24-hour Cortisol Research Articles

Comparative evaluation of 30 and 60 minutes cortisol Levels During Short Synacthen Test for diagnosis of Adrenal Insufficiency

To assess and compare diagnostic value of 30-minute cortisol level over 60-minute level in the diagnosis of adrenal insufficiency.The comparative cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from August 2017 to May 2018, and comprised patients referred to the facility for short synacthen test with suspicion of adrenal insufficiency. Blood samples for serum cortisol were taken at time-0 and then 30 and 60 minutes after the adreno-cortico-tropic hormone injection. Total serum cortisol was measured. Adrenal insufficiency was defined as stimulated cortisol level <500 nmol/l at 30 and 60 minutes post-stimulation. SPSS 24 was used for data analysis.Of the 111 subjects, 56(50.4%) were males and 55(49.5%) were females. Overall mean age was 34±20 years. Mean basal serum cortisol level was 110±98 nmol/l in patients with adrenal insufficiency and it was 294±164 nmol/l in patients with intact adrenal functions. Cortisol level at both 30 and 60 minutes was significant (p<0.001). Receiver Operating Characteristics curve was plotted which showed area under curve of 0.83 and 0.82 for 60 and 30 minutes respectively.The 30-minute cortisol level post-stimulation carried no diagnostic value . Measuring cortisol level once at 60-minute post-stimulation would be of more value apart from being cost-effective in the diagnosis of adrenal insufficiency.

Medical Correlates of Chronic Multisymptom Illness in Gulf War Veterans

BackgroundChronic multisymptom illness (CMI) is more prevalent among deployed than nondeployed veterans from the first Gulf War. Objective physiologic markers of CMI are lacking. The purpose of this study is to determine whether measurable abnormalities in the autonomic nervous system or hypothalamic-pituitary adrenal axis would distinguish CMI cases (CMI+) from controls (CMI-) among deployed veterans of the 1990-1991 Gulf War. MethodsThis is a cross-sectional case-control cohort study that examined deployed veterans who participated in the Phase III study: National Health Survey of Gulf War Veterans and Their Families. Autonomic nervous system and hypothalamic-pituitary adrenal axis function-related measures included: 24-hour heart-rate variability, urinary catecholamines and cortisol, hypertension, insulin sensitivity, dyslipidemia, body fat, bone mineral density, and ultrasensitive C-reactive protein. ResultsVeterans of the first Gulf War with CMI (n = 73) and without the condition (n = 111) were studied. Sociodemographic characteristics were similar. Veterans with CMI reported poorer mental and physical functioning, greater use of prescription medications, and more nonroutine clinic visits. These veterans were also more likely to have fibromyalgia syndrome, irritable bowel syndrome, metabolic syndrome, and among males, a larger waist-to-hip ratio. Lower values for a nonlinear heart-rate-variability parameter—the short-term fractal scaling exponent (DFA1), reflecting an increased randomness of beat-to-beat changes in heart rate—were observed in veterans with CMI than those veterans without it (1.28±0.16vs 1.35±0.15; p=0.005). Hypothalamic-pituitary-adrenal axis function measures were similar between the two groups. ConclusionIn this cohort of deployed veterans from the first Gulf War, we identified abnormal heart-rate variability in veterans with CMI compared to veterans without the condition, which suggests abnormal functioning of the autonomic nervous system and possible long-term cardiovascular effects.

Salivary Cortisone to Estimate Cortisol Exposure and Sampling Frequency Required Based on Serum Cortisol Measurements

