Suppression Of Serum Cortisol Research Articles

7822 Mild Autonomous Cortisol Secretion In High Suspicious Adrenal Incidentaloma

Abstract Disclosure: N. Zavrashvili: None. N. Margvelashvili: None. K. Chanturishvili: None. Mild Autonomous Cortisol Secretion in High Suspicious Adrenal IncidentalomaIntroduction: Incidentally discovered adrenal masses are common and mostly benign and non-functioning adenomas. However, evolving evidence suggests that a notable proportion of these adrenal adenomas may demonstrate mild autonomous cortisol secretion (MACS), which has been associated with an increased risk for hypertension, hyperglycemia, obesity, dyslipidemia, vertebral fractures, adverse cardiovascular events, and mortality. 55-year-old women with 5-year history of hypertension and hyperlipidemia. She was treated with a three-drug program: verapamil 250 mg daily, combined B-blocker, atenolol 100 mg and chlorthalidone 25 mg daily. Blood pressure control remained suboptimal. Her body mass index was 29,5 kg/m2. She had no signs or symptoms of overt Cushing syndrome.She was referred to CT coronary angiogram by her cardiologist, which revealed adrenal incidentaloma.Adrenal dedicated CT showed left-sided 3,4 cm high density node (41HU), with absolute washout <60. She was consulted by oncologist to exclude adrenal metastasis. The baseline laboratory test results excluded PA and Pheochromocytoma. The diagnosis of glucocorticoid secretory autonomy was based on positive low-dose dexamethasone suppression test (DST), low serum ACTH concentration, low-normal DHEA-S and lack of complete suppression of serum cortisol with an overnight 8-mg DST. Patient was referred to left-sided laparoscopic adrenalectomy with perioperative glucocorticoid coverage (100 mg hydrocortisone administered IV and again 8 hours later). Conclusion: Mild autonomous cortisol secretion is a term used to describe biochemical evidence of abnormal cortisol secretion in patients with adrenal incidentaloma, but without the classical external manifestations of overt CS, such as central muscle weakness, adipose tissue redistribution, and skin fragility. The management of patients with an incidentally discovered adrenal adenoma who do not have overt Cushing’s syndrome but who have MACS is more controversial as the available studies comparing outcomes of adrenalectomy vs conservative management have been generally small. It is associated with an increased risk of Type 2 diabetes mellitus, HBP, obesity, dyslipidemia, and global cardiovascular risk. Therefore, it is of great importance to correctly identify these patients. There are different tests for the screening of hypercortisolism. However, in the absence of a single test considered as the gold standard, it is necessary to combine the different tests to reach an adequate diagnostic capacity. The indication of surgery in ACS patients should be based mainly on the hormonal evaluation and the comorbidities potentially mediated by cortisol. Presentation: 6/1/2024

THU213 Posterior Reversible Encephalopathy Syndrome As A Rare Presentation Of ACTH-dependent Cushing Syndrome In A Pediatric Patient

