Urinary Free Cortisol Excretion Research Articles

The Relationship Between 24-h Urinary Cortisol and Bone in Healthy Young Women

Cortisol within the normal range has been associated with reduced bone density in the elderly, but little is known about this relationship in healthy young women. The purpose of this study is to assess whether 24-h urinary free cortisol excretion (UFC) is related to bone density in 132 healthy, non-obese, regularly menstruating women, aged 19-35. Participants completed questionnaires (food frequency, demographics, physical activity, dietary restraint, perceived stress, and daily stress) and a 24-h urine collection. UFC was determined by high-throughput liquid chromatography and tandem mass spectrometry. Anthropometrics were completed and a dual energy X-ray absorptiometry scan measured areal bone mineral density (aBMD, g/cm(2)) and bone mineral content (BMC, g) at the lumbar spine (L1-4), hip, and total body (TB) as well as total body lean (LBM) and fat mass. aBMD and BMC were significantly positively associated with height, LBM, physical activity, calcium intake, and duration of previous oral contraceptive use (except L1-4) and negatively with perceived stress. UFC was not correlated with any measured variables except urine volume (r = 0.17, p = 0.046). After adjusting for urine volume, height, LBM, ethnicity, and prior oral contraceptive use, UFC was significantly inversely associated with TB BMC (r = -0.30, p < 0.001) and aBMD (r = -0.27, p = 0.003), L1-4 aBMD (r = -0.19, p = 0.035) and BMC (r = -0.18, p = 0.049), and hip BMC (r = -0.23, p = 0.011). Further adjustment for sport activity, calcium intake and perceived stress did not change these relationships meaningfully except that L1-4 became nonsignificant (p < 0.07). Cortisol within the normal range appears to have a minor negative influence on bone density in healthy young women.

Cushing disease as possible cause of persistent growth failure despite growth hormone therapy in a small for gestational age male

Growth hormone (GH) therapy in children with small for gestational age (SGA) has been shown to be of significant therapeutic benefit. We report the case of an 11-year-old Caucasian male who developed early adrenarche, hypertension and insulin resistance on GH therapy for SGA and profound short stature (ht -5 SD). This patient demonstrated a poor response to GH therapy and developed physical and biochemical findings of insulin resistance responsive to metformin therapy. He remained hypertensive, however, and continued to have elevated serum dehydroepiandrosterone sulfate levels. Urinary free cortisol excretion was subsequently found to be elevated. The diagnosis of Cushing's disease was confirmed with inferior petrosal sinus sampling and pituitary MRI. The patient underwent partial adenohypophysectomy with resulting normalization of plasma cortisol levels and associated symptoms. Our patient's diagnosis of Cushing's disease was complicated by his past history of poor growth since birth and history of SGA. The signs of Cushing's disease did not overtly appear until GH therapy was initiated to help treat severe short stature. It is possible that the metabolic effects of GH therapy unmasked the presence of underlying Cushing's disease.

Stress‐related Development of Obesity and Cortisol in Women

Chronic exposure to environmental stress may play a role in the development of obesity, through hyperactivation of the hypothalamic-pituitary-adrenocortical (HPA) axis. This study investigated the dynamics of weight gain and the activity of the HPA axis in women who developed weight gain after a stressful event. This is a case-control retrospective study. Two groups of age-matched premenopausal women were selected. One (n = 14) included women characterized by a rapid weight gain following a stressful event, defined as the "stress-related obesity " (SRO) group, and the other (n = 21) women with nonstress-related development of obesity, defined as the "nonstress-related obesity " (NSRO) group. Twenty-one healthy premenopausal women served as normal-weight controls. Baseline hormonal and metabolic parameters, and 24-h urinary free cortisol (UFC/24 h) excretion rate (as a measure of HPA-axis activity) were measured in all women. Anthropometry, diet, and physical activity were similar in both obese groups. Both obese groups showed similar metabolic and hormonal profiles, but the SRO group had UFC/24 h values (41.1 +/- 14.3 microg) significantly higher (P < 0.001) with respect to the NSRO (26.6 +/- 17.6 microg) or the normal-weight control groups (21.1 +/- 9.8 microg). Moreover, time (years) to achieve maximum Deltaweight gain (kg) and the Deltaweight gain/time ratio were significantly shorter (P < 0.001) and higher (P < 0.001) in the SRO group with respect to the NSRO group, respectively. In the SRO group, there was a tendency to a significant correlation between UFC/24 h and the Deltaweight gain/time ratio. These findings support the concept that SRO has distinct pathophysiological mechanisms, including hyperactivity of the HPA axis.

