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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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Felix Haglund Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Gustaf Rosin Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Inga-Lena Nilsson Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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C Christofer Juhlin Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Ylva Pernow Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Sophie Norenstedt Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Andrii Dinets Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Catharina Larsson Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Johan Hartman Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Anders Höög Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness.

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Yuan Liu Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China
Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China

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Siyi Guo Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China
Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China

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Jinsong Wu Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China
Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China

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Rongai Wang Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China
Health Management Center, The Second Affiliated Hospital of Zhejiang Chinese Medicine University, Zhejiang, China

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Jinbo Liu Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China
Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China

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Yan Liu Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China
Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China

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Bin Lv Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, China

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Nan Liu Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, China

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Ling Jiang Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China
Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China

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Xiaoli Zhang Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China
Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China

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The clinical presentation of primary hyperparathyroidism (PHPT) differs between patients from developed and developing countries. In China, the clinical pattern has changed over the past few decades. Our aim was to elucidate general changes in the clinical characteristics of PHPT from 2010 to 2021. We enrolled 343 patients with PHPT at the Qilu Hospital of Shandong University, Jinan, China, from January 2010 to May 2021, including both surgical and non-surgical patients. Patients were divided into two subgroups, 2010–2016 (group A, n  = 152) and 2017–2021 (group B, n  = 191), based on the time span. We compared clinical manifestations and laboratory result data between these two groups. The mean patient age was 52.59 ± 13.55 years, and the male-to-female ratio was 1:2.54. Of the 343 patients, 183 (53.35%) had symptomatic PHPT; bone pain, urolithiasis, and fatigue were the most common symptoms. Post-operative pathology showed that 96.20% of the patients had parathyroid adenoma, whereas 2.41% had parathyroid carcinoma. Great changes occurred between 2010 and 2021; the percentage of patients with asymptomatic PHPT (aPHPT) increased from 36.18% in group A to 54.97% in group B. Moreover, patients in group B showed significantly lower serum calcium, alkaline phosphatase, parathyroid hormone, and urinary phosphate levels but higher serum 25-hydroxyvitamin D levels than those in group A. Clinical presentations in group B were also milder. In conclusion, the clinical characteristics of Chinese PHPT patients changed dramatically from 2010 to 2021, with asymptomatic PHPT (aPHPT becoming the predominant type over the last 3 years.

Open access
Ranganathan R Rao Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK

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Harpal S Randeva Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK

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Sailesh Sankaranarayanan Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK

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Murthy Narashima Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK

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Matthias Möhlig Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK

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Hisham Mehanna Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK

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Martin O Weickert Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
Warwickshire Institute for the Study of Diabetes, Warwick Medical School, Department of Endocrinology, Institute of Head and Neck Studies and Education (InHANSE), Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK

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Introduction/background

Vitamin D deficiency further increases circulating parathyroid hormone (PTH) levels in patients with primary hyperparathyroidism (pHPT), with potential detrimental effects on bone mass.

Methods

This was an observational clinical study in consecutive conservatively treated postmenopausal women (n=40) with pHPT and coexistent 25-hydroxyvitamin D deficiency (25OHD ≤50 nmol/l (≤20 ng/ml)). Patients who showed an increase in serum 25OHD above the threshold of vitamin D deficiency (>50 nmol/l; n=28) using treatment with various commonly prescribed vitamin D preparations were, for the purposes of statistical analyses, allocated to the treatment group. Patients who were retrospectively identified as having received no treatment with vitamin D and/or remained vitamin D deficient were considered as non-responders/controls (n=12). Adjusted calcium (adjCa), PTH and 25OHD concentrations were monitored in all subjects up to 54 months (mean observation period of 18±2 months).

Results

Prolonged increased vitamin D intake, regardless of the source (serum 25OHD, increase from 32.2±1.7 nmol/l at baseline to 136.4±11.6 nmol/l, P<0.0001), significantly reduced serum PTH (13.3±1.1 vs 10.5±1.0 pmol/l, P=0.0001), with no adverse effects on adjCa levels (2.60±0.03 vs 2.60±0.02 mmol/l, P=0.77) and renal function tests (P>0.73). In contrast, serum PTH remained unchanged (15.8±2.6 vs 16.3±1.9 pmol/l, P=0.64) in patients who remained vitamin D deficient, with a significant difference between groups in changes of PTH (P=0.0003). Intrapartial correlation analyses showed an independent negative correlation of changes in 25OHD with PTH levels (r ic=−0.41, P=0.014).