Abstract Disclosure: E.E. Bell-Sambataro: None. C. Tatsi: None. P. Chittiboina: None. S.A. Bowden: None. Background: Cushing disease (CD), caused by ACTH-secreting pituitary adenoma, is the most common cause of Cushing Syndrome (CS) in children > 5 years of age. Hypertension is reported in up to 50% of pediatric cases with CS. We report a challenging pediatric case with a rare presentation of hypertensive emergency associated with CD. Clinical Case: A 6-year-old female with 3 month-history of rapid weight gain (8 kg), round face, and hypertrichosis presented to emergency department for abdominal pain from nephrolithiasis and was noted to have severe hypertension. While in ED, she developed status epilepticus and altered mental status. Brain MRI findings were consistent with posterior reversible encephalopathy syndrome (PRES). Her hypertensive encephalopathy gradually improved with aggressive anti-hypertensive and anti-epileptic therapy. Further studies confirmed hypercortisolism with markedly elevated urine free cortisol of 1288 ug/day (<18 ug/day) and lack of diurnal variation of serum cortisol (8 AM cortisol of 47.9 ug/dL, midnight cortisol of 20.3 ug/dL). ACTH level of 23 pg/mL suggested ACTH-dependent CS. Low dose (1 mg) dexamethasone suppression test (DST) failed to suppress 8 am cortisol (31.4 ug/dL). High dose DST (120 mcg/kg) suppressed serum cortisol to 67%- borderline threshold for CD, likely due to increased dexamethasone clearance by anticonvulsant. Pituitary MRI did not reveal a visible lesion. Desmopressin stimulation test showed stimulation of ACTH by 700% and cortisol by 160% suggesting pituitary source. Inferior petrosal sinus sampling showed a mildly increased gradient in central to peripheral plasma ACTH of 1.7 at baseline (>2) and post-stimulation of 2.5 (>3). ACTH gradient did not reach cutoffs for pituitary source, likely due to insufficient catheterization of petrosal sinus from anatomically small blood vessels. Given her severity, she underwent surgical pituitary exploration. Postoperative morning cortisol was <5 mcg/dL, with decreased midnight salivary cortisol level obtained 2 months after surgery. She developed post-operative central hypothyroidism but did not have diabetes insipidus. She had a 4 kg weight loss with increased height percentile 5 months after surgery and remains under close monitoring. Conclusion: PRES is a clinical-radiographic disorder characterized by seizures, encephalopathy with neuroimaging findings of reversible cortical and subcortical vasogenic edema. Hypertension induced by marked hypercortisolism precipitated by pain is likely the etiologic factor. Prompt recognition and treatment of PRES are crucial to prevent further life-threatening complications and permanent neurological damage. Early diagnosis and treatment of CD are critical to prevent associated morbidities. Pituitary exploration by expert neurosurgery team should be considered in patients with MRI-negative CD. Presentation: Thursday, June 15, 2023

Successful Adrenal Vein Sampling Using Dexamethasone Premedication in Patients With Iodine Contrast Media Allergy.

ContextPreparation of patients with iodine contrast media (ICM) allergy who require adrenal vein sampling (AVS) to establish source of aldosterone excess of their confirmed primary aldosteronism (PA) is controversial. Usual premedication with high-dose prednisone can interfere with cortisol determinations, possibly altering the aldosterone to cortisol ratios for the identification of lateralized aldosterone excess.ObjectiveWe aimed to evaluate the efficacy and safety of premedication with high-dose dexamethasone to perform AVS in patients with ICM.MethodsOne hundred and seventy-seven consecutive patients with confirmed PA who underwent bilateral simultaneous basal and post-ACTH bolus AVS at our center between January 2010 and December 2020 were retrospectively analyzed for history of ICM allergy. A total of 7 patients (4%) with previous allergic reactions to ICM were prepared with 3 doses of 7.5 mg dexamethasone premedication rather than the usual 50 mg of prednisone.ResultsNo breakthrough allergic reactions were reported in the 7 patients. Despite adequate serum cortisol suppression following dexamethasone, the basal and post-ACTH selectivity index were respectively > 2 and > 5 bilaterally in all patients, confirming adequate cannulation of both adrenal veins. Four patients had lateralized ratios (A/C ratio > 2 basally and > 4 post-ACTH), while 3 had bilateral source during AVS study. In the 3 patients undergoing unilateral adrenalectomy for lateralized source and contralateral suppression and adequate follow-up data, cure of PA was achieved at mean 58 months postoperatively.ConclusionAVS using dexamethasone premedication is safe and accurate for diagnosing the source of aldosterone excess in patients with PA and ICM allergy.

A Comprehensive Approach to Predicting the Outcomes of Transsphenoidal Endoscopic Adenomectomy in Patients with Cushing's Disease.