ContextPopulation studies frequently measure cortisol as a marker of stress, and excess cortisol is associated with increased mortality. Cortisol has a circadian rhythm, and frequent blood sampling is impractical to assess cortisol exposure. We investigated measuring salivary cortisone and examined the sampling frequency required to determine cortisol exposure.MethodsSerum and saliva with cortisol and cortisone were measured by liquid chromatography–tandem mass spectrometry in independent cohorts. The relationship between serum cortisol and salivary cortisone was analyzed in cohort 1 using a linear mixed effects model. The resulting fixed effects component was applied to cohort 2. Saliva cannot easily be collected when a patient is sleeping, so we determined the minimum sampling required to estimate cortisol exposure [estimated area under the curve (eAUC)] using 24-hour cortisol profiles (AUC24) and calculated the relative error (RE) for eAUC.ResultsMore than 90% of variability in salivary cortisone could be accounted for by change in serum cortisol. A single serum cortisol measurement was a poor estimate of AUC24, especially in the morning or last thing at night (RE >68%); however, three equally spaced samples gave a median RE of 0% (interquartile range, −15.6% to 15.1%). In patients with adrenal incidentalomas, eAUC based on three serum cortisol samples showed a difference between those with autonomous cortisol secretion and those without (P = 0.03).InterpretationAccepting that most people sleep 7 to 8 hours, ∼8-hourly salivary cortisone measurements provide a noninvasive method of estimating 24-hour cortisol exposure for population studies.

Characterization of cyclic Cushing's disease using late night salivary cortisol testing.

To characterize a cohort of patients with cyclic Cushing's disease (CD) in comparison with noncyclic CD using late night salivary cortisol (LNSC) and examine the diagnostic sensitivity of LNSC in comparison with that of 24-hour urine-free cortisol (UFC) in this population. Retrospective study of patients with CD seen in our institution between 2008 and 2017. A total of 205 patients, including 17 (8%) with cyclic CD (based on a minimum of 3 peaks and 2 troughs in cortisol levels). In a secondary analysis, 38 patients (19%) with cyclic CD were identified (based on a criterion of at least 2 peaks and 1 trough). Data on presentation, laboratory tests and outcomes were extracted. The diagnostic sensitivity of LNSC vs UFC in establishing cyclic CD was calculated. Kaplan-Meier analyses of recurrence after transsphenoidal pituitary surgery (TSS) were performed. The interval between presentation and TSS was significantly longer in patients with cyclic CD (P<.0001) in comparison with those with noncyclic CD. The sensitivity of LNSC in establishing cyclic CD was 88% and was higher than that of UFC (12%, P=.007). There were no differences in remission and recurrence rates between patients with cyclic CD and those with noncyclic CD. Patients with cyclic CD account only for a minority of those with CD, but may require a lengthier diagnostic evaluation. The use of LNSC on multiple occasions provides a more sensitive method of detecting cyclic CD than UFC. Outcomes of TSS in cyclic CD are comparable to those with noncyclic disease.

The Short Synacthen (Corticotropin) Test Can Be Used to Predict Recovery of Hypothalamo-Pituitary-Adrenal Axis Function.

The 250-μg short Synacthen (corticotropin) test (SST) is the most commonly used tool to assess hypothalamo-pituitary-adrenal (HPA) axis function. There are many potentially reversible causes of adrenal insufficiency (AI), but no data to guide clinicians as to the frequency of repeat testing or likelihood of HPA axis recovery. To use the SST results to predict adrenal recovery. A retrospective analysis of 1912 SSTs data. Seven hundred seventy-six patients with reversible causes of AI were identified who had at least two SSTs performed. A subgroup analysis was performed on individuals previously treated with suppressive doses of glucocorticoids (n = 110). Recovery of HPA axis function. SST 30-minute cortisol levels above or below 350 nmol/L (12.7 μg/dL) best predicted HPA axis recovery [area under the curve (AUC) receiver operating curve (ROC) = 0.85; median recovery time: 334 vs 1368 days, P = 8.5 × 10-13]: 99% of patients with a 30-minute cortisol >350 nmol/L recovered adrenal function within 4 years, compared with 49% in those with cortisol levels <350 nmol/L. In the subgroup analysis, delta cortisol (30-minute-basal) best predicted the recovery (AUC ROC = 0.77; median recovery time: 262 vs 974 days, P = 7.0 × 10-6). No patient with a delta cortisol <100 nmol (3.6 μg/dL) and a subsequent 1-year random cortisol <200 nmol/L (7.3 μg/dL) recovered HPA axis function. Cortisol levels across an SST can be used to predict recovery of AI and may guide the frequency of repeat testing and inform both clinicians and patients as to the likelihood of restoration of HPA axis function.

