Cortisol Excretion Rate Research Articles

No effect of tattoos on local sweat concentrations of select cytokines, cortisol, glucose, blood urea nitrogen, or lactate during exercise

Due to growing interest in the investigation of exercise induced sweat biomarkers to assess an individual’s health and the increasing prevalence of tattoos in the world’s population, investigators sought to determine whether local sweat concentrations and excretion rates of epidermal growth factor (EGF), interleukin (IL) -1α, IL-6, IL-8, cortisol, glucose, blood urea nitrogen (BUN), and lactate differ between tattooed and contralateral non-tattooed skin during exercise. Sixteen recreational exercisers [female (50%)] (age = 25–48 years) with ≥ 1 unilateral permanent tattoo [median tattoo age = 6 years, IQR = 5] on the arm/torso completed an outdoor group fitness session. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate concentrations. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate excretion rate. Findings suggest that permanent tattoos older than 1 year may not impact local sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, and lactate concentrations or excretion rates during exercise.Clinical trial identifier NCT04920266 was registered on June 9, 2021.

Does sedation with AQUI-S® mitigate transport stress and post transport mortality in ballan wrasse (Labrus bergyltae)?

Ballan wrasse (Labrus bergylta) are commonly used as cleaner fish in salmon farms as a biological treatment to mitigate sea lice infestation. Improved welfare for cleaner fish both during production of these fish and when in sea-cages with salmon is crucial for the industry's development. A common operational procedure in ballan wrasse production is transporting juveniles from one land-based farm to another for further on-growing. Episodes of increased mortality have been reported after such transportations. In this study, the relationship between transport stress and post-transport mortality at the on-growing facility was examined. It was also investigated if light sedation with AQUI-S® can mitigate stress during transport. Stress was quantified by measuring cortisol release rate to the tank water during transport. This was investigated in 10 commercial live carrier truck transports (6 without AQUI-S® sedation and 4 with sedation during loading and transport). The total time of transport varied between 12 and 21 h. In general, mortality was significantly higher (1.0 ± 0.6% day-1) the first five days post-transport compared to 15-20 days post transport (0.5% day-1). There was also a strong relationship between fish weight at transport and post-transport mortality, where higher mean weight at transport reduced mortality. In contrast to what was expected, AQUI-S® treatment during transport procedures increased cortisol excretion rate, suggesting a stimulating effect of AQUI-S® on the stress axis in ballan wrasse. Considering these results, the value of using AQUI-S® to reduce stress during transport of juvenile ballan wrasse might be questioned. However, there was no relationship between cortisol release rate during transport and post-transport mortality. Furthermore, this study emphasizes that water cortisol measurements can be used as a none-invasive tool for monitoring stress and can be integrated into the welfare evaluation during commercial fish transports.

Role of glucocorticoid metabolism in childhood obesity-associated hypertension.

ObjectiveChildhood obesity is associated with alterations in hypothalamus–pituitary–adrenal axis activity. We tested the hypothesis that multiple alterations in the metabolism of glucocorticoids are required for the development of hypertension in children who become overweight.MethodsSpot urine for targeted gas chromatography-mass spectrometry steroid metabolome analysis was collected from (1) overweight/hypertensive children (n = 38), (2) overweight/non-hypertensive children (n = 83), and (3) non-overweight/non-hypertensive children (n = 56).ResultsThe mean (± s.d.) age of participants was 10.4 ± 3.4 years, and 53% of them were male. Group 1 and group 2 had higher excretion rates of cortisol and corticosterone metabolites than group 3 (869 (interquartile range: 631–1352) vs 839 (609–1123) vs 608 (439–834) μg/mmol creatinine × m2 body surface area, P < 0.01, for the sum of cortisol metabolites), and group 1 had a higher excretion rate of naive cortisol than group 3. Furthermore, groups differed in cortisol metabolism, in particular in the activities of 11β-hydroxysteroid dehydrogenases, as assessed from the ratio of cortisol:cortisone metabolites (group 2 < group 3), 5α-reductase (group 1 > group 2 or 3), and CYP3A4 activity (group 1 < group 2 or 3).DiscussionThe sequence of events leading to obesity-associated hypertension in children may involve an increase in the production of glucocorticoids, downregulation of 11β-hydroxysteroid dehydrogenase type 1 activity, and upregulation of 5α-reductase activity, along with a decrease in CYP3A4 activity and an increase in bioavailable cortisol.