Persistent and recurrent hypercortisolism after transsphenoidal endoscopic surgery (TSS) is considered to be an urgent issue prompting the search for Cushing’s disease (CD) remission predictors. The goal was to find a combination of predictors that can forecast the remission of CD after TSS. A total of 101 patients with CD who had undergone TSS were included. One year after surgery, CD remission status was evaluated. Preoperative pituitary magnetic resonance imaging (MRI) data, preoperative results of a high-dose dexamethasone suppression test (HDDST) and morning serum cortisol level collected 24 h after TSS (24 h MSeC) were compared in patients with and without remission of hypercortisolism. Remission one year after TSS was confirmed in 63 patients. CD remission predictors one year after TSS were: adenoma size ≥ 3 mm in the absence of invasive growth and the suppression of serum cortisol ≥ 74% in the HDDST, 24 h MSeC ≤ 388 nmol/L. A total of 38 patients had three favorable values of detected predictors; all of them had CD remission one year after TSS. With long-term follow-up, 36 of them remained in remission. Patients who had no one favorable predictor had no remission of hypercortisolism one year after TSS. Our data confirmed the prospects of using a combination of selected predictors to forecast CD remission after TSS.

Prediction of the transsphenoidal endoscopic adenomectomy results in patients with cushing’s disease

Introduction. Transsphenoidal adenomectomy (TSA) is the method of choice in the treatment of Cushing’s disease (CD), but remission of hypercorticism cannot be achieved in all patients. The search for predictors of CD remission after TSA remains to be an important challenge in the endocrinology today.Aim. To study the preoperative and postoperative data of patients with CD to identify the predictors of hypercorticism remission after TSA.Materials and methods. 101 patients with confirmed CD after TSA were included. One year after operation all patients were examined for the presence of hypercorticism remission and divided into two groups: with CD remission and its absence. In both groups’ preoperative pituitary magnetic resonance imaging (MRI) data, the results of preoperative high dose dexamethasone suppression test (HDDST) and the results of serum cortisol collected in the morning 2–3 days after surgery were compared.Results. One year after TSA, CD remission was confirmed in 63 patients (62.4%), whereas in 38 patients (37.6%) hypercortisolism persisted. Favorable predictors of CD remission were: the adenoma size > 3 mm without the invasive growth according to pituitary MRI (specificity 82.4%, sensitivity 82.8%), serum cortisol suppression ≥ 74% in preoperative HDDST (specificity 81.5%, sensitivity 86.3%), morning serum cortisol level in 2–3 days after surgery ≤ 388 nmol/l (specificity 79.3%, sensitivity 97.4%).Conclusions. Pituitary MRI data, the results of preoperative HDDST and morning serum cortisol in the 2–3 days after surgery can be used as predictors of CD remission.

High-dose dexamethasone suppression test is inferior to pituitary dynamic enhanced MRI in the differential diagnosis of ACTH-dependent Cushing's syndrome.

The differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome remains a challenge in clinical practice. The present study was aimed at assessing the diagnostic performance of pituitary dynamic contrast-enhanced magnetic resonance imaging (dMRI), high-dose dexamethasone suppression test (HDDST), and a combination of both tests for patients with ACTH-dependent Cushing's syndrome. A total of 119 consecutive patients with ACTH-dependent Cushing's syndrome confirmed surgically were enrolled: 101 with proven Cushing's disease and 18 with proven ectopic ACTH syndrome. All patients underwent pituitary dMRI and HDDST. The sensitivity and specificity of pituitary dMRI, HDDST, and a combination of both tests were determined. The sensitivity and specificity of pituitary dMRI for diagnosing Cushing's disease were 80.2 and 83.3%, respectively, with a positive predictive value of 96.4%. The sensitivity and specificity of HDDST were 70.3 and 77.8%, respectively, with positive predictive value of 94.7%. A combination of both tests showed that the combined criteria of more than 50% suppression of serum cortisol on HDDST and a positive pituitary dMRI finding yielded a high specificity of 94.4 and sensitivity of 59.4%. The combined criteria of more than 68% suppression on HDDST and/or a positive pituitary dMRI finding yielded a sensitivity of 86.1% and specificity of 83.3%. Pituitary dMRI was superior to HDDST in the differential diagnosis of ACTH-dependent Cushing's syndrome. HDDST is recommended in combination with pituitary dMRI to establish a diagnosis process because of the significantly increased specificity with the combination.

