scholarly journals Iatrogenic Cushing Syndrome and Secondary Adrenal Insufficiency Due to an Interaction Between Fluticasone and Ritonavir

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A136-A136
Author(s):  
Lorena Suárez Gutiérrez
Keyword(s):  
Adrenal Insufficiency ◽  
Protease Inhibitors ◽  
Cushing Syndrome ◽  
Case Series ◽  
Urinary Free Cortisol ◽  
Lower Limbs ◽  
Cytochrome P450 Enzyme ◽  
Secondary Adrenal Insufficiency ◽  
Abdominal Perimeter ◽  
Free Cortisol

Abstract Introduction: The interaction between corticosteroids and protease inhibitors (PIs) is a clearly described drug interaction. Several case series have been described.-Fluticasone is the one with the greatest potential risk of producing iatrogenic adrenal insufficiency given its pharmacokinetic characteristics. Clinical Case: 44-year-old woman diagnosed with HIV (human immunodeficiency virus) category B3 diagnosed in 1989; multiple antiretroviral treatments. Severe lipodystrophy Also HCV genotype IA. Bronchial asthma since 2000. A treatment with fluticasone 1 inh / 24h, salbutamol on demand, darunavir 800 mg / day and ritonavir 100 mg / day. He had known lipodystrophy since 2001 and the abdominal perimeter was controlled, showing an increase in it. Likewise, she presented progressive proximal weakness in the lower limbs, with increased hair, capillary fragility and alopecia, which is why she was referred to Endocrinology. Moderate hirsutism, muscle atrophy were observed and in the analytical study: normal FSH and LH. Testosterone 0.05 ng / ml (0.1–0.9), ACTH 1.0 pg / ml (7.2–63.3), Cortisol am 0.65 µg / dl (4.30–22.40). Urinary free cortisol 3.74 µg / 24h (36–137). A Synacten Test is performed: Basal 0.52; 30 min 2.33; 60 min 2.84 with ACTH 1 and a diagnosis of iatrogenic independent ACTH Cushing Syndrome associated with secondary adrenal insufficiency. With this diagnosis, he was referred to the pulmonology clinic for a change from inhaled corticosteroid to beclomethasone and replacement treatment with hydroaltenesone was started. Three months later, he was admitted for a fever after stopping hydroaltesone. It was restarted, antibiotic treatment was prescribed, and she was discharged home with a new regimen of antiretrovirals (raltegravir, tenofovir, and abacavir). Clinical Lesson: Fluticasone is a synthetic steroid that is cleared by the cytochrome P450 enzyme CYP3A4, which is inhibited or enhanced by a multitude of drugs, including ritonavir. As it is not metabolized, there is an increase in circulating levels, causing a decrease in ACTH secretion and therefore a suppression of the adrenal gland with its insufficiency and cushing syndrome. In our case and usually, the initial signs are difficult to detect due to their overlap with lipodystrophy associated with protease inhibitors. Although there is no agreement in the literature: the options are the replacement of fluticasone with another corticosteroid that is not a CYP3A4 substrate such as beclomethasone and the replacement of ritonavir with another antiretroviral (as in our case) or the reduction of the dose of fluticasone. It is recommended to avoid the initiation of fluticasone in patients receiving ritonavir. Substitution treatment with a progressive reduction in dose is performed with hydroaltesona. Most cases resolve in 9–12 months.

scholarly journals Long-Term Control of Urinary Free Cortisol With Osilodrostat in Patients With Cushing’s Disease: Final Results From the LINC 2 Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A521-A522
Author(s):  
Maria Fleseriu ◽  
Beverly M K Biller ◽  
Jerome Bertherat ◽  
Jacques Young ◽  
Giorgio Arnaldi ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Cushing’S Disease ◽  
Clinical Signs ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Efficacy And Safety ◽  
Entire Treatment Period ◽  
Free Cortisol ◽  
Long Term Treatment

