scholarly journals Persistent increase of osteoprotegerin levels after cortisol normalization in patients with Cushing's syndrome

2010 ◽  
Vol 162 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Valentina Camozzi ◽  
Francesca Sanguin ◽  
Nora Albigier ◽  
Carla Scaroni ◽  
Franco Mantero ◽  
...  

ObjectiveOsteoprotegerin (OPG) has been identified as a decoy receptor that inhibits osteoclast differentiation and, more recently, as a paracrine regulator of vascular calcification. OPG is suppressed by glucocorticoids (GC); however, results from experimental and clinical studies are not univocal. The aim of this study was to evaluate OPG and bone metabolism in patients with Cushing's syndrome (CS) before and after cure.Design and methodsTwenty-six patients with CS (all women, mean age: 39.1±11.9 years) and 24 age- and gonadal status-matched healthy women were studied for bone mineral density, bone metabolism, OPG, and receptor activator of nuclear factor-kB ligand at baseline. Twelve patients were also studied 6–18 months after surgery, with persistent normalization of cortisol levels.ResultsOPG was significantly higher and osteocalcin (OC) was significantly lower in CS patients than in controls (OPG: 4.17±1.23 vs 2.95±0.79 pmol/l, P=0.00001; OC: 15.0±6.1 vs 18.8±6.8 ng/ml, P=0.04 in CS and controls respectively). After cure, we found no difference in OPG levels, despite a significant increase in OC levels (from 16.4±11 to 37.2±15 ng/ml, P=0.03).ConclusionPatients with CS showed increased OPG serum levels that remained unchanged after recovery, despite a restoration of bone formation. We speculate that high levels of OPG could reflect the persistent damage of the GCs on cardiovascular system.

2002 ◽  
pp. 389-395 ◽  
Author(s):  
C Kristo ◽  
K Godang ◽  
T Ueland ◽  
E Lien ◽  
P Aukrust ◽  
...  

OBJECTIVE: It is well known that patients with endogenous Cushing's syndrome (CS) have decreased bone mass and enhanced risk for osteoporotic fractures, secondary to decreased bone formation and increased bone resorption. Immunological mediators, such as cytokines, have recently been shown to influence bone metabolism, and in the present study we examined serum levels of several cytokines, with known or potential effects on bone homeostasis, in 33 consecutive recruited untreated CS patients and 33 age-, sex- and body mass index-matched healthy controls. METHODS: Cytokine levels were measured by enzyme immunoassay and bone mass by dual-energy X-ray absorptiometry. RESULTS: Our main findings were (i) interleukin (IL)-8 and IL-18 levels were significantly increased in CS patients compared with controls. (ii) Levels of both IL-8 and IL-18 were positively correlated to serum cortisol. (iii) For serum levels of the 'classical' resorptive cytokines, i.e. IL-6 and tumor necrosis factor alpha, no significant differences were found between CS patients and controls. (iv) Raised IL-18 levels were correlated with decreased osteocalcin levels in CS patients. CONCLUSIONS: Our results demonstrated that CS patients have markedly elevated levels of the proinflammatory cytokines IL-8 and IL-18 in spite of high levels of the immunosuppressive hormone cortisol. These cytokines may be involved in the pathogenesis of disturbed bone homeostasis in CS.


1995 ◽  
Vol 80 (10) ◽  
pp. 2859-2865 ◽  
Author(s):  
A R Hermus ◽  
A G Smals ◽  
L M Swinkels ◽  
D A Huysmans ◽  
G F Pieters ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1895
Author(s):  
Francesca Marini ◽  
Francesca Giusti ◽  
Federica Cioppi ◽  
Davide Maraghelli ◽  
Tiziana Cavalli ◽  
...  