Cytokine Inhibition after Glucocorticoid Exposure in Healthy Men with Low versus High Basal Cortisol Levels

Objective: The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels. Methods:136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 ± 87 nmol/24 h) and the 10 with the lowest UFC (168 ± 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 μg/1.73 m²) of ACTH challenge and after 2 weeks’ exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in a whole-blood assay. Results:After exposure to DEX in vivo, inhibition of IL-6 and TNF-α decreased. Also, after DEX in vivo, low-cortisol men showed lower inhibition of IL-1β and IL-6, both compared to the high-cortisol group and their own baseline levels. Conclusion: A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels.

Urinary free cortisone, but not cortisol, is associated with urine volume in severe obesity

Background High urine volume enhances urinary free cortisol (UFF) and cortisone (UFE) excretion rates in normal-weight adults and children. Renal excretion rates of glucocorticoids (GC) and their metabolites are frequently altered in obesity. The aim of the present study was to investigate whether UFF and UFE excretion is also affected by urine volume in severely obese subjects. Experimental In 24-h urine samples of 59 extremely obese subjects (mean BMI 45.3 ± 8.9 kg/m 2) and 20 healthy lean subjects (BMI 22.1 ± 1.8 kg/m 2), UFF and UFE, tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5α-THF, and THE (GC3), the three major GC metabolites, reflects daily cortisol secretion. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity was assessed by the ratio UFE/UFF. Daily GC excretion rates were corrected for urine creatinine and adjusted for gender and body weight. Results In extremely obese subjects, urine volume was significantly associated with creatinine-corrected UFE and 11β-HSD2 activity after adjustment for gender and BMI ( r = 0.47, p = 0.0002 and r = 0.31, p = 0.02, respectively). However, urine volume was not associated with creatinine-corrected UFF and GC3 ( p = 0.4 and p = 0.6, respectively). In lean controls, urine volume was significantly associated with creatinine-corrected UFE and UFF ( r = 0.58, p = 0.01 and r = 0.55, p = 0.02, respectively), whereas urine volume was not associated with 11β-HSD2 activity after appropriate adjustment ( p = 0.3). Conclusions In severe obesity, in contrast to normal weight, renal excretion of UFE, but not of UFF is affected by fluid intake. This discrepancy may be due to the increased renal 11β-HSD2 activity in obesity.

Risk markers for depression in adolescents: sleep and HPA measures.

Previous work has demonstrated reliable electroencephalographic (EEG) sleep and hypothalamic-pituitary-adrenal (HPA) changes associated with adult major depressive disorder. These changes might be evident before clinical manifestation of the illness in at-risk persons. The aim of the study was to identify depression-related EEG sleep and HPA changes in healthy adolescents at high-risk for depression, and to examine the relationship between EEG sleep (or HPA) changes and the onset of depression. Forty-eight adolescent volunteers with no personal history of a psychiatric illness, including depression, but who were at high-risk for developing depression by virtue of parental depression (high-risk group), and 48 adolescent volunteers with no personal or family history of a psychiatric disorder (normal controls) were recruited. EEG sleep and HPA measures were collected on three consecutive evenings and nights at baseline. Clinical follow-up evaluations were conducted at regular intervals over a 5-year period. Compared with normal controls, adolescents at high-risk for depression had shorter latency to rapid eye movement (REM) sleep, increased phasic REM sleep, more REM sleep and elevated nocturnal urinary free cortisol (NUFC) excretion at baseline. Shorter REM latency, higher REM density and elevated NUFC (measured at baseline) were associated with the development of depression during follow-up. The findings that REM sleep abnormalities and elevated HPA activity occur prior to the onset of depression in at-risk adolescents suggest that these variables serve as vulnerability markers for the illness.

