scholarly journals RAPID DEVELOPMENT OF IATROGENIC CUSHING SYNDROME IN A PATIENT ON RITONAVIR: THE ADVERSE METABOLIC CONSEQUENCE OF TOPICAL STEROID USE

2020 ◽  
Vol 6 (6) ◽  
pp. e346-e348
Author(s):  
Jeremy D. Purser ◽  
Ruba Riachy ◽  
Lucas S. Blanton ◽  
L. Maria Belalcazar
Keyword(s):  
Enzyme Immunoassay ◽  
Salivary Cortisol ◽  
High Performance ◽  
Cushing Syndrome ◽  
Rapid Development ◽  
Topical Steroid ◽  
Steroid Use ◽  
Genital Mucosa ◽  
Free Cortisol ◽  
Metabolic Consequence

Objective: Topical steroid use is common, but its association with Cushing syndrome is rare. We report the rapid development of iatrogenic Cushing syndrome in a patient on ritonavir who applied a moderate-potency topical steroid cream, triamcinolone, on his genital mucosa for treatment of phimosis. Methods: Clinical and diagnostic challenges associated with topical steroid use are presented and discussed. Results: A 41-year-old man with human immunodeficiency virus infection on stable antiretroviral therapy that included ritonavir, a cytochrome P450 3A4 inhibitor, presented with new onset diabetes and development of overt cushingoid features over a 4-week period. He reported no known history of steroid use. A midnight salivary cortisol using a quantitative enzyme immunoassay was obtained and reported at >15.0 μg/dL (normal, <0.112 μg/dL). However, free cortisol in a 24-hour urine collection was undetectable by high-performance liquid chromatography and morning plasma cortisol was also unexpectedly low at 1.1 μg/dL (normal, 4.5 to 23.0 μg/dL). Further investigation revealed that the patient had been applying a topical cream with triamcinolone acetonide (0.1%) on the glans penis for treatment of phimosis. The salivary enzyme immunoassay for cortisol appears to have detected the absorbed triamcinolone, a compound known to cross-react with cortisol in this assay. Conclusion: This case raises awareness on the severe metabolic consequence resulting from the seemingly benign use of a topical steroid medication when applied to the genital mucosa in the setting of stable therapy with ritonavir and illustrates the limitations of salivary cortisol enzyme immunoassays for the evaluation of Cushing syndrome in this setting.

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 SUN-927 Ectopic Cushing Syndrome Due to a Metastatic Neuroendocrine Tumor to the Breast

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jian Zhang ◽  
Laurence Katznelson
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Neuroendocrine Tumor ◽  
Cushing Syndrome ◽  
Rapid Development ◽  
Neuroendocrine Differentiation ◽  
Bilateral Adrenalectomy ◽  
Mediastinal Lymphadenopathy ◽  
Neuroendocrine Neoplasms ◽  
Free Cortisol