Primary hyperparathyroidism (PHPT) is the most common endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Persistent levels of increased parathyroid hormone (PTH) result in a higher incidence of osteopenia and osteoporosis compared to the general population. Surgical removal of hyper-functioning parathyroid tissue is the therapy of choice. This retrospective study evaluated the effect of parathyroidectomy (PTX) on bone metabolism and bone mass in two series of patients with MEN1 PHPT and sporadic PHPT (sPHPT) by comparing bone metabolism-related biochemical markers and bone mineral density (BMD) before and after surgery. Our data confirmed, in a higher number of cases than in previously published studies, the efficacy of PTX, not only to rapidly restore normal levels of PTH and calcium, but also to normalize biochemical parameters of bone resorption and bone formation, and to improve spine and femur bone mass, in both MEN1 PHPT and sPHPT. Evaluation of single-patient BMD changes after surgery indicates an individual variable bone mass improvement in a great majority of MEN1 PHPT patients. In MEN1 patients, PTX is strongly suggested in the presence of increased PTH and hypercalcemia to prevent/reduce the early-onset bone mass loss and grant, in young patients, the achievement of the bone mass peak; routine monitoring of bone metabolism and bone mass should start from adolescence. Therapy with anti-fracture drugs is indicated in MEN1 patients with BMD lower than the age-matched normal values.


2007 ◽  
Vol 51 (8) ◽  
pp. 1329-1338 ◽  
Author(s):  
Andrea Utz ◽  
Beverly M.K. Biller

Adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome is most often due to a pituitary corticotroph adenoma, with ectopic ACTH-secreting tumors representing approximately 15% of cases. Biochemical and radiological techniques have been established to help distinguish between these two entities, and thus aid in the localization of the neoplastic lesion for surgical resection. The test that offers the highest sensitivity and specificity is bilateral inferior petrosal sinus sampling (BIPSS). BIPSS is an interventional radiology procedure in which ACTH levels obtained from venous drainage very near the pituitary gland are compared to peripheral blood levels before and after corticotropin hormone (CRH) stimulation. A gradient between these two locations indicates pituitary Cushing's, whereas the absence of a gradient suggests ectopic Cushing's. Accurate BIPSS results require hypercortisolemia to suppress normal corticotroph ACTH production and hypercortisolemia at the time of the BIPSS to assure excessive ACTH secretion. In some cases, intrapituitary gradients from side-to-side can be helpful to localize small corticotroph adenomas within the sella. BIPSS has rare complications and is considered safe when performed at centers with experience in this specialized technique.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sharmilee Vetrivel ◽  
Ru Zhang ◽  
Mareen Engel ◽  
Barbara Altieri ◽  
Leah Braun ◽  
...  

ContextCushing’s syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging.ObjectiveCirculating microRNAs (miRNAs) are minimally invasive diagnostic markers. Our aim was to characterize the circulating miRNA profiles of CS patients and to identify distinct profiles between the two major CS subtypes.MethodsWe included three groups of patients from the German Cushing’s registry: ACTH-independent CS (Cortisol-Producing-Adenoma; CPA), ACTH-dependent pituitary CS (Cushing’s Disease; CD), and patients in whom CS had been ruled out (controls). Profiling of miRNAs was performed by next-generation-sequencing (NGS) in serum samples of 15 CS patients (each before and after curative surgery) and 10 controls. Significant miRNAs were first validated by qPCR in the discovery cohort and then in an independent validation cohort of 20 CS patients and 11 controls.ResultsNGS identified 411 circulating miRNAs. Differential expression of 14 miRNAs were found in the pre- and postoperative groups. qPCR in the discovery cohort validated 5 of the significant miRNAs from the preoperative group analyses. Only, miR-182-5p was found to be significantly upregulated in the CD group of the validation cohort. Comparing all CS samples as a group with the controls did not reveal any significant differences in expression.OutcomeIn conclusion, our study identified miR-182-5p as a possible biomarker for CD, which has to be validated in a prospective cohort. Furthermore, our results suggest that presence or absence of ACTH might be at least as relevant for miRNA expression as hypercortisolism itself.


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