Dexamethasone Suppression Test Results Research Articles

Choroidal Thickness in Mild Autonomous Cortisol Secretion.

To evaluate the patients with mild autonomous cortisol secretion (MACS) by means of choroidal thickness (CT) and also investigate whether CT may be a diagnostic tool in the management of MACS or not. Twenty-seven patients with MACS and 25 age-sex-matched healthy controls were enrolled in this cross-sectional comparative study. All the participants underwent CT measurement by using Spectralis optical coherence tomography (Heidelberg Engineering, Heidelberg, Germany) with enhanced deep imaging mode at the subfoveal, 500-1000-1500 µm nasal and 500-1000-1500 µm temporal to the foveola. The groups were similar in terms of spherical equivalence, age and axial lengths. The mean CT was significantly thicker in patients with MACS than controls in all measurement quadrants (p<0.001). There was no significant correlation between CT, size of the adenoma, basal cortisol, 1mg dexamethasone suppression test, salivary cortisol, 24-hour total urine-free cortisol, ACTH and DHEAS levels. However, 2 mg dexamethasone suppression test results were found to be significantly correlated with CT in temporal 500-1000 and 1500 µm quadrants (r=0.436, p=0.023, r=0.443, p=0.021 and r=0.488, p=0.010, respectively). Five (18.5%) eyes had pachychoroid pigment epitheliopathy in the MACS group. CT increases in patients with MACS and those tend to have pachychoroid pigment epitheliopathy more frequent than healthy individuals. A thicker choroid in the patients with MACS may be a novel biomarker both as a diagnostic tool for the degree of hypercortisolemia and cortisol-related comorbidity.

Are nonfunctioning adrenal incidentalomas really nonfunctioning? A retrospective single-center study.

In patients with adrenal incidentaloma (AI), cortisol levels <1.8 μg/dL after a dexamethasone suppression test (DST) are considered nonfunctioning in terms of autonomic cortisol hypersecretion (ACH). We aimed to investigate the frequency of hypertension (HT) in patients with nonfunctioning AI. Individuals with AI who were admitted to the endocrinology clinic between September 2020 and May 2023 were included as the patient group, and age- and gender-matched individuals admitted with thyroid nodules between the same dates were included as the control group. The participants included 123 AI patients who fulfilled the study criteria and 114 age- and sex-matched patients with thyroid nodules (age: 53.0±10.9 years and 52.9±7.4 years, respectively, p=0.98; female/male distribution: 90/33 and 91/23, respectively, p=0.28). The frequency of HT was higher in the AI group than in the control group (50.4% and 31.6%, respectively, p=0.004). The frequency of HT was significantly lower in patients with a DST result <0.87 μg/dL compared to those with a DST result ≥0.87 μg/dL (42.6% and 66.1%, respectively, p=0.009). The factors affecting HT were analyzed using binary logistic regression analysis; it was found that age [β=0.068, odds ratio (OR); 1.07 (95% confidence interval (CI); 1.02-1.12), p=0.004] and DST [β=1.18, OR; 3.24 (95% CI); 1.02-10.34, p=0.047] were independent factors. The frequency of HT increases in patients with nonfunctioning AI. The reason for this increase may possibly be the presence of ACH, which is not detected by the cut-off values we currently use to exclude ACH.

Development and Validation of Liquid Chromatography/Stable Isotope-Dilution Tandem Mass Spectrometry Method for Measurement of Dexamethasone, Total Cortisol and Free Cortisol in Human Plasma

Background Cortisol plays a role in the regulation of metabolic homeostasis. Dexamethasone is a powerful synthetic glucocorticoid that acts as an anti-inflammatory and immunosuppressive agent. Plasma free cortisol, which has a low concentration in the blood, is the cortisol fraction that provides biological activity. It is emphasized that measurement of dexamethasone, total and free cortisol levels can directly affect the results of dexamethasone suppression test, which is routinely used to exclude endogenous hypercortisolemia in patients with adrenal adenoma, and is important in differential diagnosis.&#x0D; Purpose In this study, a precise and rapid method was developed for the measurement of dexamethasone, total and free cortisol levels in plasma samples, besides demonstrating the clinical applicability of the method with samples from adrenal adenoma patients. &#x0D; Methods Method optimization studies were performed using liquid chromatography-tandem mass spectrometry with stable isotope dilution-multiple reaction monitoring. &#x0D; Results The assay demonstrated a good linear dynamic range of 0.5–20 μg/L, 5–200 μg/L and 0.5–100 μg/L for dexamethasone, total and free cortisol, respectively. The values for intra- and inter-day precisions of analytes were ≤6.9% with the accuracies ranging from 91.6% to 113.0%.&#x0D; Conclusion Measurement of these parameters can be used reliably to diagnose diseases causing hypercortisolemia.

