Overnight Dexamethasone Suppression Test Research Articles

The 1-mg overnight low-dose dexamethasone suppression test cut-off in establishing the diagnosis of Cushing's syndrome

The 1-mg overnight low-dose dexamethasone suppression test cut-off in establishing the diagnosis of Cushing's syndrome

Mild autonomous cortisol secretion: pathophysiology, comorbidities and management approaches.

The majority of incidentally discovered adrenal tumours are benign adrenocortical adenomas and the prevalence of adrenocortical adenomas is around 1-7% on cross-sectional abdominal imaging. These can be non-functioning adrenal tumours or they can be associated with autonomous cortisol secretion on a spectrum that ranges from rare clinically overt adrenal Cushing syndrome to the much more prevalent mild autonomous cortisol secretion (MACS) without signs of Cushing syndrome. MACS is diagnosed (based on an abnormal overnight dexamethasone suppression test) in 20-50% of patients with adrenal adenomas. MACS is associated with cardiovascular morbidity, frailty, fragility fractures, decreased quality of life and increased mortality. Management of MACS should be individualized based on patient characteristics and includes adrenalectomy or conservative follow-up with treatment of associated comorbidities. Identifying patients with MACS who are most likely to benefit from adrenalectomy is challenging, as adrenalectomy results in improvement of cardiovascular morbidity in some, but not all, patients with MACS. Of note, diagnosis and management of patients with bilateral MACS is especially challenging. Current gaps in MACS clinical practice include a lack of specific biomarkers diagnostic of MACS-related health outcomes and a paucity of clinical trials demonstrating the efficacy of adrenalectomy on comorbidities associated with MACS. In addition, little evidence exists to demonstrate the efficacy and safety of long-term medical therapy in patients with MACS.

Clinical characteristics and prognosis of primary aldosteronism associated with subclinical Cushing syndrome

Objective: To analyze the clinical characteristics and prognosis of patients with primary aldosteronism (PA) associated with subclinical Cushing syndrome (SCS). Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University in China. Patients with PA were included between January 2014 and December 2022. According to the results of 1-mg overnight dexamethasone suppression test, the patients were divided into the PA group and PA associated with SCS (PA/SCS) group. The demographic information, hormone levels, and follow-up results were analyzed. Independent sample t-test, chi-square test and Mann-Whitney U test were used for data comparison. Results: A total of 489 PA patients were enrolled in this study, of which 109 had PA/SCS (22.3%). Patients with SCS were on average older (54.4±10.7 vs. 47.4±11.0, P<0.001); had a larger proportion of women (69.7%, 76/109 vs. 57.4%, 218/380; P=0.020); and a longer duration of hypertension [96 (36, 180) vs. 60 (12, 120) months, P=0.001] than patients without SCS. There were 215 and 51 patients in the PA group and PA/SCS group, who completed adrenalectomy and follow-up, respectively. The remission rate of autonomous cortisol secretion in the PA/SCS group was 85.3% (29/34). There was no significant difference in the remission rate of autonomous aldosterone secretion among patients between the PA/SCS and PA group (94.1%, 48/51 vs. 94.4%, 203/215; P=1.000), while the clinical remission rate in the PA/SCS group was lower than that in the PA group (39.2%, 20/51 vs. 61.9%, 133/215; P=0.003). Conclusions: SCS is common in PA patients (22.3%), and the clinical remission rate is low. Screening using the 1-mg overnight dexamethasone suppression test is recommended for all patients with PA.