Impaired dexamethasone resorption in two patients with pseudo‐Cushing after bariatric surgery: Implications for immunosuppressive treatment

Two cases of middle-aged female patients treated by gastric bypass surgery for weight loss presented to our clinic for a follow-up examination 3-6 months after the surgical procedure (a mini gastric bypass and a modified single anastomosis sleeve-ileostomy). In both patients increased ACTH levels and either high serum cortisol or an increased urinary cortisol excretion was apparent and triggered further endocrine testing. Serum cortisol could not be suppressed adequately by 2 and 4 mg dexamethasone in the standardized oral overnight suppression test while midnight salivary cortisol dropped well below the desired cut-off. This led to the hypothesis of an impaired dexamethasone resorption and could be further substantiated by suppression of serum cortisol below the cut-off by an intravenous dexamethasone application. The data presented point to an impairment of enteral synthetic corticosteroid resorption in patients after gastric bypass surgery and could be of importance for individuals in need for immunosuppressive treatment. In view of the growing number of bariatric procedures, pharmacokinetics of corticosteroids and other drugs should be tested in clinical trials.

An observational study assessing high dose opioid prescribing and associated adrenal insufficiency

BackgroundLong-term opioid use is known to affect endocrine function, with case reports indicating an association with adrenal insufficiency.AimThis study aims to investigate long-term, high-dose opioid use (≥80mg morphine or equivalent per day) at a Suffolk (UK) General Practice and its effect on adrenal function.MethodFrom a practice list of 18,300, retrospective data was collected for patients prescribed high-dose opioids for non-cancer pain for at least three months on current repeat prescription. Patient demographics and prescribing information were collected using SystmOne. Cortisol levels in the high-dose opioid patients, and short synacthen testing if indicated, were performed.ResultsThe 35 identified patients (0.2% of practice list) were predominantly female (77%) ≥70 years old (37%), and taking opioids prescribed for osteoarthritis or back pain (77%). 6% were prescribed >280mg morphine or equivalent per day, with one patient prescribed 705 mg. Routine evaluation for development of adrenal suppression and subsequent management was poor. 31% (11 of 35) had developed symptoms potentially indicative of adrenal insufficiency. One of these patients was among the 21% (7 of 35) with suppressed serum cortisol. Adrenal insufficiency secondary to opioids was confirmed in one patient using short synacthen testing. There was no statistical difference in either opioid dose or months of use for those with or without early morning cortisol suppression.ConclusionThe investigation highlights both the considerable use of high-dose opioids for non-malignant pain and their apparent association with adrenal suppression, demonstrating the need for formal guidelines to aid recognition and diagnosis.

Prognostic markers of remission of cushing's disease after transsphenoidal endoscopic adenomektomii.

Aim. To study the role of prognostic oral high-dose dexamethasone suppression test (HDDST) and pituitary MRI in the prognosis of Cushing’s disease (CD). remission after transsphenoidal endoscopic surgery (TSS). Material and methods. 59 patients with Cushing’s disease (9 men, 50 women, mean age 40 years (15-72) underwent TSS were included. Before the TSS HDDST and pituitary MRI were performed in all cases. Postoperative examination was done one year after surgery. Remission criteria were: combination of normal midnight serum cortisol levels, normal 24 hour urine free cortisol (UFC) excretion and serum cortisol suppression less than 50 nmol/l in 1-mg dexamethasone test or secondary adrenal insufficiency (the need for glucocorticoid replacement). The optimal threshold value of serum cortisol suppression in the HDDST for prediction of CD remission after TSS was calculated by ROC-analysis. Results. One year after surgery CD remission was confirmed in 39 patients, whereas in 20 patients hypercortisolism persisted. The optimal threshold value of serum cortisol suppression in the HDDST for prediction of CD remission after TSS was 72%. Test’s sensitivity and specificity were 82% and 84%, respectively. The probability of wrong prediction was 17% (p=0,0001). In our study, the results of TSS did not correlate with MRI adenoma size.

Severe Hypercortisolism with Hypokalemic Alkalosis Mimicking Ectopic Cushing Syndrome in a Patient with Cushing Disease Due to Pituitary Microadenoma.

Severe Hypercortisolism with Hypokalemic Alkalosis Mimicking Ectopic Cushing Syndrome in a Patient with Cushing Disease Due to Pituitary Microadenoma.