Influence of cortisol cosecretion on non-ACTH-stimulated adrenal venous sampling in primary aldosteronism: a retrospective cohort study.

Cortisol measurements are essential for the interpretation of adrenal venous samplings (AVS) in primary aldosteronism (PA). Cortisol cosecretion may influence AVS indices. We aimed to investigate whether cortisol cosecretion affects non-adrenocorticotrophic hormone (ACTH)-stimulated AVS results. Retrospective cohort study at a tertiary referral center. We analyzed 278 PA patients who underwent non-ACTH-stimulated AVS and had undergone at least a 1-mg dexamethasone suppression test (DST). Subsets underwent additional late-night salivary cortisol (LSC) and/or 24-h urinary free cortisol (UFC) measurements. Patients were studied from 2013 to 2020 with follow-up data of 6 months following adrenalectomy or mineralocorticoid antagonist therapy initiation. We analyzed AVS parameters including adrenal vein aldosterone/cortisol ratios, selectivity, lateralization (LI) and contralateral suppression indices and post-operative ACTH-stimulation. We classified outcomes according to the primary aldosteronism surgical outcome (PASO) criteria. Among the patients, 18.9% had a pathological DST result (1.9-5 µg/dL: n = 44 (15.8%); >5 µg/dL: n = 8 (2.9%)). Comparison of AVS results stratified according to the 1-mg DST (≤1.8 vs >1.8 µg/dL: P = 0.499; ≤1.8 vs 1.8 ≤ 5 vs >5 µg/dL: P = 0.811) showed no difference. Lateralized cases with post DST serum cortisol values > 5 µg/dL had lower LI (≤1.8 µg/dL: 11.11 (5.36; 26.76) vs 1.9-5 µg/dL: 11.76 (4.9; 31.88) vs >5 µg/dL: 2.58 (1.67; 3.3); P = 0.008). PASO outcome was not different according to cortisol cosecretion. Marked cortisol cosecretion has the potential to influence non-ACTH-stimulated AVS results. While this could result in falsely classified lateralized cases as bilateral, further analysis of substitutes for cortisol are required to unmask effects on clinical outcome.

Can serum basal cortisol values predict successful operations for bariatric surgery patients?

Obesity is a chronic metabolic disease declared as the 21st century pandemic by the World Health Organization. Obesity has become an alarming situation for society, and it has to be treated. If the appropriate criteria are met by patients, bariatric surgery is an effective treatment method that provides weight loss in a short time. There are no definitive criteria regarding which groups of patients and characteristics may benefit most from bariatric surgery. In this study, we evaluate whether serum basal cortisol levels can predict successful outcomes of bariatric surgery and whether there is any difference in outcome between diabetic and non-diabetic patients. This observational study included 244 obese patients who had undergone laparoscopic sleeve gastrectomy (LSG). Preoperative and postoperative 6-month weight, body mass index (BMI), serum basal cortisol, fasting plasma glucose, 1-mg dexamethasone suppression test (DST) results, and Type 2 Diabetes Mellitus (T2D) history were recorded. We analyzed the patients first by dividing them into two groups as excessive weight loss (%EWL) ≥50% and %EWL< 50%, and then into two groups as diabetic and nondiabetic patients. The mean age of patients with %EWL≥ 50% was found to be statistically significantly lower than that of patients with %EWL< 50% [39 (19-60) vs. 47 (36-61) years; p=0.046]. While there was no significant difference in basal cortisol values (p=0.513), DST results were statistically significantly lower in patients with %EWL≥ 50% than patients with %EWL< 50% [0.6 (0.1-2.1) vs. 0.8 (0.7-1.1); p=0.040]. In obese patients undergoing LSG, serum basal cortisol level may not predict the success of operation. However, the result of 1 mg DST may predict the operation success.

Late-night salivary cortisol and cortisone should be the initial screening test for Cushing's syndrome.