Endocrine Remission After Pituitary Stereotactic Radiosurgery: Differences in Rates of Response for Matched Cohorts of Cushing Disease and Acromegaly Patients

To compare and describe the time to endocrine remission and new hypopituitarism among patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas after radiosurgery, controlling for several known prognostic factors. An institutional review board-approved, institutional retrospective analysis of patients with GH- and ACTH-secreting pituitary adenomas was performed, with matching for patient sex, age at radiosurgery, interval between the last resection and radiosurgery, use of previous radiation therapy, whole sella treatment, suprasellar extension, cavernous sinus invasion, and margin dose. Endocrine remission was defined as a normal serum insulin-like growth factor-1 (GH secreting) or a normal 24-hour urine-free cortisol (ACTH secreting) level without suppressive medications. Endocrine remission and the incidence of new hypopituitarism after single-fraction radiosurgery were recorded and compared between the 2 groups. The data from 242 patients were evaluated, 121 with GH-secreting tumors and 121 with ACTH-secreting tumors. Of the 242 patients, 75% had cavernous sinus invasion and 10% had suprasellar extension at radiosurgery. The median radiosurgical marginal dose was 25Gy to the 50% isodose line between each group. After multivariable adjustment, the factors associated with an increased time to endocrine remission included patient age (hazard ratio [HR] 1.016; P=.023), cavernous sinus invasion (HR 1.793; P=.004), and the presence of acromegaly (HR 2.912; P<.001). The incidence of new hypopituitarism developing after stereotactic radiosurgery was 29% and did not appreciably differ by adenoma subtype (P=.180). After radiosurgery, patients with ACTH-secreting tumors achieved endocrine remission sooner than did those with GH-secreting tumors. These results provide insight into the relative tumor biology and disease course after radiosurgery that will serve to further improve clinical outcomes and patient treatment in the future.

The effect of time of day testing and utility of 30 and 60 minute cortisol values in the 250 mcg ACTH stimulation test

BackgroundDespite widespread use of the 250-mcg Cosyntropin test (ACTH test) for the diagnosis of adrenal insufficiency (AI), the effect of time of day and the utility of performing both 30- and 60-min serum cortisol values remains unclear. MethodsWe conducted a retrospective cohort study of all ACTH testing at the Halifax Neuropituitary Program, Nova Scotia, Canada between January 2006 and April 2016. Data were collected on age, gender, medication history, serum cortisol levels at 0, 30 and 60 min after ACTH administration, as well as time of and indication for testing. ResultsThere were 336 tests performed, divided by time of day (0800–1000 h, 1001–1200 h, and after 1200 h). There were no differences in mean cortisol levels at 30 (574.5, 559, 534 nmol/L, respectively; p = 0.25) and 60 min (642, 623, 619 nmol/L, respectively; p = 0.63) between groups. When comparing 30- vs. 60-min values using a cut-off of ≥500 nmol/L, 45 patients (13.4%) failed to reach the cut-off at 30 min but met the cut-off at 60 min. Conversely, only 2 patients (0.6%) who met the cut-off at 30 min failed to reach it at 60 min. ConclusionWe found that outcomes from ACTH testing are not affected by time of day. Furthermore, using a 30-min cortisol level in isolation results in more than one in seven patients having a false positive diagnosis of AI; a 60-min value of ≥500 nmol/L alone may be sufficient to diagnose AI in >99% of cases.

A Single, Post-ACTH Cortisol Measurement to Screen for Adrenal Insufficiency in the Hospitalized Patient.

