Basal Serum Cortisol Levels Research Articles

Acute and long-term associations between ApoE genetic polymorphism, cortisol levels, and declarative memory performance in older adults

For the past two decades, researchers have shown that elevated levels of circulating stress hormones may negatively impact cognitive performance in older adults. As well, genetic polymorphism of the apolipoprotein E gene (APOE) has been found to contribute to impairment in cognitive performance in old age. To date, only one study has reported a relationship between APOE status and cortisol levels, however the relationship was only found to be significant in dementia patients, with a trend observed in healthy controls. The goal of the present investigation was to examine the acute and long-term relationship between APOE status, cortisol secretion, and declarative memory performance in older adults. Two sample cohorts were assessed. In the first cohort, 24-h basal serum cortisol levels were obtained once a year over eight years to assess changes in basal cortisol levels over time. Declarative memory was also obtained in this group at three time-points over five years. In the second cohort, basal and stress-induced cortisol levels as well as basal declarative memory was tested. In the first cohort, E4 carriers were found to secrete higher serum cortisol levels than non-E4 carriers during the first 24-h visit (p=0.04) to the laboratory. However, this group difference did not remain over subsequent years. Furthermore, declarative memory performance over years did not significantly differ according to APOE status. In the second cohort, no significant group differences were found for basal or reactive cortisol levels (ps>0.05), and no group difference was found for acute declarative memory performance. The findings in this study suggest minimal to no significant effect of APOE status on cortisol secretion or declarative memory in non-demented older adults.

Early hypoadrenalism in premature infants at risk for bronchopulmonary dysplasia or death

To study the relationship between serum cortisol and dehydroepiandrosterone sulphate (DHEAS) concentrations and death or bronchopulmonary dysplasia at 36 weeks of postmenstrual age in preterm infants. Prospective measurement of cord, day of birth (D0) and day 4 (D4) serum cortisol and DHEAS concentrations and performance of low-dose (LD) ACTH tests in 89 preterm infants with gestational age <34 weeks at birth and in need of mechanical ventilation. Serum DHEAS levels correlated negatively with gestational age. At all sampling times, basal serum cortisol levels correlated positively with gestation-adjusted DHEAS levels (r = 0.39-0.46, p = 0.0032-<0.0001). The mean cord, D0 basal and stimulated cortisol, and cord and D0 DHEAS adjusted for gestational age were lower in the poor than good outcome infants (p < 0.02 for all). In the multiple logistic regression analyses, gestational age was the most significant factor affecting outcome, but low cord and D0 basal and stimulated cortisol and gestation-adjusted DHEAS levels also predicted poor outcome (OR 5.7-22; p = 0.049-0.014). Low cord and first day serum cortisol and DHEAS levels associated with poor outcome in preterm infants, which suggests general relative adrenocortical insufficiency in some premature newborns.

Diagnostic Value of Salivary Cortisol in Children with Abnormal Adrenal Cortex Functions

Aims: It has been shown that the free cortisol level in saliva may reflect plasma free cortisol. The measurement of cortisol in saliva is a simple method, and as such it is important in the pediatric age group. In this research, the diagnostic value of measurement of salivary cortisol (SC) measurement was examined in adrenal insufficiency (AI). Methods: Fifty-one patients, mean age 10.8 ± 4.29, who were investigated for possible AI, were included. Basal cortisol levels were below 18 µg/dl. Adrenal function was determined by low-dose ACTH test. During the test, samples for SC were obtained simultaneously with serum samples (at 0–10–20–30–40 min). Results: Mean basal serum cortisol level was 8.21 ± 4.10 µg/dl (mean ± SD). Basal SC was correlated to basal serum cortisol (r = 0.64, p < 0.001). A cut-off of 0.94 µg/dl for SC differentiated adrenal insufficient subjects from normals with a sensitivity and specificity of 80 and 77%, respectively. A peak SC less than 0.62 µg/dl defined AI with a specificity of 100%; however, sensitivity was 44%. Conclusion: Measurement of SC may be used in the evaluation of AI. It is well-correlated to serum cortisol. Peak SC in low-dose ACTH test can be used to differentiate patients with AI in the initial evaluation of individuals with suspected AI.