Hypercortisolism on the background of recovery of COVID-19 (сase report)

Damage to the lung tissue is a predominant complication of the viral disease COVID-19. Recently, there have been complications from other organs, including highly vascularized endocrine glands. Regarding the adrenal glands, there are reports of their damage with a decrease in their function. Сhanging the function of the adrenal glands (AG) in patients with or after COVID-19 is important. A few adrenal autopsy studies in patients have revealed vascular thrombosis, cortical lipid degeneration, ischemic necrosis, parenchymal infarcts, and other lesions leading to a decrease in AG function. The central mechanism of adrenal dysfunction through hemorrhage and necrosis of the pituitary gland is also possible. This paper presents a rare case of the development of hypercortisolism in a young woman after recovering from COVID-19. Based on high ACTH levels (157 and 122pg/ml), a negative nocturnal dexamethasone test, and high 24-hour urinary free (daily) cortisol excretion rates, we tentatively suspected Cushing’s disease. Chromogranin A was within the normal range of 21.35 (reference value &lt;100). Other tests showed an elevated dihydrotestosterone level of 780.6 pg/ml (reference values 24–368 pg/ml). The levels of other anterior pituitary hormones tested were within the normal range. According to clinical guidelines, the drug of choice for the short-term treatment of this disease is steroidogenesis inhibitors— ketoconazole. The effectiveness of such a treatment regimen was previously brought to light by others. In our case, ketoconazole was prescribed at a dose of 400 mg 2 times a day and cabergoline (dostinex) at an initial dose of 1 mg per day. Given the low levels of vitamin D in the blood serum, it was recommended to continue taking vitamin D at a dose of 4000 IU per day. It was recommended to control blood laboratory parameters— serum cortisol, ACTH, AST, ALT, electrolytes, 25(OH)D, blood glucose level after 2 months and decide on further tactics for managing the patient.

Sex-specific differences in HPA axis activity in VLBW preterm newborns.

ObjectiveSex-specific differences in hypothalamic–pituitary–adrenal axis activity might explain why male preterm infants are at higher risk of neonatal mortality and morbidity than their female counterparts. We examined whether male and female preterm infants differed in cortisol production and metabolism at 10 days post-partum.Design and methodsThis prospective study included 36 preterm born infants (18 boys) with a very low birth weight (VLBW) (<1.500 g). At 10 days postnatal age, urine was collected over a 4- to 6-h period. Glucocorticoid metabolites were measured using gas chromatography-mass spectrometry. Main outcome measures were: (1) cortisol excretion rate, (2) sum of all glucocorticoid metabolites, as an index of corticosteroid excretion rate, and (3) ratio of 11-OH/11-OXO metabolites, as an estimate of 11B-hydroxysteroid dehydrogenase (11B-HSD) activity. Differences between sexes, including interaction with Score of Neonatal Acute Physiology Perinatal Extension-II (SNAPPE II), sepsis and bronchopulmonary dysplasia (BPD), were assessed.ResultsNo differences between sexes were found for cortisol excretion rate, corticosteroid excretion rate or 11B-HSD activity. Interaction was observed between: sex and SNAPPE II score on 11B-HSD activity (P = 0.04) and sex and BPD on cortisol excretion rate (P = 0.04).ConclusionThis study did not provide evidence for sex-specific differences in adrenocortical function in preterm VLBW infants on a group level. However, in an interaction model, sex differences became manifest under stressful circumstances. These patterns might provide clues for the male disadvantage in neonatal mortality and morbidity following preterm birth. However, due to the small sample size, the data should be seen as hypothesis generating.