Abstract Introduction: During the 22-week core LINC 2 study, the oral 11β-hydroxylase inhibitor osilodrostat normalized mean urinary free cortisol (mUFC) in 79% (15/19) of patients with Cushing’s disease. This report describes long-term LINC 2 efficacy and safety results following an optional extension. Methods: Patients receiving clinical benefit at week 22 could enter the extension (that ran until Oct 22, 2019), continuing the same osilodrostat dose; dose adjustments were permitted based on efficacy and safety. Response rate (mUFC ≤ULN [controlled] or mUFC >ULN but ≥50% decrease from baseline [BL; partially controlled]) was assessed over time. Efficacy/safety were assessed for all patients from core BL until study end. Results: Of 19 enrolled patients (female:male 14:5; mean [SD] age 36.8 years [8.4]), 16 entered the optional extension and 8 of them remained on treatment until study end. Median (range) osilodrostat exposure was 282 weeks (2-351). Mean mUFC decreased from BL (9.9 x ULN) to ≤ULN by week 4 and remained stable throughout the study. All 19 patients achieved mUFC ≤ULN at least once during the study. At each assessment up to month 70 of the extension phase, 50-88% of ongoing patients were controlled, and up to 18% were partially controlled. Mean percentage change in clinical signs from BL (mean [SD]) to last assessment were: fasting plasma glucose, -10.8% (22.1) (from BL: 105.6 mg/dL [49.2]); HbA1c, -2.1% (9.0) (from BL: 5.7% [0.7]); systolic BP, -3.3% (12.6) (from BL: 132.6 mmHg [11.6]); diastolic BP, -2.0% (10.4) (from BL: 85.0 mmHg [6.5]); BMI, -5.9% (8.8) (from BL: 30.7 kg/m2 [7.0]). Overall, 9 patients discontinued treatment (n=2 core and n=7 extension), mostly because of AEs or no longer requiring treatment (n=3 each). The most common AEs during the entire treatment period were nausea (n=10), adrenal insufficiency, and headache (both n=9). AEs related to hypocortisolism and adrenal hormone precursor accumulation occurred in 11 (mostly adrenal insufficiency, n=9) and 12 patients (mostly hypertension, n=4), respectively; most were grade 1/2 and managed with dose adjustment/interruption and/or concomitant medication. Mean (SD) plasma ACTH increased from 1.8 x ULN (0.9) at BL to 7.1 x ULN (12.3) at week 22 and 6.9 x ULN (12.6) at last assessment. Mean (SD) 11-deoxycortisol increased from 1.2 x ULN (1.3) at BL to 13.6 x ULN (12.2) at week 22 and 3.6 x ULN (4.2) at last assessment. In females, mean (SD) testosterone increased from 0.8 x ULN (0.4) at BL to 2.4 x ULN (2.1) at week 22 and 1.0 x ULN (0.9) at last assessment. Two patients, both female, reported an AE of hirsutism. Conclusions: Rapid reductions in mUFC were sustained for up to 6 years of osilodrostat treatment and were accompanied by improvements in clinical signs of hypercortisolism. Osilodrostat was well tolerated, with no new safety signals during long-term treatment.

scholarly journals The Incidence of Long-Term Adrenal Insufficiency Following Unilateral Adrenalectomy is Low: Case Series and Review of Literature

2019 ◽  
pp. 1-4
Author(s):  
Jay D. Raman ◽  
Augustyna Gogoj ◽  
Brian D. Saunders ◽  
Daniel J.Canter ◽  
Jay D. Raman ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Adrenal Insufficiency ◽  
Cushing Syndrome ◽  
Case Series ◽  
Large Majority ◽  
Review Of Literature ◽  
Unilateral Adrenalectomy ◽  
Different Types ◽  
One Year