Abstract Introduction: We present a rare case of ectopic Cushing syndrome (CS) due to a neuroendocrine tumor (NET) metastatic to the breast. Case: A 38-year-old female was referred for ACTH-dependent CS. She had rapid development of cushingoid features and hypertension three months prior to presentation. A 24-hour urinary free cortisol (UFC) was elevated to 2548 μg (0-50 μg/24hr), and ACTH was 228 pg/mL (10-60 pg/mL). A pituitary MRI was normal, and inferior petrosal sinus sampling was not consistent with a central ACTH source. A DOTA-TATE scan showed mediastinal lymphadenopathy and a 0.8cm area of uptake in the right breast. The patient was placed on ketoconazole and UFC normalized. Following biopsy, she underwent breast lumpectomy at an outside hospital, and pathology showed triple negative invasive carcinoma of the breast. Chemotherapy was initiated. However, her CS rapidly worsened: repeat UFC was 4867 μg, and ACTH was 369 pg/mL. Re-review of her pathology slides at our facility showed that the tumor stained negative for breast markers and positive for markers of NET and ACTH. Ki67 staining was approximately 30%. Chemotherapy for breast cancer was immediately stopped. A follow-up PET-CT continued to show uptake in the mediastinal lymph nodes. FNA of these lymph nodes revealed metastatic NET. In order to maximize control of her CS prior to chemotherapy, she underwent bilateral adrenalectomy (BLA). Afterwards, the patient received 10 cycles of chemotherapy with modified FOLFOX-7 for her NET. Thus far, the tumor burden appears stable, and she has been recommended to hold off on radiation therapy. She is currently taking replacement doses of hydrocortisone and fludrocortisone. Conclusion: In this challenging case, determination of source of ACTH hypersecretion led to an initial diagnosis of breast cancer. Primary breast carcinoma with neuroendocrine differentiation has been reported to show significant overlap in pathology with NET metastatic to the breast1. However, worsening of the CS in this case led to consideration of an alternative diagnosis, resulting in diagnosis of an ACTH producing NET metastatic to the breast. Prior to chemotherapy, she underwent BLA, which may lower morbidity and mortality associated with ACTH-dependent CS2, particularly given plan for further chemotherapy. Reference: 1. Mohanty SK, Kim SA, DeLair DF, et al. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation. Mod Pathol. 2016;29(8):788-798. doi:10.1038/modpathol.2016.69.2. 2. Morris LF, Harris RS, Milton DR, et al. Impact and timing of bilateral adrenalectomy for refractory adrenocorticotropic hormone-dependent Cushing’s syndrome. Surgery. 2013;154(6):1174-1183; discussion 1183-1184.

LC-MSMS assays of urinary cortisol, a comparison between four in-house assays

2018 ◽  
Vol 56 (7) ◽  
pp. 1109-1116 ◽  
Author(s):  
Julie Brossaud ◽  
Monique Leban ◽  
Jean-Benoit Corcuff ◽  
Florence Boux de Casson ◽  
Anne-Gaëlle Leloupp ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
High Performance ◽  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Normal Ranges ◽  
Free Cortisol ◽  
Solid Liquid

Abstract Background: Twenty-four hour urinary free cortisol (UFC) determination can be used for screening and follow-up of Cushing syndrome (CS). As immunoassay methods lack specificity for UFC measurement, the use of high-performance liquid chromatography coupled to mass spectrometer (LC-MSMS) is recommended. The aim of our study was to compare UFC results using four LC-MSMS methods performed in four independent laboratories in order to evaluate interlaboratory agreement. Methods: Frozen aliquots of 24-h urine samples (78 healthy volunteers and 20 patients with CS) were sent to four different laboratories for analysis. Following liquid-liquid or solid-liquid extraction, UFC were determined using four different LC-MSMS assay. Results: UFC intra- and interassays variation coefficients were lower than 10% for each centre. External quality control results were not significantly different. UFC normal ranges (established from healthy volunteers) were 17–126, 15–134, 12–118 and 27–157 nmol/day, respectively. Classification of UFC from healthy volunteers and patients with CS using a 95th percentile threshold was similar. However, for extreme UFC values (<50 or >270 nmol/day), negative or positive bias was noted. Conclusions: Even for highly specific methods such as LC-MSMS, variations of results can be found depending on analytical process. Validation of LC-MSMS methods including determination of the reference range is essential.

Is salivary cortisol a better index than free cortisol in serum or urine for diagnosis of Cushing syndrome?

1993 ◽  
Vol 39 (6) ◽  
pp. 1353-1354 ◽  
Author(s):  
R Bonnin ◽  
C Villabona ◽  
A Rivera ◽  
E Guillen ◽  
E Sagarra ◽  
...  
Keyword(s):  
Salivary Cortisol ◽  
Cushing Syndrome ◽  
Free Cortisol

scholarly journals Bedtime Salivary Cortisol as a Screening Test for Cushing Syndrome in Children