Conclusions

Prolonged treatment with vitamin D in various commonly prescribed preparations appeared to be safe and significantly reduced PTH levels by 21%.

Open access
Natércia Neves Marques de Queiroz University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Franciane Trindade Cunha de Melo University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Fabrício de Souza Resende University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Luísa Corrêa Janaú University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Norberto Jorge Kzan de Souza Neto University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Manuela Nascimento de Lemos University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Ana Carolina Lobato Virgolino University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Maria Clara Neres Iunes de Oliveira University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Angélica Leite de Alcântara University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Lorena Vilhena de Moraes University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Tiago Franco David University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Wanderson Maia da Silva University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Scarlatt Souza Reis University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Márcia Costa dos Santos University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Ana Carolina Contente Braga de Souza University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Pedro Paulo Freire Piani University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Neyla Arroyo Lara Mourão University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Karem Mileo Felício University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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João Felício Abrahão Neto University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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João Soares Felício University Hospital João de Barros Barreto, Federal University of Pará, Endocrinology Division, Belem, Pará, Brazil

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Objective:

Investigate the prevalence of vitamin D deficiency in an equatorial population through a large-sample study.

Methods:

Cross-sectional study with 30,224 healthy individuals from the North Region, in Brazil (Amazônia – state of Pará), who had 25-hydroxy-vitamin D (25(OH)D) and intact parathyroid hormone (PTH) serum levels measured by immunoassay method. Those with history of acute or chronic diseases were excluded. Abnormal levels of calcium, creatinine, glycemia and albumin were also exclusion criteria.

Results:

25(OH)D levels were 29.1 ± 8.2 ng/mL and values <12.7 ng/mL were equal to < −2 s.d. below average. Hypovitaminosis D was present in 10% of subjects according to the Institute of Medicine (values <20 ng/mL) and in 59%, in consonance with Endocrine Society (values 20–30 ng/mL as insufficiency and <20 ng/mL as deficiency) criteria. Individuals were divided according to four age brackets: children, adolescents, adults and elderly, and their 25(OH)D levels were: 33 ± 9; 28.5 ± 7.4; 28.3 ± 7.7; 29.3 ± 8.5 ng/mL, respectively. All groups differed in 25(OH)D, except adolescents vs adults. Regression model showed BMI, sex, living zone (urban or rural) and age as independent variables to 25(OH)D levels. Comparing subjects with vitamin D deficiency (<20 ng/mL) to those with vitamin D insufficiency (20–30 ng/mL), a difference between PTH levels in these two groups was observed (95.9 ± 24.7 pg/mL vs 44.2 ± 64.5 pg/mL; P < 0.01). Additionally, the most accurate predictive vitamin D level for subclinical hyperparathyroidism in ROC curve was 26 ng/mL.

Conclusion:

Our equatorial population showed low prevalence of vitamin D hypovitaminosis ranging with age bracket. The insufficient category by Endocrine Society was corroborated by our PTH data.

Open access
Sharon A Huish University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK
The University of Warwick, Coventry, UK
Royal Devon and Exeter NHS Foundation Trust, Exeter, UK

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Carl Jenkinson The University of Birmingham, Birmingham, UK

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Janet A Dunn The University of Warwick, Coventry, UK

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David J Meredith Royal Devon and Exeter NHS Foundation Trust, Exeter, UK

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Rosemary Bland The University of Warwick, Coventry, UK

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Martin Hewison The University of Birmingham, Birmingham, UK