Introduction: Acquired adrenal insufficiency is a known risk of unilateral adrenalectomy. However, the rates of early and prolonged adrenal insufficiency following unilateral adrenalectomy are not well defined in the literature. Patients and Methods: We reviewed a case series of 184 consecutive patients to determine the likelihood of steroid supplementation at 30 days and 1 year following adrenalectomy. 109 lesions were non-functional and 75 (41%) demonstrated functionality, including 33 pheochromocytomas, 20 cortisol-producing adenomas, 19 aldosteronomas, and 3 cases of cortisol-secreting hyperplasia. No patients with a nonfunctional lesion, pheochromocytoma, or aldosteronoma required steroid supplementation following surgery. Eleven of 23 patients (48%) with primary adrenal Cushing syndrome required cortisol supplementation at 30 days, and only 1 patient (4%) necessitated supplementation one year following surgery. Discussion: Approximately 50% of patients with cortisol-producing lesions in the adrenal gland will require supplementation 30-days following surgery. Only 4% will require persistent exogenous steroids at 1-year. Conversely, less than 1% of patients with different types of functional or non-functional tumors required supplementation after surgery. Conclusion: The incidence of adrenal insufficiency following unilateral adrenalectomy is low. A large majority of patients requiring steroid supplementation 30 days following surgery are able to wean off this requirement by 1 year. With this information, we can better counsel our patients and set clearer expectations for the potential need of cortisol supplementation following adrenalectomy

scholarly journals OR03-05 Novel Lipidome Signature in Active Cushing Syndrome Revealed by UHPLC-MS Metabolomics

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Arturo Vega-Beyhart ◽  
Marta Iruarrizaga ◽  
Guillermo Garcia-Eguren ◽  
Adriana Pane ◽  
Oriol Giró ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Glutamate Metabolism ◽  
Serum Samples ◽  
Topological Network ◽  
Free Cortisol ◽  
Canonical Pathways ◽  
Omega 6 ◽  
Lipid Metabolites

Abstract Background: Alterations in circulating amino acids, polyamines and acylcarnitines have been reported in patients with endogenous chronic hypercortisolism. However, lipid metabolites profiling and its interplay with the serum metabolome and degree of hypercortisolism in patients with active Cushing syndrome (CS) has not been previously assessed. Objective: To identify new metabolomic biomarkers associated with active CS. Methodology: Multiple UHPLC-MS platforms were used to analyze the metabolome of serum samples obtained from 25 patients with active endogenous CS and 25 controls subjects matched by propensity score (sex, BMI, T2D, DLP, HBP). Results: Metabolome of CS patients was deeply disrupted with 122 (27%) of the assessed metabolites significantly altered (p adj. <0.05) out of which 5 bile acids resulted with the highest perturbation (> 2-fold decrease). From the altered metabolites, 3 amino acids (AA), 2 acylcarnitines (ACs), 2 ceramides (CER) and 5 glycerophospholipids showed direction of effect independently associated with 24-h urinary free cortisol (MS) levels. A highly discriminant (AUC 96%) metabolome signature (n=59) characterized by lower levels of AA, ACs, polyunsaturated fatty acids (PUFA) and monoglycerophosphocolines (MGPC) together with increased levels of triacyclglycerols (TG), CER, diacylglycerophosphocholines (DGPC) and cholesteryl esters was identified and cross-validated (R2Y= 0.92, Q2Y= 0.68) using PLS-DA VIP scores >1.5. PUFA omega-6, and alanine, aspartate and glutamate metabolism resulted the most impacted canonical pathways (q-stat 19.7, 10.8 (p<0.001). Finally, topological network analysis detected 158 pairwise differential correlations (p <0.005, 10,000-fold permutation) between 141 metabolites due to CS where the acylPC (P-18:1/0:0) resulted a key metabolite in the network (betweenness =0.117 & closeness centrality =0.467). Conclusion: Active Cushing syndrome leads to a global proatherogenic shift in the circulating ceramides, glycerophospholipids and sphingolipids metabolites which are independently associated to the levels of urinary free cortisol being potential biomarkers of patients’ cardiovascular risk.

