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Silvia Ciancia Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium

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Vanessa Dubois Basic and Translational Endocrinology (BaTE), Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

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Martine Cools Department of Internal Medicine and Pediatrics, Ghent University, Pediatric Endocrinology Service, Ghent University Hospital, Ghent, Belgium

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Both in the United States and Europe, the number of minors who present at transgender healthcare services before the onset of puberty is rapidly expanding. Many of those who will have persistent gender dysphoria at the onset of puberty will pursue long-term puberty suppression before reaching the appropriate age to start using gender-affirming hormones. Exposure to pubertal sex steroids is thus significantly deferred in these individuals. Puberty is a critical period for bone development: increasing concentrations of estrogens and androgens (directly or after aromatization to estrogens) promote progressive bone growth and mineralization and induce sexually dimorphic skeletal changes. As a consequence, safety concerns regarding bone development and increased future fracture risk in transgender youth have been raised. We here review published data on bone development in transgender adolescents, focusing in particular on differences in age and pubertal stage at the start of puberty suppression, chosen strategy to block puberty progression, duration of puberty suppression, and the timing of re-evaluation after estradiol or testosterone administration. Results consistently indicate a negative impact of long-term puberty suppression on bone mineral density, especially at the lumbar spine, which is only partially restored after sex steroid administration. Trans girls are more vulnerable than trans boys for compromised bone health. Behavioral health measures that can promote bone mineralization, such as weight-bearing exercise and calcium and vitamin D supplementation, are strongly recommended in transgender youth, during the phase of puberty suppression and thereafter.

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Sara Lomelino Pinheiro Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Ana Saramago Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Branca Maria Cavaco Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Carmo Martins Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Valeriano Leite Serviço de Endocrinologia e Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Tiago Nunes da Silva Serviço de Endocrinologia e Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which 11 carry an inactivating germline mutation in the MEN1 gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery. Serum calcium and parathyroid hormone levels were 15.0 mg/dL (8.4–10.2) and 472 pg/mL (12–65), respectively. The patient underwent parathyroid surgery, and histological findings were consistent with parathyroid carcinoma. Analysis of the MEN1 gene by next-generation sequencing (NGS) identified a novel germline heterozygous nonsense pathogenic variant (c.978C>A; p.(Tyr326*)), predicted to encode a truncated protein. Genetic analysis of the parathyroid carcinoma revealed a c.307del, p.(Leu103Cysfs*16) frameshift truncating somatic MEN1 variant in the MEN1 gene, which is consistent with MEN1 tumor-suppressor role, confirming its involvement in parathyroid carcinoma etiology. Genetic analysis of CDC73, GCM2, TP53, RB1, AKT1, MTOR, PIK3CA and CCND1 genes in the parathyroid carcinoma DNA did not detect any somatic mutations. To our knowledge, this is the first report of a PC case presenting both germline (first-hit) and somatic (second-hit) inactivation of the MEN1 gene.

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Victor Jing-Wei Kang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Bo-Ching Lee Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Jia-Zheng Huang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Vin-Cent Wu Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Yen-Hung Lin Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Chin-Chen Chang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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TAIPAI group
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Primary aldosteronism (PA) is associated with urolithiasis as it causes hypercalciuria and hypocitraturia. However, the influence of different subtypes of PA on urinary stone formation remains unclear. This study aimed to evaluate the association between aldosterone-producing adenoma (APA) and the burden of urolithiasis in patients with PA. In the present study, we enrolled 312 patients with PA from a prospectively maintained database, of whom 179 had APA. Clinical, biochemical, and imaging data (including the presence, volume, and density of urinary stones on abdominal computed tomography) were compared between groups, with employment of propensity score matching (PSM) analysis to balance possible confounding factors. Kaplan–Meier analysis was used to estimate the acute renal colic event during follow-up. After PSM for age, sex, serum calcium, phosphate, blood urea nitrogen, creatinine, and uric acid, the APA and non-APA groups had 106 patients each. Patients with APA had higher serum intact parathyroid hormone (iPTH) (79.1 ± 45.0 vs 56.1 ± 30.3, P < 0.001) and a higher prevalence of urolithiasis (27.4% vs 12.3%, P = 0.006) than non-APA patients. During follow-up, a higher incidence of acute renal colic events was noted in the APA group than the non-APA group (P = 0.011); this association remained significant (P = 0.038) after adjustment for age and sex in Cox-regression analysis. Our data suggest that APA is associated with a heavier burden of urolithiasis and higher incidence of renal colic events compared to the non-APA subtype of PA.