Dysfunction of the hypothalamic-pituitary-adrenal axis and functional somatic symptoms: A longitudinal cohort study in the general population

In persons with functional somatic symptoms (FSS), no conventionally defined organic pathology is apparent. It has been suggested that complex interactions of psychological, physiological, and social factors are involved in the etiology of FSS. One of the physiological mechanisms that may contribute to FSS is the function of the hypothalamic-pituitary-adrenal (HPA)-axis. This study investigates the association of HPA-axis function with cross-sectional presence and prospective development of FSS in the general population. This study was performed in a population-based cohort of 741 male and female adults (mean age 53.1, S.D. 10.9). Participants completed the somatization section of the Composite International Diagnostic Interview (CIDI) in which the presence of 43 FSS is surveyed. In addition to the total number of FSS, bodily system FSS clusters with musculoskeletal, gastrointestinal, cardiorespiratory, and general symptoms were constructed. HPA-axis function was assessed by measuring 24-h urinary free cortisol (24-h UFC) excretion. Follow-up measurements were performed approximately 2 years later. All analyses were adjusted for age, gender, body mass index, smoking, alcohol use, depression, exercise frequency, and urinary volume. Regression analysis detected no cross-sectional association between 24-h UFC excretion and the number of FSS (beta=-0.021, t=-0.521, p=0.603). In addition, 24-h UFC excretion was not associated with any of the bodily system FSS clusters (all p>0.050). Furthermore, 24-h UFC excretion did not predict new-onset FSS in the 2-year follow-up period (beta=0.021, t=0.566, p=0.572). We conclude that this study does not provide evidence for an association between altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general population. We conclude that this study does not provide evidence for an association between altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general population.

Cyclic Cushing syndrome due to an ectopic pituitary adenoma

A 39-year-old man was referred to an endocrinology clinic for evaluation of his Cushing syndrome. He had gained 20 kg over 5 years and complained of intermittent headaches and easy bruisability. His medical history included a left foot fracture associated with minimal trauma 2 years earlier, hypertension, and stable Crohn disease with no use of exogenous glucocorticoids for at least 10 years. Measurements of plasma adrenocorticotropic hormone, 24 h urine free cortisol excretion, late-night salivary cortisol, serum cortisol levels before and after corticotropin-releasing hormone administration during a dexamethasone suppression/corticotropin-releasing hormone-stimulation test, pituitary MRI, and inferior petrosal sinus sampling. Cyclic Cushing syndrome secondary to an ectopic pituitary adenoma. The cyclic nature of Cushing syndrome was suggested by the absence of hypercortisolemia during inferior petrosal sinus sampling, and was confirmed by multiple 24 h urine free cortisol measurements. The patient underwent transsphenoidal surgery, during which a 5 mm firm, round, midline sphenoid sinus lesion was identified and resected. In preoperative imaging studies, this lesion had been interpreted as being a mucosal polyp. At microscopic examination, the lesion was found to be a pituitary adenoma, which stained diffusely with antiadrenocorticotropic-hormone antibodies. Explorations of the sella and pituitary did not reveal any abnormalities. Postoperatively, the patient became hypocortisolemic and his cushingoid features resolved. His adrenal function normalized 3 months after surgery. At 18 months, the patient continued to be symptom-free with normal levels of urinary-free cortisol and midnight salivary cortisol.

Reversibles metabolisches Syndrom hormoneller Ursache

A 52-year-old male patient was admitted to the emergency department with dyspnea and hypertensive urgency. During the previous 6 months, the patient had noticed leg edema, weight gain (particularly in the face and abdomen), and impotence. 1.5 years ago, he was diagnosed with hypertension resistant to medication. After an accident at work 1 year ago, osteoporosis was diagnosed with vertebral and rib fractures. Measurement of sleeping midnight salivary cortisol levels together with 24-h urine free cortisol excretion and an overnight low-dose 1-mg dexamethasone suppression test proved overt hypercortisolism. The high-dose 8-mg dexamethasone suppression suggested an adrenal or ectopic source of hypercortisolism. By contrast, elevated adreno-corticotropic hormone (ACTH) levels and a corticotropin-releasing hormone stimulation test gave evidence for a pituitary source of hypercortisolism. However, pituitary magnetic resonance imaging failed to reveal a pituitary adenoma. Moreover, computed tomography scans of thorax and abdomen were negative. In this situation, an inferior petrosal vein sampling was performed and revealed an ACTH gradient (central-systemic) >3 with lateralization to the right side. The patient underwent a selective, partial, transsphenoidal resection and was cured from clinical signs and symptoms caused by hypercortisolism. Subsequent hormonal replacement therapy of postoperative pituitary insufficiency was necessary.