scholarly journals Hypercoagulability in Cushing Syndrome, Prevalence of Thrombotic Events: A Large, Single-Center, Retrospective Study

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Maria Gabriela Suarez ◽  
Madeleine Stack ◽  
Jose Miguel Hinojosa-Amaya ◽  
Michael D Mitchell ◽  
Elena V Varlamov ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Cushing Syndrome ◽  
Thrombotic Event ◽  
Urinary Free Cortisol ◽  
Bilateral Adrenalectomy ◽  
Bleeding Complications ◽  
Single Center ◽  
Free Cortisol ◽  
Prophylactic Anticoagulation

Abstract Background The risk of Cushing syndrome (CS) patients experiencing a thrombotic event (TE) is significantly higher (odds ratio; OR 18%) than that of the general population. However, there are currently no anticoagulation guidelines. Methods A retrospective, single-center, longitudinal study of patients undergoing all types of treatment—surgical (pituitary, unilateral, and bilateral adrenalectomy) and medical treatment—was undertaken. TEs were recorded at any point up until last patient follow-up; myocardial infarction (MI), deep venous thrombosis (DVT), and pulmonary embolism (PE) or stroke. Patients’ doses and complications of anticoagulation were recorded. Results Included were 208 patients; a total of 165 (79.3%) were women, and mean age at presentation was 44 ± 14.7 years. Thirty-nine (18.2%) patients had a TE; extremity DVT (38%), cerebrovascular accident (27%), MI (21%), and PE (14%). Of 56 TEs, 27 (48%) were arterial and 29 (52%) were venous. Patients who underwent bilateral adrenalectomy (BLA) had an odds ratio of 3.74 (95% CI 1.69-8.27) of developing a TE. Of patients with TEs, 40.5% experienced the event within the first 60 days after surgery. Baseline 24-hour urinary free cortisol levels did not differ in patients with or without TE after BLA. Of 197 patients who underwent surgery, 50 (25.38%) received anticoagulation after surgery, with 2% having bleeding complications. Conclusions The risk of TEs in patients with CS was approximately 20%. Many patients had more than 1 event, with higher risk 30 to 60 days postoperatively. The optimal prophylactic anticoagulation duration is unknown, but most likely needs to continue up to 60 days postoperatively, particularly after BLA.

scholarly journals Pseudo-Cushing Syndrome Caused by Fenofibrate Interference with Urinary Cortisol Assayed by High-Performance Liquid Chromatography

2003 ◽  
Vol 88 (8) ◽  
pp. 3521-3524 ◽  
Author(s):  
A. Wayne Meikle ◽  
James Findling ◽  
Mark M. Kushnir ◽  
Alan L. Rockwood ◽  
Gordon J. Nelson ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance ◽  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Urinary Cortisol ◽  
Free Cortisol ◽  
Hplc Peak ◽  
Major Transition ◽  
Single Transition ◽  
Mass Spectrometry Mass Spectrometry

Urinary free cortisol (UFC) excretion over 24 h reflects the production rate of cortisol and is used commonly in the diagnosis of Cushing syndrome. We report on two patients evaluated for Cushing syndrome who had elevated UFC when analyzed by HPLC but normal values for the analysis performed by RIA and HPLC-mass spectrometry/mass spectrometry (HPLC-MS/MS). Other laboratory testing was inconsistent with the diagnosis of Cushing syndrome and raised doubts about the diagnosis. We identified a probable cause of analytical interference as coming from fenofibrate (Tricor), medication taken by the patients. Fenofibrate peak overlapped with the HPLC peak of cortisol and produced an MS/MS transition overlapping the major transition of cortisol. A second MS/MS transition was free from interference. In summary, fenofibrate administration may cause false elevation of UFC values determined by HPLC or HPLC-MS/MS in patients evaluated for Cushing syndrome. An HPLC-MS/MS method using multiple mass transitions, rather than a single transition, allows accurate quantitation of urinary cortisol in patients taking fenofibrate.