Low basal serum cortisol in patients with severe atopic dermatitis: potent topical corticosteroids wrongfully accused

Topical corticosteroids are used extensively to treat inflammatory skin disorders including atopic dermatitis (AD). Several studies have described temporary reversible suppression of hypothalamic-pituitary-adrenal function. However, sound evidence of permanent disturbance of adrenal gland function is lacking. To relate basal cortisol levels to prior use of topical corticosteroids and disease activity in patients with moderate to severe AD and to investigate the effect on basal serum cortisol levels of topical corticosteroid treatment during hospitalization. Two groups of patients with AD were evaluated: 25 inpatients with severe AD who required hospitalization (group 1) and 28 outpatients with moderate to severe AD (group 2). In group 1, morning basal serum cortisol levels were measured twice, at admission and at discharge; in group 2, morning basal serum cortisol levels were measured once. Use of topical corticosteroids in the 3 months prior to the cortisol measurement was recorded and disease activity was monitored using the Six Area, Six Sign Atopic Dermatitis (SASSAD) score and serum thymus and activation-regulated chemokine (TARC) levels. On admission, basal cortisol levels in group 1 were significantly (P < 0.001) decreased in 80% of the patients. In group 2, the basal cortisol levels were normal in all but three patients. Comparing the two groups, group 1 on admission had a significantly lower cortisol level than that of group 2 (P < 0.001). Disease activity in group 1 on admission was significantly higher than that of group 2 (P < 0.001). There was no difference in use of topical corticosteroids in the 3 months before cortisol measurement. At discharge in group 1 there was a significant increase (P < 0.0001) of basal cortisol levels and a significant (P < 0.001) decrease in disease activity reflected by the decrease in serum TARC levels and SASSAD score. Disease activity, rather than the use of topical corticosteroids, is responsible for the low basal cortisol values in patients with severe AD.

Basal Serum Cortisol Levels are not Predictive of Response to Corticotropin but Have Prognostic Significance in Patients with Septic Shock

Because high levels of cortisol are frequently observed in patients with septic shock, low levels of serum cortisol are considered indicative of relative adrenal insufficiency (RAI). This study was performed to investigate whether pretest clinical characteristics, including basal serum cortisol levels, are predictive of serum cortisol response to corticotropin and whether basal cortisol levels have a prognostic significance in patients with septic shock. We performed a retrospective analysis of 68 patients with septic shock who underwent short corticotropin stimulation testing. RAI was defined as an increase in cortisol level <9 µg/dL from baseline, and results showed that 48 patients (70.6%) had this insufficiency. According to the univariate analysis, the RAI group had significantly higher simplified acute physiology score II (SAPS II) and sequential organ failure assessment (SOFA) scores than the non-RAI group. The incidence of RAI was the same regardless of the basal serum cortisol level (p=0.447). The hospital mortality rate was 58.8% and was not significantly different between the RAI and non-RAI groups. However, a high basal serum cortisol level (≥30 µg/dL) was significantly associated with in-hospital mortality. In conclusion, our data suggest that basal serum cortisol levels are not predictive of serum cortisol response to corticotropin but have a significant prognostic value in patients with septic shock.

A Case of Ectopic ACTH Syndrome Associated with Small Cell Lung Cancer Presented with Hypokalemia

We report a case of a 73-year-old female patient who was diagnosed with ectopic ACTH syndrome caused by small cell lung cancer. We initially presumed that the patient was in a state of mineralocorticoid excess, because she had hypertension and hypokalemic alkalosis. This was however excluded because her plasma renin activity was not suppressed and her plasma aldosterone/plasma renin activity ratio was below 25. Moreover, her 24 hour urine free cortisol level was elevated and her serum cortisol levels after a low dose dexamethasone suppression test, were not suppressed. Furthermore, her basal plasma ACTH and serum cortisol levels increased and her serum cortisol level after a high dose dexamethasone suppression test was not suppressed. We performed studies to identify the source of ectopic ACTH syndrome and found a 3 cm-sized mass in the patient’s right lower lobe of her lung, which was eventually diagnosed as small cell lung cancer following a bronchoscopic biopsy. In conclusion, Cushing’s syndrome, and in particular ectopic ACTH syndrome, must be considered in the differential diagnosis of mineralocorticoid-induced hypertension. The excessive cortisol saturates the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity, which in turn, inactivates the conversion of cortisol to cortisone in the renal tubules. Moreover, excessive cortisol causes binding to the mineralocorticoid receptors, causing mineralocorticoid hypertension, characterized by severe hypercortisolism.