Endogenous Cushing’s syndrome (CS) poses considerable diagnostic challenges. Although late-night salivary cortisol (LNSC) is recommended as a first-line screening investigation, it remains the least widely used test in many countries. The combined measurement of LNSC and late-night salivary cortisone (LNS cortisone) has shown to further improve diagnostic accuracy. We present a retrospective study in a tertiary referral centre comparing LNSC, LNS cortisone, overnight dexamethasone suppression test, low-dose dexamethasone suppression test and 24-h urinary free cortisol results of patients investigated for CS. Patients were categorised into those who had CS (21 patients) and those who did not (33 patients). LNSC had a sensitivity of 95% and a specificity of 91%. LNS cortisone had a specificity of 100% and a sensitivity of 86%. With an optimal cut-off for LNS cortisone of >14.5 nmol/L the sensitivity was 95.2%, and the specificity was 100% with an area under the curve of 0.997, for diagnosing CS. Saliva collection is non-invasive and can be carried out at home. We therefore advocate simultaneous measurement of LNSC and LNS cortisone as the first-line screening test to evaluate patients with suspected CS.

Primary aldosteronism with mild autonomous cortisol secretion increases renal complication risk.

In primary aldosteronism (PA), renal impairment has been identified as an important comorbidity. Excess cortisol production also may lead to renal damage; thus, concomitant mild autonomous cortisol secretion (MACS) may predispose PA patients to renal disorders. However, there is limited evidence to support this claim. Therefore, this study aimed to determine whether the concurrence of MACS and PA increases the risk of renal complications. This study is a retrospective cross-sectional study. A total of 1310 patients with PA were stratified into two groups according to 1 mg dexamethasone suppression test (DST) results (cut-off post-DST serum cortisol 1.8 µg/dL): MACS (n = 340) and non-MACS (n = 970). The prevalence of renal complications was compared between the group. We also performed multiple logistic regression analysis to determine factors that increase the risk for renal complications. The prevalence of lowered estimated glomerular filtration rate (eGFR) and proteinuria was nearly twice higher in the MACS group than in the non-MACS group. Not only plasma aldosterone concentration (PAC) but also the presence of MACS was selected as independent factors that were associated with the two renal outcomes. The risk of lower eGFR or proteinuria in patients who had MACS and higher levels PAC was several folds higher than in those who had an absence of MACS and lower levels of PAC. MACS is an independent risk factor for renal complications in patients with PA, and MACS concomitant with higher aldosterone secretion in PA patients causes an increase in the risk of developing renal complications.

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.

46, XY 5-Alpha Reductase Deficiency in a 36-Year-Old Phenotypic Female Patient

46, XY 5-Alpha Reductase Deficiency in a 36-Year-Old Phenotypic Female Patient

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 &gt; 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.

Case Report: An Unusual Case of Ectopic ACTH Syndrome Caused by Mediastinal Paraganglioma

Ectopic adrenocorticotrophic hormone (ACTH) syndrome is not common, which is more unusual when caused by paraganglioma. We herein present a 40-year-old Chinese male who was diagnosed with ACTH-dependent Cushing’s syndrome. However, the localization of the ACTH source was troublesome due to the inconsistent results of the high-dose dexamethasone suppression test and the desmopressin stimulation test. Bilateral inferior petrosal sinus sampling was performed, and ectopic ACTH syndrome was diagnosed. After 68Ga-DOTATATE-PET/CT and 18F-FDG-PET/CT were performed, it was localized in the anterior mediastinum. Post-operation histopathology demonstrated an ACTH-secreting mediastinal paraganglioma. The patient obtained complete clinical remission after a mediastinal tumorectomy.

Accuracy of the dexamethasone suppression test for the prediction of autonomous cortisol secretion-related comorbidities in adrenal incidentalomas.

