Filter

Refine by Access

Refine by Date

—
  • Print
  • Save

Browse

You are looking at 71 - 80 of 20,504 items for

  • Refine by Access: All content x
Clear All
Restricted access

Subtype-specific pattern of white blood cell differential in endogenous hypercortisolism

Mario Detomas, Barbara Altieri, Irina Chifu, Hanna Remde, Xiang Zhou, Laura-Sophie Landwehr, Silviu Sbiera, Matthias Kroiss, Martin Fassnacht, and Timo Deutschbein

Objective

Endogenous hypercortisolism predisposes to impaired immune function and infections. To date, however, it is unknown whether there is a subtype-specific pattern in white blood cell (WBC) and WBC differential (WBCD) count.

Methods

A retrospective monocentric cohort study was carried out in patients with overt endogenous Cushing’s syndrome (CS) or adrenal incidentalomas and autonomous cortisol secretion (ACS), with WBC/WBCD analysis at initial diagnosis and after biochemical remission. Cut-offs were obtained by receiver-operating characteristics analysis.

Results

In total, 253 patients were analyzed (Cushing’s disease (CD); n  = 88; ectopic CS (ECS), n  = 31; cortisol-producing adrenal adenomas (CPA), n  = 40; ACS, n  = 45; adrenocortical carcinomas (ACC), n  = 49). Total leukocytes and neutrophils correlated positively with serum cortisol after 1-mg dexamethasone (r = 0.314 and r = 0.428), while a negative correlation was observed for lymphocytes and eosinophils (r = −0.374 and r= −0.380) (each P < 0.0001). Similar observations were made for 24 h-urinary free cortisol. CD and ECS differed in numbers of neutrophils and lymphocytes (P < 0.0001) and were well differentiated at a cut-off of 6.1 for the neutrophil/lymphocyte ratio (sensitivity 90.0%, specificity 89.4%, and areas under the curve (AUC) 0.918). For adrenocorticotropic hormone (ACTH)-independent CS, the best diagnostic outcome was obtained for the discrimination of CPA and ACC at a cut-off of 187.9 for the platelet/lymphocyte ratio (sensitivity 59.6%, specificity 80.6%, and AUC 0.713). For ECS, CPA, and CD, neutrophils decreased (delta −47.0, −29.7, and −26.2%) and lymphocytes increased (+123.2, +78.1, and +17.7%) already 3 months after remission.

Conclusion

Most immune cells correlate with the degree of hypercortisolism and differ among CS subtypes. WBCD changes are already identified 3 months after remission from endogenous hypercortisolism.

Open access

Women with polycystic ovary syndrome have poorer work ability and higher disability retirement rate at midlife: a Northern Finland Birth Cohort 1966 study

Linda Kujanpää, Riikka K Arffman, Eeva Vaaramo, Henna-Riikka Rossi, Jaana Laitinen, Laure Morin-Papunen, Juha Tapanainen, Leena Ala-Mursula, and Terhi T Piltonen

Objective

Polycystic ovary syndrome (PCOS) presents with multiple comorbidities potentially affecting function. This was the first general population-based study to evaluate work ability, participation in working life, and disability retirement in middle-aged women with and without PCOS.

Design

This is a cohort study.

Methods

Women with PCOS (n = 280) and women without PCOS symptoms or diagnosis (n = 1573) were identified in the Northern Finland Birth Cohort in 1966 and were evaluated for self-rated work ability and potential confounders at age 46. Next, incidence rate ratios (IRRs) for disability and unemployment days were extracted from national registers during a prospective 2-year follow-up. Lastly, we assessed hazard ratios (HRs) for disability retirement between 16 and 52 years of age from national registers.

Results

The women with PCOS reported poorer ability to work at age 46, especially due to poorer health. During the 2-year follow-up period, the affected women gained on average an additional month of disability and unemployment days, corresponding to an approximately 25% higher risk for both disability (IRR (95% CI): 1.25 (1.22–1.27)) and unemployment days (IRR (95% CI): 1.26 (1.23–1.28)) in models adjusted for health and socioeconomic factors. Lastly, we found a two-fold higher cumulative risk for disability retirement by age 52 compared to non-PCOS women (HR (95% CI): 1.98 (1.40–2.80)), which remained after adjusting for confounding factors (aHR (95% CI): 1.55 (1.01–2.38)).