Cortisol Secretion in Patients With Type 2 Diabetes

The presence of an enhanced cortisol secretion in patients with type 2 diabetes is debated. In type 2 diabetic subjects, cortisol secretion was found to be associated with the complications and metabolic control of diabetes. We evaluated cortisol secretion in 170 type 2 diabetic subjects and in 71 sex-, age-, and BMI-matched nondiabetic subjects. In all subjects, we evaluated ACTH at 8:00 a.m. in basal conditions and serum cortisol levels at 12:00 p.m. (F24) and at 9:00 a.m. after a 1-mg overnight dexamethasone suppression test and 24-h urinary free cortisol (UFC). In diabetic patients, we evaluated the presence of chronic complications (incipient nephropathy, asymptomatic neuropathy, background retinopathy, and silent macroangiopathy). Patients were subdivided according to the absence (group 1, n = 53) or presence (group 2, n = 117) of diabetes complications. In group 2, UFC (125.2 +/- 4.6 nmol/24 h) and F24 (120.6 +/- 4.1 nmol/l) were higher than in group 1 (109.2 +/- 6.8 nmol/24 h, P = 0.057, and 99.7 +/- 6.1 nmol/l, P = 0.005, respectively) and in nondiabetic patients (101.7 +/- 5.9 nmol/24 h, P = 0.002, and 100.3 +/- 5.3 nmol/l, P = 0.003, respectively). In diabetic patients, the number of complications was associated with F24 (R = 0.345; P < 0.0001) and diabetes duration (R = 0.39; P < 0.0001). Logistic regression analysis showed that the presence of diabetes complications was significantly associated with F24, sex, duration of diabetes, and glycated hemoglobin. In type 2 diabetic subjects, hypothalamic-pituitary-adrenal activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and number of diabetes complications.

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.

Effect of electro-ejaculation on the serum cortisol response of Criollo goats ( Capra hircus)

Concern has been expressed on animal welfare in the use of electro-ejaculation (EE) as a semen collection technique. Furthermore, even though breed differences in stress response have been demonstrated in goats, a lack of background information characterizes the Criollo genotype. Therefore, in the present experiment, changes in concentrations of serum cortisol in serial blood samples were used to quantify stress response to EE in Criollo goats. Twenty intact Criollo bucks aged 1.5–3 years and weighing between 33 and 40 kg were randomly assigned to one of two treatments: bucks that were electro-ejaculated (T1) compared to males that a rectal probe was inserted without EE (T0). Blood samples were collected by venipuncture at 0 (immediately before inserting the rectal probe), 20, 40, 60 and 90 min after the onset of the experiment. To compare blood cortisol concentrations between treatments and the sequential data recorded on the same set of animals, a repeated measures analysis of variance model was used. The increases in concentrations of serum cortisol were significantly higher ( P < 0.05) for EE animals in comparison with the T0 group, 20 min after EE (10.76 ± 4.45 and 2.93 ± 0.83 ng/ml in T1 and T0, respectively) and then declined to pre-EE levels 40 min post-EE (2.86 ± 1.06 and 2.00 ± 0.00 ng/ml for T1 and T0, respectively). It could be concluded that a >350% increase in serum cortisol concentration 20 min after EE indicates an acute stress response despite the peak values being only slightly above the basal serum cortisol levels found in other goat breeds.