The aim of this study was to evaluate the diagnostic accuracy of the 1mg dexamethasone suppression test (DST) for the prediction of autonomous cortisol secretion (ACS)-related comorbidities in patients with adrenal incidentalomas (AIs). This was a retrospective multicenter study. We recruited patients with AI/s ≥ 1cm, excluding those who, during the study, were found during theextensionstudy of an extra-adrenal cancer, with a known diagnosis of hereditary syndromes characterized by adrenal tumors, those presenting with overt hormonal excess syndromes, and those in whom the DST results were missing. A total of 823 patients met the inclusion criteria. Based on the 1.8, 3.0, and 5.0µg/dl post-DST cortisol thresholds, the prevalence of ACS was 33.5%, 13.7%, and 5.6%, respectively. The prevalence of hypertension (OR = 1.8, 95% CI = 1.3-2.4), diabetes (OR = 1.6, 95% CI = 1.2-2.2), and dyslipidemia (OR = 1.4, 95% CI = 1.0-1.9) was higher with cortisol post-DST ≥ 1.8µg/dl; the prevalence of hypertension (OR = 2.1, 95% CI = 1.4-3.3) and diabetes (OR = 1.7, 95% CI = 1.1-2.6) was higher with values ≥ 3.0µg/dl; and the prevalence of hypertension (OR = 2.0, 95% CI = 1.0-3.7) was higher with levels ≥ 5.0µg/dl. However, the diagnostic accuracy of the DST for the prediction of cardiometabolic comorbidities in patients with AIs was poor, with areas under the ROC curve < 0.61. The DST is a poor predictor of cardiometabolic comorbidities in patients with AIs regardless of the cortisol cut-off values applied. This finding suggests that the diagnosis of ACS should not be based solely on the results of the DST. Other clinical, metabolic, or imaging markers showing a better performance for the prediction of the development and progression of cardiometabolic comorbidities in AIs need to be identified.

Synacthen Stimulation Test Following Unilateral Adrenalectomy Needs to Be Interpreted With Caution.

BackgroundCortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center.MethodsData were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing’s syndrome were excluded.ResultsThe median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement.ConclusionsSynacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.

A rare case of ectopic ACTH syndrome with rhabdomyolysis

BackgroundManifestations of hypokalaemia in ectopic adrenocorticotropic hormonesyndrome(EAS) vary from mild muscle weakness to life-threatening arrhythmia. Herein, we present a rare case of EAS with concomitant rhabdomyolysis(RM) as a result of intractable hypokalaemia.Case presentationA 64-year-old man was admitted for limb weakness and facial hyperpigmentation for 2 weeks. Lab tests revealed intractable hypokalaemia (lowest at 1.8 mmol/L) and metabolic alkalosis. The diagnosis of RM was based on a creatine kinase(CK)level of 5 times the upper limit. The elevated CK and myohemoglobin (Mb) levels returned to within the normal range after the alleviation of hypokalaemia. The patient was diagnosed with ACTH-dependent Cushing’s syndrome (CS) based on unsuppressed serum cortisol after a low-dose dexamethasone suppression test(LDDST) and remarkably elevated ACTH levels. The diagnosis of EAS was made based on the results of a high-dose dexamethasone suppression test(HDDST) and bilateral inferior petrosal sinus sampling(BIPSS). Multiple lymph nodes in the left supraclavicular fossa, right root of neck, mediastinum and bilateral hili of the lung were found with abnormal uptake of 68Ga-DOTA-NOC. Mediastinoscopic lymph node biopsy was performed. The pathological diagnosis was small-cell and large-cell neuroendocrine carcinoma with positive ACTH staining. The patient was prescribed mifepristone and received one cycle of chemotherapy. The patient could not tolerate subsequent chemotherapy and died of dyscrasia.ConclusionsRM is a rare complication of EAS with insidious onset and atypical clinical manifestations. Serum potassium levels should be vigilantly monitored to avoid RM in EAS.

Mild Autonomous Cortisol Secretion in Primary Aldosteronism Enhances Renal and Hemorrhagic Cerebrovascular Complications

Background: It is well known that primary aldosteronism (PA) is often associated with renal dysfunction and cardiovascular events (CVEs). However, the synergic effect of mild autonomous cortisol secretion (MACS) on the co-morbidities among PA has not been clarified yet. Thus, we retrospectively assessed whether the presence of MACS in PA patients with adrenal tumor, which may have MACS, to enhance the risk of the complications using a large Japanese multicenter database. Methods: We enrolled patients with both confirmed PA and obvious adrenal tumor (diameter > 1 cm) on computed tomography. The subtype of PA was diagnosed based on the results of adrenal venous sampling with ACTH stimulation. A total of 575 study subjects were stratified into two groups according to 1-mg dexamethasone suppression test (DST) results (cut-off post-DST serum cortisol 1.8 µg/dL): MACS group (N=174, 30.2%) and non-MACS group (N=401, 69.8%). Decreased estimated glomerular filtration rate (eGFR) was defined as <60 ml/min per 1.73m2. Results: The percentage of unilateral PA between the MACS and non-MACS group was equivalent (50.0% vs. 48.1%). Prevalence of decreased eGFR in the MACS group was higher than in the non-MACS group [odds ratio (OR) 1.91, 95% confidence interval (95% CI) 1.20–3.04, P=0.006]. Conversely, prevalence of MACS was higher in patients with decreased eGFR than those without decreased eGFR (42.7% vs 28.0%, P=0.008). Proteinuria was deteriorated with the increase in post-DST serum cortisol concentration as well as the basal plasma aldosterone concentration (PAC) (P=0.028 and P<0.001, respectively), although PAC but not the presence of MACS was selected as an independent factor related with decreased eGFR. Prevalence of cerebral hemorrhage in the MACS group was higher than the non-MACS group. (OR 5.35, 95%CI 1.83–15.6, P=0.002). We found that MACS was the only significant factor which increased the odds of developing cerebral hemorrhage (OR 9.13, 95%CI 2.15–38.90, P=0.003). Prevalence of other CVEs between the two groups was similar. Regardless of the PA subtype, complication rate of decreased eGFR and cerebral bleeding in the MACS group were significantly or tend to be higher than non-MACS group. Conclusion: Our date strongly suggested that co-secretion of cortisol in PA directly and/or indirectly increase renal and cerebrovascular comorbidities. Given that MACS is common in PA, endocrinological testing with DST is recommended in PA patients, especially those with adrenal tumor on imaging. (Supported by Research Grants of AMED:JP17ek0109122, JP20ek0109352; National Center for Global Health and Medicine:27–1402, 30–1008), and Ministry of Health, Labour, and Welfare, Japan (046).