scholarly journals A Challenging Case of an Ectopic Cushing Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Joana Menezes Nunes ◽  
Elika Pinho ◽  
Isabel Camões ◽  
João Maciel ◽  
Pedro Cabral Bastos ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Lung Resection ◽  
Signs And Symptoms ◽  
Urinary Free Cortisol ◽  
Community Acquired Pneumonia ◽  
Interesting Case ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Free Cortisol ◽  
Fdg Pet Scan

Bronchopulmonary carcinoids are rare pulmonary neoplasms although they account for most cases of ectopic ACTH syndromes. When feasible, the mainstay treatment is surgical resection of the tumor. We report the case of a 52-year-old woman with signs and symptoms suggestive of hypercortisolism for 12 months, admitted to our department because of community acquired pneumonia. Blood hormone analysis showed increased levels of ACTH and urinary free cortisol and nonsuppressibility to high- and low-dose dexamethasone tests. Pituitary MRI showed no lesion and no central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. CRH stimulation test suggested an ectopic ACTH source. Thoracic CT scan revealed a nodular region measuring 12 mm located in the inferior lingular lobule of the left superior lung with negative uptake by18-FDG-PET scan and negative SRS. The patient was successfully treated with an atypical lung resection and histology revealed an atypical bronchial carcinoid tumor with positive ACTH immunoreactivity. This was an interesting case because the patient was admitted due to pneumonia that may have been associated with her untreated and chronic hypercortisolism and a challenging case of ectopic ACTH syndrome due to conflicting results on the diagnostic exams.

scholarly journals Ectopic ACTH-Producing Pheochromocytoma as a Rare Cause for Rapid Progressing Cushing Syndrome: A Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A128-A128
Author(s):  
Daniela Salazar ◽  
Cláudia Fernandes Costa ◽  
Joana Oliveira ◽  
Liliana Violante ◽  
Ana Luísa Cunha ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Cushing Syndrome ◽  
Somatostatin Receptors ◽  
Osteoporotic Fractures ◽  
Urinary Free Cortisol ◽  
Hand Tremor ◽  
Ectopic Acth ◽  
Late Night ◽  
Free Cortisol ◽  
The Right

Abstract Background: Cushing syndrome due to ectopic CRH or ACTH secretion can be rarely caused by pheochromocytoma, commonly as part of genetic conditions. Case: A 21 year-old male, previously healthy, with no usual medication, went to the physician assistant for hematuria. The kidney US revealed, besides lithiasis, a highly vascularized mass in the right adrenal gland with 10 cm. In his first evaluation the patient had no complaints or pheochromocitoma/hypercortisolism stigmata, other than hand tremor and slight rounding of the face. Blood pressure was 149/88 mmHg, and heart rate 86 bpm. There was no family history of endocrine disease. He rapidly developed increased appetite, insomnia, and severe myalgias, with filling of supraclavicular fossae, facial plethora, and cervical and truncal acne. Laboratory analysis showed abnormal overnight dexamethasone suppression test (57.4 µg/dL, N < 1.8), elevated ACTH 378 pg/mL (N 9.0–52.0), 24h-urinary free cortisol (UFC) (5334.0 µg/24h, N 4.3–176.0), and late-night salivar cortisol (1.44 µg/dL, N < 0.32), hypokalemia (2.8 mEq/L, N 3.8–5.0), and leukocytosis (22.4*109/L, N 4.0–11.0); DHEA-S 962 µg/dL (N 80–560), 4-androstenedione 380 ng/dL (N 70–360), 17-OH progesterone 4.5 ng/mL (N 0.59–3.44), cromogranine A 6063 ng/mL (N 0–100), and markedly elevated urinary amines (adrenaline 173 nmol/24h, N 0–109; noradrenaline 5033 nmol/24h, N 89–473; normetanephrine 334605 nmol/24h, N 480–2424; metanephrine 15998 nmol/24h, N 264–1729; dopamine 4808 nmol/24h, N 424–2612). Hypercalcemia with hypophosphatemia and supressed PTH level was also detected. 68Ga-DOTANOC PET revealed a mass of the right adrenal gland with overexpression of somatostatin receptors (likely pheochromocytoma), without evidence of other tumor lesions of neuroendocrine origin. Pituitary MRI showed normal pituitary gland. Potassium supplementation, alpha-blockade with phenoxybenzamine, and metyrapone were initiated. Due to severe back pain, a CT scan of the spine was performed detecting compressive osteoporotic fractures in the mid dorsal and low dorsal segments. The patient was submitted to right adrenalectomy. Histology revealed pheochromocytoma with 11.2*9mm, with capsular and vascular invasion, extra-adrenal extension, necrosis, and atypical mitosis, with Ki67 of 9.5% and PASS score of 16. Postoperative analysis showed ACTH 45.6 pg/mL (N 7.2-63,3), late-night salivar cortisol < 0,0544 µg/dL (N < 0,32) and free urinary cortisol 41.4 µg/24h (N 4.3–176.0). Discussion: Ectopic cushing syndrome caused by pheochromocytoma is a rarely described entity. In this young patient, it caused rapid clinical progression of hypercortisolism with important hydroelectrolytic disturbances and compressive vertebral fractures, requiring prompt surgical intervention for clinical remission and improvement.