Significance of Corticosteroids and Their Relationship with Other Parameters in Patients with Sepsis

Background: Corticosteroids are known to be significant prognostic parameters in sepsis. Recently, an absolute and relative insufficiency of the corticosteroids system has often been reported to often develop particularly in severe sepsis. Degree of such an adrenal insufficiency not only has prognostic implications but also can be used to guide corticosteroids replacement therapy. The 24-hour urinary cortisol levels as well as serum cortisol concentrations were measured to assess the clinical significance and their relationship with the other parameters of sepsis, and also evaluated the clinical implications of the relative adrenal insufficiency. Methods: 26 consecutive patients with sepsis were enrolled. The basal random serum cortisol, ACTH, ADH, lactate levels and 24-hour urinary free cortisol amount were measured. The rapid ACTH (250 μg) stimulation test was also performed. Results: Basal serum cortisol levels were higher in the non-survivors than in the survivors. The 24-hour urinary free cortisol levels were higher in the patients with severe sepsis than in those without. The serum cortisol levels strongly correlated with the serum ADH and lactate levels. The 24-hour urinary free cortisol levels strongly correlated with the serum cortisol and lactate levels. The fractional changes in the cortisol levels after the rapid ACTH stimulation tests correlated with the serum cortisol, ADH, and lactate levels. Conclusion: Both the serum cortisol and 24-hour urinary cortisol were found to be significant prognostic factors in sepsis, and showed a strong correlation with the other parameters. The relative adrenal insufficiency might also be an important clinical parameter. (Tuberc Respir Dis 2006; 61: 356-365)

Long‐term remission rates after pituitary surgery for Cushing's disease: the need for long‐term surveillance

There have been a few reports on long-term remission rates after apparent early remission following pituitary surgery in the management of Cushing's disease. An undetectable postoperative serum cortisol has been regarded as the result most likely to predict long-term remission. Our objective was to assess the relapse rates in patients who underwent transsphenoidal surgery in order to determine whether undetectable cortisol following surgery was predictive of long-term remission and whether it was possible to have long-term remission when early morning cortisol was measurable but not grossly elevated. Endocrinological factors associated with late relapse were also studied. We reviewed the long-term outcome in 63 patients who had pituitary surgery for the treatment of Cushing's disease between 1979 and 2000. Case notes were reviewed and the current clinical and biochemical status assessed. Our usual practice was that early after the operation, an 08:00 h serum cortisol was measured 24 h after the last dose of hydrocortisone. This was followed by a formal low-dose dexamethasone suppression test. Current clinical status and recent 24-h urinary free cortisol values were used as an index of activity of the Cushing's disease. If there was evidence suggesting relapse, a low-dose dexamethasone suppression test was performed. In many patients, sequential collections of early morning urine specimens for urinary cortisol to creatinine ratio were also performed in an attempt to diagnose cyclical and intermittent forms of recurrent hypercortisolism. We did this if there was conflicting endocrine data, or if patients were slow to lose abnormal clinical features. Mean age at diagnosis was 40.3 years (range 14-70 years). Mean follow-up up time was 9.6 years (range 1-21 years). Forty-five patients (9 males/36 females) achieved apparent remission immediately after surgery and were subsequently studied long term. Of these 45 patients, four have subsequently died while in remission from hypercortisolism. Ten of the remaining 41 patients have relapsed. Of those 10, six demonstrated definite cyclical cortisol secretion. Two of the 10 had undetectable basal serum cortisol levels in the immediate postoperative period. Thirty-one patients are still alive and in remission. Fourteen (45%) of the 31 who remained in remission had detectable serum cortisol levels (> 50 nmol/l) immediately postoperatively, and remain in remission after a mean of 8.8 years. Our relapse rate was therefore 10/45 (22%), after a mean follow-up time of 9.6 years, with mean time to relapse 5.3 years. The overall remission rate of 56% (35/63) at 9.6 years follow-up is disappointing and merits some re-appraisal of the widely accepted principle that pituitary surgery must be the initial treatment of choice in pituitary-dependent Cushing's syndrome. Following pituitary surgery, careful ongoing expert endocrine assessment is mandatory as the incidence of relapse increases with time and also with increasing rigour of the endocrine evaluation. A significant number of our patients were shown to have relapsed with a cyclical form of hypercortisolism.

Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity

Background Recent studies showed an activation of the cytokine system and the HPA axis in major depression, although with inconsistent results. While the non-melancholic subtype displayed a proinflammatory cytokine pattern, the melancholic subtype showed signs of impaired cytokine production. In order to understand the potential pathogenic significance of these systems further, the interplay between the cytokine system and the HPA axis in depressive subtypes as well as potential changes of these systems during the course of disease were investigated. Methods N = 37 initially unmedicated patients with acute major depression were sub-classified (melancholic vs. non-melancholic) and compared with N = 37 matched healthy controls. Upon admission and after complete clinical remission, basal plasma ACTH and serum cortisol levels as well as cytokine productions (IL-1β, IL-1 receptor antagonist (IL-1RA)) upon mitogen stimulation (PHA) were measured in a whole blood assay. Results ACTH and cortisol concentrations were significantly elevated on admission in the melancholic but not the non-melancholic subgroup. Non-melancholic patients produced significantly more IL-1β and IL-1RA upon admission than controls or melancholic patients. The IL-1 RA/IL-1β ratio was significantly lower in the non-melancholic compared to the melancholic subgroup and increased significantly upon remission. Limitations Patient treatment was not standardized. No Dex/CRH test was performed. Conclusions Melancholic patients demonstrated an activation of the HPA axis in acute stage with partial normalization upon remission but no signs of inflammation. Non-melancholic patients showed signs of inflammation in acute depression with normalization upon remission while the function of the HPA axis was normal.

Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases

Objective: Severe hyponatremia due to hypopituitarism and adrenal insufficiency can be life-threatening, and treatment with glucocorticoids is very effective once the diagnosis of the underlying disorder has been made. In our experience, the diagnosis of hypopituitarism in hyponatremic patients is often overlooked. Methods: In a retrospective study we screened the files of 185 patients with severe hyponatremia (<130 mmol/l) that had been seen in one endocrinological unit of a university hospital between 1981 and 2001 in order to describe the clinical spectrum of patients with hyponatremia and hypopituitarism including secondary adrenal insufficiency. Results: In 139 cases it was possible to clearly ascribe the patients to the pathophysiological groups of (i) primary sodium deficiency, (ii) edematous disorders, and (iii) normovolemic disorders including the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Twenty-eight patients with severe ‘normovolemic hyponatremia’ (serum sodium: 116±7 mmol/l, mean±s.d.) had hypopituitarism and secondary adrenal insufficiency as shown by basal cortisol measurements and dynamic tests of adrenal function. In 25 cases of this group hypopituitarism (mostly due to empty sella, Sheehan's syndrome and pituitary tumors) had not been recognized previously, and in 12 cases recurrent hyponatremia during previous hospital admissions (up to four times) could be documented. The mean age of these patients (21 women, seven men) was 68 years. The most frequently occurring clinical signs were missing or scanty pubic and axillary hair, pale and doughy skin, and small testicles in the men. Frequent symptoms like nausea and vomiting, confusion, disorientation, somnolence or coma were similar to those in 91 patients with SIADH. Basal serum cortisol levels in the acutely ill state ranged from 20 to 439 nmol/l (mean±s.d.: 157±123), while in 30 other severely hyponatremic patients it ranged from 274 to 1732 nmol/l (732±351 nmol/l). In most patients with hyponatremic hypopituitarism, plasma antidiuretic hormone levels were inappropriately high, probably due to a failure of endogenous cortisol to suppress the hormone in a stressful situation. All patients recovered after low-dose hydrocortisone substitution. Most patients had other pituitary hormone deficiencies and were appropriately substituted subsequently. Conclusions: Hypopituitarism including secondary adrenal insufficiency seems to be a frequently overlooked cause of severe hyponatremia. A high level of suspicion is the best way to recognize the underlying disorder. Treatment with hydrocortisone is very effective.