Vitamin A failed to ameliorate clinical signs in dogs with pituitary-dependent hypercortisolaemia.

In dogs with pituitary-dependent hypercortisolaemia, retinoic acid was shown to lower cortisol, reduce pituitary tumour size and decrease clinical signs when administered for six months. Oral vitamin A (retinol) has been used to treat various canine dermatoses in which retinoic acid has been efficacious. To determine if orally administered vitamin A lowers cortisol and reduces clinical signs in dogs with pituitary-dependent hypercortisolaemia over a five month period. Five dogs were enrolled in this study. Diagnosis of hypercortisolaemia was based on the presence of at least three clinical signs and one abnormal screening test. Diagnosis of pituitary-dependent disease was based on low dose dexamethasone suppression (LDDS) test results and symmetrical adrenal glands on ultrasound. Adrenocorticotropic hormone (ACTH) stimulation testing and adrenal ultrasound were performed at each visit. Plasma was collected at each visit and stored at -80°C for batch analysis of endogenous ACTH at conclusion of the study. Four dogs completed the study. A fifth dog died from complications of hypercortisolaemia before the third month. One dog showed improvement in clinical signs, yet there was no significant decrease in adrenal gland size or cortisol concentrations. Endogenous ACTH concentrations at the fifth month were decreased from baseline in two dogs and increased from baseline in one dog. The treatment had no adverse effects. Results from this study failed to show an improvement in clinical signs or cortisol concentration after five months of oral daily vitamin A in dogs with hypercortisolaemia.

Metabolic changes in serum steroids for diagnosing and subtyping Cushing’s syndrome

To evaluate the diagnostic value of serum levels of adrenal steroids for diagnosing and subtyping Cushing’s syndrome. Patients diagnosed with endogenous Cushing’s syndrome (34 and 19 patients with adrenal and pituitary Cushing’s syndrome, respectively) and healthy controls (n = 34) were consecutively enrolled at Seoul National University from 2016 to 2020. Morning serum samples were collected before and 3 months after treatment. Serum steroids were profiled using liquid chromatography-mass spectrometry. The diagnostic value of each and the combination of steroids were assessed using the area under the curve of receiver operating characteristic (AUROC) and decision tree analysis. Tetrahydrocortisone and 6β-hydroxycortisol showed the highest AUROC (0.893 and 0.890, respectively) for the diagnosis of endogenous Cushing’s syndrome. The decision tree composed of tetrahydrocortisone and 6β-hydroxycortisol correctly classified 79/87 (90.8 %) subjects. For subtyping into adrenal or pituitary Cushing’s syndrome, dehydroepiandrosterone sulfate (DHEA-S) showed the highest AUROC (0.988), which was similar to that of plasma ACTH (0.994, P = 0.458). The decision tree composed of only DHEA-S correctly classified 51/53 (96.2 %) of the Cushing’s syndrome subtype. DHEA-S showed a significant linear correlation with the plasma ACTH level, but not with the 24 -h urine free cortisol or dexamethasone suppression test results. All steroids, except allo-tetrahydrocortisol and tetrahydrocortisone, decreased significantly at 3 months post-treatment with similar patterns in both adrenal and pituitary Cushing’s syndrome. Serum steroid profiling using a single morning serum sample provides valuable information for diagnosing and subtyping Cushing’s syndrome.

