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Background
The diagnosis of primary hyperparathyroidism (PHPT) remains a challenge because of increased asymptomatic PHPT or patients with normocalcaemic PHPT (NPHPT). In addition, some primary hospitals in China have no equipment to measure parathyroid hormone (PTH) levels. Therefore, an additional, simple, and inexpensive laboratory biochemical marker is urgently needed. The calcium/phosphate (Ca/P) ratio and chloride/phosphate (Cl/P) ratio have been proposed as suitable tools to diagnose PHPT in Europe; however, the Ca/P ratio has never been tested in China. We aimed to conduct a confirmatory study to explore the diagnostic performance of the Ca/P ratio for PHPT in China.
Methods
From January 2015 to December 2020, a total of 155 patients who underwent parathyroidectomy (143 PHPT patients and 12 NPHPT patients) and 153 controls were enrolled in this single-center , retrospective study. Serum calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin vitamin D (25(OH) vitamin D), chloride, alanine transaminase (ALT), aspartate aminotransaminase (AST), estimated glomerular filtration rate (eGFR), and creatinine levels were recorded for all the study participants. Pairwise comparisons were made between groups, and the diagnostic performance of the Ca/P ratio was determined using receiver-operating characteristic (ROC) analysis.
Results
Patients with PHPT had a higher Ca/P ratio than controls (P < 0.001). A Ca/P ratio above 2.94 with a sensitivity of 95.5% and specificity of 98.7% can distinguish PHPT patients from healthy individuals. This index was positively correlated with the PTH level (r = 0.875, P < 0.001).
Conclusion
The Ca/P ratio is an ideal and inexpensive indicator for diagnosing PHPT in China when using a cut-off value of 2.94.
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Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland
Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland
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Health-related quality of life (HRQoL) is frequently impaired in primary hyperparathyroidism (PHPT) but it is unclear if surgery is beneficial. The objective was to prospectively assess HRQoL in PHPT (n=124) with the 15D instrument before and after surgery, to compare it with that of a comparable sample of the general population (n=4295), and search for predictors of HRQoL and its change. HRQoL, and clinical and laboratory parameters were measured before and at 6 and 12 months after surgery. Regression techniques were used to search for predictors of HRQoL and gains from treatment. Before surgery, PHPT patients had significantly lower mean 15D score compared to controls (0.813 vs 0.904, P<0.001). Excretion, mental function, discomfort and symptoms, distress, depression, vitality, and sexual activity were most impaired (all P<0.001). Number of medications (P=0.001) and subjective symptoms (P<0.05) but not calcium or parathyroid hormone (PTH) predicted impaired HRQoL. Serum 25-hydroxyvitamin D (25OHD) was of borderline significance (P=0.051). Compared to baseline, mean 15D score improved significantly 6 months after surgery (0.813 vs 0.865, P<0.001) and the effect sustained at 1 year (0.878, P<0.001). The improvement was clinically important in 77.4% of patients (P<0.001). Educational level independently predicted improvement (P<0.005). HRQoL is severely impaired in PHPT but improves significantly after surgery. The 15D is a sensitive tool for assessing HRQoL and recognizing patients likely to benefit from surgery.
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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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Objective
Chronic hypoparathyroidism (HP) is associated with acute and chronic complications, especially those related to hypocalcemia. We aimed to analyze details on hospital admissions and the reported deaths in affected patients.
Design and methods
In a retrospective analysis, we reviewed the medical history of 198 patients diagnosed with chronic HP over a continuous period of up to 17 years at the Medical University Graz.
Results
The mean age in our mostly female cohort (70.2%) was 62.6 ± 18.7 years. The etiology was predominantly postsurgical (84.8%). About 87.4% of patients received standard medication (oral calcium/vitamin D), 15 patients (7.6%) used rhPTH1–84/Natpar® and 10 patients (4.5%) had no/unknown medication. Two hundred and nineteen emergency room (ER) visits and 627 hospitalizations were documented among 149 patients, and 49 patients (24.7%) did not record any hospital admissions. According to symptoms and decreased serum calcium levels, 12% of ER (n = 26) visits and 7% of hospitalizations (n = 44) were likely attributable to HP. A subgroup of 13 patients (6.5%) received kidney transplants prior to the HP diagnosis. In eight of these patients, parathyroidectomy for tertiary renal hyperparathyroidism was the cause of permanent HP. The mortality was 7.8% (n = 12), and the causes of death appeared to be unrelated to HP. Although the awareness for HP was low, calcium levels were documented in 71% (n = 447) of hospitalizations.