Low plasma tryptophan in carcinoid patients is associated with increased urinary cortisol excretion

Previously we observed in patients suffering from a metastatic carcinoid tumor that irritability, aggression and lack of impulse control are associated with low levels of plasma tryptophan and presumably with low brain serotonin function. In rats we showed that a diet of low tryptophan resulted in higher stress responses and higher corticosterone production. Here we tested in carcinoid patients whether tryptophan depletion due to tumor 5-HT overproduction is associated with high cortisol production. Urinary excretion of cortisol, serotonin, 5-hydroxyindole acetic acid (the main metabolite of serotonin a marker of tumor activity), plasma levels of tryptophan and platelet content of serotonin (index of peripheral serotonin synthesis) were determined in metastatic midgut carcinoid patients. Patients (N = 25) were divided into two groups based on their plasma tryptophan levels (< or = 25 micromol/l, n = 12 and > or = 49 micromol/l, n = 13). Carcinoid patients with low plasma tryptophan levels had significantly higher urinary excretion of free cortisol (p < 0.01), independent of tumor activity. The inter-individual differences in the low tryptophan group, however, were substantial. In a subgroup of the patients suffering from metastatic carcinoid disease the cerebral access of plasma tryptophan is impaired, thus rendering cerebral serotonin neurotransmission suboptimal and leading to hypercortisolism. The present study provides further support to the idea that low serotonergic function is a risk for developing stress-associated psychopathology.

Daily urinary free cortisol and cortisone excretion is associated with urine volume in healthy children

Background In experimental studies, a high fluid intake and a corresponding high urine volume have been shown to increase renal excretion rates of urinary free cortisol (UFF) and cortisone (UFE) in adults. We aimed to examine whether 24-h UFF and UFE excretion rates are also affected by urine volume in children. Methods In 24-h urine samples of 100 pre-pubertal and 100 pubertal healthy children UFF, UFE, tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5α-THF, and THE, the 3 primarily glucuronidated tetrahydrometabolites (GC3), reflects daily cortisol secretion. Associations of urine volume with outcome variables UFF, UFE, and GC3 were examined in both developmental groups using multiple regression models adjusted for sex, body weight and height. Results Significant positive associations were observed between 24-h urine volume and UFF and UFE in both groups with the highest explained variation for UFE [partial R 2 = 0.11 in pre-pubertal group ( P < 0.005); partial R 2 = 0.15 in pubertal group ( P < 0.0001)]. However, for outcome GC3, urine volume was not significant in either of the groups. Conclusion Urinary 24-h excretion rates of UFF and UFE but not of the marker of glucocorticoid secretion are affected by daily urine volume in healthy free-living children. For a specific assessment of associations of UFF and UFE with (patho)physiologically relevant factors, urine volume should be considered as a confounder.

Incidental pheochromocytoma presenting with sublaboratory findings in asymptomatic surrenal masses: a case report.

