who are at risk of trauma and infection, justifies screening tests to detect adrenal insufficiency.

Pituitary–adrenal axis function in dogs with neoplasia*

Abstract Adrenocorticotropic hormone (ACTH) stimulation tests were done in healthy and tumour-bearing dogs. In the tumour-bearing dogs, plasma endogenous ACTH (eACTH) concentration was measured and adrenal gland size was assessed ultrasonographically. Measurements in the tumour-bearing dogs were taken prior to therapy. No difference existed in basal or ACTH-stimulated cortisol concentration between tumour-bearing and healthy dogs. No difference existed in eACTH concentration between dogs with non-haematopoietic neoplasia (NHN) and lymphoma. However, of 20 dogs with lymphoma, 15% had increased basal serum cortisol concentration, 5% had an exaggerated response to ACTH and 5% had an increased eACTH concentration. Of 15 dogs with NHN, 20% had increased basal cortisol concentration, 7% had an exaggerated ACTH response and no dogs had an increased eACTH concentration. Of the dogs with lymphoma and NHN, 5 and 13%, respectively, had decreased basal cortisol concentrations; 20% of dogs with lymphoma and 13% with NHN had a subnormal ACTH response. eACTH levels were below the reference range in 10% of dogs with lymphoma and 7% with NHN. Overall, 10 adrenal glands were enlarged in seven dogs, five with lymphoma and two with NHN. The clinical significance of these findings remains to be determined.

A defect in cortisol production in rheumatoid arthritis: why are we still looking?

The question of whether patients with rheumatoid arthritis (RA) might have a defective hypothalamo–pituitary–adrenal (HPA) axis was first raised when RA patients who were treated with glucocorticoids in the 1950s showed dramatic improvement in their symptoms. It was initially hypothesized that this was due to an impaired ability of RA patients to synthesize sufficient amounts of endogenous glucocorticoids, but intensive investigations over the next few decades failed to reveal any significant defects in HPA axis activity in RA patients. In our review of the literature [1] we found no compelling evidence for significant differences in either basal or stress-stimulated HPA axis activity in RA compared with normal healthy individuals. However, we did highlight an inherent defect, which resided in the inability of RA patients to mount an appropriately enhanced glucocorticoid response to increased secretion of proinflammatory cytokines such as interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-. ‘In other words’, we concluded, ‘the HPA axis response in RA is defective precisely because it is normal’. Since then, studies by ourselves and others have suggested that this statement may be an oversimplification and that subtle differences in HPA axis activity may exist in subpopulations of RA patients. The purpose of this review is to evaluate progress in assessing the integrity of the HPA axis in RA since this area was previously reviewed [1–3], to determine whether generating information about HPA axis dysfunction in RA is clinically useful, and to discuss whether this area of research remains a fruitful line of enquiry. Persuasive evidence for a major dysfunction in basal circadian HPA axis activity in RA patients remains elusive. In a study of 10 postmenopausal females, plasma adrenocorticotrophic hormone (ACTH) and cortisol were slightly decreased around midnight but were not different from those in healthy controls at other circadian time points [4]. In 17 RA patients of mixed sex with recent disease onset, morning ACTH and cortisol concentrations were similar to those of controls, although the correlation between these hormones was weaker in RA [5]. In contrast, Straub et al. observed significantly higher morning serum cortisol in untreated patients with early RA (34 subjects, largely females) compared with healthy subjects, but no difference in ACTH [6]. However, the ratios of ACTH and cortisol in RA patients in relation to the markedly elevated levels of proinflammatory cytokines IL-6 and TNF- were significantly low compared with healthy controls. Furthermore, the number of swollen joints correlated inversely with the ratio of serum cortisol to IL-6. This suggests that measuring alterations in a single hormonal parameter may be less revealing of the underlying processes of inflammation in RA than measuring a change in the overall milieu of pro- and anti-inflammatory modulators. The low ratios of serum cortisol to IL-6 and TNFin RA cannot be explained by an increased metabolic clearance rate of cortisol [7, 8]. Curiously, in more recent studies by the same group, basal serum cortisol concentrations in RA patients with mild to moderate disease activity were slightly lower [9] and ACTH concentrations were significantly lower [7] compared with healthy controls. Serum cortisol and 24-h urinary cortisol were similar in the two groups [7]. These variations reported in the literature, which may be due to differences in disease duration and/or activity, age and sex of the patient, medication, or sampling time, emphasize the difficulty in pinpointing any specific and reproducible defect in HPA axis activity in RA. In a separate study, diurnal salivary cortisol was elevated in RA patients with recent onset compared with healthy controls, and this effect was positively correlated with disease activity but not with sex or age [10]. However, in these patients the awakening