Hypothalamic-pituitary-adrenal axis hyperactivity is normalized after successful intermittent theta-burst stimulation in resistant depressed patients

The present pilot study assessed the effects of multi-session intermittent theta-burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex in 17 treatment resistant depressed inpatients (TRDs) showing cortisol non-suppression to the overnight dexamethasone suppression test (DST) at baseline (i.e., maximum post-DST cortisol [CORmax] level > 130 nmol/L). After 20 iTBS sessions, the DST was repeated in all TRDs. At baseline, post-DST CORmax levels were higher in TRDs compared to healthy control subjects (HCs; n = 17) (p < 0.0001). After 20 iTBS sessions, post-DST CORmax levels decreased from baseline (p < 0.03) and were comparable to HCs. Decreases in post-DST CORmax levels were related to decreases in 17-item Hamilton Depression Rating Scale (HAMD-17) scores (ρ = 0.53; p < 0.03). At endpoint, 10 TRDs showed DST normalization (among them 7 were responders [i.e., HAMD-17 total score > 50% decrease from baseline]), and 7 did not normalize their DST (among them 6 were non-responders) (p < 0.05). Our results suggest that successful iTBS treatment may restore normal glucocorticoid receptor feedback inhibition at the pituitary level.

Development of diagnostic algorithm for Cushing's syndrome: a tertiary centre experience.

No consensus exists as the gold standard for Cushing's Syndrome (CS) screening. This study aimed to evaluate the diagnostic accuracy and utility of late-night salivary cortisol (LNSC) and cortisone (LNSE), overnight dexamethasone suppression test (ODST), and urinary free cortisol (UFC) in developing a screening algorithm for CS. A retrospective, single-centre analysis on 93 adult patients referred to the Oxford Centre for Diabetes, Endocrinology, and Metabolism for CS evaluation (2017-2022). Data were analysed using binomial logistic regression and area under the receiver-operating curve (AUROC). Fifty-three patients were diagnosed with CS. LNSC (sensitivity 87.5%, specificity 64.9%, AUC 0.76), LNSE (sensitivity 72.4%, specificity 85.7%, AUC 0.79), and ODST (sensitivity 94.7%, specificity 52.1%; AUC 0.74) demonstrated comparable effectiveness for CS diagnosis. Their combined application increased diagnostic accuracy (AUC 0.91). UFC was not statistically significant. Pre-test clinical symptom inclusion improved screening test performance (AUC LNSC: 0.83; LNSE: 0.84; ODST: 0.82). For CD diagnosis, LNSE + LNSC (AUC 0.95) outperformed ODST. Combining these with ACTH levels < 12.6pmol/L perfectly distinguished MACS (AUC 1.00). ODST (AUC 0.76) exhibited superior performance (sensitivity 100.0%, specificity 52.2%) in MACS detection. LNSC, LNSE, and ODST are robust tools for CS screening, with their combined use offering the highest diagnostic precision. LNSE, especially when used with LNSC, is highly effective for CD diagnosis, exceeding ODST accuracy. ODST is preferable for MACS identification. Integrating ACTH levels markedly improves differentiation between CD and MACS. Conversely, UFC shows limited diagnostic utility.

Assessment of plasma dexamethasone levels after 1-mg dexamethasone suppression test in adults with obesity.

The 1-mg overnight dexamethasone suppression test is the most frequently used screening test for Cushing's syndrome. It has been proposed that people with obesity may have insufficient plasma dexamethasone levels for the test which may result in false positives. We sought to compare the plasma dexamethasone levels after 1-mg dexamethasone suppression test in healthy obese participants and in optimal-weight participants. A total of 30 optimal-weight participants (BMI ≤ 25 kg/m2 ) and 62 obese participants (BMI > 25 kg/m2 ) were enroled in the study. Obese participants were further divided into class 1 (25-29.9 kg/m2 ) and class 2 (>30 kg/m2 ). After a standard overnight 1-mg dexamethasone suppression test, blood samples were obtained for serum cortisol and plasma dexamethasone levels. Plasma dexamethasone levels were quantified using liquid chromatography - mass spectrometry (LC-MS/MS). No significant difference in plasma dexamethasone levels were found between obese and optimal-weight participants (3.31 ± 1.35 vs. 2.82 ± 1.11 nmol/L, mean ± SD; p = .09 respectively). There were also no correlations found between sex, BMI, body surface area and plasma dexamethasone levels. There was also no significant difference in the proportion of participants who achieved a plasma dexamethasone level >3.3 nmol/L in comparison between obesity class 1, obesity class 2, and optimal-weight groups. Our results suggest that obesity does not affect plasma dexamethasone levels. However, dexamethasone measurement may still be helpful in patients who are being investigated for Cushing's syndrome and suspected to have a false-positive DST.