IntroductionAdrenal incidentaloma can be described as adrenal lesions that are incidentally diagnosed during abdominal laparotomy or any abdominal screening without prior suspicion of adrenal disease. It is important to diagnose adrenal lesions to learn if they are hormonally active or malignant. The most common clinical sign of pheochromocytoma is sustained or paroxysmal hypertension, and the most common symptoms are headache, excessive truncal sweating, and palpitation. In some cases, the clinical symptoms are not clear. Roughly 70% of adrenal incidentalomas are non-functional. A small group of 5–7% of the functional ones (30%) may exist as pheochromocytoma. Ten percent of pheochromocytoma cases are diagnosed incidentally during computed tomography (CT) or magnetic resonance imaging (MRI) screenings for other reasons. The most frequent symptom of the pheochromocytoma is hypertension, and 90–100% of cases exhibit it. The literature indicates that incidental pheochromocytoma cases that are smaller than 1 cm have no clinical symptoms. Rarely, some large pheochromocytoma cases do not show any clinical symptoms, and it is difficult to diagnose very small ones.Case presentationA 45-year-old male patient experienced an epigastric ache and distended stomach for 7 years. The serum cortisol level was 19.2 ng/dL (normal range: 5–20 ng/dL), and urinary free cortisol excretion was 25.00 μg/24 h (normal range:10.00–100.00 μg/24 h). The serum basal level of adrenocorticotropic hormone (ACTH) was 21 pg/mL (normal range: 9 to 52 pg/mL). Plasma cortisol was under 1.00 μg/dL after low dose (1 mg) overnight dexamethasone suppression test. 24 hours urinary catecholamines level were vanil mandilic acid (VMA) 8.90 mg/day (normal range, 3 to 90 mg/day), metanefrin 330 μg/day (normal range, 52 to 341 μg/day), epinefrin 13 μg/day (normal range, 2 to 24 μg/day), norepinefrin 41 μg/day (normal range; 15 to 100 μg/day). During abdominal ultrasonography (USG), a tumor was diagnosed in the right perirenal space. A regular-shaped mass (dimension 36 × 35 × 35 mm) with a homogeneous and solid structure was diagnosed in CT. The density of the mass was 80 Hounsfield units (HU) in postcontrast CT. The patient was given a diagnosis of a non-functional adrenal incidental lesion, underwent a right adrenalectomy. Histopathological data correlated with pheochromocytoma as wellConclusionPheochromocytoma can be diagnosed by establishing an increase in catecholamines and metabolites in the plasma and urine. The level of catecholamines and metabolites in the plasma and urine provide 95% of the evidence of the disease. Because the dimensions of the lesion were large and the HU was very clear, the patient was underwent surrenalectomy. During laboratory investigation, there was no evidence of abnormality; we, therefore, think that these cases can be named sublaboratory pheochromocytoma.

Lack of effect on adult and adolescent hypothalamic-pituitary-adrenal axis function with use of fluticasone furoate nasal spray

Intranasal corticosteroids are recommended as first-line therapy for allergic rhinitis (AR), and because of their pharmacologic class, hypothalamic-pituitary-adrenal (HPA) axis function is evaluated. To evaluate whether cortisol production was suppressed (as a measure of HPA axis function) by 6 weeks of treatment with fluticasone furoate nasal spray, 110 microg once daily, in patients with perennial AR. A double-blind, randomized, placebo- and active-controlled (prednisone), parallel-group study. Outpatients aged 12 to 65 years with perennial AR for 2 years or more were from 1 center in the United States and 1 center in Canada. Pharmacodynamic and pharmacokinetic samples were collected during 24-hour domiciled visits (overnight in clinic). Measurements included change from baseline in 24-hour serum cortisol weighted mean and 24-hour urinary free cortisol excretion, total 24-hour urinary free cortisol excretion and 6-beta hydroxycortisol excretion, and plasma concentration of fluticasone furoate. A total of 112 of 183 patients were randomized. Fluticasone furoate was noninferior to placebo with respect to the ratio from baseline in serum cortisol weighted mean (treatment ratio, 0.98; 95% confidence interval, 0.89 to 1.07). In contrast, use of prednisone, 10 mg once daily, significantly reduced the ratio from baseline compared with placebo. Change from baseline in 24-hour urinary cortisol excretion was similar in the fluticasone furoate and placebo groups. Plasma levels of fluticasone furoate were undetectable after 6 weeks of treatment. Fluticasone furoate nasal spray, 110 microg once daily, was not associated with HPA axis suppression in patients 12 years and older with perennial AR.

Peri-operative glucocorticoid replacement therapy in transsphenoidal pituitary adenoma surgery: a prospective controlled study