The cortisol burden in elderly subjects with metabolic syndrome and its association with low-grade inflammation.

Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders. To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol). From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine). In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) μg/g creatinine/12h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3μg/g creatinine/12h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively. The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects. The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

The effects of age and ethnicity on the circadian variation of catecholamines and cortisol in employed women

BackgroundWomen employed outside the home in urban settings must adapt to changing circadian microenvironments. The pattern and extent of vasoactive hormone responses to these changes may depend upon age and ethnic background. The purpose of this study was to evaluate the effects of age and ethnicity on the circadian variation of urinary norepinephrine, epinephrine, and cortisol excretion across work, home and sleep microenvironments.MethodsThe subjects of the study were 95 women (38 European-American, age = 35.4 ± 7.4; 28 African-American, age = 33.4 ± 7.9; 12 Asian-American, age = 36.7 ± 9.3 and 17 Hispanic-American age = 31.6 ± 10.9) employed as secretaries, lab technicians or office supervisors in New York City. Variation in the hormones across the microenvironments was evaluated using repeated measures ANCOVA with age group (18–29.9; 30–39.9; 40–49.9) and ethnicity as fixed factors.ResultsThe results show that for norepinephrine and epinephrine, work excretion rates are substantially higher than sleep rates (p < .001), and for epinephrine home rates were higher than sleep rates (p < .001). Work and sleep cortisol excretion rates were also significantly higher than the rate at home, consistent with cortisol’s circadian rhythm. (p < .002). Women in their twenties had substantially lower norepinephrine excretion rates than women over 30 (p < .04). There were also ethnic differences in norepinephrine (p < .04) and epinephrine (p = .11) output with Asian-American women having the lowest and African-American women having the highest rates. This variation is likely related to the ethnic variation in weight. There was no significant variation in cortisol excretion with age or ethnicity.ConclusionThe circadian rates of norepinephrine excretion differ by age and that of both catecholamines differ by ethnicity among women working outside the home. It is speculated that the age variation in norepinephrine may contribute to the development of vasomotor symptoms.

Serum Cortisol and the Risk of Osteoporosis in Nigerians on Medroxyprogesterone Acetate

Depo-Provera®; Depot-Medroxyprogesterone Acetate (DMPA) is one of the most used contraceptives and it is currently used by more than 30 million women in most of developed and developing countries. The study was designed to investigate the relationship between serum cortisol and the risk of osteoporosis in Nigerians using Depo-Provera®. We investigated 50 women using Depo-Provera® and 50 age-matched control, not on DPMA. Serum cortisol, progesterone, estrogen, estradiol, serum calcium, cathepsin K and urinary excretion rate of calcium were determined in subjects and controls. Serum cortisol and cathepsin K were significantly higher in women using DPMA Vs controls (P<0.01), we also found a significantly lower estradiol, serum calcium and an increased urinary excretion rate of calcium in subjects using DPMA as compared to controls (P<0.05). We found a positive correlation between serum cortisol and serum calcium (r=0.553) (P<0.01), serum cortisol and cathepsin K (r=0.568, P<0.05). Our study shows that hypercortisolaemia may be responsible for calcium loss, further investigation is needed to determine if cortisol induced calcium loss is responsible for bone demineralization associated with the use of DPMA.

Low Impact of Urinary Cortisol in the Assessment of Hydrocortisone Replacement Therapy.