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Low serum 1,25-dihydroxyvitamin D (1,25(OH)2D) in end-stage renal disease (ESRD) is considered a consequence of elevated fibroblast growth factor 23 (FGF23) and concomitant reduced activity of renal 1α-hydroxylase (CYP27B1). Current ESRD treatment strategies to increase serum calcium and suppress secondary hyperparathyroidism involve supplementation with vitamin D analogues that circumvent 1α-hydroxylase. This overlooks the potential importance of 25-hydroxyvitamin D (25(OH)D) deficiency as a contributor to low serum 1,25(OH)2D. We investigated the effects of vitamin D (cholecalciferol) supplementation (40,000 IU for 12 weeks and maintenance dose of 20,000 IU fortnightly), on multiple serum vitamin D metabolites (25(OH)D, 1,25(OH)2D3 and 24,25(OH)2D3) in 55 haemodialysis patients. Baseline and 12 month data were compared using related-samples Wilcoxon signed rank test. All patients remained on active vitamin D analogues as part of routine ESRD care. 1,25(OH)2D3 levels were low at baseline (normal range: 60–120 pmol/L). Cholecalciferol supplementation normalised both serum 25(OH)D and 1,25(OH)2D3. Median serum 25(OH)D increased from 35.1 nmol/L (IQR: 23.0–47.5 nmol/L) to 119.9 nmol/L (IQR: 99.5–143.3 nmol/L) (P < 0.001). Median serum 1,25(OH)2D3 and 24,25(OH)2D3 increased from 48.3 pmol/L (IQR: 35.9–57.9 pmol/L) and 3.8 nmol/L (IQR: 2.3–6.0 nmol/L) to 96.2 pmol/L (IQR: 77.1–130.6 pmol/L) and 12.3 nmol/L (IQR: 9–16.4 nmol/L), respectively (P < 0.001). A non-significant reduction in daily active vitamin D analogue dose occurred, 0.94 µmcg at baseline to 0.77 µmcg at 12 months (P = 0.73). The ability to synthesise 1,25(OH)2D3 in ESRD is maintained but is substrate dependent, and serum 25(OH)D was a limiting factor at baseline. Therefore, 1,25(OH)2D3 deficiency in ESRD is partly a consequence of 25(OH)D deficiency, rather than solely due to reduced 1α-hydroxylase activity as suggested by current treatment strategies.

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Maria Stelmachowska-Banaś Department of Endocrinology, The Centre of Postgraduate Medical Education, Warsaw, Polska, Poland

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Izabella Czajka-Oraniec Department of Endocrinology, The Centre of Postgraduate Medical Education, Warsaw, Polska, Poland

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Immune checkpoint inhibitors (ICIs) belong to a new group of anticancer drugs targeting T-cell proteins involved in the activation of immune response toward malignancies. Their introduction into clinical practice was a milestone in modern cancer treatment. However, the significant advantage of ICIs over conventional chemotherapy in terms of therapeutic efficacy is accompanied by new challenges related to specific side effects. ICI-induced immune system activation could lead to the loss of self-tolerance, presenting as autoimmune inflammation and dysfunction of various tissues and organs. Thus, the typical side effects of ICIs include immune-related adverse events (irAEs), among which endocrine irAEs, affecting numerous endocrine glands, have been commonly recognized. This review aimed to outline the current knowledge regarding ICI-induced endocrine disorders from a clinical perspective. We present updated information on the incidence and clinical development of ICI-induced endocrinopathies, including the most frequent thyroiditis and hypophysitis, the rarely observed insulin-dependent diabetes mellitus and primary adrenal insufficiency, and the recently described cases of hypoparathyroidism and lipodystrophy. Practical guidelines for monitoring, diagnosis, and treatment of ICI-related endocrine toxicities are also offered. Rising awareness of endocrine irAEs among oncologists, endocrinologists, and other health professionals caring for patients receiving ICIs could contribute to better safety and efficacy. As immunotherapy becomes widespread and approved for new types of malignancies, increased incidences of endocrine irAEs are expected in the future.

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Ghazala Zaidi Departments of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Vijayalakshmi Bhatia Departments of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Saroj K Sahoo Departments of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Aditya Narayan Sarangi Departments of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Niharika Bharti Departments of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Li Zhang Department of Immunology, Barbara Davis Centre for Childhood Diabetes, Denver, USA

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Liping Yu Department of Immunology, Barbara Davis Centre for Childhood Diabetes, Denver, USA

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Daniel Eriksson Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

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Sophie Bensing Department of Molecular Medicine and Surgery, Karolinska Institutet, and Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden

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Olle Kämpe Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden

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Nisha Bharani Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, India

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Surendra Kumar Yachha Departments of Paediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Anil Bhansali Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

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Alok Sachan Department of Endocrinology, Sri Venkateshwara Institute of Medical Sciences, Tirupathi, India

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Vandana Jain Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India

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Nalini Shah Department of Endocrinology, King Edward Memorial Hospital, Seth GS Medical College, Mumbai, India

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Rakesh Aggarwal Departments of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Amita Aggarwal Departments of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Muthuswamy Srinivasan Departments of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Sarita Agarwal Departments of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Eesh Bhatia Departments of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Objective

Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients.