An update on the biochemical diagnosis of congenital ACTH insufficiency

Congenital ACTH insufficiency due to disorders of the hypothalamo-pituitary axis is life threatening. However, the optimal method for establishing the diagnosis remains controversial. The standard Synacthen test (SST) is safe and easy to perform in infancy, but its performance has not been well evaluated in infants and children with ACTH insufficiency. We aimed to determine the value of the SST by comparing the 30-min SST cortisol concentration with physiological (spontaneous) cortisol secretion (2-hourly measurements for 24 h) in 28 patients (13 male; age range 0-5.1 years) with one or a combination of optic nerve (25) midline forebrain (17) and other pituitary hormone (17) abnormalities. Spontaneous cortisol secretion (mean < 145 nmol/l) was arbitrarily used as the 'gold-standard' in the diagnosis of ACTH insufficiency as it offered a reflection of endogenous cortisol mileu. A normal SST was defined as a 30-min serum cortisol > 540 nmol/l. The SST basal, 30-min and 60-min serum cortisol concentrations were significantly (P < 0.001) lower in patients with ACTH insufficiency (mean spontaneous cortisol < 145 nmol/l). 3/13 patients without and 12/15 patients with ACTH insufficiency failed the SST (specificity 76.9%; sensitivity 80%). Two out of three patients with ACTH insufficiency who passed the test were symptomatic with fatigue, poor growth and hypoglycaemia that resolved with hydrocortisone treatment. An 08:00 h serum cortisol cut-off of 175 nmol/l provided a sensitivity of 93.3% and a specificity of 92.3% as compared with spontaneous cortisol secretion. The 30-min increment and the 60-min SST cortisol concentrations although highly specific (100%) had reduced sensitivity (40% and 60%, respectively). A normal SST does not rule out ACTH insufficiency and measurement of physiological cortisol secretion may be required to confirm the diagnosis. A combination of 08:00 h serum cortisol > 175 nmol/l and a 30-min SST serum cortisol > 540 nmol/l to exclude ACTH insufficiency (sensitivity 69%, specificity 100%) would ensure that no child with ACTH insufficiency would be missed and hence would prevent serious consequences, although it may lead to over-diagnosis in some cases.

Adrenal suppression and failure to thrive after steroid injections for periocular hemangioma

Purpose To evaluate the effects of steroid injections for periocular capillary hemangioma on adrenal function and body composition. Design Noncomparative, interventional case series. Participants Four patients with periocular hemangioma. Methods Four white female infants with sight-threatening periocular hemangiomata received a combination of steroid injections of triamcinolone and betamethasone. In the first 2 cases, injections were perilesional and in the other 2, intralesional. Main outcome measures The infants were monitored by serial measurements of basal serum cortisol concentrations, responses to the Synacthen stimulation test, measurement of growth and of weight gain, and, in one case, more detailed anthropometric measures of body composition. Results Prolonged suppression of circulating serum cortisol concentrations and cortisol responses to the Synacthen stimulation test were noted in 3 cases, and marked failure to thrive was noted in all 4 cases. Conclusions Adrenal suppression after steroid injection for periocular capillary hemangioma is a potentially life-threatening complication. Failure to thrive is also a frequent side effect of treatment. Ophthalmologists should undertake the above treatment in consultation with a pediatric endocrinologist.