Hydrocortisone replacement therapy is a cornerstone in the treatment of adrenal insufficiency (AI). While urinary cortisol has been used as a diagnostic tool for AI, it remains unclear whether it is a useful parameter to monitor hydrocortisone replacement therapy. Aim of this study was to evaluate possible differences in cortisol metabolism between adrenal insufficient patients and healthy subjects and to assess the value of urinary cortisol in AI management. In a case-control study, urinary cortisol excretion was determined in 14 patients with primary and secondary AI receiving hydrocortisone infusions from midnight to 8:00 AM. Results were correlated with serum cortisol levels and compared to urinary values obtained from 53 healthy volunteers. Urinary cortisol excretion in healthy subjects was 14.0±7.8 μg/8 h (range: 0.24-35.4), levels did not differ between 3 groups aged 20-34 years, 35-49 years, and ≥50 years. Patients with AI receiving hydrocortisone infusions demonstrated significantly higher rates of urinary cortisol excretion (51.6±37.8 μg/8 h; range 17.1-120.0, p<0.001); the values correlated with serum cortisol levels (r(2)=0.98). Of interest, patients with secondary AI showed significantly higher serum cortisol levels after hydrocortisone infusion than those with primary AI, conceivably due to residual adrenal function. In conclusion, we showed that: (i) there is a wide inter-individual variability in urinary cortisol excretion rates; (ii) cortisol metabolism in adrenal insufficient patients differs when compared to controls; (iii) there is a strong correlation between urinary and serum cortisol levels; and (iv) urinary cortisol levels despite their variability may help to discriminate between secondary and primary adrenal insufficiency.

An Unusual Presentation of Pediatric Cushing Disease: Diabetic Ketoacidosis

<h3>ABSTRACT</h3> <b>Objective:</b> Cushing syndrome (CS) is very rare in pediatric patients. The major cause of endogenous CS is Cushing disease (CD), which is due to excessive adreno-corticotropic hormone (ACTH) secretion from pituitary cells. CS that presented with diabetic ketoacidosis (DKA) has rarely been reported in adults. However, to our knowledge, there is no report of a pediatric case of CD presenting with DKA. <b>Methods:</b> A case report and literature review. <b>Results:</b> A 16-year-old female suffering from polyuria and polydipsia for 2 weeks was admitted with amenorrhea and oral moniliasis. Due to her hyperglycemia, ketonuria, glucosuria, and metabolic acidosis on arterial blood gas, she was diagnosed with DKA. Oral moniliasis, acanthosis nigricans, moon face, central obesity, and striae were detected on physical examination. Based on the results of overnight and low-dose dexamethasone suppression tests, the patient was diagnosed with CS. In a high-dose dexa-methasone suppression test (HDDST), her urinary free cortisol (UFC) excretion rate was suppressed by 73.3%. Brain magnetic resonance imaging (MRI) revealed a 4-mm pituitary microadenoma. Because serum cortisol and 24-hour UFC levels were not sufficiently suppressed by the HDDST and the diameter of adenoma in the MRI was <5 mm, bilateral inferior petrosal sinus (BIPS) sampling was performed. A diagnosis of CD was confirmed by determining a high central/peripheral ACTH ratio (12.88, normal <3) <b>Conclusion:</b> Although very rare in childhood, CS should be considered in pediatric patients with obesity, acanthosis nigricans, moniliasis, and striae. DKA may be the presenting clinical feature in patients with impaired glucose metabolism. <b>Abbreviations: ACTH</b> adrenocorticotropic hormone <b>BIPS</b> bilateral inferior petrosal sinus <b>C</b> cholesterol <b>CD</b> Cushing disease <b>CS</b> Cushing syndrome <b>DKA</b> diabetic ketoacidosis <b>DM</b> diabetes mellitus <b>HDDST</b> high-dose dexamethasone suppression test <b>MRI</b> magnetic resonance imaging <b>TSS</b> transsphenoidal surgery <b>UFC</b> urinary free cortisol

Stress and Fatigue in Operators Under Radiofrequency Electromagnetic Radiation and Shift Work