Cosyntropin stimulation testing (CST) is used to screen patients for adrenal insufficiency (AI). Traditionally, CST includes baseline cortisol concentration, the administration of cosyntropin, and cortisol concentration at 30 and 60 minutes poststimulation. There is debate surrounding the utility of testing and cut-off points for concentrations at each time point. To determine if a single cortisol measurement at 30 or 60 minutes could replace the traditional approach. looked retrospectively at inpatients who underwent standard, high-dose CST (n = 702) and evaluated the number of patients who would screen positive for AI by using a single time point (30 or 60 minutes) compared with the traditional CST. A tertiary-care, academic medical center. Hospital inpatients present between January 2012 and September 2013. Of tests, 84.3% were normal, which was defined as at least 1 cortisol concentration of 18 mcg/dL or higher at any time after stimulation. The average 60-minute concentration was higher than the average 30-minute concentration (P < .001). A single 60-minute concentration is 100% concordant with the full CST in the intensive care unit (ICU) subgroup and 99.6% concordant in floor patients. A single 30-minute concentration is significantly less concordant, 91.9% and 86.9%, in the ICU and floor subgroups, respectively. Overall, a single 60-minute cortisol concentration to screen for AI was 99.7% concordant with the traditional CST, and the positive percent agreement was 98%. Fewer false-positive screens would occur with a single 60-minute cortisol concentration compared with a single 30-minute concentration (P < .001). High-dose CST screening may safely be interpreted with single 60-minute poststimulation cortisol serum concentrations.

Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations.

Low birth weight (LBW; <2500 g) is linked to the development of insulin resistance and limbic-hypothalamic-pituitary-adrenal (LHPA) axis hyperactivity. Our first aim was to study insulin action, LHPA axis function, and limbic brain structures in young, healthy LBW men vs normal birthweight (NBW) controls (part 1). Our second aim was to investigate the effects of escitalopram vs placebo in LBW men in the LHPA axis and insulin sensitivity (part 2). The maximal (Rdmax) and submaximal (Rdsubmax) rates of insulin-stimulated glucose turnover, LHPA axis, and brain morphology were examined in 40 LBW men and 20 matched NBW men using two-stage hyperinsulinemic euglycemic clamp, 24-hour hormone plasma profiles, and magnetic resonance imaging. Subsequently, all LBW subjects underwent randomized and double-blind treatment with escitalopram 20 mg/d or placebo for 3 months followed by a complete reexamination. Changes in Rdmax/Rdsubmax and plasma-free cortisol 24-hour area under the curve. In LBW vs NBW, Rdsubmax and Rdmax were ∼16% (P = 0.01) and ∼12% (P = 0.01) lower, respectively, and 24-hour free cortisol levels were ∼20% higher (P = 0.02), primarily driven by a ∼99% increase at 05:00 am (P < 0.001). Furthermore, these changes were related to structural alterations within left thalamus and ventromedial prefrontal cortex. However, in LBW men, exposure to escitalopram normalized the free cortisol levels and improved the Rdsubmax by ∼24% (P = 0.04) compared with placebo. LBW vs NBW displayed alterations in key brain structures modulating the LHPA axis, elevated free cortisol levels, and insulin resistance. Escitalopram administration ameliorated these defects, suggesting a potential for LHPA axis modulation compounds to improve insulin action in LBW subjects.

Diagnostic Accuracy of Basal Cortisol Level to Predict Adrenal Insufficiency in Cosyntropin Testing: Results from an Observational Cohort Study with 804 Patients

Adrenocorticotrophic hormone (ACTH) stimulation testing is the current standard for assessing primary and secondary adrenal insufficiency (AI). We aimed to investigate the value of basal cortisol level for prediction of AI. We retrospectively analyzed 804 consecutive patients who had high-dose (250 μg, HDT) or low-dose (1 μg, LDT) ACTH testing as part of their diagnostic work-up. Site-specific cut-off levels for AI were <550 in and <500 nmol/L in HDT and LDT, respectively. Overall, 70/400 (17.5%) in the LDT group and 118/404 (29.2%) in the HDT group showed an insufficient increase of cortisol and were categorized as AI. The receiver operating characteristic curve analysis showed an overall area under the curve (AUC) for basal cortisol of 0.88, which was comparable in LDT (area under the curve [AUC] 0.88) and HDT (AUC 0.88). If basal cortisol levels were ≥450 nmol/L (n = 234/804, 29.1%), the negative predictive value to rule out AI was 98.7%. If cortisol was ≤100 nmol/L (n = 69/804, 8.6%) the positive predictive value was 93.2% to rule in AI. There was a minimal additional value of the 30-minute cortisol level in HDT as compared to the 60-minute result, as well as for delta values. Basal cortisol levels ≤100 and ≥450 nmol/L were found in almost half of patients tested for possible AI and had high diagnostic accuracy, abolishing the need for formal ACTH testing. The 30-minute cortisol value in HDT did not increase diagnostic accuracy. These data may help guide clinicians when testing can safely be omitted, thereby reducing expenses and simplifying test protocols. ACTH = adrenocorticotropic hormone AI = adrenal insufficiency AUC = area under the curve CI = confidence interval HDT = high-dose test HPA axis = hypothalamus-pituitary-adrenal axis ITT = insulin tolerance test LDT = low-dose test NR = normal responders LR+/- = positive/negative likelihood ratio NPV = negative predictive value PPV = positive predictive value.

