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Carine Richa, Hazar Haidar, Margot Dupeux, Jean-François Papon, Benoit Lambert, Sylvie Salenave, Mohammed Bouyacoub, Jacques Young, Philippe Chanson, Séverine Trabado, and Luigi Maione

Context

The measurement of parathyroid hormone(PTH) in situ (PTHis) by fine-needle aspiration (FNA) has been proposed as a tool to preoperatively help localize parathyroid glands detected on ultrasound. However, the accuracy of PTHis is highly variable according to the few available studies.

Aim

We aimed to develop and validate the PTHis procedure and assessed the performance of PTHis in a large series of patients with hyperparathyroidism and/or undetermined cervical lesions.

Patients and methods

The technique set-up consisted of PTHis measurement in thyroid samples from patients with thyroid nodules and patients with high circulating PTH levels (tertiary hyperparathyroidism). Consecutive patients were recruited at one tertiary referral centre from 2017 to 2020 and submitted to ultrasound-guided FNA-PTHis determination.

Results

During the method set-up, we obtained undetectable PTHis levels in all non-parathyroid tissues after sample dilutions. PTHis was higher in patients with hyperparathyroidism (n = 145; 1817 ± 3739 ng/L; range: <4.6–31 140) than in those with thyroid or undetermined cervical lesions (n= 34; <4.6 ng/mL; P  < 0.0001). When evaluating PTHis performance in histologically proven samples (158 lesions from 121 patients), PTHis was detectable in 85/97 parathyroid lesions (87%; range: 22–31;140 ng/L) and undetectable in all non-parathyroid lesions (n = 61; P  < 0.0001). The specificity and positive predictive value were 100%, and the sensitivity was 87.6%. False-negative lesions (n= 12) were smaller (9.4 ± 5.9 mm) and more often consisted of hyperplasias (75%) than true-positive lesions (16.1 ± 8.4 mm and 33%, P = 0.009 and P = 0.0089, respectively). The method was safe and well tolerated. Four educational cases are also provided.

Conclusions

PTHis determination is a safe and well-tolerated procedure that enhances the specificity of ultrasound-detected lesions. If accurately set-up, it confirms the parathyroid origin of uncharacterized cervical lesions.

Open access

Kristina Laugesen, Henrik Toft Sørensen, Jens Otto L Jorgensen, and Irene Petersen

Objective

Prenatal exposure to excess cortisol can affect postnatal metabolic health by epigenetic mechanisms. We aimed to investigate if prenatal exposure to pharmacological glucocorticoids increases the risk of overweight/obesity in childhood.

Design

A nationwide population registry-based cohort study.

Methods

We identified 383 877 children born in Denmark (2007–2012), who underwent routine anthropometric evaluation at 5–8 years of age. Prenatal exposure to glucocorticoids was divided into systemic and topical glucocorticoids, cumulative systemic dose, and use by trimester. The comparison cohort included children without exposure, born to maternal never-users. Negative control exposures were used to investigate confounding from an underlying disease or unmeasured characteristics. Such exposures included children without glucocorticoid exposure born to maternal users of non-steroidal anti-inflammatory drugs or immunotherapy during pregnancy, maternal former users of glucocorticoids, or paternal users of glucocorticoids during the pregnancy of their partner. We estimated sex-stratified adjusted prevalence ratios (aPR) of overweight/obesity at 5–8 years of age, as epigenetic modifications have shown to be sex-specific.

Results

In the study, 21 246 (11%) boys and 27 851 (15%) girls were overweight/obese at 5–8 years of age. Overall, neither systemic nor topical glucocorticoids were associated with overweight/obesity. In boys, high-dose systemic glucocorticoids was associated with higher prevalence of overweight/obesity vs the comparison cohort (aPR: 1.41 (95% CI: 1.07–1.86), prevalence: 16% vs 11%). Negative control exposures indicated robustness to confounding.

Conclusion

Overweight/obesity might be an adverse effect of prenatal exposure to high-dose systemic glucocorticoids in boys. We found no association for neither prenatal exposure to lower doses of systemic nor topical glucocorticoids. These results merit clinical attention.

Free access

Marloes Nies, Eus G J M Arts, Astrid E P Cantineau, and Thera P Links

Open access

Yejin Kim, Yoosoo Chang, Seungho Ryu, In Young Cho, Min-Jung Kwon, Sarah H Wild, and Christopher D Byrne

Objective

Despite the known benefit of vitamin D in reducing sarcopenia risk in older adults, its effect against muscle loss in the young population is unknown. We aimed to examine the association of serum 25-hydroxy vitamin D [25(OH)D] level and its changes over time with the risk of incident low muscle mass (LMM) in young and middle-aged adults.