scholarly journals Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with Cushing Syndrome

2018 ◽  
Vol 64 (3) ◽  
pp. 586-596 ◽  
Author(s):  
Graeme Eisenhofer ◽  
Jimmy Masjkur ◽  
Mirko Peitzsch ◽  
Guido Di Dalmazi ◽  
Martin Bidlingmaier ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Free Cortisol ◽  
Multistep Process ◽  
Steroid Profiles ◽  
Plasma Steroids ◽  
Metabolome Profiling ◽  
Adrenal Disease

Abstract BACKGROUND Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis. METHODS In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome. Disease was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome, 12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for comparison. RESULTS Compared with patients without disease, the largest increases in plasma steroids among patients with Cushing syndrome were observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients with ectopic disease showed the most prominent increases, but there was considerable variation for other steroids according to subtype. Patients with adrenal disease had the lowest concentrations of androgens, whereas those with ectopic and pituitary disease showed the lowest concentrations of aldosterone. Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10 selected steroids, subjects with and without different Cushing syndrome subtypes could be discriminated nearly as closely as with the use of salivary and urinary free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin (9.5% vs 5.8% misclassification). CONCLUSIONS Patients with different subtypes of Cushing syndrome show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes.

Serum Visfatin does not seem to be a Useful Marker to Guide Glucocorticoid Substitution in Adrenal Insufficiency

2020 ◽  
Vol 52 (05) ◽  
pp. 322-328
Author(s):  
Marta Fichna ◽  
Agata Czarnywojtek ◽  
Anna Sowińska ◽  
Maria Gryczyńska ◽  
Paweł Gut ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Elevated Serum ◽  
Urinary Free Cortisol ◽  
Control Group ◽  
Fasting Insulin ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Free Cortisol ◽  
Biochemical Analyses ◽  
Visfatin Level ◽  
Factor Α