The Overnight Low-Dose Dexamethasone Suppression Test Can Be Used to Evaluate Patients With Chronic Kidney Disease.

The Overnight Low-Dose Dexamethasone Suppression Test Can Be Used to Evaluate Patients With Chronic Kidney Disease.

Subcentimeter Corticotroph Adenoma: an Evaluation of Diagnostic Elements

Cushing’s disease (CD) is an uncommon yet serious disorder, linked to increased morbidity and mortality. Diagnosis of these patients are complex, and emphasis should be placed on early detection for better management of these patients. The objective of this case report is to evaluate the diagnostic elements in the identification of a subcentimeter adrenocorticotrophic hormone (ACTH)-dependent pituitary adenoma. We report a case of a 26-year-old man who presented with extensive superficial fungal infection of the skin, unintentional weight gain, hypertension, dyslipidaemia as well as cushingoid appearance suspicious of hypercortisolism. Raised midnight plasma cortisol and 24-hour urinary cortisol levels warranted further investigation. Overnight and 48-hour low-dose dexamethasone suppression test (LDDST) were non-suppressed. Subsequent bilateral inferior petrosal sinus sampling (BIPSS) was not only efficient in differentiating pituitary from ectopic Cushing’s syndrome (CS) but was shown to be superior to magnetic resonance imaging (MRI) in lateralisation of the pituitary adenoma.

FRI110 Prevalence Of Thromboembolic Events In 51 Patients Treated For Cushing’s Disease With Pituitary Surgery At University Hospital Of Wales Over A 15-year Period

Abstract Disclosure: R. Suresh John: None. J. Witczak: None. A. Rees: None. C. Hayhurst: None. A. Lansdown: None. Background: Hypercortisolism is associated with a hypercoagulable state and both arterial and venous thromboembolic events (TE). Aim: To determine the prevalence of TE in our cohort of patients with Cushing’s Disease (CD) undergoing pituitary surgery. Methods: Patients with a clinical &amp; biochemical diagnosis of Cushing’s Disease who had undergone pituitary surgery at University Hospital of Wales between 2007-2022 were identified from a database. Clinical, biochemical and radiological data were studied from the time of diagnosis to the period of 6 months following pituitary surgery. Results: 51 patients were identified: 15 Male, 36 Female, median age 46 (11-77)y. Total group: 5/51 (9.8%) patients had a TE. Pre-surgery: 2/51 (3.9%) had a TE (Deep vein thrombosis (DVT) = 1; Aortic thrombus = 1), both at time of diagnosis. Mean 24-h Urinary Free Cortisol (UFC) was 1126nmol in TE group vs 662nmol in non-TE group (p=0.64) and mean cortisol after overnight dexamethasone suppression test (ODST) was 251nmol/L in the TE group vs 327nmol/L in the non-TE group (p=0.64). Post-surgery: All patients received standard thrombo-prophylaxis with low-molecular weight heparin peri-operatively. 3/51 (5.9%) had TE within 6-months post-surgery (DVT=1, pulmonary embolism (PE)=1, cavernous sinus thrombosis=1), all occurred within 21 days of surgery and none had other risk factors for VTE. Mean time from diagnosis to surgery was 187 days in TE group vs 127 in non-TE group (p=0.43). At diagnosis, mean 24-h UFC was 560nmol in TE group vs 699nmol in non-TE group (p=0.82), mean cortisol after ODST was 420nmol/L in TE group vs 321nmol/L in non-TE group (p=0.46). Mean post-op cortisol was 221nmol/L in TE group vs 257nmol/L in no TE group (p=0.85). No TE events occurred between 22 days-6 months post-surgery. Conclusion: In our cohort, 9.8% patients had a TE event. 3.9% occurred pre-surgery and 5.9% in the early post-operative period, which concurs with data from other studies. There was no correlation with level of hypercortisolism and TE events in our group. Timing, dose &amp; duration of prophylactic anticoagulation in CD patients needs careful consideration. Presentation: Friday, June 16, 2023