Adrenocortical tumors: prevalence of impaired glucose tolerance and of "Paradoxical Rise" of cortisol during an oral glucose tolerance test.

Glucose tolerance and the behaviour of cortisol during an oral glucose tolerance test (OGTT) was investigated in 126 patients with adrenal "incidentalomas" (age: > 45 years) and in 129 age-matched controls. Impaired glucose tolerance (IGT) was found to be more common (p < 0.02) among patients with adrenal incidentalomas. Subdividing these patients by their body weight it was found that 29% (controls: 25%) of those with normal body weight (BMI 20 - 25 kg/m2) had IGT/DM. In overweight (BMI 25 - 30 kg/m2) and obese patients (BMI 30 - 40 kg/m2) the share of IGT/DM was 32% (controls: 19%) and 66% (controls 42%), respectively. The prevalence of a "paradoxical" rise in serum cortisol concentrations during the OGTT was slightly higher (p < 0.05) among patients with adrenal incidentaloma than among controls. Patients as well as controls with this abnormal behaviour of cortisol were characterized by lower basal serum cortisol concentrations (p < 0.01) but no association was seen with either the presence of IGT or with post-dexamethasone concentrations of serum cortisol. Thus both in patients with and without adrenal incidentalomas abnormal glucose tolerance is an age- and weight-dependent phenomenon unrelated to the post-prandial behaviour of serum cortisol concentrations.

Adrenal function in the human immunodeficiency virus-infected patient.

Although clinical manifestations of adrenal dysfunction are uncommon in patients infected with human immunodeficiency virus (HIV), subclinical functional abnormalities of the hypothalamic-pituitary-adrenal axis are frequent. Patients infected with HIV usually have higher basal serum cortisol and lower serum dehydroepiandrosterone concentrations than HIV-seronegative individuals. This imbalance has been related to progression of the infection by inducing a shift from T(H)1 to T(H)2 immunologic responses. Although, adrenal reserve may be marginal in HIV-infected patients, clinically evident adrenal insufficiency is uncommon and, when present, it is observed in advanced stages of the infection. Hypocortisolemia should be treated regardless of the existence of associated symptoms. On the contrary, hypercortisolemia in the absence of features of Cushing syndrome is common and should not promote treatment nor specific studies. The possible influence that alterations of the adrenal function could have on the patients' immune status and the eventual effect of antiretrovirals on these alterations merit further investigation.

Effect of spray-dried plasma and lipopolysaccharide exposure on weaned pigs: II. Effects on the hypothalamic-pituitary-adrenal axis of weaned pigs.

A study was conducted with 20 weaned barrows (14 d, 4.98 +/- 0.21 kg) to determine the effect of feeding spray-dried plasma (SDP) after weaning on the pig's stress response to a lipopolysaccharide (LPS) challenge. After weaning, pigs were fed a diet containing 0 or 7% SDP for 7 d. On d 6 after weaning, all pigs were nonsurgically fitted with a jugular catheter. On d 7 after weaning, the pigs were given i.p. injections of either saline or LPS (150 microg/kg BW) followed by serial blood collection every 15 min for a 3-h period. Following the 3-h blood collection, all pigs were killed and tissue was collected for mRNA analysis. Pig weight on d 7 after weaning was not affected by dietary treatment (P > 0.21). Pigs fed the diet with SDP had lower (P < 0.05) levels of hypothalamic corticotropin-releasing hormone (CRH) mRNA, pituitary gland CRH receptor mRNA, and adrenal gland adrenocorticotropin-releasing hormone (ACTH) receptor mRNA. Dietary treatment did not affect pituitary gland proopiomelanocortin (POMC) mRNA. No effect of LPS treatment was observed in any of the mRNA levels examined. For both serum ACTH and cortisol, there was a significant diet x LPS treatment interaction (P < 0.01) such that both the ACTH and cortisol responses to the LPS challenge were greater in the pigs fed the diet with SDP than in the pigs fed the diet without SDP. For pigs given the saline injection, diet did not affect basal serum cortisol concentration; however, basal serum ACTH concentration was lower in those pigs fed the diet with SDP (P < 0.0001). A diet x LPS treatment interaction (P < 0.024) was observed for adrenal gland mRNA expression for steroidogenic acute regulatory (StAR) protein such that the LPS-induced increase in StAR mRNA was greater in the pigs fed SDP than in pigs fed the diet without SDP. These results demonstrate that pigs fed a diet with SDP have an increased activation of the pituitary-adrenal axis following an LPS challenge compared to pigs fed a diet without SDP.