Summary The aim was to study the effect of radiofrequency electromagnetic radiation (EMR) on stress indices, health complaints and fatigue of operators working fast-rotating extended shifts. Working conditions, job content, job control, social support, health complaints and fatigue were followed in 220 operators, 110 exposed to EMR and 110 control operators, matched by age and sex. The EMR was measured and time-weighted average (TWA) was calculated. The excretion rates of stress hormones cortisol, adrenaline and noradrenaline were followed during the extended shifts in 36 operators, working at different levels of exposure and 24-hour exposure was calculated. The exposed group pointed more problems with the working conditions, including EMR, noise, currents and risk of accidents, more health complaints and higher level of fatigue. The most common health complaints were mental and physical exhaustion after work, pains in the chest, musculoskeletal complaints, headache, and apathy. High level EMR exposure (TWAmean = 3.10 μW/cm2, TWAmax = 137.00 μW/cm2) significantly increased the 24-hour excretion of cortisol and noradrenaline, whereas the increase of adrenaline excretion did not reach significance, as well as hormone excretion rates under low level exposure (TWAmean = 1.89 μW/cm2, TWAmax = 5.24 μW/cm2). In conclusion, higher number of health complaints, higher stress hormone excretion rates and fatigue were found in operators under EMR.

Colour and contrast of female faces: attraction of attention and its dependence on male hormone status in Macaca fuscata

Colour signals play a major role in social and sexual communication in a broad range of animal species. Previous studies on nonhuman primates showed that intense female skin coloration attracts male attention. We investigated (1) whether sexually active male Japanese macaques are attracted by intensely coloured female skin, (2) whether a preference for intense skin coloration results from the increased colour contrast between the skin area and its surroundings irrespective of the red chromaticity, and (3) whether the endocrine status of sexually active males affects their attentional selectivity (or preference) for salient female sexual skin coloration. We conducted two behavioural experiments in two consecutive mating seasons. First, we presented two female face images coloured in a natural range of red skin coloration on monitors. Second, we presented the same faces dissociated from the red chromaticity while maintaining their initial colour contrast properties. In both experiments we analysed male selective visual attention and approaches as a function of stimulus type. Faecal samples were collected after each experiment to analyse focal males' cortisol and testosterone excretion rates. We found that female facial skin coloration triggered selective behaviour in social-living male Japanese macaques. Variances in colour contrast also triggered males' selective orienting towards an intensely coloured face image but the red chromaticity remained essential to induce prolonged male interest. Furthermore, elevated cortisol facilitated male preferences for the intensely coloured female faces, sociosexual stimuli that are presumably highly relevant during the mating season. Future studies may pursue the principle of colour contrast in male attentional behaviour with respect to subtle colour changes expressed by females throughout the reproductive cycle. Cortisol-related physiological processes should be considered in studies on mating-relevant selective attention. • We investigated colour and colour contrast preferences in male Japanese macaques. • We analysed males' endocrine status in relation to their selective behaviour. • Female facial skin coloration triggers visual and behavioural selection of males. • Dissociated from the red colour, variances in colour contrast are less decisive. • Cortisol excretion rates correlate with males' selective behaviour.

Combined food intake and exercise unmask different hormonal responses in lean and obese children