We set out to prospectively study the peri-operative changes of the hypothalamic-pituitary-adrenal axis (HPA), and to test the hypothesis that the peri-operative corticoid replacement regimen used at the authors' institution in patients with impaired HPA undergoing transsphenoidal pituitary adenoma surgery is adequate. Thirty seven patients (21 females, 16 males, mean age 50.6 years) underwent transsphenoidal pituitary adenoma surgery (mean tumour diameter 20.6 mm, 13 tumours hormone-secreting). The HPA functions of these patients were classified as impaired (group A, n = 15) or preserved (group B, n = 22) according to the results of a pre-operative corticotrophin releasing-hormone test (CRHT). Eleven patients (9 female, 2 male, mean age 53.6 years) without pituitary adenomas and with a preserved HPA (as assessed by medical history and morning serum cortisol (MSC) measurements), undergoing decompressive surgery for degenerative lumbar disc disease, were also studied (group C). On the day of surgery, the patients of group A received 100 mg hydrocortisone (HC) replacement therapy, which was thereafter gradually tapered off in a standardised fashion. The patients of groups B and C were not treated with corticoids. Pre-operative, intra-operative and post-operative variables of these three patient groups were compared. The urinary free cortisol excretion (UFC) in group A declined from 6732 +/- 7683 microg/d on the day of surgery to 305 +/- 358 microg/d on the 10(th) post-operative day. In group B, the respective UFC values were 12,851 +/- 16,278 microg/d and 223 +/- 235 microg/d. In both of these groups, the mean UFC did not fall into the normal range during the first ten post-operative days. On none of the post-operative days, was there a significant difference between the UFC of groups A and B. The UFC values of group C dropped from 177 +/- 157 microg/d on the day of surgery to 87 +/- 61 microg/d on post-operative day six, reaching the normal range from the 2(nd) post-operative day onwards. All UFC values of group C were significantly lower than those of group A and B. None of the evaluated clinical, laboratory and MRI parameters, as disclosed by uni- and multivariate analysis, showed any significant influence on the peri-operative UFC values. The peri-operative UFC of pituitary adenoma patients with preserved HPA was very high, as compared to patients with degenerative lumbar disc disease. The present study showed for the first time, that the proposed regimen of peri-operative corticoid replacement therapy used in patients with pituitary adenomas and impaired HPA raised cortisol levels to match the physiological increase of UFC in patients with pituitary adenoma surgery and preserved HPA. However, although statistically not significant, the UFC of patients with pituitary adenomas and preserved HPA seemed considerably higher on the day of surgery than in patients with pituitary adenomas and HPA impairment. Although there is no evidence to make it mandatory, administration of 150 mg instead of 100 mg HC substitution on the day of pituitary adenoma surgery in patients with HPA impairment may be prudent.

A ‘smart’ type of Cushing's syndrome

Cushing's syndrome results from lengthy and inappropriate exposure to excessive concentrations of either endogenous or exogenous glucocorticoids. This case report describes a patient with a novel type of Cushing's syndrome due to the use of party drugs. A 35-year-old woman had gained 8 kg body weight in 5 months and complained of anxiety. She showed a Cushing-like appearance and mild hypertension (blood pressure, BP 150/95 mmHg). She reported daily use of increasing doses of gamma-hydroxybutyric acid (GHB), a popular party drug. ACTH plasma levels were in the upper normal range (41 ng/l), with normal plasma cortisol (0.36 micromol/l). She showed an abnormal overnight 1 mg dexamethasone suppression test (cortisol 0.38 micromol/l). The urinary excretion of free cortisol in 24 h was also increased (0.47 micromol/24 h). CT scanning of the abdomen showed normal adrenals. After stopping GHB intake she lost 7 kg body weight and her BP normalized (BP 135/80 mmHg). GHB is a popular party drug in the Netherlands, but it is also used as a narcotic and for the treatment of narcolepsy. We hypothesize that GHB may bind to the pituitary gland gamma-aminobutyric acid-B receptors leading to ACTH overproduction.

Urinary Free Cortisol Excretion in Humans: A Comment on the Article by Huang and Co-Workers

Urinary Free Cortisol Excretion in Humans: A Comment on the Article by Huang and Co-Workers

Simultaneous Measurements of Urinary Free Cortisol and Cortisone for the Assessment of Functional Glucocorticoid Activity