Cortisol response to two different doses of intravenous synthetic ACTH (tetracosactrin) in overweight cats.

Fifteen middle-aged to older, overweight cats attending a first-opinion clinic were investigated to rule out hyperadrenocorticism as a cause of their weight problem, using two different protocols for the adrenocorticotropic hormone (ACTH) stimulation test. The cats received intravenous synthetic ACTH (tetracosactrin) at an initial dose of 125 microg; a second test was performed between two and three weeks later, using a dose of 250 microg intravenously. The mean basal serum cortisol concentration was 203 nmol/litre (range 81 to 354 nmol/litre). The highest mean serum cortisol concentration occurred at 60 minutes following the 125 microg dose and at 120 minutes following the 250 microg dose. There was, however, no statistically significant difference between these peak cortisol concentrations attained using either dose of tetracosactrin. A significantly higher mean serum cortisol concentration was attained after the higher dose at the 180 minutes time point, indicating a more prolonged response when compared with the lower dose. The cats were followed up for one year after the initial investigations and none were found to develop hyperadrenocorticism during this time.

Study of glucose tolerance in consecutive patients harbouring incidental adrenal tumours. Study Group of Incidental Adrenal Adenoma.

Clinically silent cortisol hypersecretion has been frequently observed in recent series of adrenal 'incidentalomas'. A significant body of data indicates that a spectrum of cortisol excess exists. Up to 90% of patients with cortisol hypersecretion are glucose intolerant. The aim of this study was (1) to assess glucose tolerance in consecutive patients with 'nonfunctioning' adrenal adenomas, and (2) to study the influence of the status of the hypothalamo-pituitary-adrenal axis (HPAA) on carbohydrate tolerance. Sixty-four consecutive patients with nonfunctioning adrenal adenomas (non-hypersecretory) diagnosed between September 1995 and July 1996 in five hospitals were included in the study. The prevalence of glucose intolerance or diabetes mellitus was determined with an oral glucose tolerance test (oGTT) according to the recommendations of the National Diabetes Data Group. Twenty-three consecutive unselected patients diagnosed with 'nonfunctioning' adrenal adenoma were enrolled in a study to determine the influence of HPAA status on carbohydrate tolerance. In these patients, in addition to basal and post-dexamethasone serum and urinary free cortisol concentrations, assessment of peripheral sensitivity to insulin (estimated during the oGTT according to a previously validated method) and adrenal sensitivity to ACTH (calculated from the CRH test) were performed. Twenty-five patients were considered to have normal glucose tolerance (95% confidence interval (95% CI) for the mean of 2 h glucose, 5.5-6.5 mmol/l); 17 showed glucose intolerance (95% CI 8.5-9.3 mmol/l); and 22 were classified as having diabetes mellitus (95% CI 12.1-14.6 mmol/l), including six patients with previously known diabetes mellitus. These three groups were comparable in age, sex, body mass index, waist-hip ratio and concomitant diseases. Thus, the prevalence of disturbed glucose tolerance was 39/64 (61%), well above the prevalence of NIDDM described in a population of similar age in our area. Among the 23 patients included in the study of HPAA status, the size of the tumour correlated with serum cortisol after dexamethasone (DXM) (r = 0.52, P < 0.01) and 24-h urinary free cortisol (UFC) after DXM (r = 0.55, P < 0.01), and negatively with DHEAs (r = -0.42, P = 0.04). The area under the curve for ACTH after hCRH (AUCacth) correlated negatively with both UFC (r = -0.40, P = 0.04) and serum cortisol after dexamethasone (r = -0.47, P = 0.02). The degree of peripheral sensitivity to insulin (SI) positively correlated with adrenal sensitivity (r = 0.56, P = 0.005). A high prevalence (61%) of disturbed glucose tolerance was found among consecutive patients harbouring incidental 'nonfunctional' adrenal adenomas. Therefore, patients with incidental adrenal tumours should be tested for glucose tolerance. The positive correlation between insulin sensitivity and adrenal sensitivity to ACTH suggests that, in these patients, insulin resistance hampers ACTH action at the level of the adrenal.