Conclusions
Acute symptoms directly related to HP did not represent the primary cause of ER visits. However, comorbidities (e.g. renal/cardiovascular diseases) associated with HP played a key role in hospitalizations and deaths.
Significance statement
Hypoparathyroidism (HP) is the most common complication after anterior neck surgery. Yet, it remains underdiagnosed as well as undertreated, and the burden of disease and long-term complications are usually underestimated. There are few detailed data on emergency room (ER) visits hospitalizations and death in patients with chronic HP, although acute symptoms due to hypo-/hypercalcemia are easily detectable. We show that HP is not the primary cause for presentation but that hypocalcemia is a typical laboratory finding (when ordered) and thus may contribute to subjective symptoms. Patients often present with renal/cardiovascular/oncologic illness for which HP is known to be a contributing factor. A small but very special group (n = 13, 6.5%) are patients after kidney transplantations who showed a high ER hospitalization rate. Surprisingly, HP was never the cause for their frequent hospitalizations but rather the result of chronic kidney disease. The most frequent cause for HP in these patients was parathyroidectomy due to tertiary hyperparathyroidism. The causes of death in 12 patients appeared to be unrelated to HP, but we found a high prevalence of chronic organ damages/comorbidities related to it in this group. Less than 25% documented HP correctly in the discharge letters, which indicates a high potential for improvement.
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This competency framework was developed by a working group of endocrine specialist nurses with the support of the Society for Endocrinology to enhance the clinical care that adults with an endocrine disorder receive. Nurses should be able to demonstrate that they are functioning at an optimal level in order for patients to receive appropriate care. By formulating a competency framework from which an adult endocrine nurse specialist can work, it is envisaged that their development as professional practitioners can be enhanced. This is the second edition of the Competency Framework for Adult Endocrine Nursing. It introduces four new competencies on benign adrenal tumours, hypo- and hyperparathyroidism, osteoporosis and polycystic ovary syndrome. The authors and the Society for Endocrinology welcome constructive feedback on the document, both nationally and internationally, in anticipation that further developments and ideas can be incorporated into future versions.
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Multiple endocrine neoplasia type 1 (MEN1) is the most common cause of hereditary primary hyperparathyroidism (PHPT). Bone disorders are considered one of the key symptoms in PHPT present with the significant reduction in bone mineral density and low-energy fractures. Previously, these bone disorders were believed to be caused solely by the increase in the level of parathyroid hormone and its subsequent effect on bone resorption. The current paradigm, however, states that the mutations in the menin gene, which cause the development of MEN1, can also affect the metabolism of the cells of the osteoid lineage. This review analyzes both the proven and the potential intracellular mechanisms through which menin can affect bone metabolism.
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Osteoporosis (OP) is a systemic bone disease in which bone density and quality decrease and bone fragility increases due to a variety of causes, making it prone to fractures. The development of OP is closely related to oxidative stress. Uric acid (UA) is the end product of purine metabolism in the human body. Extracellular UA has antioxidant properties and is thought to have a protective effect on bone metabolism. However, the process of UA degradation can lead to intracellular oxidative stress, which together with UA-induced inflammatory factors, leads to increased bone destruction. In addition, UA can inhibit vitamin D production, resulting in secondary hyperparathyroidism and further exacerbating UA-associated bone loss. This review summarizes the relationship between serum UA levels and bone mineral density, bone turnover markers, and so on, in the hope of providing new insights into the pathogenesis and treatment of OP.
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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.
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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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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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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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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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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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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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.
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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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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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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Health Management Center, The Second Affiliated Hospital of Zhejiang Chinese Medicine University, Zhejiang, China
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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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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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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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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.