Urinary free cortisol (UFF) excretion in 24-h urine samples is frequently measured in clinical laboratories to assess functional glucocorticoid activity (fGcA). The 24-h UFF excretion serves as an integrated measure of blood free cortisol concentrations during the entire day (1). Increasing evidence suggests that simultaneous measurements of more than 1 analyte in the same sample material will bring more confidence to the acceptance or rejection of specific diagnoses(2)(3)(4). Accordingly, clear advantages have been reported regarding the identification of hypercortisolism, e.g., in patients with confirmed Cushing syndrome(2) and type1 diabetes mellitus(4), with simultaneous measurements of UFF and urinary free cortisone (UFE) compared with UFF alone. Variations in activity of 11β-hydroxysteroid dehydrogenase type2, a highly expressed enzyme in the human kidney that inactivates cortisol to cortisone, can confound renal cortisol output (UFF). Accordingly, the usual renal 24-h UFE excretion is about twice that of UFF(2)(3)(4). Recent examinations have shown a correlation coefficient of 0.71 for the relation …

Systemic effects of epidural and intra-articular glucocorticoid injections in diabetic and non-diabetic patients

Introduction Whereas the systemic effects of glucocorticoid therapy have been extensively reported, little is known about those of local glucocorticoid injections. The objective of this study was to look for systemic effects of local glucocorticoid injections at two sites in diabetic and non-diabetic patients. Methods We studied 29 patients (18 women and 11 men with an age range of 18–86 years). The injection site was the epidural space in 18 patients (4 with and 14 without diabetes) with disk-related sciatica and the shoulder in 11 patients (8 with and 3 without diabetes) with frozen shoulder. Each patient was given three injections of 1.5 ml cortivazol (5.625 mg of cortivazol or about 85 mg prednisone-equivalent per injection and about 250 mg prednisone-equivalent in all), at 3-day intervals. Of the 12 patients with diabetes, 2 were on insulin therapy. At baseline and at the post-treatment visits 1, 7, and 21 days after the third injection, the following tests were done: plasma cortisol and ACTH at 8 am, urinary free cortisol excretion in 24 hours, fasting and postprandial blood glucose, serum cholesterol and triglycerides, and serum sodium and potassium. Blood pressure was measured at each visit. Results Mean systolic blood pressure increased significantly between baseline (123 ± 10 mmHg) and the first two post-treatment visits (day 1, 127 ± 9 mmHg; and day 7, 128 ± 10 mmHg) but returned to baseline values by the third post-treatment visit (day 21). Mean postprandial blood glucose was significantly higher at the day 1 post-treatment visit (10.1 ± 5.4 mmol/l) than at baseline (7.5 ± 2.9 mmol/l). At the day 7 post-treatment visit, blood glucose remained significantly elevated compared to baseline in the 12 diabetic patients (13.9 ± 4.8 mmol/l versus 9.4 ± 3.3 mmol/l at baseline). In both the overall population and the various subgroups, plasma cortisol and ACTH and urinary free cortisol were markedly reduced at the day 1 and day 7 post-treatment visits, compared to baseline. At the day 21 visit, these variables were diminished in the group given epidural injections, whereas plasma cortisol and ACTH were normal in the group treated intra-articularly. No significant variations were noted for fasting blood glucose or for serum levels of cholesterol, triglycerides, sodium, and potassium. Conclusion The administration of three local cortivazol injections was followed by suppression of the corticotropic axis that persisted beyond 21 days after epidural injection and recovered more rapidly after intra-articular injection. Systolic blood pressure increased transiently. Elevations in postprandial glucose levels lasted longer in diabetic than non-diabetic patients.

Neuroendocrine features in extreme longevity

In order to evaluate the effects of some neuro-endocrine changes during aging we have studied adrenal, thyroid and pineal secretion in young, healthy old and centenarians. The number of subjects in each hormone group varied. The following parameters were evaluated: serum levels of cortisol, dehydroepiandrosterone-sulfate (DHEAS), free triiodothyronine (FT3), thyroxine (FT4), reverse triiodothyronine (rT3) and thyroid-stimulating hormone (TSH). Urinary 6-hydroxymelatonin sulfate (aMT6s) and free cortisol were measured twice daily. Centenarians exhibited significantly lower TSH levels together with slightly higher rT3 levels than old controls. These changes could be due to reduced 5′-deiodinase activity occurring also in absence of substantial changes of the nutritional pattern. Morning serum cortisol levels were found to be similar in the 3 age groups, whereas the decline of serum DHEAS levels was well evident also after the ninth decade of life. The cortisol/DHEAS molar ratio, which usually increases with age and considered to be an expression of a neurotoxic pattern of the steroidal milieu in the central nervous system, did not shown any further increase in centenarians. The urinary free cortisol and aMT6s excretion declined with age; however only in centenarians and in young controls aMT6s excretion was significantly higher at night than during the day. These findings suggest that the circadian rhythm of melatonin secretion is maintained in centenarians and, based on the limitations of this study, could be considered one factor in successful aging.