Cyclical Cushing's: how best to catch the ups and downs

A 68-year-old man with a background of hypertension and type 2 diabetes presented with fluctuating symptoms of muscle aches and pains and tiredness. His initial work-up for the possibility of...

Laparoscopic Subcutaneous Transposition of a Pedicled Adrenal for ACTH-Independent Bilateral Macronodular Adrenal Hyperplasia.

Bilateral adrenalectomy or unilateral adrenalectomy and contralateral partial adrenalectomy are indicated for the treatment of ACTH-independent macronodular adrenal hyperplasia. Independent of the surgical procedure, the prognosis is poor. This article discusses a new treatment method and its efficacy for treating nodular adrenal hyperplasia. We performed a retrospective review of the medical records of 12 patients operated on between January 2008 and October 2014 at the First Affiliated Hospital of Zhengzhou University. All patients were treated by laparoscopic subcutaneous transposition of a pedicled adrenal. We performed postoperative monitoring of patients, including clinical symptoms and 24-hour levels of serum-free and urinary-free cortisol. All 12 patients were pathologically confirmed to have nodular adrenal hyperplasia and were followed for an average of 45.5 months (range 24-60 months). The clinical symptoms of all patients disappeared, and the 24-hour plasma-free cortisol and urinary-free cortisol levels were within the normal range. Laparoscopic subcutaneous transposition of a pedicled adrenal is a new and effective method for treating bilateral macronodular adrenal hyperplasia and can achieve long-term remission of Cushing's syndrome.

Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition.

Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high-functioning group (−4.6 pg/mL, 95% CI: −7.84, −1.36, P=0.006). The 24-hour mean melatonin concentration (high-functioning group: 4.80±0.70 pg/mL, vs cognitively impaired group: 4.81±0.76 pg/mL; P>0.05) (or the area under the curve, AUC) was not significantly different between the two groups. Cortisol levels were low during the night, and peaked at approximately 8 am. Median cortisol concentrations were similar at all times, as were the 24-hour mean cortisol concentrations and AUC. To the best of our knowledge, ours is the first study to assess circadian measures (ie, melatonin and cortisol) in healthy middle-aged men with different cognitive trajectories in midlife. We found evidence of altered circadian rhythms with a reduced nocturnal melatonin response at 4 am in men with cognitive impairment. The 24-hour concentration and AUC of melatonin and cortisol were similar in the cognitively high-functioning group and in the cognitively impaired.

No hypothalamic-pituitary-adrenal function effect with beclomethasone dipropionate nasal aerosol, based on 24-hour serum cortisol in pediatric allergic rhinitis