Yield of Serum Dexamethasone Measurement for Reducing False-Positive Results of Low-Dose Dexamethasone Suppression Testing.

The low-dose dexamethasone suppression test (DST) using a cortisol cutoff of 1.8 µg/dL has approximate sensitivity of 95% and specificity of 80% for detecting Cushing syndrome. False-positive DST results can be caused by a variety of conditions, by low dexamethasone bioavailability, or by failure to take dexamethasone as instructed. In an effort to reduce false positives caused by low bioavailability or medication noncompliance, we evaluated the yield of serum dexamethasone measurement for identifying invalid results. Data were queried for orders requesting concurrent measurement of serum cortisol and dexamethasone over a 41-month period. Inclusion criteria were serum cortisol and dexamethasone measured from the same specimen, specimen collection before 9 AM after 1 mg dexamethasone administration, and results for both analytes documented in the electronic medical record. Seventy paired measurements were identified with these criteria. Results were categorized into 4 groups based on observed cortisol and dexamethasone concentrations: (a) suppressed cortisol, low dexamethasone; (b) suppressed cortisol, therapeutic dexamethasone; (c) unsuppressed cortisol, low dexamethasone; or (d) unsuppressed cortisol, therapeutic dexamethasone. Overall, 35 (50%) results demonstrated suppressed cortisol and therapeutic dexamethasone levels. The next largest group was unsuppressed cortisol and therapeutic dexamethasone, representing approximately 32% (n = 22) of the study population. Ten result sets (14%) fell into the unsuppressed cortisol and low dexamethasone category, and 3 paired measurements (4%) fit the criteria for suppressed cortisol and low dexamethasone. The measurement of serum dexamethasone following DST reduces the false-positive rate associated with subtherapeutic dexamethasone levels.

Circannual variation in plasma adrenocorticotropic hormone concentrations and dexamethasone suppression test results in Standardbred horses, Andalusian horses and mixed-breed ponies.

To compare circannual plasma concentrations of adrenocorticotropic hormone (ACTH) and seasonal dexamethasone suppression test (DST) results between three different equine breed groups. Six Standardbred horses, six Andalusian horses and six mixed-breed ponies were followed over a 1-year period, during which time groups were managed identically. Blood samples were collected monthly (around the autumn equinox) or in every second month (other times of the year) for the determination of plasma ACTH concentrations using a chemiluminescent immunoassay. Overnight DSTs were performed quarterly, with suppression of plasma cortisol to below 27 nmol/L at 19 h considered a normal result. Seasonal variation in plasma ACTH concentrations was present among all breed groups with, as expected, higher levels detected around the autumn equinox, from February to April (P < 0.001). Plasma ACTH concentrations were different between breed groups in March, with higher levels in Andalusians compared with Standardbreds (P = 0.048) and in ponies compared with Standardbreds (P = 0.010). Suppression of cortisol during the DST was normal for all animals in winter, spring and summer, but five Andalusians and three ponies returned abnormally high results in autumn, compared with zero Standardbreds. Higher plasma ACTH concentrations and more false-positive DST results were obtained during autumn in ponies and Andalusian horses when compared with Standardbred horses. Potential differences between breeds should be considered when interpreting test results for horses and ponies that are evaluated for pituitary pars intermedia dysfunction. Further work is recommended to establish population-based reference intervals and clinical cut-off values for ACTH in different equine breeds.

Influence of dental restoration under general anaesthesia on the low-dose dexamethasone suppression test in dogs

It was the aim of the study to assess the impact of a minor surgical intervention under general anaesthesia on results of a low-dose dexamethasone suppression test (LDDST) in dogs. Five clinically healthy dogs underwent a LDDST (standard protocol) prior and 1, 4, 7, 14 and 28 days after a dental restoration under general anaesthesia. All LDDSTs revealed negative results. On all test days after intervention some dogs had basal cortisol concentrations below the reference range. Accordingly, plasma cortisol concentrations 4 and 8 h after dexamethasone injection were noticeably lower than before surgery and often even below the lower detection limit of 2.0 ng/ml. The study results may indicate a suppressive effect of a minor surgery under general anaesthesia on cortisol measurements during LDDSTs. It may be speculated that this could possibly lead to false negative test results in the postsurgical period, although transfer of these results to clinical cases is subject to limitations.