Tolerability of a Salmeterol Xinafoate/Fluticasone Propionate Hydrofluoroalkane Metered-Dose Inhaler in Adolescent and Adult Patients with Persistent Asthma: A 52-Week, Open-Label, Stratified, Parallel-Group, Multicenter Study

Background: Many patients with asthma require an inhaled long-acting β 2-agonist (LABA) in addition to an inhaled corticosteroid to adequately control their disease. Objective: The purpose of this study was to assess the long-term tolerability of a salmeterol xinafoate/ fluticasone propionate (SFC) hydrofluoroalkane metered-dose inhaler (MDI) at 3 different doses BID. Methods: This 52-week, open-label, stratified, parallel-group study assessed SFC in patients with persistent asthma. Patients, aged ≥12 years, with a diagnosis of asthma for ≥6 months, and a percent predicted forced expiratory volume in 1 second (FEV 1) or peak expiratory flow (PEF) between 40% and 90% were enrolled between January 1999 and June 1999. The last patient completed the 12-month study in June 2000. Patients were allowed to continue their current asthma treatment during run-in, with the exception that short-acting β 2-agonists (SABAs), LABAs, and oral bronchodilators were not to be used 6, 12, and 24 hours, respectively, prior to the randomization visit. During the open-label randomized treatment period, patients were instructed to discontinue all other asthma medications with the exception of the albuterol MDI to use on an as-needed basis. Patients were assigned to treatment based on their existing asthma regimen: SABA monotherapy or LABA with or without fluticasone propionate (FP) <250 tlg/d or equivalent (group 1); FP 250 to 500 tlg/d or equivalent with or without LABA (group 2); and FP >500 to 1000 tlg/d or equivalent with or without LABA (group 3). Patients administered 2 inhalations BID of SFC hydrofluoroalkane at doses of 25/50 μg/actuation (group 1), 25/125 μg/actuation (group 2), or 25/250 pg/actuation (group 3). The primary end point was tolerability as assessed by adverse events (AEs). AEs were determined via diary cards and investigator inquiry at visits. Serious AEs were defined as death, any life-threatening event, hospitalization, disability, congenital anomaly in the patient's offspring, or other important medical events judged by the investigator to be serious. Other outcomes included clinical laboratory tests (hematology, chemistry, electrolytes), 24-hour urinary-free cortisol excretion, 12-lead electrocardiograms, oropharyn- geal examinations, vital signs, clinic visit lung function tests (FEV 1 and PEF), daily diary card entries of morn- ing PEF, and rescue medication usage. Results: Of the 372 patients assessed for eligibility, 325 from 22 centers across Canada were enrolled and randomized to treatment. Group 1 consisted of 98 pa- tients (55% women; 86% white; mean age, 37 years; mean [SD] weight, 79 [20] kg). Group 2 consisted of 109 patients (46% women; 94% white; mean age, 44 years; mean [SD] weight, 80 [17] kg). Group 3 consisted of 118 patients (47% women; 90% white; mean age, 45 years; mean [SD] weight, 80 [18] kg). A total of 15 adolescents (aged 12–17 years) comprised 11%, 2%, and 2% of groups 1, 2, and 3, respectively. Treatments were well tolerated, and 274 (84%) of the 325 patients enrolled completed the study. Upper respiratory tract infection was the most common AE reported: 52%, 37%, and 49% of patients in groups 1, 2, and 3, respectively. Twenty (6%) patients withdrew because of an AE, with worsening asthma being the most frequent reason (n = 9). None of the serious AEs (11 [3 %]) were considered drug related by the investigators. Improvements in FEV 1 and PEF and re- duction in symptomatic albuterol use occurred during the first 4 weeks and were maintained in all groups throughout the 52-week study. Conclusions: BID doses of SFC hydrofluoroalkane 50/100 pg, 50/250 pg, and 50/500 pg administered via MDI for 52 weeks were well tolerated in this population of adolescents and adults with persistent asthma.