FRI203 A Case Of Pseudoadrenal Tumor Mimicking Left Adrenal Pheochromocytoma

Abstract Disclosure: A. Tanabe: None. E. Sugito: None. H. Kajio: None. Approximately 50% of adrenal incidentalomas are non-functional cortical adenomas, and 25% are adrenocortical hormone-secreting adenomas and pheochromocytomas. Adrenocortical carcinomas, and pheochromocytomas which have malignant potential, need to be differentiated and removed even if the tumors are hormonally inactive. In addition to these adrenal origin tumors, anatomic structures and tumors that develop in tissues neighboring the adrenal glands (pseudoadrenal tumors) may be confused with primary adrenal tumors. The larger the tumor, the more difficult it is to determine continuity with the adrenal glands. Herein we report a patient with gastrointestinal stromal tumor (GIST) that mimicked a left adrenal pheochromocytoma. A 47-year-old man was diagnosed with a left adrenal incidentaloma at 40 years of age. The tumor had irregular margins and grew from 18 mm to 30 mm in maximum diameter over 7 years. The mass appeared to be in the tip of the lateral limb of the left adrenal gland and was located between the left adrenal gland and the posterior wall of the stomach. The patient had no abnormal findings other than general obesity. The blood pressure was 106/72 mmHg with antihypertensive agents. The plasma corticotropin and cortisol concentrations were normal and suppressed normally after a 1-mg overnight dexamethasone suppression test. The plasma aldosterone concentration and renin activity were increased with angiotensin receptor blocker and diuretic therapy. The 24-h urine fractionated metanephrines levels were at the upper limit of the reference range. Because the tumor showed unenhanced computed tomography (CT) attenuation of 40-50 Hounsfield units, hormonally-inactive adrenocortical carcinoma or pheochromocytoma had to be differentiated. I-123-metaiodobenylguanidine (I-123-MIBG) scintigraphy showed tumor avidity consistent with a pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal CT postoperatively showed that the tumor remained intact and appeared to connect to the posterior wall of the stomach. A laparotomy was performed and the tumor was removed. The tumor was localized to the intraperitoneal space and isolated from the posterior wall of the stomach. The pathological diagnosis was a GIST. Although it has been reported that I-123-MIBG may accumulate in tumors other than neuroendocrine tumors, reports on GISTs are rare. Lessons learned from our case include the importance of clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathologic analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies. Presentation: Friday, June 16, 2023

FRI172 Assessment Of Plasma Dexamethasone Levels After 1-mg Dexamethasone Suppression Test In Adults With Obesity

Abstract Disclosure: P. Paopongpaiboon: None. P. Santisitthanon: None. N. Houngngam: None. T. Snabboon: None. P. Boonchaya-anant: None. Background: The 1-mg overnight dexamethasone suppression test is the most frequently used screening test for Cushing’s syndrome. It has been proposed that obese patients may have insufficient plasma dexamethasone levels for the test which may result in false positives. We sought to compare the plasma dexamethasone levels after 1-mg DST in healthy obese participants and in normal-weight participants. Methods: A total of 30 normal-weight participants (BMI ≤ 25 kg/m2) and 62 obese participants (BMI &amp;gt;25 kg/m2) were enrolled in the study. Obese patients were further divided into class 1 (25 - 29.9 kg/m2) and class 2 (&amp;gt;30 kg/m2). After a standard overnight 1-mg dexamethasone suppression test, blood samples were obtained for serum cortisol and plasma dexamethasone levels. Plasma dexamethasone levels were quantified using liquid chromatography - mass spectrometry (LC-MS/MS). Results: No significant difference in plasma dexamethasone levels were found between obese and normal-weight participants (3.31 ± 1.35 vs 2.82 ± 1.11 nmol/L, mean ± SD; P=0.09 respectively). There were also no correlations found between sex, BMI, body surface area (BSA) and plasma dexamethasone levels. There was also no significant difference in the proportion of participants who achieved a plasma dexamethasone level &amp;gt; 3.3 nmol/L in comparison between obesity class 1, obesity class 2, and normal-weight groups. Conclusion: We did not find a difference in plasma dexamethasone levels after 1-mg DST between obese and normal-weight participants. Our results suggest that BMI does not affect plasma dexamethasone levels and routine dexamethasone measurement may not help to identify false-positives using the 1-mg DST. Presentation: Friday, June 16, 2023

