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 ◽  
...  

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.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A521-A522
Author(s):  
Maria Fleseriu ◽  
Beverly M K Biller ◽  
Jerome Bertherat ◽  
Jacques Young ◽  
Giorgio Arnaldi ◽  
...  

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 &gt;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.


Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4329
Author(s):  
Alexandra Povaliaeva ◽  
Viktor Bogdanov ◽  
Ekaterina Pigarova ◽  
Artem Zhukov ◽  
Larisa Dzeranova ◽  
...  

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently lower 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Natalia Gabriela Deligiannis ◽  
Soledad Sosa ◽  
Diego Gonzalez ◽  
Carolina Ibar ◽  
Dario Gustavo Jacobsen ◽  
...  

Abstract Diagnosis of endogenous Cushing’s syndrome entails corticotropic autonomy, lack of circadian rhythm and/or hypercortisolism, evaluated through 24h urinary free cortisol (UFC). Hair cortisol measurement (HCM) has been described as an alternative marker of cortisol exposure over the preceding three months. OBJECTIVES To evaluate HCM in Cushing’s disease (CD). To analyze the correlation between HCM and UFC. To compare HCM values in CD vs controls. PATIENTS AND METHODS 3 cm hair from posterior vertex in CD and in controls age- and gender-matched between May 2017 and May 2019. Controls were low level stressed individuals (Holmes-Rahe’s scale) without adrenal disease. Normal reference interval of HCM was defined (40-128 pg/mg hair). Measurement: Siemens Immulite 2000 (Gwynedd, UK) automated chemoluminiscent immunoassay (CLIA) UFC values within the 3 months previous to hair collection were considered. Controlled CD defined as UFC ≤1 upper normal limit (UNL) with or without treatment, remission as UFC ≤1 without pituitary lesion. Results are presented as median (m) and range. Kruskal-Wallis ANOVA used for median difference evaluation and Kappa index for concordance determination. Chi2 test for comparison of recategorized UFC and HCM. Statistical analysis performed with SPSS 23.0 RESULTS 23 CD patients recruited, median age 42 ± 11 years; 91% (n=21) female; 10 samples collected at diagnosis and 13 during follow-up. Control group composed of 50 individuals 45% (n=10) had controlled CD (mUFC 0.42 UNL, range 0.1-0.9) and a mHCM of 134.5 pg/mg (62-334) and 55% (n=12) did not have control (mUFC 2.2, 1.1-6) and a mHCM of 150.5 (75-459). After recategorization of UFC (&gt; o ≤ 1 UNL) and HCM (&gt; o ≤ 128 pg/mg), determinations were associated (Chi2, p= 0.18), however, the concordance was acceptable (Kappa index = 0.276). After dividing CD patients according to HCM, 35% (n=8) had normal HCM: mHCM 113.5 (62-126) and mUFC 0.45 (0.1- 4.4). Among them, 63% (n=5) had controlled CD (mHCM 110, 62-121; mUFC 0.39, 0.1-0.85); 25% (n=2) had active CD (mUFC 2.7, 1.1-4.4; mHCM 121, 75-126). 65% had high HCM (n=15): mHCM 167 (132-459) and mUFC 1.36 (0.1-6). Most of them had active CD (n=11, 73%): mHCM 160 (132-459) and mUFC 2.2 (1.1-6). Four patients with elevated HCM (m 248, 148-334) had normal UFC (m 0.61, 0.12-0.92): 2 were in remission, 1 had normal postsurgical UFC with active disease in the follow-up and 1 had normal UFC under medical treatment. Controls (n=50) had mHCM 62.5 (40-126), significantly different from CD. CONCLUSIONS We evaluated HCM in CD, proposing this method as an additional diagnostic test for hypercortisolism. The acceptable concordance between UFC and HCM is possibly due to the different duration of the evaluated periods. The difference in the HCM values observed between controlled or active CD patients and controls permits the consideration of the method as an alternative in the diagnosis and/or follow-up of CD.