Pituitary-adrenal suppression and recovery in preterm very low birth weight infants after dexamethasone treatment for bronchopulmonary dysplasia.

High dose dexamethasone is frequently used for the treatment of neonatal respiratory conditions and to facilitate weaning from mechanical ventilation in preterm, very low birth weight infants. However, very little is known about the severity, site, and duration of steroid-induced hypothalamic-pituitary-adrenal axis suppression in this category of patients. Twenty-three preterm, very low birth weight infants who received a full 3-week dose-tapering course of dexamethasone were prospectively studied, with a human CRH stimulation test performed at three different times: before the start of steroid treatment (week 0), immediately after the course (week 3), and 4 weeks after stopping dexamethasone (week 7). Plasma ACTH and serum cortisol concentrations were measured at 0 (baseline), 15, 30, and 60 min. Immediately after the steroid course (week 3), both basal and poststimulation plasma ACTH and serum cortisol concentrations were markedly suppressed. The hormone concentrations at 0, 15, 30, and 60 min in week 3 were significantly lower than their corresponding levels in week 0 (P < 0.0001 for both ACTH and cortisol) and week 7 (P < 0.0001 and P < 0.005 for ACTH and cortisol, respectively). In contrast, when the hormone levels in week 7 were compared to their corresponding concentrations in week 0, only the 60 min serum cortisol concentration in week 7 was significantly lower (P = 0.02). The currently used dosage of dexamethasone caused severe pituitary-adrenal suppression immediately after treatment, but substantial recovery of the endocrine axis was observed 4 weeks after discontinuation of therapy. Although the recovery appeared to be earlier with the pituitary center, both pituitary and adrenal glands were capable of mounting a biochemically adequate response to exogenous human CRH stimulation at this stage. Steroid replacement therapy may be desirable at a time of stress in the immediate posttreatment period, but it would seem unnecessary 1 month after stopping dexamethasone treatment.

Endocrine profiles for outcome prediction from the intensive care unit

To evaluate the discriminating ability of various specific endocrine studies on patient outcome from the intensive care unit (ICU). Prospective cohort study of patients requiring intensive care. Adult medical and coronary care units in a military referral hospital. A total of 61 consecutive patients requiring intensive care over a 5-month period and 20 control subjects. Patients were evaluated within 24 hrs of ICU admission (day 1) with determination of the following variables: serum triiodothyronine, thyroxine, triiodothyronine resin uptake, thyrotropin, luteinizing hormone, follicle-stimulating hormone, testosterone, basal cortisol, adrenocorticotropic hormone-stimulated cortisol, cortisol increment, and Acute Physiology and Chronic Health Evaluation (APACHE II) score. A total of 24 hrs later (day 2), the same battery of tests was repeated with the exception of the adrenocorticotropic hormone-stimulated cortisol, cortisol increment, and APACHE II score. Individual variables were compared between survivors and nonsurvivors. The best discriminators of patient outcome in descending order were the basal serum cortisol and triiodothyronine concentrations obtained on day 2 and the APACHE II score with predictive abilities of 81%, 74%, and 70%, respectively. No combination of variables was superior to the day 2 basal cortisol concentration for discrimination of outcome. The basal cortisol and triiodothyronine concentrations obtained from blood samples collected within 48 hrs of ICU admission appear to be better discriminators of patient outcome than the APACHE II score.