Síndrome de Cushing exógeno e insuficiencia adrenal relacionada con consumo de producto natural

La insuficiencia adrenal es una endocrinopatía cuya principal causa se debe a la deficiencia en la producción de hormona adrenocorticotrópica, generalmente explicada por factores iatrogénicos y en menor número de casos al defecto primario de la glándula adrenal (enfermedad de Adisson). Su diagnóstico y la búsqueda de una etiología específica es muy importante, dado las implicaciones a largo plazo que conlleva por necesidad de suplencia hormonal, manejo en condiciones críticas, riesgo de muerte y compromiso de la actividad laboral. Presentamos el caso de una mujer quien consultó por ganancia excesiva de peso, signos de hipercortisolismo e hipertensión, se documentó una probable fuente exógena de esteroides, encontrando un cortisol sérico suprimido. Dos años antes estaba recibiendo artrivid PLUS, un producto natural para el manejo del dolor articular. Después de suspender ésta medicación presentó síntomas compatibles con insuficiencia adrenal, requiriendo el reinicio de prednisolona, con mejoría clínica y logrando su desmonte gradual posterior

PS 11-28 ADRENAL INSUFFICIENCY UNDER STANDARD DOSAGE OF POST-OPERATIVE GLUCOCORTICOID REPLACEMENT AFTER HEMI-LATERAL ADRENALECTOMY FOR CUSHING'S SYNDROME

Objective: The patients who have undergone hemi-lateral adrenalectomy for Cushing's syndrome become steroid-dependent. Therefore, sufficient replacement of glucocorticoid is needed in the post-operative period, though, determination of the adequate dosage for post-operative glucocorticoid replacement is difficult. Design and Method: A 62 year old Japanese woman presented hypertension 5 years ago and since then she showed loss of muscle strength and edematous face. Because facial edema, general fatigue, and muscle weakness were progressively worsened, she consulted us. Radiological examinations detected a 30 mm left adrenal mass. Endocrinological evaluations revealed an elevated urinary free cortisol (114 μg/day), without suppression of serum cortisol in midnight and with suppression of ACTH (<1.0 pg/ml) in the morning. After overnight 8 mg dexamethasone challenge, the serum cortisol level was maintained at 34.4 μg/dl and ACTH was <1.0 pg/ml. 131-IAdosterol scintigraphy revealed higher uptake in the left adrenal mass. Under a diagnosis of Cushing's syndrome due to left adrenal adenoma, laparoscopic left adrenalectomy was performed and 200 mg/day of hydrocortisone was administrated during peri-operative days. The dose was reduced gradually and she discharged with 30 mg/day of hydrocortisone. Results: She was transferred to emergency unit because of the symptoms of adrenal insufficiency on post-operative day 15. After an infusion of hydrocortisone 200 mg, the symptoms were immediately disappeared. The dose of hydrocortisone was slowly decreased under hospitalization; however, reduction of hydrocortisone lower than 60 mg/day was difficult because of nausea and fatigue. Hydrocortisone was gradually reduced and she discharged on post-operative day 92 at the dose of 30 mg/day. Conclusions: The glucocorticoid receptor would be down-regulated due to long-term exposure to excessive cortisol before surgery. Complicated heart failure was suggested to reduce absorption of hydrocortisone from intestine. In such cases, we should consider enough hydrocortisone administration with a dose of more than 30 mg/day to avoid adrenal insufficiency after surgery of Cushing's syndrome.

Management of Cushing's disease: a single-center experience.