FRI171 Can 11-Dehydrodexamethasone Improve The Salivary Dexamethasone Suppression Test?

Abstract Disclosure: D. Marshall: None. B.G. Issa: None. B.G. Keevil: None. Background: The 1 mg overnight dexamethasone suppression test (ONDST) is recommended as a first-line test for the investigation of Cushing Syndrome. Measurement of dexamethasone alongside cortisol in a 9am serum sample has been credited with improving diagnostic sensitivity of the test. Previous studies have also looked at the utility of salivary dexamethasone and have observed poor correlation with serum dexamethasone. Herein we introduce the concept of measuring 11-dehydrodexamethasone: a dexamethasone metabolite produced in the salivary duct through metabolism with 11β-hydroxysteroid dehydrogenase type 2 (11Β-HSD2). Methods: Paired 9am serum and saliva samples (n=44) were collected post ONDST. The saliva samples were analysed utilising a novel in-house LC-MS/MS assay which measured cortisol, cortisone, dexamethasone and 11-dehydrodexamethasone. Serum cortisol and dexamethasone had previously been analysed separately by LC-MS/MS. Results were compared and correlations were assessed using Pearson regression. Results: Serum and salivary dexamethasone exhibited poor correlation (R-squared = 0.16), supporting what has been observed previously. Salivary dexamethasone and 11-dehydrodexamethasone also showed poor correlation (R-squared = 0.19). Serum dexamethasone and salivary 11-dehydrodexamethasone yielded a positive correlation with an R-squared of 0.65. However, at higher concentrations the correlation appeared non-linear. Conclusion: Correlation of serum dexamethasone with 11-dehydrodexamethasone is a novel finding, which to the author’s knowledge, has not been previously established/investigated. It is hypothesized that the non-linear correlation might be due to saturation kinetics of the enzyme 11Β-HSD2 in the salivary duct, a similar relationship was observed when comparison of salivary cortisol and cortisone was assessed. The development of this LC-MS/MS assay for salivary measurement of 11-dehydrodexamethasone opens the possibility for a fully remote DST, whereby patients could administer the drug and take a 9am saliva sample. Further sample comparisons are required to develop a 11-dehydrodexamethasone cut-off which equates to a serum dexamethasone concentration of 3.3 nmol/L. Presentation: Friday, June 16, 2023

Hair cortisol and endocannabinoid measurement in patients with adrenal incidentalomas: a case-control study.

The role of endocannabinoids (ECs) in the regulation of the hypothalamic-pituitary-adrenocortical axis has already been studied; however, data are scarce in humans. The aim of our study was to analyze EC [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and cortisol (F) levels in hair samples of patients with adrenal incidentalomas (AIs) in comparison with those found in controls and assess their association with the hormone profile. Forty-four patients with AIs [32 with non-functioning AIs (NFAIs) and 12 with possible autonomous secretion (PACS)] and 44 controls were recruited. Basal and post-1mg overnight dexamethasone suppression test (ODST) F, adrenocorticotropic hormone, dehydroepiandrosterone sulfate, and 24-h urinary free cortisol were analyzed. After hair collection, EC and F levels were measured by liquid chromatography tandem-mass spectrometry. There was no difference between the groups regarding age, sex, and metabolic status. Significantly decreased hair AEA and 2-AG levels were found in patients with AIs compared to controls (p < 0.001 and p = 0.002, respectively) as well as between NFAI or PACS and controls (p < 0.001 or p = 0.002 and p = 0.038 or p = 0.02, respectively). Among the AI patients, EC levels tended to be lower in the PACS group. AEA hair levels were negatively correlated with F levels post-1mg ODST (rs = -0.257, p = 0.033). We found no significant difference comparing hair F between the groups. Our findings suggest that hair EC measurement could be a potential biomarker in the evaluation of patients with AIs, whereas hair F analysis is not a useful diagnostic test for mild hypercortisolemia.