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Charissa van Zwol-Janssens Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Aglaia Hage Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Kim van der Ham Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Birgitta K Velthuis Department of Radiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands

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Ricardo P J Budde Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

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Maria P H Koster Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Arie Franx Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Bart C J M Fauser Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht & University of Utrecht, Utrecht, the Netherlands

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Eric Boersma Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Daniel Bos Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Joop S E Laven Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Yvonne V Louwers Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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the CREW consortium
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the CREW consortium

Besides age, estrogen exposure plays a crucial role in changes in bone density (BD) in women. Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are conditions in reproductive-aged women in which the exposure to estrogen is substantially different. Women with a history of preeclampsia (PE) are expected to have normal estrogen exposure. Within the CREw-IMAGO study, we investigated if trabecular BD is different in these women because of differences in the duration of estrogen exposure. Trabecular BD was measured in thoracic vertebrae on coronary CT scans. Women with a reduced estrogen exposure (POI) have a lower BD compared to women with an intermediate exposure (PE) (mean difference (MD) −26.8, 95% CI −37.2 to −16.3). Women with a prolonged estrogen exposure (PCOS) have the highest BD (MD 15.0, 95% CI 4.3–25.7). These results support the hypothesis that the duration of estrogen exposure in these women is associated with trabecular BD.

Significance statement

Our results suggest that middle-aged women with PCOS have a higher BD and women with POI have a lower BD. We hypothesized that this is due to either a prolonged estrogen exposure, as seen in women with PCOS, or a reduced estrogen exposure, as in women with POI. In the counseling of women with reproductive disorders on long-term health issues, coronary CT provides a unique opportunity to assess both coronary artery calcium score for cardiovascular screening as well as trabecular BD.

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Niek F Dirks Atalmedial Diagnostics Centre, Spaarne Gasthuis, Haarlem, The Netherlands
Department of Clinical Chemistry, Hematology and Immunology, Noordwest Ziekenhuis, Alkmaar, The Netherlands

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Etienne Cavalier Department of Clinical Chemistry, University of Liège, CHU de Liège, Liège, Belgium

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Annemieke C Heijboer Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Boelelaan, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

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The measurement of vitamin D metabolites aids in assessing vitamin D status and in diagnosing disorders of calcium homeostasis. Most laboratories measure total 25-hydroxyvitamin D (25(OH)D), while others have taken the extra effort to measure 25(OH)D2 and 25(OH)D3 separately and additional metabolites such as 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D. The aim of this review is to provide an updated overview of the main markers of vitamin D metabolism, define the intended measurands, and discuss the advantages and disadvantages of the two most widely used assays, automated assays and liquid chromatography–tandem mass spectrometry (LC-MS/MS). Whether using the easy and fast automated assays or the more complex LC-MS/MS, one should know the pitfalls of the used technique in order to interpret the measurements. In conclusion, automated assays are unable to accurately measure 25(OH)D in all patient groups, including persons using D2. In these cases, an LC-MS/MS method, when appropriately developed and standardized, produces a more reliable measurement.

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Budoor Alemadi Endocrinology Department, Dubai Hospital, Dubai Health, Dubai, UAE

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Fauzia Rashid Endocrinology Department, Dubai Hospital, Dubai Health, Dubai, UAE

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Ali Alzahrani King Faisal Specialist Hospital & Research Centre, Department of Medicine, Riyadh, Saudi Arabia

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Primary hyperparathyroidism has emerged as a prevalent endocrine disorder in clinical settings, necessitating in most cases, surgical intervention for the removal of the diseased gland. This condition is characterised by overactivity of the parathyroid glands, resulting in excessive parathyroid hormone production and subsequent disturbances in calcium homeostasis. The primary mode of management is surgical treatment, relying on the accurate localisation of the pathological parathyroid gland. Precise identification is paramount to ensuring that the surgical intervention effectively targets and removes the diseased gland, alleviating the hyperfunctioning state. However, localising the gland becomes challenging, as discrepancies between the clinical manifestation of active parathyroid and radiological identification are common. Based on our current knowledge, to date, no comprehensive review has been conducted that considers all factors collectively. This comprehensive review delves into the factors contributing to false-negative 99mTc-Sestamibi scans. Our research involved an exhaustive search in the PubMed database for hyperparathyroidism, with the identified literature meticulously filtered and reviewed by the authors. The results highlighted various factors, including multiple parathyroid diseases, nodular goitre, mild disease, or the presence of an ectopic gland that causes discordance. Hence, a thorough consideration of these factors is crucial during the diagnostic workup of hyperparathyroidism. Employing intraoperative PTH assays can significantly contribute to a successful cure of the disease, thereby providing a more comprehensive approach to managing this prevalent endocrine disorder.