AbstractPrimary adrenal insufficiency (Addison’s disease, AD) requires lifelong steroid substitution. Excess exogenous glucocorticoids promote abdominal obesity, insulin-glucose imbalance, and hypertension. Reliable markers of the adequate glucocorticoid replacement are lacking. Visfatin is a pro-inflammatory adipokine, with enzymatic activity of nicotinamide phosphoribosyltransferase. It enhances leukocyte function and synthesis of tumour necrosis factor α (TNFα) and interleukin-6 (IL-6). Serum visfatin is elevated in autoimmunity, but also in obesity, insulin resistance, and metabolic syndrome. This study was aimed to investigate whether serum visfatin could guide the glucocorticoid substitution in AD. Biochemical analyses were performed in 96 patients with AD (mean age 43.3±14.9 years) and 91 controls (43.5±12.5 years). Visfatin level was significantly elevated in patients with AD compared to controls (p<0.0001). Higher circulating IL-6 was also detected among subjects with AD (p=0.006). In AD, visfatin level was positively correlated with IL-6 (p=0.014), TNFα (p=0.001), body mass (p=0.015), fasting insulin (p=0.001) and HOMA-IR (p=0.001). No relationship was noticed with daily hydrocortisone (p=0.096) and urinary free cortisol excretion (p=0.499). Only the correlations with IL-6 and fasting insulin survived multiple regression analysis (p=0.049 and p=0.005, respectively). Additionally, positive correlation between visfatin and autoantibodies to 21-hydroxylase was noted (p=0.005). In the control group serum visfatin was correlated with IL-6 (p=0.009) and TNFα (p=0.0002). The current study reveals elevated serum visfatin in autoimmune AD. Visfatin does not seem a useful marker of the glucocorticoid replacement, although it correlates with fasting insulin and pro-inflammatory molecules. Further functional analyses are warranted to elucidate the role of visfatin in autoimmunity.

Accuracy of Laboratory Tests for the Diagnosis of Cushing Syndrome

2020 ◽  
Vol 105 (6) ◽  
pp. 2081-2094 ◽  
Author(s):  
Brandon P Galm ◽  
Nidan Qiao ◽  
Anne Klibanski ◽  
Beverly M K Biller ◽  
Nicholas A Tritos
Keyword(s):  
Likelihood Ratio ◽  
Diagnostic Tests ◽  
Cushing Syndrome ◽  
Data Extraction ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Late Night ◽  
Free Cortisol

Abstract Context The diagnosis of Cushing syndrome (CS) can be challenging. It remains to be determined which diagnostic tests are the most accurate. Objective To summarize the accuracy of diagnostic tests for CS using contemporary meta-analytic techniques (hierarchical models). Data Sources PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systemic Reviews (inception until August 3, 2018). Study Selection Studies performed in adults that determined the accuracy of one or more diagnostic tests: overnight 1-mg dexamethasone suppression test (DST), 2-day low-dose DST (2d DST), 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC), midnight serum cortisol (MSC), and the dexamethasone-suppressed CRH (dex-CRH) and desmopressin (dex-DDAVP) tests. Data Extraction Two authors independently extracted data and performed methodological assessments. Data Synthesis One hundred thirty-nine studies (14 140 participants) were included in the analysis. The respective sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio (95% confidence interval [CI]) estimates include the following: DST 98.6% (96.9%-99.4%), 90.6% (86.4%-93.6%), 10.5 (7.2-15.3), and 0.016 (0.007-0.035); 2d DST 95.3% (91.3%-97.5%), 92.8% (85.7%-96.5%), 13.2 (6.47-27.1), and 0.051 (0.027-0.095); UFC 94.0% (91.6%-95.7%), 93.0% (89.0%-95.5%), 13.3 (8.47-21.0), and 0.065 (0.046-0.092); LNSC 95.8% (93.%-97.2%), 93.4% (90.7%-95.4%), 14.6 (10.3-20.7), and 0.045 (0.030-0.066); MSC 96.1% (93.5%-97.6%), 93.2% (88.1%-96.3%), 14.2 (7.96-25.2), and 0.042 (0.026-0.069); and dex-CRH 98.6% (90.4%-99.8%), 85.9% (67.6%-94.7%), 7.0 (2.80-17.6), and 0.016 (0.002-0.118). A single study evaluated dex-DDAVP. Meta-regression and a novel network meta-analytic approach suggest that DST is the most sensitive while UFC is the least sensitive. Conclusions All of the included diagnostic tests for CS are highly sensitive and specific. It appears that the DST is the most sensitive while the UFC is less sensitive. The specificity of all first-line tests appears comparable.

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