The purpose of this study was to review therapeutic outcomes and comorbidities of patients with Cushing's disease (CD) in a single center. We conducted a retrospective study of 33 patients with CD undergoing transsphenoidal surgery from January 2007 to February 2014 (27 females and 6 males, median age 38 years, range 18-71 years). The diagnosis of Cushing's syndrome was established on the basis of the patient's history, characteristic clinical features, and laboratory data including an elevated 24-h urinary free cortisol level, lack of serum cortisol suppression after dexamethasone suppression tests and an elevated midnight cortisol level. In 28/33 patients, the tumor was visualized on MR of the sellar region, while in 5 it was diagnosed using an inferior petrosal sinus sampling. Out of the 33 patients, 10 had macroadenoma and the remaining 23 had microadenoma. Twenty-one patients (63.6%) had hypertension, 17 (51.5%) dyslipidemia, and 7 (21.2%) had type 2 diabetes or impaired glucose tolerance. The median follow-up period was 28 months. Remission after transsphenoidal surgery was achieved in 78.8% of patients, while 7 patients failed to achieve disease remission. Those patients were treated with second-line treatment modalities (second operation, radiotherapy, bilateral adrenalectomy, and/or ketoconazole). One patient rejected all the treatment modalities after surgery. Cumulative remission after all the treatment modalities was achieved in 87.9% patients. Patients with Cushing's disease should be managed in centers with much experience due to high patient load. In our Center, the remission of the disease has been achieved in 78.8% of the patients following transsphenoidal surgery. Multimodal treatment which included radiotherapy and medical treatment led to biochemical remission of the disease in 87.9% of patients.

Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease.

BackgroundMeasurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level.MethodsWe performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured.ResultsFifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively.ConclusionSignificant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.

Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently.

A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses.

Serum cortisol concentration in horses with heaves treated with fluticasone proprionate over a 1 year period

The purpose of this study is to measure the effect of long-term administration of inhaled fluticasone proprionate on cortisol concentrations in heaves-affected horses. Eleven horses with heaves were treated with fluticasone at least once daily at dosages required to improve lung function or with antigen avoidance alone for 1 year. Morning serum cortisol was measured before and after 10, 30, 110, 190, 230, 280, and 320 days of treatment. Cortisol was also measured in the afternoon of day 330. Cortisol was significantly lower in the Fluticasone group on days 30, 110, and 190 when compared with the Antigen avoidance group. Cortisol measured on day 330 was also significantly lower in the Fluticasone group. Results indicate that inhaled fluticasone, when administered at therapeutic dosages, can significantly suppress serum cortisol concentrations for 8–24 h. The clinical significance of this finding remains to be ascertained, as no clinical signs were associated with this cortisol suppression.

Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests

To evaluate the diagnostic performance of four different tests in order to differentiate between Cushing's disease (CD) and pseudo-Cushing's syndrome (PCS). In this prospective study, a total of 73 patients with clinical features of hypercortisolism and insufficient suppression of serum cortisol after 1 mg overnight dexamethasone and/or an elevated excretion of cortisol in 24-h urine samples were included. The circadian rhythm of serum cortisol levels as well as midnight serum cortisol (MserC) levels were assessed in all 73 patients. Late-night salivary cortisol (LNSC) concentrations were obtained in 44 patients. The dexamethasone-CRH (Dex-CRH) test was performed in 54 patients. FIFTY-THREE PATIENTS WERE DIAGNOSED WITH CD AND SUBSEQUENTLY TREATED. TWENTY PATIENTS WERE CLASSIFIED AS HAVING PSC. SERUM CORTISOL CIRCADIAN RHYTHM: the diurnal rhythmicity of cortisol secretion was retained in PCS. A cortisol midnight:morning ratio of >0.67 is highly suggestive of CD (positive predictive value (PPV) 100% and negative predictive value (NPV) 73%). MserC concentration >243 nmol/l has a PPV of 98% in predicting true CD (NPV 95%). LNSC level >9.3 nmol/l predicted CD in 94% of patients (NPV 100%). Dex-CRH test: after 2 days of dexamethasone suppression, a CRH-stimulated cortisol level >87 nmol/l (T=15 min) resulted in a PPV of 100% and an NPV of 90%. The Dex-CRH test as well as a single measurement of cortisol in serum or saliva at late (mid-) night demonstrated high diagnostic accuracy in differentiating PCS from true CD.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of fluticasone furoate, a novel inhaled corticosteroid, in children aged 5-11 years with persistent asthma: A randomized trial.