BackgroundIntranasal corticosteroids are the mainstay of allergic rhinitis (AR) treatment. Their potential to suppress the hypothalamic-pituitary-adrenal axis should be evaluated, especially after long-term daily use in children. ObjectiveTo evaluate the effects of treatment with non-aqueous beclomethasone dipropionate (BDP) nasal aerosol on hypothalamic-pituitary-adrenal axis function in children with perennial AR. MethodsIn this double-blinded, placebo-controlled, parallel-group study, patients (6–11 years old) with perennial AR were randomized (2:1) to BDP nasal aerosol at 80 μg/day (n = 67) or placebo (n = 32). The primary end point was change from baseline in 24-hour serum cortisol (SC) weighted mean for BDP nasal aerosol and placebo after 6 weeks of treatment, which was analyzed in the per-protocol population. ResultsThe per-protocol population included 97 patients (BDP nasal aerosol, n = 66; placebo, n = 31). Baseline geometric mean SC weighted mean values were similar in the 80-μg/day BDP nasal aerosol and placebo groups (5.97 and 6.47 μg/dL, respectively). After 6 weeks’ treatment, geometric mean values were 6.19 and 7.13 μg/dL, respectively, with no decrease from baseline in either group. Geometric mean SC ratio of BDP nasal aerosol at 80 μg/day to placebo was 0.91 (95% confidence interval 0.81–1.03), indicating predefined noninferiority. SC concentration-time profiles were similar for the placebo and 80-μg/day BDP nasal aerosol groups at baseline and week 6. BDP nasal aerosol at 80 μg/day was generally well tolerated. ConclusionIn pediatric patients with perennial AR, 24-hour SC profiles were comparable for BDP nasal aerosol and placebo, indicating that once-daily BDP nasal aerosol treatment did not significantly affect hypothalamic-pituitary-adrenal axis function. Trial RegistrationClinicalTrials.gov; NCT01697956.

Primary Endoscopic Transnasal Transsphenoidal Surgery for Magnetic Resonance Image–Positive Cushing Disease: Outcomes of a Series over 14 Years

There are scant data of endoscopic transsphenoidal surgery (ETS) with adjuvant therapies of Cushing disease (CD). To report the remission rate, secondary management, and outcomes of a series of CD patients. Patients with CD with magnetic resonance imaging (MRI)-positive adenoma who underwent ETS as the first and primary treatment were included. The diagnostic criteria were a combination of 24-hour urine-free cortisol, elevated serum cortisol levels, or other tests (e.g., inferior petrosal sinus sampling). All clinical and laboratory evaluations and radiological examinations were reviewed. Forty consecutive CD patients, with an average age of 41.0 years, were analyzed with a mean follow-up of 40.2 ± 29.6 months. These included 22 patients with microadenoma and 18 with macroadenoma, including 9 cavernous invasions. The overall remission rate of CD after ETS was 72.5% throughout the entire follow-up. Patients with microadenoma or noninvasive macroadenoma had a higher remission rate than those who had macroadenoma with cavernous sinus invasion (81.8% or 77.8% vs. 44.4%, P = 0.02). After ETS, the patients who had adrenocorticotropic hormone-positive adenoma had a higher remission rate than those who had not (76.5% vs. 50%, P = 0.03). In the 11 patients who had persistent/recurrent CD after the first ETS, 1 underwent secondary ETS, 8 received gamma-knife radiosurgery (GKRS), and 2 underwent both. At the study end point, two (5%) of these CD patients had persistent CD and were under the medication of ketoconazole. For MRI-positive CD patients, primary (i.e., the first) ETS yielded an overall remission rate of 72.5%. Adjuvant therapies, including secondary ETS, GKRS, or both, yielded an ultimate remission rate of 95%.

The Low-Dose Acth Stimulation Test: is 30 Minutes Long Enough?

Controversy persists regarding the use of the low-dose adrenocorticotropic hormone (ACTH) stimulation test (LDST) for the diagnosis of adrenal insufficiency (AI) and optimal test result interpretation. However, many centers are now using the LDST to assess cortisol secretion adequacy, and some only use a 30-minute cortisol level to determine adrenal sufficiency or AI. This study examined both 30- and 60-minute cortisol levels to assess whether the interpretation of the test was affected when both cortisol levels were taken into consideration. Data were obtained by retrospective chart review from a single pediatric endocrinology unit over a 7-year period. We identified 82 patients who completed the LDST. Their mean age was 11.7 years, and 37% were female. Cortisol levels were evaluated at baseline and 30 and 60 minutes after cosyntropin administration. A cutoff value ≥18 μg/dL was used to define adrenal sufficiency. We found that 54% of patients reached peak cortisol levels at 60 minutes, and 11 patients who did not pass the test at 30 minutes did so at 60 minutes. The only predictive characteristic was weight status; overweight and obese individuals tended to peak at 30 minutes, and normal and underweight individuals tended to peak at 60 minutes. Although further studies are necessary to confirm our findings, it appears that measuring cortisol both 30 and 60 minutes following synthetic ACTH administration may be necessary to avoid overdiagnosing AI.