2021 ◽  
Vol 5 (5) ◽  
Author(s):  
Grethe Å Ueland ◽  
Ralf Kellmann ◽  
Melissa Jørstad Davidsen ◽  
Kristin Viste ◽  
Eystein S Husebye ◽  
...  
Keyword(s):  
Salivary Cortisol ◽  
Screening Test ◽  
Healthy Subjects ◽  
Cushing Syndrome ◽  
Healthy Children ◽  
Late Night ◽  
Diagnostic Threshold ◽  
Free Cortisol ◽  
Cutoff Levels ◽  
Obesity Clinic

Abstract Background Diagnosing Cushing syndrome (CS) can be challenging. The 24-hour urine free cortisol (UFC) measurement is considered gold standard. This is a laborious test, dependent on correct urine collection. Late-night salivary cortisol is easier and is used as a screening test for CS in adults, but has not been validated for use in children. Objective To define liquid chromatography tandem mass spectrometry (LC-MS/MS)-based cutoff values for bedtime and morning salivary cortisol and cortisone in children, and validate the results in children with and without CS. Methods Bedtime and morning salivary samples were collected from 320 healthy children aged 4 to 16 years. Fifty-four patients from the children’s outpatient obesity clinic and 3 children with pituitary CS were used for validation. Steroid hormones were assayed by LC-MS/MS. Cutoff levels for bedtime salivary cortisol and cortisone were defined by the 97.5% percentile in healthy subjects. Results Bedtime cutoff levels for cortisol and cortisone were 2.4 and 12.0 nmol/L, respectively. Applying these cutoff levels on the verification cohort, 1 child from the obesity clinic had bedtime salivary cortisol exceeding the defined cutoff level, but normal salivary cortisone. All 3 children with pituitary CS had salivary cortisol and cortisone far above the defined bedtime cutoff levels. Healthy subjects showed a significant decrease in salivary cortisol from early morning to bedtime. Conclusions We propose that bedtime salivary cortisol measured by LC-MS/MS with a diagnostic threshold above 2.4 nmol/L can be applied as a screening test for CS in children. Age- and gender-specific cutoff levels are not needed.

Surface/interface nanoengineering for rechargeable Zn–air batteries

2020 ◽  
Vol 13 (4) ◽  
pp. 1132-1153 ◽  
Author(s):  
Tianpei Zhou ◽  
Nan Zhang ◽  
Changzheng Wu ◽  
Yi Xie
Keyword(s):  
High Performance ◽  
Rapid Development

Surface/interface nanoengineering of electrocatalysts and air electrodes will promote the rapid development of high-performance rechargeable Zn–air batteries.

High Performance Thin Layer Chromatography (HPTLC) for the Investigation of Medicinal Plants

2020 ◽  
Vol 16 ◽  
Author(s):  
Alper Gökbulut
Keyword(s):  
Medicinal Plants ◽  
High Performance ◽  
Separation Efficiency ◽  
Rapid Development ◽  
Herbal Remedies ◽  
Qualitative And Quantitative ◽  
Powerful Analytical Tool ◽  
Quantitative Examination ◽  
Data Acquisition And Processing ◽  
Layer Chromatography

Background: Chromatographic techniques such as TLC basically and, HPLC, GC, HPTLC equipped with various detectors are most frequently used for the qualitative and quantitative examination of herbals. Method: An overview of the recent literature concerning the usage of HPTLC for the analysis of medicinal plants has been reviewed. Results: During the last decade/s, HPTLC, a modern, sophisticated and automatized TLC technique with better and advanced separation efficiency, detection limit, data acquisition and processing, has been used for the analysis of herbal materials and preparations since the rapid development of technology in chromatography world. HPTLC with various detectors is a powerful analytical tool especially for the phytochemical applications such as herbal drug quantification and fingerprint analysis. Conclusion: In this review, a latest perspective has been established and some of the previous studies were summarized for the usage of HPTLC in the analysis of herbal remedies, dietary supplements and nutraceuticals.

scholarly journals A RF Redundant TSV Interconnection for High Resistance Si Interposer