2021 ◽  
Author(s):  
Yodpong Chantarasorn ◽  
Kochapong Rasmidatta ◽  
Itsara Pokawattana ◽  
Sukhum Silpa-archa

Abstract Background: Hypercortisolism has long been correlated with choroidal vasorelaxation in central serous chorioretinopathy (CSCR). This may explain the inconsistency of therapeutic responses of the mineralocorticoid receptor (MR) antagonist since hyperaldosteronism has rarely been detected in such cases. Hence, an early treatment using ketoconazole, the first line cortisol inhibitor that also blocks the MR ligand, appears to be rational. This study aimed to evaluate the effects of ketoconazole on CSCR, and to analyze correlations between choroidal thickness and steroid hormones.Method: In this three-center retrospective cohort, forty-one naïve CSCR eyes of 41 patients were categorized into control (20 eyes) and treatment group (21 eyes). Patients in the treatment group were given oral ketoconazole at a daily dose of 400 or 600 mg for three to six weeks. At week 12, rescue laser therapy was applied to patients exhibiting persistent subretinal fluid (SRF). We performed a survival analysis to determine the time interval from presentation to clinical resolution of SRF. The secondary outcomes consisted of proportion of eyes with persistent SRF, and factors affecting therapeutic response.Results: Mean 24-hour urinary free cortisol (UFC) were elevated at 181 ± 70 and 150 ± 68 µg/day (range = 20-150) in the treatment and control group (p = 0.21). After controlling for age and gender, baseline UFC levels demonstrated a positive correlation with choroidal thickness in both eyes (p < 0.05). Ketoconazole significantly accelerated the resolution of CSCR with the median time to resolution of 7 versus 16 weeks (p < 0.01), and reduced the proportion of eyes receiving rescue therapy at 12 weeks (23.8% versus 50%, p = 0.01). Prolonged CSCR durations were likely found in elderly patients who had thick choroid in fellow eyes.Conclusions: Elevated glucocorticoids are likely responsible for the pathogenesis of CSCR. Therefore, a temporary decrease in choroidal hyperpermeability using the cortisol blocker could reduce the persistency of CSCR.


2017 ◽  
Vol 5 (3) ◽  
pp. 299-304 ◽  
Author(s):  
Mona H. El Samahi ◽  
Nagwa Abdallah Ismail ◽  
Randa M. Matter ◽  
Abeer Selim ◽  
Alshaymaa Ahmed Ibrahim ◽  
...  

BACKGROUND: Visfatin is an intracellular enzyme, known as nicotinamide phosphoribosyltransferase (Nampt) and pre-B-cell colony-enhancing factor (PBEF-1). It has insulin-mimetic effects and lowers plasma glucose levels.AIM: The aim of the work was to assess serum concentration of Visfatin in type 1 diabetic children and adolescents and study its relationships with duration of diabetes, body mass index (BMI), glycemic control, insulin dosage, lipid profile and microvascular complications.MATERIAL AND METHODS: Fifty children and adolescents with type 1 diabetes mellitus were recruited with 30 ages and gender-matched healthy subjects. They were subjected to history taking; anthropometric measurements and chronic diabetic complications were recorded if present. Laboratory analysis included urinary microalbumin, serum triglycerides, HDL, LDL, cholesterol, fasting blood glucose, glycosylated Hb (HbA1c) and serum visfatin which was measured with enzyme-linked immunosorbent assay.RESULTS: Diabetic patients showed highly significant decrease in the level of visfatin compared to the control group (P = 0.0001).There was significant further decrease in visfatin level in diabetics with microalbuminuria (n = 13) compared to normoalbuminuric patients (n = 37) (P = 0.015). There was highly significant inverse correlation between visfatin level with age (r = -0.379, p = 0.007), BMI (r = -0.418, p = 0.003), waist circumference (r = -0.430, p = 0.002), hip circumference (r = -0.389, p = 0.005) and microalbuminuria (r = -0.323, p = 0.022).CONCLUSIONS: Type 1 diabetic children and adolescents had a significantly lower visfatin level compared to controls. A marked decrease in the level of visfatin was shown in patients with microalbuminuria with an inverse correlation with BMI suggesting an important role of visfatin in the pathogenesis of type 1 diabetics and type 1 diabetic nephropathy.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A136-A136
Author(s):  
Lorena Suárez Gutiérrez

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.


2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Nahla Hamed Anber ◽  
Ahmed H. EL-Sebaie ◽  
Noureldien H.E. Darwish ◽  
Shaker A. Mousa ◽  
Sameh S. Shamaa