Conclusions

PCOS is associated with lower participation in working life already in midlife. Acknowledging PCOS-related multimorbidity, concerted efforts are needed to support sustainable careers for women with PCOS.

Open access

Association between domains of quality of life and patients with Klinefelter syndrome: a systematic review

Brien Mehmet, Steve Gillard, Channa N Jayasena, and Sofia Llahana

Objective

Klinefelter syndrome (KS) is the second-most prevalent chromosomal disorder in men, though late diagnosis is very common and 50–75% of men remain undiagnosed. Evidence suggests that men with KS have impaired quality of life (QoL) but research on how the diagnosis of KS is associated with different QoL domains and what factors influence patients’ QoL is limited. This study aimed to provide a systematic review of the published evidence on factors that influence QoL in men with KS.

Design

Systematic review and meta-analysis with narrative synthesis.

Methods

Medline, Cochrane, Embase, Psychinfo, CINAHL, BASE and relevant publication reference lists were searched in January 2021. Eligible studies included randomised control trials, cohort studies, cross-sectional studies and epidemiology studies on KS and its effect on QoL and all domains of World Health Organisation (WHO) Quality of Life 100 (WHOQOL-100). Clinical studies with no date restriction published in English were included.

Results

Thematic analysis was completed on 13 studies, with a meta-analysis of intelligence quotient completed on 7 studies. Twelve out of the 13 studies suggested that KS negatively affected the QoL outcomes and KS was associated with impairments in physical, psychological, level independence and social relationship domains of WHOQOL-100. Meta-analysis suggested that men with KS have significantly lower full-scale Intelligence Quotient vs controls (P < 0.00001).

Conclusions

This is the first evidence synthesis of QoL in men with KS. Current evidence suggests that combined physical and psychological impairments affect men with KS who also experience impairments in relationships and independence in society. Further research is needed to identify factors that influence the QoL in men with KS.

Restricted access

Differences in the spectrum of steroidogenic enzyme inhibition between Osilodrostat and Metyrapone in ACTH-dependent Cushing syndrome patients

Fidéline Bonnet-Serrano, Jonathan Poirier, Anna Vaczlavik, Christelle Laguillier-Morizot, Benoît Blanchet, Stéphanie Baron, Laurence Guignat, Laura Bessiene, Léopoldine Bricaire, Lionel Groussin, Guillaume Assié, Jean Guibourdenche, and Jérôme Bertherat

Introduction

Osilodrostat is a new 11β-hydroxylase inhibitor with a mode of action analogous to Metyrapone. The objective of this study was to compare steroidogenic profiles in patients treated with either Osilodrostat or Metyrapone for adrenocorticotrophic hormone (ACTH)-dependent Cushing’s syndrome (CS).

Methods

Patients followed up at Cochin hospital Endocrinology department between March 2019 and December 2021 for an ACTH-dependent CS, controlled by either Osilodrostat or Metyrapone, were included. A serum profile of five steroids (cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, androstenedione and testosterone) was determined using UPLC- tandem mass spectrometry (UPLC-MS/MS).

Results

Nineteen patients treated with Osilodrostat, eight patients treated with Metyrapone and six patients treated with consecutive Metyrapone then Osilodrostat were included. Hypocortisolism (basal cortisol <100 nmol/L) was found in 48% of patients treated with Osilodrostat and 7% of patients treated with Metyrapone. 11-deoxycortisol and androstenedione levels were higher in patients treated with Metyrapone (80.9 (2.2–688.4) and 14.9 (2.5–54.3) nmol/L, respectively) than in patients treated with Osilodrostat (10.3 (0.5–71.9) and 4.0 (0.3–13.3) nmol/L) (P = 0.0009 and P = 0.0005). Testosterone level in women was also higher in Metyrapone group (3.3 (0.93–4.82) nmol/L vs 1.31(0.13–5.09) nmol/L, P = 0.0146). CYP11B1 activity (11-deoxycortisol/cortisol) was not significantly different between the two groups. CYP21A2 activity (17OHprogesterone/11-deoxycortisol) and CYP17A1 activity (17OHprogesterone/androstenedione) were significantly decreased in Osilodrostat group (P < 0.0001).

