Browse

You are looking at 31 - 40 of 20,468 items for

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

Anders Sundin

The increasing use of cross-sectional imaging, mainly CT, results in an accelerating number of incidental findings, for instance of adrenal tumours. Although most ‘adrenal incidentalomas’ are benign, it is important to identify the malignant and the hormone producing (functional) tumours. For a small fraction of adrenal incidentalomas, the diagnosis is apparent on imaging, but the large majority requires radiological characterisation. To this end, a previous joint European Society of Endocrinology and European Network for the Study of Adrenal Tumours publication in this jounal, recommends CT measurements of the native (non-contrast) tumour attenuation ≤10 Hounsfield units, consistent with a lipid-rich benign adrenocortical adenoma, and imaging at least 6 months apart, on which unchanged tumour size implies a benign tumour. Because of weak evidence, calculation of CT contrast medium washout was not recommended as a means for tumour characterisation, but this technique has nevertheless still been applied in several countries. The recent article by Schloetelburg et al. in this journal is important because, in the largest study to date, the authors confirm that calculation of CT contrast medium washout with established thresholds is insufficient to reliably characterise adrenal tumours. Their results are therefore expected to impact the management of these patients.

Restricted access

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

Introduction: Osilodrostat is a new 11 ß-hydroxylase inhibitor with a mode of action analogue to Metyrapone. The objective of this study was to compare steroidogenic profiles in patients treated by either Osilodrostat or Metyrapone for ACTH-dependent Cushing’s Syndrome (CS).

Methods: Patients followed in 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 5 steroids (cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, androstenedione and testosterone) was determined using UPLC – tandem mass spectrometry (UPLC-MS/MS).

Results: Nineteen patients treated by Osilodrostat, 8 patients treated by Metyrapone and 6 patients treated by consecutive Metyrapone then Osilodrostat were included. Hypocortisolism (basal cortisol < 100 nmol/L) was found in 48% of patients treated by Osilodrostat and 7% of patients treated by Metyrapone. 11-deoxycortisol and androstenedione levels were higher in patients treated by Metyrapone (respectively, 80.9 [2.2-688.4] and 14.9 [2.5-54.3] nmol/L) than in patients treated by 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 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 androgens levels in patients treated by Osilodrostat.

Restricted access

Esra Dülger, Melike Mut, Tomris Erbas, Levent Sahiner, Naciye Vardar Yağlı, and Sevil Bilgin

Objective

The pituitary gland is responsible for hormonal balance in the body, and disruption of hormonal balance in patients with pituitary adenoma (PA) indirectly affects the quality of life. This study aimed to examine the effects of yoga and combined aerobic and strength training (A+ST) on quality of life and related parameters such as sleep, fatigue, emotional state, sexual function, and cognitive status in women with PA.

Design

Ten women with PA were included in this randomized crossover study. Group 1 (n = 5, mean age: 52 ± 13.5 years) received A+ST for the first 6 weeks, a 2-week washout period, and yoga for the second 6 weeks. Group 2 (n = 5, mean age: 41.8 ± 14 years) received the yoga program first, followed by the A+ST program.

Methods

Participants were assessed using the following tools before and after each exercise intervention: Functional Assessment of Cancer Therapy–Brain (FACT-Br) (quality of life), Pittsburg Sleep Quality Index, Fatigue Severity Scale (FSS), Female Sexual Function Index (FSFI), Hospital Anxiety and Depression Scale (HADS), and Montreal Cognitive Assessment Scale (MOCA).

Results

FACT-Br scores were higher after the yoga program, HADS anxiety score was lower after the A+ST program, and MOCA scores increased after both exercise programs (P  < 0.05). FSS score decreased after both exercise programs, but not significantly. In addition, nonsignificant decreases in HADS anxiety and depression scores and increased FSFI scores were observed after the yoga program.

Conclusion

A+ST and yoga have positive effects on the quality of life in PA. We recommend yoga and A+ST as a supportive therapy for this population that may face comorbidities after surgical and medical treatment. Our results indicate these patients may benefit from physiotherapist-guided exercise programs.