Abstract Background: Lymphoma is a group of blood cell tumors which develop from lymphocytes. The main forms of lymphoma are Hodgkin lymphoma (HL) and non-HL (NHL). Cytokines may contribute to lymphoma and they are related to risk NHL and HL. Aim: Assessment of the serum level of certain inflammatory markers as complementary indicators to confirm diagnosis of lymphoma patients that may be subjected to more invasive biopsy methods. Method: The serum levels of interleukin (IL)-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF), and eotaxin were assessed by Bio-Plex Pro assays in 81 lymphoma patients and 44 NHL and 37 HL patients before and after chemotherapy treatment as well as 20 healthy persons as a control group. Results: Lymphoma patients showed significantly raised marker levels before treatment and significantly reduced levels related to pre-treatment and controls of post-treatment for most of the markers. MCP-1 reported the highest diagnostic accuracy. G-CSF significantly raised pre-treatment and TNF-α. MCP-1 significantly increased in post treated HL compared with NHL. In order to distinguish HL from NHL, G-CSF reported the highest diagnostic accuracy. NHL patients reported complete remission (CR) and those who reported stable disease (SD) and progressive disease (PD) represented 25% and 38% respectively compared with 16% and 27% of HL patients, while partial remission (PR) of HL patients were 56% compared with 36% of NHL patients. Conclusion: Most of the markers were significantly increased in pre-treatment but significantly decreased post-treatment. However, it was not considerably enough to get better prognosis of the disease. Elevated serum levels of inflammatory markers correlate with disease severity and low benefit from treatment.


2018 ◽  
Author(s):  
Ahmed Hanafy ◽  
Chinnadorai Rajeswaran ◽  
Saad Saddiq ◽  
Warren Gillibrand ◽  
John Stephenson

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Quénéhervé ◽  
D. Drui ◽  
J. Blin ◽  
M. Péré ◽  
E. Coron ◽  
...  

AbstractGastrointestinal symptoms are frequent in acute adrenal insufficiency. Although digestive symptoms can significantly reduce quality of life, they are rarely described in patients with treated chronic adrenal insufficiency (CAI). We aimed to characterize digestive symptoms in CAI patients. We used the section pertaining functional bowel disorders of the Rome IV questionnaire. A questionnaire was published on the website of the non-profit patient association “Adrenals” (NPPA of CAI patients) for five months. Information on demographics, characteristics of adrenal insufficiency, digestive symptoms and quality of life was collected. The relatives of CAI patients served as a control group. We analyzed responses of 33 control subjects and 119 patients (68 primary adrenal insufficiency (PAI), 30 secondary adrenal insufficiency (SAI) and 21 congenital adrenal hyperplasia (CAH)). Abdominal pain at least once a week over the past 3 months was reported by 40%, 47% and 33% of patients with PAI, SAI and CAH respectively versus 15% for the controls (p = 0.01). Symptoms were consistent with the Rome IV criteria for irritable bowel syndrome in 27%, 33% and 33% of patients respectively versus 6% for the controls (p < 0.0001). Quality of life was described as poor or very poor in 35%, 57% and 24% of patients respectively versus 5% for the controls (p < 0.0001). In conclusion, digestive symptoms are frequent and incapacitating in CAI patients and similar to symptoms of irritable bowel syndrome in 30% of CAI patients. Assessment and management of digestive symptoms should be considered a priority for physicians treating patients with CAI.


Author(s):  
Theresia Indah Budhy ◽  
Ira Arundina ◽  
Meircurius Dwi Condro Surboyo ◽  
Anisa Nur Halimah

Abstract Objectives The purpose of this study is to analyze the effects of rice husk liquid smoke in Porphyromonas gingivalis-induced periodontitis in the inflammatory and proliferation marker such as nuclear factor kappa β (NF-kB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), fibroblast growth factor 2 (FGF2), collagen type 1 (COL-1) expression, and the number of macrophages, lymphocytes, and fibroblasts. Materials and Methods Rice husk liquid smoke is obtained by the pyrolysis process. Porphyromonas gingivalis-induced periodontitis in 20 μL phosphate-buffered saline containing 1 × 109 CFU was injected into the lower anterior gingival sulcus of Wistar rats. The periodontitis was then treated with 20 μL/20 g body weight of rice husk liquid smoke once a day for 2 and 7 days, respectively. After treatment, the bone and lower anterior gingival sulcus were analyzed with immunohistochemistry and hematoxylin–eosin staining. Results The treatment of periodontitis with rice husk liquid smoke showed a lower NF-kB, TNF-α, and IL-6 expression and a higher TGF-β, FGF2, and COL-1 expression than the control after treatment for 2 and 7 days (p < 0.05), respectively. The number of macrophages and fibroblasts was also higher when compared with the control group (p < 0.05), but the number of lymphocytes was lower than the control (p < 0.05). Conclusion Rice husk liquid smoke showed its effects on Porphyromonas gingivalis-induced periodontitis with a decrease in inflammatory markers and an increase in proliferation markers. The development of a rice husk liquid smoke periodontitis treatment is promising.


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