Critical size of residual adrenal tissue and recovery from impaired early postoperative adrenocortical function after subtotal bilateral adrenalectomy

Background Subtotal bilateral adrenalectomy may preserve adrenocortical function. Little is known about the early postoperative function of the adrenal remnant. Method In 10 patients with bilateral adrenal tumors (pheochromocytomas, adrenocortical nodular hyperplasia, and adrenal metastases), plasma adrenocorticotropic hormone (ACTH), serum cortisol, and maximal cortisol liberation were examined with an ACTH test after subtotal bilateral adrenalectomy, which left 15% to 30% of adrenal tissue in situ. Results In the early postoperative period, all patients had normal basal serum cortisol levels (mean, 415±208 nmol/L; normal morning range, 138-690 nmol/L) but pathologically increased plasma ACTH levels (mean, 55±42 pmol/mL; normal, <10.1 pmol/L). In 6 patients, a pathologic ACTH test result was observed. During follow-up (mean, 11.3±7.6 months), all patients were found to have a normal ACTH test result. None of the patients required steroid supplementation. However, in patients with both familial pheochromocytoma and impaired adrenocortical function during the early postoperative period, the maximal increase of serum cortisol after ACTH stimulation was significantly reduced (mean, 301±86.8 nmol/L) compared with control subjects (mean, 490±132.6 nmol/L; P = .019). Conclusion After subtotal bilateral adrenalectomy left 15% to 30% of adrenal tissue in situ, functional recovery could be observed in all patients. However, subclinical impairment of the adrenocortical function with questionable clinical significance has to be considered in some of the patients. Especially during the early postoperative period, careful observation of the patients without exogenous steroid administration is required.

Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases.

Severe hyponatremia due to hypopituitarism and adrenal insufficiency can be life-threatening, and treatment with glucocorticoids is very effective once the diagnosis of the underlying disorder has been made. In our experience, the diagnosis of hypopituitarism in hyponatremic patients is often overlooked. In a retrospective study we screened the files of 185 patients with severe hyponatremia (<130 mmol/l) that had been seen in one endocrinological unit of a university hospital between 1981 and 2001 in order to describe the clinical spectrum of patients with hyponatremia and hypopituitarism including secondary adrenal insufficiency. In 139 cases it was possible to clearly ascribe the patients to the pathophysiological groups of (i) primary sodium deficiency, (ii) edematous disorders, and (iii) normovolemic disorders including the "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH). Twenty-eight patients with severe "normovolemic hyponatremia" (serum sodium: 116+/-7 mmol/l, mean+/-s.d.) had hypopituitarism and secondary adrenal insufficiency as shown by basal cortisol measurements and dynamic tests of adrenal function. In 25 cases of this group hypopituitarism (mostly due to empty sella, Sheehan's syndrome and pituitary tumors) had not been recognized previously, and in 12 cases recurrent hyponatremia during previous hospital admissions (up to four times) could be documented. The mean age of these patients (21 women, seven men) was 68 Years. The most frequently occurring clinical signs were missing or scanty pubic and axillary hair, pale and doughy skin, and small testicles in the men. Frequent symptoms like nausea and vomiting, confusion, disorientation, somnolence or coma were similar to those in 91 patients with SIADH. Basal serum cortisol levels in the acutely ill state ranged from 20 to 439 nmol/l (mean+/-s.d.: 157+/-123), while in 30 other severely hyponatremic patients it ranged from 274 to 1732 nmol/l (732+/-351 nmol/l). In most patients with hyponatremic hypopituitarism, plasma antidiuretic hormone levels were inappropriately high, probably due to a failure of endogenous cortisol to suppress the hormone in a stressful situation. All patients recovered after low-dose hydrocortisone substitution. Most patients had other pituitary hormone deficiencies and were appropriately substituted subsequently. Hypopituitarism including secondary adrenal insufficiency seems to be a frequently overlooked cause of severe hyponatremia. A high level of suspicion is the best way to recognize the underlying disorder. Treatment with hydrocortisone is very effective.