Evaluation of Anthropometric and Metabolic Parameters in Obstructive Sleep Apnea.

Aims. Sleep disorders have recently become a significant public health problem worldwide and have deleterious health consequences. Obstructive sleep apnea (OSA) is the most common type of sleep-related breathing disorders. We aimed to evaluate anthropometric measurements, glucose metabolism, and cortisol levels in patients with obstructive sleep apnea (OSA). Materials and Methods. A total of 50 patients with a body mass index ≥30 and major OSA symptoms were included in this study. Anthropometric measurements of the patients were recorded and blood samples were drawn for laboratory analysis. A 24-hour urine sample was also collected from each subject for measurement of 24-hour cortisol excretion. Patients were divided equally into 2 groups according to polysomnography results: control group with an apnea-hypopnea index (AHI) <5 (n = 25) and OSA group with an AHI ≥5 (n = 25). Results. Neck and waist circumference, fasting plasma glucose, HbA1c, late-night serum cortisol, morning serum cortisol after 1 mg dexamethasone suppression test, and 24-hour urinary cortisol levels were significantly higher in OSA patients compared to control subjects. Newly diagnosed DM was more frequent in patients with OSA than control subjects (32% versus 8%, p = 0.034). There was a significant positive correlation between AHI and neck circumference, glucose, and late-night serum cortisol. Conclusions. Our study indicates that increased waist and neck circumferences constitute a risk for OSA regardless of obesity status. In addition, OSA has adverse effects on endocrine function and glucose metabolism.

Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.

BackgroundGlucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following “physiological” and “stress” doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement.MethodsCortisol profiles were measured in plasma, saliva and urine following “physiological” (20 mg oral) or “stress” (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens’ equation.ResultsPlasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P <0.0001, correlation coefficient between 0.61 and 0.94). There was no difference in CBG levels across the sampling period.ConclusionsAn oral dose of hydrocortisone 20 mg is supraphysiological for routine maintenance, while stress doses above 50 mg 6-hourly would rarely be necessary in managing acute illness. Salivary cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.

Psychotropic Medication and Osteoporosis

Psychotropic Medication and Osteoporosis

Utility of 30 and 60 minute cortisol samples after high-dose synthetic ACTH-1-24 injection in the diagnosis of adrenal insufficiency.

In clinical practise the high dose ACTH stimulation test (HDT) is frequently used in the assessment of adrenal insufficiency (AI). However, there is uncertainty regarding optimal time-points and number of blood samplings. The present study compared the utility of a single cortisol value taken either 30 or 60 minutes after ACTH stimulation with the traditional interpretation of the HDT. Retrospective analysis of 73 HDT performed at a single tertiary endocrine centre. Serum cortisol was measured at baseline, 30 and 60 minutes after intravenous administration of 250 µg synthetic ACTH1-24. Adrenal insufficiency (AI) was defined as a stimulated cortisol level <550 nmol/l. There were twenty patients (27.4%) who showed an insufficient rise in serum cortisol using traditional HDT criteria and were diagnosed to suffer from AI. There were ten individuals who showed insufficient cortisol values after 30 minutes, rising to sufficient levels at 60 minutes. All patients revealing an insufficient cortisol response result after 60 minutes also had an insufficient result after 30 minutes. The cortisol value taken after 30 minutes did not add incremental diagnostic value in any of the cases under investigation compared with the 60 minutes' sample. Based on the findings of the present analysis the utility of a cortisol measurement 30 minutes after high dose ACTH injection was low and did not add incremental diagnostic value to a single measurement after 60 minutes.