Are disturbances in opioid and adrenergic systems involved in the hormonal dysfunction of anorexia nervosa?

Opioid peptides and catecholamines play an important role in the control of appetite, behaviour and hormonal secretion. To evaluate the role of the opioid and adrenergic systems in the hormonal dysfunction of anorexia nervosa (AN), we investigated the effects of naloxone and clonidine on serum GH, LH, FSH, β-endorphin, TSH, prolactin and cortisol concentrations in 35 women with AN. Basal plasma β-endorphin concentrations were significantly lower than those in healthy controls. The response of β-endorphin to clonidine in the AN patients was increased, whereas the response of β-endorphin to naloxone was decreased. Basal serum cortisol concentrations were significantly higher in the AN patients than that in the controls. There was significant increase in the cortisol response to naloxone in the controls but a lack of cortisol response to naloxone in the patients with AN. Naloxone produced a significant increase in LH release in the controls during the luteal phase of the menstrual cycle, as well as in the majority of AN patients. Clonidine caused a diminution of LH in the controls and did not alter LH in the patients. After clonidine injection, a significant increase in GH release was observed in both groups of subjects. If these disturbances persist after normalization of body weight, it might suggest that altered opioid and adrenergic activity is an aetiological factor in the pathogenesis of anorexia nervosa.

Adrenal cortical response in clinically normal dogs before and after adaptation to a housing environment

58 dogs (29 males and 29 females) selected as healthy on clinical and biochemical evaluations were subjected to an ACTH adrenal function test 2 days after their admission to a veterinary hospital (t + 0). Basal female serum cortisol concentrations were significantly higher than concentrations in males (77 nmol/l versus 43 nmol/l; P less than 0.01). Concentrations post stimulation were not statistically different (P greater than 0.05) between males and females: 306 (+/- 69) nmol/l versus 291 (+/- 73) nmol/l, respectively. Twelve dogs (6 males and 6 females), randomly selected from the 58, were subjected to the same test 5 weeks later (t + 5) and 12 weeks later (t + 12). Basal cortisol concentrations were lower at t + 5 or at t + 12 than at t + 0. Post stimulation mean cortisol concentrations were lower in males than in females at t + 5 (162 versus 232 nmol/l; P less than 0.05) but not at t + 0 (262 versus 320 nmol/l; P greater than 0.05) and t + 12 (188 versus 233 nmol/l; P greater than 0.05). These findings are indicating an increased susceptibility of bitches to environmental stress.

Adrenal function in patients with active tuberculosis.

Although tuberculosis is a recognised cause of adrenal insufficiency, little is known about adrenal function in patients with active tuberculosis. Ninety Melanesian adults with active tuberculosis (30 pulmonary, 30 miliary, 30 extrapulmonary) had adrenal function assessed prospectively before and three to four weeks after starting antituberculous chemotherapy. Basal serum cortisol concentrations were normal in 55 (61%) and raised in 35 (39%) of the subjects. No patient had a low basal cortisol concentration. After Synacthen stimulation, cortisol responses were normal in 81 (92%) of the patients and subnormal in seven (8%). After antituberculous chemotherapy the response to Synacthen stimulation was normal in all but one patient. It is concluded that adrenal dysfunction is an uncommon problem in patients with active tuberculosis, and that, contrary to recent reports, antituberculous chemotherapy regimens that include rifampicin do not have an adverse effect on adrenal function.