Restricted access

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: 6-month randomised, placebo-controlled trial with the hypothesis that E2 would slow 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 randomised to 0.9mg 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) 2.0mgHA/cm3 (95%CI -0.8 – 4.8), p=0.17. Cortical vBMD at the distal radius increased in the E2 group relative to placebo, MAD 14.8mgHA/cm3 (95%CI 4.5-25.0), p=0.005. Relative to placebo, E2 increased estimated failure load at tibia, MAD 250N (95%CI 36-465), p=0.02 and radius, MAD 193N (95%CI 65-320), p=0.003. Relative to placebo, E2 increased aBMD at the lumbar spine, MAD 0.02g/cm2 (95%CI 0.01-0.03), p=0.01, and ultra-distal radius, MAD 0.01g/cm2 (95%CI 0.00 – 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 absence of endogenous T.

Open access

Steven G Waguespack, Alexander Drilon, Jessica J Lin, Marcia S Brose, Ray McDermott, Mohammed Almubarak, Jessica Bauman, Michela Casanova, Anuradha Krishnamurthy, Shivaani Kummar, Serge Leyvraz, Do-Youn Oh, Keunchil Park, Davendra Sohal, Eric Sherman, Ricarda Norenberg, Josh D Silvertown, Nicoletta Brega, David S Hong, and Maria E Cabanillas

Objective

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with demonstrated efficacy across various TRK fusion-positive solid tumours. We assessed the efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma (TC).

Methods

We pooled data from three phase I/II larotrectinib clinical trials (NCT02576431, NCT02122913, and NCT02637687). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Data cut-off: July 2020.

Results

Twenty-nine patients (median age: 60; range: 6–80) with TRK fusion-positive TC were treated. Tumour histology was papillary (PTC) in 20 (69%) patients, follicular (FTC) in 2 (7%), and anaplastic (ATC) in 7 (24%) patients. Among 28 evaluable patients, ORR was 71% (95% CI: 51–87); best responses were complete response in 2 (7%) patients, partial response in 18 (64%), stable disease in 4 (14%), progressive disease in 3 (11%), and undetermined in 1 (4%) due to clinical progression prior to the first post-baseline assessment. ORR was 86% (95% CI: 64–97) for PTC/FTC and 29% (95% CI 4–71) for ATC. Median time to response was 1.87 months (range 1.64–3.68). The 24-month DoR, PFS, and OS rates were 81, 69, and 76%, respectively. Treatment-related adverse events were mainly grades 1–2.

Conclusion

In TRK fusion-positive TC, larotrectinib demonstrates rapid and durable disease control and a favourable safety profile in patients with advanced disease requiring systemic therapy.

Significance statement

NTRK gene fusions are known oncogenic drivers and have been identified in various histologies of thyroid carcinoma, most commonly in papillary thyroid carcinoma. This is the first publication specifically studying a TRK inhibitor in a cohort of TRK fusion-positive thyroid carcinoma patients. In the current study, the highly selective TRK inhibitor larotrectinib showed durable antitumour efficacy and a favourable safety profile in patients with TRK fusion-positive thyroid carcinoma. Our findings show that patients with advanced non-medullary thyroid carcinoma who may require systemic therapy could be considered for testing for gene fusions by next-generation sequencing.

Free access

Sabina Ruiz, Federico Vázquez, Silvia Pellitero, and Manel Puig-Domingo

Obesity, the growing pandemic of the 21st century, is associated with multiple organ dysfunction, either by a direct increase in fatty organ content or by indirect modifications related to general metabolic changes driven by a specific increase in biologic products. The pituitary gland is not protected against such a situation. Different hypothalamic–pituitary axes experience functional modifications initially oriented to an adaptive situation that, with years of obesity, turn to maladaptive dynamics that contribute to perpetuating obesity and specific symptoms of their hormonal nature. This paper reviews the recent knowledge on obesity-related pituitary dysfunction and its pathogenic mechanisms and discusses potential therapeutic actions aimed at contributing to ameliorating the complex treatment of severe cases of obesity.