Comparison of the bioavailability and systemic effects of beclometasone dipropionate suspension for nebulization and beclometasone dipropionate via a metered-dose inhaler after single-dose administration in healty male volunteers

Pharmacokinetic properties of a drug, and selection and correct usage of an appropriate delivery device, are factors that can affect the outcome of inhaled therapy. The use of nebulization on can overcome problems that are associated with other delivery systems used for inhalation therapy. The objective of this open, randomized, single-dose study was to compare the systemic exposure and safety of beclometasone cipropionate (BDP) suspension for nebulization with BDP via metered-dose inhaler (MDI) in healthy subjects. Following a run-in period to assess basal 24-h serum cortisol levels and cortisol urinary excretion, 12 healthy males were administered BDP 1600 μg given via MDI and were then randomized to receive a single dose of either 1600 μg ( n=6) or 3200 μg BDP ( n=6) suspension for nebulization given via a nebulizer. Results with respect to systemic exposure to beclometasone-17-monopropionate (B17MP) (the active metabolite of BDP) and systemic effects on the hypothalamic-pituitary-adrenal (HPA) axis were determined by evaluation of a number of pharmacokinetic parameters for plasma B17MP and serum and urinary coritsol, respectively. A statistically significantly greater peak plasma concentration (C max) of B17MP was reported with BDP via MDI (1587 pg ml −1) compared with BDP 1600 μg (455 pg ml −1) and BDP 3200 μg suspensions for nebulization (758 pg ml −1), and was achieved more rapidly (T max) (1 · 3 h, 3 h, and 2 · 5 h, respectively). In addition, elimination half-life (t 1 2 el) was statistically significantly shorter with BDP via MDI (4·6 h) than with both dosages of BDP suspensions for nebulization (7·4 h and 6·3 h with 1600 μg and 3200 μg, respectively), as was mean residence time (MRT) (5·4 h, 11·1 h, and 10·0 h, respectively). Total systemci exposure to B17MP (as determined by the area under the concentration-time curve: AUC ∞) was comparable for BDP via MDI (6883 pg ml −1h −1) and BDP 3200 μg suspension for nebulization (8201 pg ml −1h −1), but significantly greater than with BDP 1600 μg suspension for nebulization (4870 pg ml −1; P<0·05 vs BDP via MDI). All treatments were well tolerated, and no significant differences were found between them with respect to the serum or urinary cortisol pharmacokinetic parameters assessed. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 3200 μg given via a nebulizer and BDP 1600 μg given via an MDI are equivalent in terms of systemic exposure to B17MP and systemic effects on the HPA axis, with BDP suspension for nebulization having a potentially more prolonged activity. It confirms that use of a double dose of BDP suspension for nebulization administered by nebulizer compared with BDP given via metered-dose inhalation is justified and poses no risk with regard to safety.

Body Composition Modulates the Effects of Hormone Replacement Therapy on Growth Hormone and Insulin-Like Growth Factor-I Levels in Postmenopausal Women

Objective: To examine the relationships of body composition with basal serum estrone, estradiol, androstenedione, cortisol, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in 73 postmenopausal women. Design: Cross-sectional study of hormone levels and body composition determined by dual-energy X-ray absorptiometry and anthropometry in women who were not taking oral hormone replacement therapy (HRT) and women taking HRT. Because high adiposity may modify hormone levels, subjects were grouped by fatness into obese (BMI >25 kg/m² and waist circumference >80 cm) and lean groups, as well as by HRT use. Results: Total levels of estrone, estradiol, GH and cortisol were significantly higher and IGF-1 was lower in HRT users. In HRT users, estradiol levels were higher and GH levels were lower in obese than lean women. IGF-1 levels were lower in obese HRT users than lean nonusers. Total cortisol levels were significantly higher in lean HRT users than lean nonusers and obese users. GH and IGF-1 were significantly inversely correlated with trunk fat and percent body fat. Multiple regression revealed that only trunk fat was a significant (negative) determinant of GH and IGF-1 levels, whereas HRT use positively and negatively predicted GH and IGF-1, respectively. Percent body fat significantly predicted estradiol levels. Body composition did not differ by HRT use. Conclusions: Our results suggest that trunk fat attenuates the HRT-induced increase on GH levels. In addition, trunk fat is a significant determinant of low IGF-1 levels in postmenopausal women, and IGF-1 levels decline more with HRT use.