Utilizing dehydroepiandrosterone sulfate and its ratio for detecting mild autonomous cortisol excess in patients with adrenal incidentaloma.

Subclinical Cushing syndrome is a condition of mild autonomous cortisol excess (MACE) that lacks typical features of Cushing syndrome but is associated with many complications. It represents a common hormonal dysfunction among patients with adrenal incidentaloma (AI), defined as unexpected masses or lesions found in the adrenal glands during radiological examinations of the chest or abdomen unrelated to adrenal gland assessment. The study evaluated the accuracy of dehydroepiandrosterone sulfate (DHEA-S) and dehydroepiandrosterone sulfate ratio (calculated by dividing the DHEA-S value by the age and sex-adjusted normal range of DHEA-S) in detecting MACE in AI patients. A cross-sectional study was conducted from April 2021 to July 2022 at the Faiha Specialized Diabetes, Endocrine, and Metabolism Centre (FDEMC) in Basrah, southern Iraq, involving 38 AI patients. Comprehensive laboratory and radiological evaluations were performed, including tests for adrenocorticotropic hormone (ACTH), renin, aldosterone, aldosterone/renin ratio (ARR), metanephrine, normetanephrine, cortisol, DHEA-S, and the 1-mg overnight dexamethasone suppression test (1-mg ONDST). Among the AI patients, 14% had MACE. Both DHEA-S ≤75 µg/dL and a DHEA-S ratio ≤1.7 exhibited a sensitivity of 80% each, with specificities of 73.3% and 76.6%, respectively, in diagnosing MACE in individuals aged ≤65 years. The negative predictive values were 95.7% and 95.8%, respectively. Low DHEA-S and DHEA-S ratio had high sensitivity and specificity in predicting MACE among AI patients aged ≤65 years, with strong negative predictive value.

Overnight 1-mg Dexamethasone Suppression Test for Screening Cushing Syndrome and Mild Autonomous Cortisol Secretion (MACS): What Happens when Serum Dexamethasone Is Below Cutoff? How Frequent Is it?

ObjectiveTo determine the frequency of “invalid” 1-mg overnight dexamethasone (Dex) suppression tests (DSTs) (1-mg DST) on a large series of patients investigated for hypercortisolism and examine the interference of substances and clinical conditions that may explain low serum Dex levels. MethodsA retrospective analysis of 1300 Dex-controlled 1-mg DST applied to patients screened for Cushing syndrome or mild autonomous cortisol secretion in a single center for which there were identified invalid tests and distinctive characteristics that may have interfered with the outcome. ResultsAmong all tests, 146 (11.2%) were considered invalid (serum Dex levels <140 ng/dL, 36 [24.7%] of which were undetectable [<19.5 ng/dL]). In the Dex-undetectable group, 17% failed to take Dex correctly, 25% were on glucocorticoids (GCs), and 20% were on anticonvulsants and moderate CYP3A4 inducers. In the remaining 110 tests (serum Dex 20-140 ng/dL), 6.5% did not take Dex or were using GC, 22% were on anticonvulsants or CYP3A4 inducers, and another 13% had previous gastrointestinal tract abnormalities impairing drug absorption. ConclusionInappropriately low serum Dex levels during the 1-mg DST may lead to false-positive results. This is associated with recurrent use of CYP3A4-inducing drugs and/or gastrointestinal abnormalities. When serum Dex is undetectable, the key reason is failure to take the medication or the use of GC (when cortisol is suppressed). Simultaneous measurement of serum cortisol and Dex allows for DST validation, improving its accuracy and avoiding unnecessary repetitions. Adherence to verbal/written recommendations and actual use of medication are critical for interpreting the test.