Our purpose was to investigate the effect of obesity in prepubertal children on the hormonal response to exercise performed under different conditions of nutrient availability. Prepubertal obese (age, 10.3 ± 1.8 years; %body fat, 36.1 ± 6.1; n = 9) and lean (age, 9.2 ± 1.6 years; %body fat, 22.2 ± 4.1; n = 7) children completed 2 experimental sessions in which they performed a 30 min of cycling exercise at 50% of their maximal aerobic power either 1 h (T1h) or 3 h (T3h) after a standardized breakfast. Plasma insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1), and IGFBP-3 levels were assessed at baseline and after exercise. Urine was collected during the sessions, and catecholamine and glucocorticoid excretions were analyzed. A significant time effect was observed for IGFBP-1; postexercise levels decreased in lean and obese children (p ≤ 0.001). IGF-1 and IGFBP-3 were not affected by obesity or food intake combined with exercise. In lean children, urinary excretion rates of epinephrine, norepinephrine, cortisol, and cortisone were significantly higher during the sessions than during the overnight resting period; in obese children, only epinephrine in T1h was significantly increased (p ≤ 0.05 for all). Our study indicates that the activity of the hypothalamic-pituitary-adrenal axis and sympathetic adrenal medullary axis was similar in lean and obese children, based on measurement under resting conditions, but response to exercise performed in postprandial conditions was altered in obese children for both axes. In addition, exercise in the postprandial state elicited a decrease in IGFBP-1 plasma levels, whereas IGF-1 and IGFBP-3 levels were not significantly altered.

Luteinizing hormone correlates with adrenal function in postmenopausal women

In postmenopausal women, a relationship between luteinizing hormone (LH) and cortisol levels has been suggested. Furthermore, LH receptors in the adrenal gland have been shown to mediate adrenocorticotropic hormone-independent Cushing syndrome. In contrast, follicle-stimulating hormone (FSH) receptors have not been found in the adrenal gland. Our objective was to explore the relationship of LH with adrenal function in postmenopausal women, as assessed by 24-hour urinary free cortisol (UFC) and aldosterone excretion rate (AER). Participants were studied at a single time point in the fasting state in the Clinical Research Center of Brigham and Women's Hospital. We studied 36 postmenopausal women in sodium balance to control for variation in endogenous levels of plasma renin activity and angiotensin II. Serum cortisol, aldosterone, LH, and FSH levels were measured, as were 24-hour UFC and AER. Correlations were performed by calculation of Pearson's correlation coefficient. Serum LH correlated significantly with log-transformed UFC (r = 0.43, P = 0.01) and inversely with log AER (r = -0.50, P = 0.002). We found no correlation of serum LH with serum cortisol or aldosterone, nor did we find correlation of FSH with these parameters. In postmenopausal women, serum LH levels correlate significantly with UFC (positively) and AER (negatively). LH stimulation may induce subtle shifts in adrenal function toward cortisol secretion.

Obesity and the hypothalamic-pituitary-adrenal axis in adolescent girls

Stress and stress-related concomitants, including hypothalamic-pituitary-adrenal (HPA) axis activation, are implicated in obesity and its attendant comorbidities. Little is known about this relationship in adolescents. To begin to address this important knowledge gap, we studied HPA axis activity in 262 healthy adolescent girls aged 11, 13, 15, and 17 years. We hypothesized that obesity would be correlated with increased HPA axis activity and reactivity. Measures of HPA axis activity included 3 blood samples obtained midday (between 1:00 and 2:00 pm) over the course of 40 minutes; overnight urine free cortisol; and cortisol levels 0, 20, and 40 minutes after venipuncture (cortisol reactivity). Measures of adiposity included body mass index (BMI), BMI z score (BMI-Z), percentage body fat, and fat distribution (central adiposity) assessed by dual-energy x-ray absorptiometry. Daytime levels of serum cortisol were inversely associated with BMI-Z and central adiposity (P < .05). The urine free cortisol excretion rate was positively correlated with BMI, BMI-Z, and central adiposity. There was blunting of cortisol response to venipuncture with increasing adiposity. Our results suggest that there may be reduced cortisol levels during the day and increased levels at night with increasing degree of adiposity. This study provides preliminary findings indicating an alteration of the circadian rhythm of cortisol with obesity. We conclude that obesity is associated with altered HPA activity in adolescent girls. The clinical implications of our findings require further investigation.