This multi-center, randomized, double-blind, placebo-controlled, two-way crossover study characterized the safety, tolerability, pharmacokinetics, and pharmacodynamics of fluticasone furoate (FF) in children (5-11 years) with persistent asthma. Twenty-seven children received inhaled FF 100 µg or placebo via the ELLIPTA™ dry powder inhaler once daily for 14 days, with a ≥7 day washout period. Adverse events (AEs) were reported by eight (31%) and four (16%) subjects during FF 100 µg and placebo treatment, respectively. Headache was reported by three subjects during FF 100 µg treatment and by no subjects during placebo treatment, all other AEs were reported by only one subject on either treatment; there were no serious AEs. Following repeat dosing, the arithmetic mean (SD) FF Cmax was 26.71 pg/mL (9.16) at 31 minutes post-dose. Arithmetic mean (SD) FF AUC(0-t) was 121.44 pg h/mL (83.04). Arithmetic mean values for weighted mean (SD) serum cortisol (0-12 hours) on day 14 were 56.49 (16.51) and 67.57 (20.66) ng/mL for FF 100 µg and placebo, respectively. No clinically significant effect of FF on serum cortisol levels was observed. FF was well tolerated. Pharmacokinetic profiles were well defined and did not differ between age groups in the study population, and no clinically significant suppression of serum cortisol was observed.

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Doses of GW870086: Two Randomised Studies

Aim and Methods: We conducted two studies in healthy male subjects to assess the effect on serum cortisol levels of the novel inhaled corticosteroid GW870086, dosed at 6 mg, 12 mg and 15 mg/day (dry powder inhaler; NCT00549497) for 3 days and 5 mg and 8.75 mg/day (nebules; NCT01160003) for 14 days. Results: In the 3-Day Study, the greatest suppression of serum cortisol weighted mean (0-24 hour) of GW870086, compared with placebo, was observed on Day 1 (29% suppression at the 15 mg dose). In the 14-Day Study, the greatest suppression was 15% for GW870086 5 mg. None of these values was considered clinically significant. After 3 days’ dosing, GW870086 was absorbed slowly (tmax: 0.8-3.5 hours) and eliminated with a t1/2 of 22.7 hours; the highest systemic exposure (AUC) was 26.7 ng.hour/mL. After 14 days, GW870086 tmax was 0.3-0.4 hours and t1/2 25.0-29.6 hours; the highest AUC was 16.7 ng.hour/mL. No safety issues were identified in these studies. Conclusion: At estimated therapeutic and supratherapeutic doses, which achieved high exposure (AUC) in both studies, GW870086 did not exhibit the usual level of hypothalamic-pituitary-adrenal axis suppression that would be expected with traditional inhaled corticosteroids.

Systemic Effects and Safety of Triamcinolone-Impregnated Nasal Packing after Endoscopic Sinus Surgery: A Randomized, Double-Blinded, Placebo-Controlled Study

Steroid-infused absorbable nasal dressings after endoscopic sinus surgery (ESS) have been used to improve wound healing and to reduce the recurrence of polyps. However, their systemic effects are not well known. The purpose of this study was to evaluate the systemic effects and safety of steroid-impregnated absorbable nasal packing after ESS. Patients who underwent bilateral ESS for chronic rhinosinusitis were recruited and randomized into two groups. Ten patients in the triamcinolone (TA) group received a TA (20 mg)-soaked bioabsorbable dressing in both nasal cavities while 10 patients in the control group took saline-impregnated dressing in both nasal cavities. Nasal dressings were not removed until postoperative day 10. Serum cortisol, 12-hour urine cortisol, serum adrenal-corticotropic hormone (ACTH), and serum osteocalcin were measured preoperatively and on postoperative days 2 and 10. Serum cortisol levels were checked 1 day after surgery additionally, while urine cortisol levels were not checked at postoperative day 10. All 20 patients completed this study. The serum cortisol levels were significantly suppressed at postoperative days 1 and 2 in the TA group. Serum ACTH and 12-hour urine cortisol levels were lower 2 days after surgery in the TA group, although these changes were not statistically significant. There were no differences in all other parameters between the TA and control groups on postoperative day 10. TA-impregnated nasal dressings suppress serum cortisol levels during the early postoperative period. This systemic effect was recovered gradually and normalized 10 days after the operation.