RhIGF-1 treatment increases bone mineral density and trabecular bone structure in children with PAPP-A2 deficiency

KARGER: "This is the peer-reviewed but unedited manuscript version of the following article: Hormone Research in Paediatrics 89.3 (2018): 200-204 DOI: 10.1159/000486336. The final, published version is available at http://www.karger.com/. http://doi.org/10.1159/000486336]."Aim: Our objective was to determine changes in bone mineral density (BMD), trabecular bone score (TBS), and body composition after 2 years of therapy with recombinant human insulin-like growth factor-1 (rhIGF-1) in 2 prepubertal children with a complete lack of circulating PAPP-A2 due to a homozygous mutation in PAPP-A2 (p.D643fs25∗) resulting in a premature stop codon. Methods: Body composition, BMD, and bone structure were determined by dual-energy X-ray absorptiometry at baseline and after 1 and 2 years of rhIGF-1 treatment. Results: Height increased from 132 to 145.5 cm (patient 1) and from 111.5 to 124.5 cm (patient 2). Bone mineral content increased from 933.40 to 1,057.97 and 1,152.77 g in patient 1, and from 696.12 to 773.26 and 911.51 g in patient 2, after 1 and 2 years, respectively. Whole-body BMD also increased after 2 years of rhIGF-1 from baseline 0.788 to 0.869 g/cm2in patient 1 and from 0.763 to 0.829 g/cm2in patient 2. After 2 years of treatment, both children had an improvement in TBS. During therapy, a slight increase in body fat mass was seen, with a concomitant increase in lean mass. No adverse effects were reported. Conclusion: Two years of rhIGF-1 improved growth, with a tendency to improve bone mass and bone microstructure and to modulate body composition.The authors are funded by Fondos de Investigación Sanitaria and FEDER (Grants PI1302195 and PI1600485 to J.A.), Ministerio de Ciencia e Innovación (BFU2014-51836-C2-2-R to J.A.C.), Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (J.A.), and Fundación Endocrinología y Nutrició

Diferente evolución de la esclerostina sérica respecto de otros marcadores de remodelado óseo en el primer año tras un trasplante hepático

Objetivo: Nuestro estudio tiene como objetivo principal valorar la evolución de los niveles de esclerostina en pacientes con trasplante hepático, e investigar su relación con otros marcadores de remodelado óseo. Material y método: Estudio observacional prospectivo. Se incluyeron 83 pacientes con trasplante hepático. Se determinaron los valores de esclerostina, β-crosslaps, fosfatasa alcalina ósea, osteocalcina y proteína C reactiva la semana anterior al trasplante y posteriormente, a los 1, 3, 6 y 12 meses. Se determinaron basalmente la 25 hidroxi-vitamina D y la paratohormona. En cada revisión se evaluó la existencia de fracturas. La evolución de los marcadores respecto del valor basal se determinó mediante la prueba t-Student. Un valor de p inferior a 0,05 se consideró estadísticamente significativo. Resultados: 56 varones y 27 mujeres (edad media: 56,2±10,4 años). Los niveles basales de esclerostina (0,76±0,35 ng/ml) disminuyeron de forma significativa precozmente (0,55±0,22 ng/ml en el primer mes, p=0,034), tendencia que se mantuvo hasta los 12 meses (0,62±0,22 ng/ml, p=0,047). Al contrario, los niveles basales de osteocalcina (17±10,3 ng/ml) y β-crosslaps (0,44±0,3 ng/ml) se incrementaron significativamente a los largo del estudio; en el caso de la osteocalcina, hasta los 12 meses (37,27±26,84 ng/ml, p<0,01) y el β-crosslaps, hasta los 6 meses (0,62±0,34 ng/ml, p<0,01), con un descenso posterior (0,47±0,31 ng/ml, p=0,2). Conclusiones: Tras el trasplante hepático existe un descenso de los niveles de esclerostina, opuesto a la elevación de otros marcadores de remodelado, β-crosslaps y osteocalcina. Son necesarios más estudios para determinar si estos cambios tienen un impacto en la aparición de osteoporosis en pacientes sometidos a trasplante

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. Methods: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. Findings: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p&lt;0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p&lt;0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). Interpretation: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. Funding: None