Failure of functional imaging with gallium-68-DOTA-D-Phe1-Tyr3-octreotide positron emission tomography to localize the site of ectopic adrenocorticotropic hormone secretion: a case report

IntroductionThe diagnostic efficacy of biochemical and imaging modalities for investigating the causes of Cushing's syndrome are limited. We report a case demonstrating the limitations of these modalities, especially the inability of functional imaging to help localize the site of ectopic adrenocorticotropic hormone secretion.Case presentationA 37-year-old Arabian woman presented with 12 months of progressive Cushing's syndrome-like symptoms. Biochemical evaluation confirmed adrenocorticotropic hormone -dependent Cushing's syndrome. However, the anatomical site of her excess adrenocorticotropic hormone secretion was not clearly delineated by further investigations. Magnetic resonance imaging of our patient's pituitary gland failed to demonstrate the presence of an adenoma. Spiral computed tomography of her chest only revealed the presence of a non-specific 7 mm lesion in her left inferobasal lung segment. Functional imaging, including a positron emission tomography scan using 18-fluorodeoxyglucose and gallium-68-DOTA-D-Phe1-Tyr3-octreotide, also failed to show increased metabolic activity in the lung lesion or in her pituitary gland. Our patient was commenced on medical treatment with ketoconazole and metyrapone to control the clinical features associated with her excess cortisol secretion. Despite initial normalization of her urinary free cortisol excretion rate, levels began to rise eight months after commencement of medical treatment. Repeated imaging of her pituitary gland, chest and pelvis again failed to clearly localize a source of her excess adrenocorticotropic hormone secretion. The bronchial nodule was stable in size on serial imaging and repeatedly reported as having a nonspecific appearance of a small granuloma or lymph node. We re-explored the treatment options and endorsed our patient's favored choice of resection of the bronchial nodule, especially given that her symptoms of cortisol excess were difficult to control and refractory. Subsequently, our patient had the bronchial nodule resected. The histological appearance of the lesion was consistent with that of a carcinoid tumor and immunohistochemical analysis revealed that the tumor stained strongly positive for adrenocorticotropic hormone. Furthermore, removal of the lung lesion resulted in a normalization of our patient's 24-hour urinary free cortisol excretion rate and resolution of her symptoms and signs of hypercortisolemia.ConclusionThis case report demonstrates the complexities and challenges in diagnosing the causes of adrenocorticotropic hormone -dependent Cushing's syndrome. Functional imaging may not always localize the site of ectopic adrenocorticotropic hormone secretion.

Effects of hyperlipidaemia on glucocorticoid metabolism: results of a randomized controlled trial in healthy young women

It is well established that the hypothalamic-pituitary-adrenal (HPA) axis is altered in obese individuals. Hyperlipidaemia with elevated levels of free fatty acids (FFAs) is also frequently seen in obesity and in the metabolic syndrome. We hypothesized, therefore, that hyperlipidaemia may alter the activity of the HPA axis. The effects of hyperlipidaemia, including increased circulating FFAs, on ACTH secretion and cortisol metabolism were analysed in 13 healthy young women during the early follicular phase of two subsequent cycles. We administered a 20% lipid/heparin (LHI) or a saline/heparin infusion (SHI) using a crossover design in random order for 330 min. A detailed characterization of glucocorticoid metabolism was performed by measurement of plasma ACTH, cortisol and urinary excretion rates of adrenal glucocorticoids and the glucocorticoid metabolites. We observed that LHI-induced hyperlipidaemia elevated serum cortisol levels compared to SHI. No changes in plasma ACTH levels, daily urinary excretion rates of adrenal glucocorticoids, glucocorticoid precursors/metabolites and the calculated activities of the 5α-reductase, 3β-hydroxysteroid dehydrogenase (HSD), 11-, 17-, 21-hydroxylase and 11β-HSD 1 or 2 were found. Our randomized controlled trial suggests that the adrenal sensitivity to ACTH may be enhanced by LHI-induced hyperlipidaemia in normal-weight healthy young women. This effect might contribute to the disturbances of the HPA axis described in women with abdominal obesity and impaired lipid metabolism.