Adrenal Function as Assessed by Low-Dose Adrenocorticotropin Hormone Test Before and After Switching from Inhaled Beclomethasone Dipropionate to Inhaled Fluticasone Propionate

Low-dose adrenocorticotropin hormone (ACTH) tests (0.5 µg/L 73 m2) were done before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate in 12 patients 33–77 years old who had mild-to-severe asthma to compare the effects of these drugs on adrenal function. Low-dose ACTH tests were performed after the subjects had received inhaled beclomethasone dipropionate (200–900 µg/day) for at least 12 wk. Treatment was then switched to inhaled fluticasone propionate (200–600 µg/day) for at least 12 wk, and a second low-dose ACTH test was done. Pulmonary function was assessed on the basis of peak expiratory flow rate (PEFR, % of predicted value). After switching treatment, the daily dose of inhaled corticosteroid decreased by about 40%. Basal serum cortisol and ACTH levels were similar with both treatments. The adrenal response, as assessed by incremental rise in the serum cortisol level (peak minus basal) after ACTH challenge, improved significantly (5.6–7.9 µg/dL, p<0.01) after switching to fluticasone. All three patients who had lower serum cortisol levels during beclomethasone treatment than during fluticasone treatment showed improvement in both the peak cortisol level and the incremental rise in cortisol. Mean morning and evening PEFRs significantly increased after switching from beclomethasone to fluticasone (morning: 71.2 to 76.0%, p<0.01; evening: 67.3 to 72.1%, both p<0.05). The diurnal variation of PEFR significantly decreased from 10.9% to 8.3% after switching treatment (p<0.01). We conclude that switching from beclomethasone to fluticasone reduces the risk of adrenal dysfunction associated with inhaled steroids and improves pulmonary function.

A low-dose adrenocorticotropin test reveals impaired adrenal function in cancer patients receiving megestrol acetate therapy

Megestrol acetate (MA) has glucocorticoid activity and can induce significant secondary adrenal suppression. We designed this study to determine the extent of adrenal insufficiency in cancer patients receiving MA by utilising a sensitive low-dose adrenocorticotropin (ACTH) stimulation test. Adrenal function was assessed by a low-dose (0.625 μg) ACTH (1-24) stimulation test in 30 patients receiving MA for metastatic cancer. 10 of the patients who failed this test underwent a standard (250 μg) test on another day. Adrenal function was also evaluated in 15 of the patients by measuring the excretion of free cortisol in 24-h urine samples. Peak serum cortisol levels following stimulation with low-dose (0.625 μg) ACTH (1-24) were <18 μg/dl in 16 of 30 (53%) patients, of whom 9 had a basal serum cortisol level of <5 μg/dl. Five of 16 poor responders to the low-dose test showed normal stimulation with the standard (250 μg) ACTH (1-24) test. Thus, adrenal insufficiency would fail to be detected by the standard high dose test in these patients. Patients who failed the low-dose ACTH (1-24) test had lower 24-h urinary free cortisol excretion (8.7±10.3 μg/24 h) than normal responders (35±12.7 μg/24 h). Impaired adrenal function is common in cancer patients receiving MA. The low-dose ACTH (1-24) test is apparently capable of revealing adrenal insufficiency undetected by the standard high-dose ACTH test. Patients receiving MA might have inadequate adrenal function during episodes of infection or after withdrawal of MA therapy and this may require prompt corticosteroid treatment.

Comparison between Low- and Standard-Dose ACTH Tests in Premature Infants at Risk for Chronic Lung Disease

In order to find a sensitive method to evaluate adrenocortical function in premature infants, we compared low- (0.5 μg/1.73 m²) and standard-dose (250 μg/1.73 m²) adrenocorticotropin tests (LD- and SD-ACTH) in 12 very-low-birth-weight infants before and 2 days after the end of dexamethasone therapy (duration 9–14 days) for chronic lung disease. Basal serum cortisol levels were inappropriately low in several infants already before dexamethasone therapy (median 190, range 60–357 nmol/l). The 95% confidence intervals of mean serum cortisol levels at 20 min were equal in LD- and SD-ACTH, while at 60 min, the low-dose gave a clearly lower response than the standard-dose test. The LD-ACTH can be used in premature infants as in older children and adults, but the criteria for adrenocortical insufficiency need to be defined.