Anorexia nervosa and adrenal hormones: a systematic review and meta-analysis.

Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in response to starvation and low body weight including changes in adrenocortical hormones. Our objective was to systematically review adrenocortical hormone levels in anorexia nervosa. We searched MEDLINE and EMBASE for studies that reported at least one adrenocortical hormone, including dehydroepiandrosterone (DHEA), DHEA-sulphate (DHEA-S), progesterone, 17-hydroxyprogesterone, pregnenolone, cortisol (serum, urine, cerebrospinal fluid, and hair sample), aldosterone, androstenedione, and testosterone in patients with anorexia nervosa and normal-weight healthy controls from inception until October 2021. Means and standard deviations for each hormone were extracted from the studies to calculate a mean difference (MD). A pooled MD was then calculated by combining MDs of each study using the random-effects model. We included a total of 101 studies with over 2500 females with anorexia nervosa. Mean cortisol levels were significantly higher in anorexia nervosa as compared to normal-weight controls for multiple forms of measurement, including morning cortisol, 12-hour and 24-hour pooled serum cortisol, 24-hour urine cortisol, and after an overnight dexamethasone suppression test. In contrast, mean serum total testosterone and DHEA-S levels were significantly lower among patients with anorexia nervosa. Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa. This finding is important to consider when evaluating low-weight women for disorders involving the adrenal axis, especially Cushing's syndrome.

Hepatoid adenocarcinoma masquerading as adrenocortical carcinoma in an elderly male

Background: Hepatoid adenocarcinoma is a malignant lesion arising from an anatomic site other than the liver with histological features similar to hepatocellular carcinoma. Hepatoid adenocarcinoma has been reported from various anatomical sites, but adrenal hepatoid adenocarcinomas are extremely rare.Case Description: A 70-year-old male with well-controlled hypertension presented with chronic abdominal pain and was found to have a large left-sided supra renal mass. The lesion showed radiological features suggestive of malignancy with local invasion. There was biochemical evidence of primary aldosteronism and a non-suppressed overnight dexamethasone suppression test. He underwent open left-sided adrenalectomy: histologically the tumour demonstrated features typical of a hepatoid carcinoma with bile production and immunohistochemical staining for Hep Par-1 and CD10 demonstrating a hepatic canalicular pattern. Adrenocortical-specific immunohistochemical markers (Inhibin and melan A) and neuroendocrine markers (synaptophysin and chromogranin) were negative. He did not have clinical or biochemical evidence of cirrhosis, Hepatitis B or C infection. Triple-phase CT scanning of the abdomen before resection of the adrenal lesion and five months following surgery did not show any significant lesion in the liver suggestive of primary hepatocellular carcinoma, except an 8 mm non enhancing benign-appearing cystic lesion.Conclusion: Most hepatoid adenocarcinomas originate from the gastro-intestinal tract. We present a patient with hepatoid adenocarcinoma masquerading as adrenocortical carcinoma due to misleading imaging and biochemical evidence. Very little is known about their pathogenesis, especially those with an atypical site of origin such as the adrenal gland.

Serum cortisol assay performance following the 1mg overnight dexamethasone suppression test.

The 1mg overnight dexamethasone suppression test (ONDST) is recommended for the differential diagnosis of Cushing's syndrome and the investigation of adrenal incidentalomas. Despite documented variation in serum cortisol immunoassay performance, little has been published regarding its effect on the ONDST. Assess the performance of three immunoassay platforms (Roche Elecsys II, Abbott Alinity & Siemens Centaur) when compared to a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Samples (n = 77) sent to the laboratory as part of an ONDST were retrieved prior to disposal, anonymized, and analysed on all platforms. Samples with factors impacting immunoassay analysis quality were excluded. Results were statistically compared to an LC-MS/MS method that previously demonstrated excellent comparability to a candidate reference method. The Roche gen II showed a mean bias of -2.4nmol/L and a Passing-Bablok fit of y = -0.9 + 0.97x. This was not affected by sex. The Abbott showed a mean bias -18.8nmol/L, and a fit of y = -11.3 + 0.88x. This bias was -20.7nmol/L in females versus -17.2nmol/L in males. The Siemens had a mean bias of 2.3nmol/L and a fit of y = 1.4 + 1.07x. This bias was 5.7nmol/L in males versus -1.0nmol/L in females. Clinicians should be aware of the method-dependent variation that exists within serum cortisol analysis during the ONDSTs. Roche and Siemens aligned more closely with LC-MS/MS while the Abbot may cause a reduction in ONDST sensitivity. This data supports assay-specific cut-offs for the ONDST.