Cortisol, energy intake, and food frequency in overweight/obese women

Objective This retrospective study investigated the relation between daily urinary free cortisol excretion rate, as a marker of cortisol production rate, to daily caloric intake, food choice, body mass index (BMI), and waist circumference. Methods One hundred twenty-seven overweight/obese women and 21 normal-weight subjects were enrolled in the study. Fasting blood samples for metabolic parameters were taken from each subject, followed by an oral glucose tolerance test. Cortisol excretion rate was assessed on 24-h urine collection (UFC/24 h). In obese patients, the daily caloric intake was calculated, and a weekly food-frequency questionnaire was assessed. Analysis of variance was used to assess the differences between groups. The relations between parameters were investigated by simple and multiple regressions. Results Obese women had significantly higher UFC/24 h than the normal-weight women ( P < 0.001). The obese subjects had an unbalanced diet, particularly rich in saturated lipids, and weekly food choice showed a preference for highly caloric foods. UFC/24 h values and waist circumference were significantly correlated ( P < 0.001), regardless of BMI. In the obese group, after adjustment for BMI, the UFC/24 h values were also significantly and positively correlated to daily carbohydrate and lipid intake and to weekly starchy food consumption. Conclusion We demonstrated a significant association between higher UFC/24 h and energy intake, fats, and consumption of starchy foods, and that these relations were independent of BMI.

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.

Administration of glycyrrhetinic acid: significant correlation between serum levels and the cortisol/cortisone-ratio in serum and urine.

In vitro, cortisol and aldosterone have a similar affinity to the mineralocorticoid receptor. The 11beta-hydroxysteroid dehydrogenase catalyzes the interconversion of cortisol to its inactive 11-oxo-metabolite cortisone. This interconversion is responsible for the in vivo specificity of the mineralocorticoid receptor. A defect of this enzyme leads to a pseudohyperaldosteronism with hypertension and hypokalemia, the so-called apparent mineralocorticoid excess syndrome. Glycyrrhetinic acid, a compound of licorice, also leads to pseudohyperaldosteronism by an inhibition of the 11beta-hydroxysteroid dehydrogenase. We studied the pharmacokinetics of glycyrrhetinic acid and its effect on the 11beta-hydroxysteroid dehydrogenase. Ten healthy students, aged 24 to 38 years, were included in the study. On the first day 500 mg glycyrrhetinic acid were given orally at 08.00 h. Blood and urine samples were taken prior to and 2, 4, 7, 10 and 24 hours after ingestion of glycyrrhetinic acid. We measured the serum level of cortisol, cortisone and glycyrrhetinic acid and the urinary excretion rates of cortisol, cortisone and their 20-dihydrometabolites. For determination of glycyrrhetinic acid and steroid levels we used a fully automated liquid chromatographic analyzer which allows the highly specific and simultaneous determination of steroid profiles even in the matrix of urine. Ratios of the 11-hydroxy- and 11-oxo-metabolites were calculated and correlated to the serum level of glycyrrhetinic acid. We found a significant correlation of the steroid-ratios to the serum levels of glycyrrhetinic acid. Coefficients of correlation were 0.9873, 0.7812, 0.7396 and 0.5844 between the serum level of glycyrrhetinic acid and the cortisol/cortisone-ratio in serum (p < 0.0001), the cortisol/cortisone-ratio in urine (p = 0.0279), the 20alpha-dihydrocortisol/20alpha-dihydrocortisone-ratio in urine (p = 0.0119) and the 20beta-dihydrocortisol/20beta-dihydrocortisone-ratio in urine (p = 0.0419), respectively. We conclude that the ratios of cortisol to cortisone and of the 20-dihydrometabolites of cortisol to the 20-dihydrometabolites of cortisone provide a simple noninvasive tool for monitoring the in-vivo activity of the 11beta-hydroxysteroid dehydrogenase.