Micromachines ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 169
Author(s):  
Mengcheng Wang ◽  
Shenglin Ma ◽  
Yufeng Jin ◽  
Wei Wang ◽  
Jing Chen ◽  
...  
Keyword(s):  
Millimeter Wave ◽  
High Frequency ◽  
High Performance ◽  
Rapid Development ◽  
Coplanar Waveguide ◽  
Equivalent Circuit Model ◽  
High Resistivity ◽  
Performance Requirements ◽  
Wave Radar ◽  
Interconnect Design

Through Silicon Via (TSV) technology is capable meeting effective, compact, high density, high integration, and high-performance requirements. In high-frequency applications, with the rapid development of 5G and millimeter-wave radar, the TSV interposer will become a competitive choice for radio frequency system-in-package (RF SIP) substrates. This paper presents a redundant TSV interconnect design for high resistivity Si interposers for millimeter-wave applications. To verify its feasibility, a set of test structures capable of working at millimeter waves are designed, which are composed of three pieces of CPW (coplanar waveguide) lines connected by single TSV, dual redundant TSV, and quad redundant TSV interconnects. First, HFSS software is used for modeling and simulation, then, a modified equivalent circuit model is established to analysis the effect of the redundant TSVs on the high-frequency transmission performance to solidify the HFSS based simulation. At the same time, a failure simulation was carried out and results prove that redundant TSV can still work normally at 44 GHz frequency when failure occurs. Using the developed TSV process, the sample is then fabricated and tested. Using L-2L de-embedding method to extract S-parameters of the TSV interconnection. The insertion loss of dual and quad redundant TSVs are 0.19 dB and 0.46 dB at 40 GHz, respectively.

scholarly journals Diurnal Salivary Cortisol in Sarcopenic Postmenopausal Women: The OsteoLaus Cohort

2021 ◽  
Author(s):  
Elena Gonzalez Rodriguez ◽  
Pedro Marques-Vidal ◽  
Bérengère Aubry-Rozier ◽  
Georgios Papadakis ◽  
Martin Preisig ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Salivary Cortisol ◽  
Population Based ◽  
Cross Sectional Study ◽  
Body Composition Assessment ◽  
Cross Sectional ◽  
X Ray ◽  
Free Cortisol ◽  
Cortisol Levels ◽  
The Relationship

AbstractSarcopenia, similar to hypercortisolism, is characterized by loss of muscle mass and strength. Cortisol circadian rhythm changes with aging (blunted late-day nadir values) were suggested to contribute to this decline. We aimed to explore the relationship between diurnal salivary cortisol values and sarcopenia diagnosis and its components in postmenopausal women. This is a cross-sectional study within the OsteoLaus population-based cohort in Lausanne (Switzerland). Participants had a body composition assessment by dual X-ray absorptiometry (DXA), a grip strength (GS) measure, and salivary cortisol measures (at awakening, 30 min thereafter, 11 AM (sc-11AM) and 8 PM (sc-8PM)). Associations between salivary cortisol and sarcopenia diagnosed by six different criteria (based on appendicular lean mass (ALM) assessed by DXA, and muscle strength by GS), and its components, were analyzed. 471 women aged > 50 years (63.0 ± 7.5) were included. Various definitions identified different participants as sarcopenic, who consistently presented higher salivary cortisol at 11 AM and/or 8 PM. There were no associations between salivary cortisol levels and ALM measures, either absolute or after correction to height squared (ALM index) or body mass index. GS was inversely correlated to sc-11AM (r = − 0.153, p < 0.001) and sc-8PM (r = − 0.118, p = 0.002). Each 10 nmol/l increase of sc-11AM, respectively sc-8PM, was associated with a GS decrease of 1.758 (SE 0.472) kg, respectively 2.929 (SE 1.115) kg. In postmenopausal women, sarcopenia is associated with higher salivary cortisol levels at 11 AM and 8 PM. An increase of daily free cortisol levels in the physiological range could participate to sarcopenia development by decreasing muscle function in postmenopausal women.

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