Conclusion

In patients with ACTH-dependent CS, the use of CYP11B1 inhibitors in routine care suggests that Osilodrostat has a less specific effect on the inhibition of steroidogenic enzymes than Metyrapone. This might explain a smaller increase in 11-deoxycortisol and androgen levels in patients treated with Osilodrostat.

Restricted access

Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomized placebo-controlled trial

Nicholas Russell, Ali Ghasem-Zadeh, Rudolf Hoermann, Ada S Cheung, Jeffrey D Zajac, Cat Shore-Lorenti, Peter R Ebeling, David J Handelsman, and Mathis Grossmann

Objective

In men, many effects of testosterone (T) on the skeleton are thought to be mediated by estradiol (E2), but trial evidence is largely lacking. This study aimed to determine the effects of E2 on bone health in men in the absence of endogenous T.

Design

This study is a 6-month randomized, placebo-controlled trial with the hypothesis that E2 would slow the decline of volumetric bone mineral density (vBMD) and bone microstructure, maintain areal bone mineral density (aBMD), and reduce bone remodelling.

Methods

78 participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel daily or matched placebo. The outcome measures were vBMD and microarchitecture at the distal tibia and distal radius by high-resolution peripheral quantitative CT, aBMD at the spine and hip by dual-energy x-ray absorptiometry, and serum bone remodelling markers.

Results

For the primary endpoint, total vBMD at the distal tibia, there was no significant difference between groups, mean adjusted difference (MAD) 2.0 mgHA/cm3 (95% CI: −0.8 to 4.8), P = 0.17. Cortical vBMD at the distal radius increased in the E2 group relative to placebo, MAD 14.8 mgHA/cm3 (95% CI: 4.5 to 25.0), P = 0.005. Relative to placebo, E2 increased estimated failure load at tibia, MAD 250 N (95% CI: 36 to 465), P = 0.02, and radius, MAD 193 N (95% CI: 65 to 320), P = 0.003. Relative to placebo, E2 increased aBMD at the lumbar spine, MAD 0.02 g/cm2 (95% CI: 0.01 to 0.03), P = 0.01, and ultra-distal radius, MAD 0.01 g/cm2 (95% CI: 0.00 to 0.02), P = 0.01, and reduced serum bone remodelling markers.

Conclusion

Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in the absence of endogenous T.

Restricted access

Erratum to: “Relationships between insulin resistance and frailty with body composition and testosterone in men undergoing androgen deprivation therapy for prostate cancer”

Free access

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: My quarter century quest to understand the paradox of marrow adiposity

Clifford J Rosen

Understanding the development and regulation of marrow adiposity, as well as its impact on skeletal remodeling has been a major challenge for our field and during my career as well. The story behind this unique phenotype and its relationship to bone turnover is highlighted in my own quest to defining the physiology and pathophysiology of marrow adipocytes.

Open access

Increased systemic and adipose 11β-HSD1 activity in idiopathic intracranial hypertension

Connar S J Westgate, Keira Markey, James L Mitchell, Andreas Yiangou, Rishi Singhal, Paul Stewart, Jeremy W Tomlinson, Gareth G Lavery, Susan P Mollan, and Alexandra J Sinclair

Context

Idiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure (ICP) of unknown etiology. Reductions in glucocorticoid metabolism are associated with improvements in IIH disease activity. The basal IIH glucocorticoid metabolism is yet to be assessed.

Objective

The objective of this study was to determine the basal glucocorticoid phenotype in IIH and assess the effects of weight loss on the IIH glucocorticoid phenotype.

Design

A retrospective case–control study and a separate exploratory analysis of a prospective randomized intervention study were carried out.

Methods

The case–control study compared female IIH patients to BMI, age, and sex-matched controls. In the randomized intervention study, different IIH patients were randomized to either a community weight management intervention or bariatric surgery, with patients assessed at baseline and 12 months. Glucocorticoid levels were determined utilizing 24-h urinary steroid profiles alongside the measurement of adipose tissue 11β-HSD1 activity.

Results

Compared to control subjects, patients with active IIH had increased systemic 11β-hydroxysteroid dehydrogenase (11β-HSD1) and 5α-reductase activity. The intervention study demonstrated that weight loss following bariatric surgery reduced systemic 11β-HSD1 and 5α-reductase activity. Reductions in these were associated with reduced ICP. Subcutaneous adipose tissue explants demonstrated elevated 11β-HSD1 activity compared to samples from matched controls.