Design

Twenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2–19) years.

Methods

Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied.

Results

Patients varied widely in their age of presentation [3.5 (0.1–17) years] and number of clinical manifestations [5 (2–11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3–23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians.

Conclusions

Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.

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W N H Koek Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands

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N Campos-Obando Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands

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B C J van der Eerden Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands

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Y B de Rijke Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, the Netherlands

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M A Ikram Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands

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A G Uitterlinden Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands

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J P T M van Leeuwen Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands

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M C Zillikens Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands

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Background

Sex differences in calcium and phosphate have been observed. We aimed to assess a relation with age.

Methods

We used the laboratory values of serum calcium, phosphate and albumin from three different samples ( 2005, 2010 and 2014 years) using the hospital information system of Erasmus MC, Rotterdam. The samples were divided into three age groups: 1–17, 18–44 and ≥45 years. Sex differences in calcium and phosphate were analyzed using ANCOVA, adjusting for age and serum albumin. Furthermore, sex by age interactions were determined and we analyzed differences between age groups stratified by sex.

Results

In all three samples there was a significant sex × age interaction for serum calcium and phosphate, whose levels were significantly higher in women compared to men above 45 years. No sex differences in the younger age groups were found. In men, serum calcium and phosphate levels were highest in the youngest age group compared to age groups of 18–44 and ≥45 years. In women, serum calcium levels were significantly higher in the age group 1–17 and the age group ≥45 years compared to the 18–44 years age group. In women, serum phosphate was different between the three different age groups with highest level in the group 1–17 years and lowest in the group 18–44 years.

Conclusion

There are age- dependent sex differences in serum calcium and phosphate. Furthermore, we found differences in serum calcium and phosphate between different age groups. Underlying mechanisms for these age- and sex- differences are not yet fully elucidated.

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Mieke Van Hemelrijck
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Thurkaa Shanmugalingam
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Cecilia Bosco
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Wahyu Wulaningsih
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Sabine Rohrmann Cancer Epidemiology Group, Division of Chronic Disease Epidemiology, Division of Cancer Studies, King's College London, London, UK

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Background

Despite mounting evidence linking both calcium and IGF1, there is a lack of studies investigating any association between circulating levels of IGF1 and serum calcium.

Methods

Serum calcium, IGF1, and IGF-binding protein 3 (IGFBP3) were measured for 5368 participants in NHANES III. We calculated multivariable-adjusted geometric means of serum concentrations of IGF1, IGFBP3, and IGF1/IGFBP3 by categories of calcium (lowest 5% (<1.16 mmol/l), mid 90%, and top 5% (≥1.31 mmol/l)). We also performed stratified analyses by sex, age, ethnicity, BMI, serum levels of vitamin D, and bone mineral density (BMD).

Results

Overall, we found that circulating calcium was positively associated with circulating levels of IGF1 and IGFBP3, but not their molar ratio (i.e., geometric mean of IGF1 by increasing calcium categories: 237.63, 246.51, and 264.22 ng/nl; P trend: 0.43; P first vs third category: 0.01). In particular, these associations were observed in women, people aged <60, non-Hispanic whites, those with vitamin D levels above the mean, and those with low BMD. In contrast, there was an inverse association with the molar ratio for those with BMI ≥30 kg/m2.

Conclusion

We found an overall positive association between circulating levels of IGF1 and IGFBP3 and serum calcium. However, stratification by potential effect-modifiers did not support all suggested hypotheses. Our findings provide more insight into the interplay between calcium and IGF1, which in the future can be investigated in larger observational studies allowing for additional stratifications based on a combination of the different effect-modifiers investigated here.

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