Design

This study is a cohort study.

Methods

The study included Korean adults (median age: 36.9 years) without LMM at baseline followed up for a median of 3.9 years (maximum: 7.3 years). LMM was defined as the appendicular skeletal muscle (ASM) mass by body weight (ASM/weight) of 1 s.d. below the sex-specific mean for the young reference group. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% CIs.

Results

Of the 192,908 individuals without LMM at baseline, 19,526 developed LMM. After adjusting for potential confounders, the multivariable-adjusted HRs (95% CIs) for incident LMM comparing 25(OH)D levels of 25–<50, 50–<75, and ≥75 nmol/L to 25(OH)D <25 nmol/L were 0.93 (0.90–0.97), 0.85 (0.81–0.89), and 0.77 (0.71–0.83), respectively. The inverse association of 25(OH)D with incident LMM was consistently observed in young (aged <40 years) and older individuals (aged ≥40 years). Individuals with increased 25(OH)D levels (<50–≥50 nmol/L) or persistently adequate 25(OH)D levels (≥50 nmol/L) between baseline and follow-up visit had a lower risk of incident LMM than those with persistently low 25(OH)D levels.

Conclusions

Maintaining sufficient serum 25(OH)D could prevent unfavourable changes in muscle mass in both young and middle-aged Korean adults.

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Andreas Machens, Kerstin Lorenz, Frank Weber, and Henning Dralle

Objective

This study aimed to delineate the age-dependent clinical penetrance and expression of heterozygous rearranged during transfection (RET) missense mutations associated with multiple endocrine neoplasia 2A (MEN2A) according to parental inheritance.

Design

This was an observational study of RET carriers operated for MEN2A-associated tumors between 1985 and 2021.

Methods

Kaplan−Meier time-to-event and multivariable Cox proportional hazards regression analyses were performed on node metastases from medullary thyroid cancer, pheochromocytoma, bilateral pheochromocytoma, and primary hyperparathyroidism.

Results

Some 405 (70.1%) of 578 patients carrying heterozygous MEN2A RET missense mutations had information about the parental inheritance of the trait. On Kaplan−Meier analysis, offspring who inherited the trait from the father developed node metastases (P log-rank= 0.007), pheochromocytoma (P log-rank= 0.029), bilateral pheochromocytoma (P log-rank= 0.002), and primary hyperparathyroidism (P log-rank= 0.018) at a significantly younger age than offspring who inherited the trait from the mother. On multivariable Cox regression, controlling for index status, offspring sex, and (where feasible) mutational risk, parental inheritance was consistently associated with each MEN2A-associated tumor (hazard ratios (HR) = 1.7–1.8 for the earlier manifestations node metastases and pheochromocytoma vs HR of 2.9–3.4 for the late manifestations bilateral pheochromocytoma and primary hyperparathyroidism). Herein, node metastases were 3.1- and 1.7-fold more closely associated with mutational risk (HR of 5.3 for high and 2.9 for moderate-high risk mutations vs low-moderate risk mutations) than parental inheritance (HR = 1.7).

Conclusion

These findings illustrate the importance of considering not just mutational risk but also parental inheritance when it comes to personalization of screening for and early detection of the various components of MEN2A-associated tumors.

Open access

Evanthia Giannoula, Ioannis Iakovou, Luca Giovanella, and Alexis Vrachimis

Healthcare settings, including nuclear medicine (NM) departments, promptly adjusted their standard operating procedures to cope with the unprecedented crisis caused by coronavirus disease 19 (COVID-19) pandemic. Nuclear thyroidology has adopted changes and predicated on a careful risk–benefit analysis, in order to prevent a potential spread of the virus while being at the same time effective, safe and preserving their quality of essential services. Since most thyroid nodules (TNs) are benign, and malignant neoplasms are characterized by an indolent natural history, it is generally safe to delay diagnostic and therapeutic procedures. In this respect, the main adjustments that nuclear thyroidology has adopted are summarized into the following: general workplace adjustments including remote work for NM staff; postponing appointments for consultation, diagnostic and therapeutic purposes and rescheduling based on individualized risk stratification; telemedicine; preparation for possible issues on radiopharmaceuticals synthesis and delivery; preventing measures and protocols to minimize or avoid potential COVID-19 infection of patients and medical staff. This document should be considered as updated guidance on how clinical management of TNs and thyroid cancer has been altered, remodeled and adapted to the new circumstances in the COVID-19 era, based on the rapidly growing volume of scientific information regarding the new coronavirus.