Conclusion

The study demonstrates that in IIH, there is a phenotype of elevated systemic and adipose 11β-HSD1 activity in excess to that mediated by obesity. Bariatric surgery to induce weight loss was associated with reductions in 11β-HSD1 activity and decreased ICP. These data reflect new insights into the IIH phenotype and further point toward metabolic dysregulation as a feature of IIH.

Restricted access

The landscape of retesting in childhood-onset idiopathic growth hormone deficiency and its reversibility: a systematic review and meta-analysis

Elisabeth Laurer, Antonio Sirovina, Alexandra Blaschitz, Katharina Tischlinger, Rodrigo Montero-Lopez, Thomas Hörtenhuber, Marlene Wimleitner, and Wolfgang Högler

Objective

Children diagnosed with idiopathic isolated growth hormone deficiency (IGHD) are frequently observed to no longer be GH-deficient at a later stage of growth as a result of ‘GHD reversal’. Reevaluation of GH status by stimulation test is currently incorporated into management guidelines at attainment of final height (FH). Over the past three decades, numerous studies have evaluated reversal rates using different methodologies including crucial parameters like GHD aetiology, GH cut-off and retesting time point, with heterogeneous results.

We aimed to systematically analyse the reversibility of childhood-onset IGHD dependent on retesting GH cut-offs and retesting time points.

Methods

PubMed, Cochrane Library, TRIP database and NHS Evidence were searched for publications investigating the reversibility of IGHD from database initiation to 30 June 2020 following PRISMA recommendations. Study cohorts were pooled according to retesting GH cut-off and time point. Reversal rates were calculated using random-effects models.

Results

Of the 29 studies initially identified, 25 provided sufficient detail for IGHD analysis, resulting in 2030 IGHD patient data. Reversal rates decreased significantly as the retesting GH cut-off increased (P  = 0.0013). Pooled (95% CI) reversal rates were 80% (59–92%, n  = 227), 73% (62–81%, n  = 516) and 55% (41–68%, n  = 1287) for cohorts using retesting GH cut-offs of 3–4 ng/mL, 5–6 ng/mL and 7.7–10 ng/mL, respectively. Individuals retested at FH (n  = 674) showed a pooled reversal rate of 74% (64–82%) compared to 48% (25–71%) when retested before FH (n  = 653).

Conclusion

Provided evidence supports reevaluation of current IGHD management guidelines. The high reversal rates should instigate consideration of early retesting.

Restricted access

Localized islet nuclear enlargement hyperinsulinism (LINE-HI) due to ABCC8 and GCK mosaic mutations

Kara E Boodhansingh, Zhongying Yang, Changhong Li, Pan Chen, Katherine Lord, Susan A Becker, Lisa J States, N Scott Adzick, Tricia Bhatti, Show-Ling Shyng, Arupa Ganguly, Charles A Stanley, and Diva D De Leon

Objective

Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in children. In addition to typical focal or diffuse HI, some cases with diazoxide-unresponsive congenital HI have atypical pancreatic histology termed Localized Islet Nuclear Enlargement (LINE) or mosaic HI, characterized by histologic features similar to diffuse HI, but confined to only a region of pancreas. Our objective was to characterize the phenotype and genotype of children with LINE-HI.

Design

The phenotype and genotype features of 12 children with pancreatic histology consistent with LINE-HI were examined.

Methods

We compiled clinical features of 12 children with LINE-HI and performed next-generation sequencing on specimens of pancreas from eight of these children to look for mosaic mutations in genes known to be associated with diazoxide-unresponsive HI (ABCC8, KCNJ11, and GCK).

Results

Children with LINE-HI had lower birth weights and later ages of presentation compared to children with typical focal or diffuse HI. Partial pancreatectomy in LINE-HI cases resulted in euglycemia in 75% of cases; no cases have developed diabetes. Low-level mosaic mutations were identified in the pancreas of six cases with LINE-HI (three in ABCC8, three in GCK). Expression studies confirmed that all novel mutations were pathogenic.

Conclusion

These results indicate that post-zygotic low-level mosaic mutations of known HI genes are responsible for some cases of LINE-HI that lack an identifiable germ-line mutation and that partial pancreatectomy may be curative for these cases.