Open access

Niamh-Maire McLennan, Jonathan Hazlehurst, Shakila Thangaratinam, and Rebecca M Reynolds

There is an increase in maternal metabolic burden due to the rise in pregnancies complicated by obesity, gestational diabetes, type 2 diabetes and polycystic ovary syndrome. Metabolic dysfunction during pregnancy is associated with increased risks of long-term morbidity and mortality for women and their offspring. Lifestyle interventions in pregnancy in women at risk of metabolic dysfunction have demonstrated short-term improvements such as reduced gestational weight gain and lowered risk of gestational diabetes. It is not known whether these interventions lead to sustained improvements in the metabolic health of the mother and baby. Pharmacological interventions have also shown benefits for the mother and baby in pregnancy, including improvements in glycaemic control, reduction in gestational weight gain and reduction in large for gestational age infants; however, there remains uncertainty over long-term outcomes for mother and child. Existing studies on interventions targeting metabolic health are limited to selected populations in the preconception and postpartum periods and lack follow-up beyond delivery of the intervention. The COVID-19 pandemic has refocused our attention on the effects of maternal metabolic ill-health that play a role in contributing to premature morbidity and mortality. There is an urgent need for strategies to accurately identify the growing number of women and offspring at risk of long-term adverse metabolic health. Strategies which focus on early identification and risk stratification using individualised risk scores in the pre and inter-conception periods must take priority if we are to target and improve the metabolic health of women and their offspring who are at highest risk.

Restricted access

Laura E Dichtel, Melanie S Haines, Anu V Gerweck, Bryan Bollinger, Allison Kimball, David Schoenfeld, Miriam A Bredella, and Karen K Miller

Objective

Overweight/obesity is associated with relative growth hormone (GH) deficiency and increased fracture risk. We hypothesized that GH administration would improve bone endpoints in individuals with overweight/obesity.

Design

An 18-month, randomized, double-blind, placebo-controlled study of GH, followed by 6-month observation.

Methods

In this study, 77 adults (53% men), aged 18–65 years, BMI ≥ 25 kg/m2, and BMD T- or Z-score ≤ −1.0 were randomized to daily subcutaneous GH or placebo, targeting IGF1 in the upper quartile of the age-appropriate normal range. Forty-nine completed 18 months. DXA, volumetric quantitative CT, and high-resolution peripheral quantitative CT were performed.

Results

Pre-treatment mean age (48 ± 12 years), BMI (33.1 ± 5.7 kg/m2), and BMD were similar between groups. P1NP, osteocalcin, and CTX increased (P < 0.005) and visceral adipose tissue decreased (P = 0.04) at 18 months in the GH vs placebo group. Hip and radius aBMD, spine and tibial vBMD, tibial cortical thickness, and radial and tibial failure load decreased in the GH vs placebo group (P < 0.05). Between 18 and 24 months (post-treatment observation period), radius aBMD and tibia cortical thickness increased in the GH vs placebo group. At 24 months, there were no differences between the GH and placebo groups in bone density, structure, or strength compared to baseline.

Conclusions

GH administration for 18 months increased bone turnover in adults with overweight/obesity. It also decreased some measures of BMD, bone microarchitecture, and bone strength, which all returned to pre-treatment levels 6 months post-therapy. Whether GH administration increases BMD with longer treatment duration, or after mineralization of an expanded remodeling space post-treatment, requires further investigation.

Restricted access

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

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 etiology, GH cut-off and retesting time point, with heterogeneous results.

We aimed to systematically analyze 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 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 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

Kara E. Boodhansingh, Zhongying Yang, Changhong Li, Pan Chen, Katherine Lord, Susan A Becker, Lisa J States, N. Scott Adzick, Tricia Bhatti, Shyng Show-Ling, 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 hyperinsulinism (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 (NGS) 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 which lack an identifiable germline mutation and that partial pancreatectomy may be curative for these cases.