Free access

Sophie H Bots, Rolf H H Groenwold, and Olaf M Dekkers

Electronic health record (EHR) data not only offer many exciting research opportunities but also come with their own inherent limitations. Researchers may not always realise the challenges associated with the use of EHR data for research, or the fact that using large datasets of ‘real-world data’ does not necessarily provide valuable real-world evidence. This article discusses some of the main differences between EHR data and data collected primarily for research purposes, and the challenges encountered when using EHR data for research. It also offers suggestions on how to deal with these challenges based on worked-out examples. It therefore serves as a quick guide for researchers interested in either reading or performing EHR-based research.

Free access

Nivedita Patni, Robert A Hegele, and Abhimanyu Garg

Restricted access

Mirko Parasiliti-Caprino, Fabio Bioletto, Chiara Lopez, Francesca Maletta, Marina Caputo, Valentina Gasco, Antonio La Grotta, Paolo Limone, Giorgio Borretta, Marco Volante, Mauro Papotti, Massimo Terzolo, Mario Morino, Barbara Pasini, Franco Veglio, Ezio Ghigo, Emanuela Arvat, and Mauro Maccario

Objective

Various features have been identified as predictors of relapse after complete resection of pheochromocytoma, but a comprehensive multivariable model for recurrence risk prediction is lacking. The aim of this study was to develop and internally validate an integrated predictive model for post-surgical recurrence of pheochromocytoma.

Methods

The present research retrospectively enrolled 177 patients affected by pheochromocytoma and submitted to radical surgery from 1990 to 2016, in nine referral centers for adrenal diseases. Cox regression analysis was adopted for model development, and a bootstrapping procedure was used for internal validation.

Results

Variables independently associated with recurrence were tumor size (hazard ratio (HR): 1.01, 95% CI: 1.00–1.02), positive genetic testing (HR: 5.14, 95% CI: 2.10–12.55), age (HR: 0.97, 95% CI: 0.94–0.99), and Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) (HR: 1.16, 95% CI: 1.04–1.29). The predictive performance of the overall model, evaluated by Somers’ D, was equal to 0.594, and was significantly higher than the ones of any single predictor alone (P  = 0.002 compared to tumor size; P  = 0.004 compared to genetic testing; P  = 0.048 compared to age; P  = 0.006 compared to PASS). Internal validation by bootstrapping techniques estimated an optimistic bias of 6.3%, which reassured about a small tendency towards overfit.

Conclusions

We proposed a multivariable model for the prediction of post-surgical recurrence of pheochromocytoma, derived by the integration of genetic, histopathological, and clinical data. This predictive tool may be of value for a comprehensive tailoring of post-surgical follow-up in radically operated pheochromocytoma patients.

Restricted access

Evert F S van Velsen, Robin P Peeters, Merel T Stegenga, Uwe Mäder, Christoph Reiners, F J van Kemenade, Tessa M van Ginhoven, W Edward Visser, and Frederik Anton Verburg

Background

The joint Union International Contre le Cancer and American Joint Committee on Cancer (UICC/AJCC) Tumor, Node, Metastasis (TNM) staging system for differentiated thyroid cancer (DTC) involves a single age cutoff as a prognostic criterion. Because a single cutoff is a dichotomization of what might be a sliding scale, using multiple age cutoffs might result into a better stage definition. The aim of our study was to investigate if using a two-step age-based cutoff would improve the TNM staging system regarding disease-specific survival (DSS).

Methods

We retrospectively studied two cohorts of adult DTC patients from The Netherlands and Germany. DSS was analyzed for papillary (PTC) and follicular thyroid cancer (FTC) separately, investigating several two-step age-based cutoffs for those with distant metastases; below lower threshold classified as stage I, between lower and upper threshold as stage II, and above upper threshold as stage IV.

Results

We included 3074 DTC patients (77% PTC). For PTC, an age cutoff of 45 with 50 years had the best statistical model performance, while this was 25 with 40 years for FTC. However, differences with the optimal single age cutoffs of 50 years for PTC and 40 years for FTC were small.

Conclusions

The optimal two-step age-based cutoff to predict DSS is 45 with 50 years for PTC and 25 with 40 years for FTC, rather than 55 years currently used for DTC. Although these two-step age-based cutoffs were marginally better from a statistical point of view, from a clinical point of view, the recently defined optimal single age cutoffs of 50 years for PTC and 40 years for FTC might be preferable.