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Liubov G Yanevskaya Almazov National Medical Research Centre, St. Petersburg, Russia

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Tatiana Karonova Almazov National Medical Research Centre, St. Petersburg, Russia
First Pavlov State Medical University, St. Petersburg, Russia

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Ilya V Sleptsov Saint-Petersburg State University N.I. Pirogov Clinic of High Medical Technologies, St. Petersburg, Russia

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Marina Evgenevna Boriskova First Pavlov State Medical University, St. Petersburg, Russia

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Aluza Ramilevna Bakhtiyarova Almazov National Medical Research Centre, St. Petersburg, Russia

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Roman A Chernikov Saint-Petersburg State University N.I. Pirogov Clinic of High Medical Technologies, St. Petersburg, Russia

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Karina Aleksandrovna Pogosian Almazov National Medical Research Centre, St. Petersburg, Russia

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Alena Timurovna Andreeva Almazov National Medical Research Centre, St. Petersburg, Russia

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Denis Andreevich Lebedev Almazov National Medical Research Centre, St. Petersburg, Russia

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Elena Nikolaevna Grineva Almazov National Medical Research Centre, St. Petersburg, Russia
First Pavlov State Medical University, St. Petersburg, Russia

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John P Bilezikian College of Physicians and Surgeons, Columbia University, New York, New York, USA

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Objective

The aim of our study was to investigate the distribution of the PHPT clinical manifestations and biochemical features in patients who underwent parathyroidectomy.

Materials and methods

Medical records of 449 patients from three Medical Centers (Saint-Petersburg, Russia), hospitalized during a period from 2011 to 2018, were reviewed. History and anthropometric data, laboratory results (iPTH, total and iCa, phosphorus, ALP, 24-h urinary calcium, 25(OH)D) and imaging data (ultrasonography, scintigraphy, CT/MRI scan, DXA) were analyzed.

Results

Three hundred ninety-four patients were included in the final analysis. Median age was 60 years with 94.2% being women. Symptomatic disease was evident in 222 (56.4%) patients, asymptomatic in 172 (43.6%). Skeletal involvement was more common for women, while frequency of other manifestations did not differ in both genders. There was no difference between symptomatic and asymptomatic patients in age. Serum iPTH level was higher in symptomatic patients (202.9 and 181.0 pg/mL, P = 0.022). Serum 25(OH)D level was estimated in few patients and negatively correlated with PTH (r = ¯0.294, P = 0.005), iCa (r = ¯0.268, P = 0.010) and total Ca (r = ¯0.284, P = 0.014) levels. Manifestations of CVD were observed in 67.7% of cases and affected equally both symptomatic and asymptomatic patients (70.7 and 63.4%, P = 0.076). Both age and BMI were higher in patients with CVD, whether or not they were symptomatic (62 and 53 years, P < 0.0001; 30.4 vs 26.0 kg/m2, P < 0.0001, respectively).

Conclusions

This experience illustrates that symptomatic phenotype is still the most common form of PHPT.

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Bekir Cakir Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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F Neslihan Cuhaci Seyrek Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Oya Topaloglu Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Didem Ozdemir Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Ahmet Dirikoc Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Cevdet Aydin Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Sefika Burcak Polat Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Berna Evranos Ogmen Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Ali Abbas Tam Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Husniye Baser Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Aylin Kilic Yazgan Department of Pathology, Ankara Ataturk Education and Research Hospital, Ankara, Turkey

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Mehmet Kilic Department of General Surgery, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Afra Alkan Department of Biostatistics, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Reyhan Ersoy Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

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Background

Despite significant improvement in imaging quality and advanced scientific knowledge, it may still sometimes be difficult to distinguish different parathyroid lesions. The aims of this prospective study were to evaluate parathyroid lesions with ultrasound elastography and to determine whether strain index can help to differentiate parathyroid lesions.

Methods

Patients with biochemically confirmed hyperparathyroidism and localised parathyroid lesions in ultrasonography were included. All patients underwent B-mode US and USE examination. Ultrasound elastography scores and strain index of lesions were determined. Strain index was defined as the ratio of strain of the thyroid parenchyma to the strain of the parathyroid lesion.