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors.

Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are non-functioning adrenocortical adenomas, but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas. We followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system and updated systematic reviews on four predefined clinical questions crucial for the management of incidentalomas: A) How to assess risk of malignancy? ; B) How to define and manage mild autonomous cortisol secretion? ; C) Who should have surgical treatment and how should it be performed? ; D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected Recommendations: 1) Each adrenal mass requires dedicated adrenal imaging. Recent advances now allow discrimination between risk categories: Homogeneous lesions with HU ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size. All other patients should be discussed in a multidisciplinary expert meeting, but only lesions >4 cm that are inhomogeneous or have HU >20 have sufficiently high risk of malignancy that surgery will be the usual management of choice. 2) Every patient needs a thorough clinical and endocrine work-up to exclude hormone excess including the measurement of plasma or urinary metanephrines and a 1-mg overnight dexamethasone suppression test (applying a cutoff value of serum cortisol ≤50 nmol/l (≤1.8 µg/dl)). Recent studies have provided evidence that most patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post dexamethasone >50 nmol/l (>1.8 µg/dl) harbor increased risk of morbidity and mortality. For this condition, we propose the term 'mild autonomous cortisol secretion' (MACS). 3) All patients with MACS should be screened for potential cortisol-related comorbidities that are potentially attributably to cortisol (e.g. hypertension and type 2 diabetes mellitus), to ensure these are appropriately treated. 4) In patients with MACS who also have relevant comorbidities surgical treatment should be considered in an individualized approach. 5) The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. 6) Surgery is not usually indicated in patients with an asymptomatic, non-functioning unilateral adrenal mass and obvious benign features on imaging studies. Furthermore, we offer recommendations for the follow-up of non-operated patients, management of patients with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses, and for young and elderly patients with adrenal incidentalomas. Finally, we suggest ten important research questions for the future.

PAEDIATRIC ADRENOCORTICAL CARCINOMA: A CASE REPORT

Adrenocortical carcinoma (ACC) is a relatively rare but an aggressive neoplasm that can have variety of manifes­tations. It can manifest in the form of virilization, hyperaldosteronism, cushingoid features or combination of that. Due to rapid appearance of signs and symptoms in children, these tumours can be diagnosed early however if delayed can bear worse prognosis as they tend to metastasize early in course of disease progression. We report a case of 4 years old female patient from Chitral, Pakistan who was referred to Endocrinology Department from Paediatric Department of Hayatabad Medical Complex, Peshawar Patient presented at paediatric OPD with com­plaints of weight gain, hirsutism, rashes over the face and acne. Patient had typical moon facies, buffalo hump and distended abdomen without striae as well as mass in the left hypochondrium on examination. On further evaluation clitoromegaly and pubic hair tanner stage 4 were found. Both Ultrasound and CT-Scan showed left supra-renal soft tissue mass invading the inferior venacava (IVC). She was further evaluated and her overnight dexamethasone suppression test (ODST) and serum testosterone levels were high although serum sodium and potassium were normal ruling out hyperaldosteronism. Next, biopsy was performed which was consistent with adrenocortical carcinoma. ACC although rare is highly aggressive tumor that requires early detection and diagnosis specially in children. If diagnosis is delayed prognosis may not be favourable. It therefore requires avid clinical suspicion to proceed onto diagnostic lines for patient’s benefit as well as physician’s satisfaction.