Results

Data of 245 lesions of 230 patients were analysed. Histopathologically, there were 202 (82.45%) parathyroid adenomas, 26 (10.61%) atypical parathyroid adenomas, and 17 (6.94%) cases of parathyroid hyperplasia. Median serum Ca was significantly higher in atypical parathyroid adenoma patients than parathyroid hyperplasia patients (P = 0.019) and median PTH was significantly higher in APA compared to PA patients (P < 0.001). In 221 (90.2%) of the parathyroid lesions, USE score was 1 or 2. The median SI of atypical parathyroid adenomas was significantly higher than parathyroid adenomas and hyperplasia lesions (1.5 (0.56–4.86), 1.01 (0.21–8.43) and 0.91 (0.26–2.02), respectively, P = 0.003).

Conclusion

Our study revealed that SI of parathyroid lesions as well as serum calcium, parathyroid hormone levels, and B-mode US features may help to predict the atypical parathyroid adenoma. Ultrasound elastography can be used to differentiate among parathyroid lesions and guide a surgical approach.

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Melissa Braga Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA

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Zena Simmons Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA

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Keith C Norris Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

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Monica G Ferrini Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

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Jorge N Artaza Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

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Skeletal muscle wasting is a serious disorder associated with health conditions such as aging, chronic kidney disease and AIDS. Vitamin D is most widely recognized for its regulation of calcium and phosphate homeostasis in relation to bone development and maintenance. Recently, vitamin D supplementation has been shown to improve muscle performance and reduce the risk of falls in vitamin D deficient older adults. However, little is known of the underlying molecular mechanism(s) or the role it plays in myogenic differentiation. We examined the effect of 1,25-D3 on myogenic cell differentiation in skeletal muscle derived stem cells. Primary cultures of skeletal muscle satellite cells were isolated from the tibialis anterior, soleus and gastrocnemius muscles of 8-week-old C57/BL6 male mice and then treated with 1,25-D3. The efficiency of satellite cells isolation determined by PAX7+ cells was 81%, and they expressed VDR. Incubation of satellite cells with 1,25-D3 induces increased expression of: (i) MYOD, (ii) MYOG, (iii) MYC2, (iv) skeletal muscle fast troponin I and T, (v) MYH1, (vi) IGF1 and 2, (vii) FGF1 and 2, (viii) BMP4, (ix) MMP9 and (x) FST. It also promotes myotube formation and decreases the expression of MSTN. In conclusion, 1,25-D3 promoted a robust myogenic effect on satellite cells responsible for the regeneration of muscle after injury or muscle waste. This study provides a mechanistic justification for vitamin D supplementation in conditions characterized by loss of muscle mass and also in vitamin D deficient older adults with reduced muscle mass and strength, and increased risk of falls.

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Mirjam M Oosterwerff Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Rosa Meijnen Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Natasja M Van Schoor Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Dirk L Knol Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Mark H H Kramer Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Mireille N M Van Poppel Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Paul Lips Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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E Marelise W Eekhoff Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Vitamin D deficiency is highly prevalent among non-western immigrants in The Netherlands and associated with poor physical performance. The aim of this study was to assess the effect of vitamin D supplementation on physical performance, exercise capacity, and daily physical activity in vitamin D-deficient, overweight non-western immigrants. A randomized double-blind, placebo-controlled trial was conducted to assess the effect of vitamin D on physical performance. A total of 130 participants were included. Eligibility criteria included overweight (BMI >27 kg/m2), 25-hydroxy vitamin D (25(OH)D) ≤50 nmol/l, and an age range of 20–65 years. The intervention group received 1200 IU vitamin D3 daily for 4 months; the control group received placebo. Both groups received 500 mg calcium daily. Outcome measures included physical performance (physical performance score), exercise capacity (a 6-min walk test (6-MWT)), and daily physical activity (questionnaire and accelerometer). There was no significant effect on physical performance, exercise capacity, or physical activity in the intention to treat analysis. In an explorative post hoc analysis restricted to participants reaching a serum 25(OH)D concentration of >60 nmol/l after intervention, there was an improvement of 19 m in the 6-MWT compared with the control group (P=0.053). Moderate dose vitamin D supplementation did not significantly improve physical performance, exercise capacity, or physical activity. However, when 25(OH)D concentrations reached >60 nmol/l after intervention, there was a borderline significant improvement in exercise capacity. Although the clinical relevance is not clear, this is a promising result, as all participants were overweight and did not improve their overall activity levels.

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