Search Results

You are looking at 41 - 50 of 110 items for

  • Abstract: Hyperparathyroidism x
  • Abstract: Hypoparathyroidism x
  • Abstract: Osteo* x
  • Abstract: Skeleton x
Clear All Modify Search
Kelly Brewer Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut, USA

Search for other papers by Kelly Brewer in
Google Scholar
PubMed
Close
,
Isabel Nip Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut, USA

Search for other papers by Isabel Nip in
Google Scholar
PubMed
Close
,
Justin Bellizzi Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut, USA

Search for other papers by Justin Bellizzi in
Google Scholar
PubMed
Close
,
Jessica Costa-Guda Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut School of Dental Medicine, Farmington, Connecticut, USA

Search for other papers by Jessica Costa-Guda in
Google Scholar
PubMed
Close
, and
Andrew Arnold Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
Division of Endocrinology and Metabolism, University of Connecticut School of Medicine, Farmington, Connecticut, USA

Search for other papers by Andrew Arnold in
Google Scholar
PubMed
Close

Objective

Primary hyperparathyroidism is most often caused by a sporadic single-gland parathyroid adenoma (PTA), a tumor type for which cyclin D1 is the only known and experimentally validated oncoprotein. However, the molecular origins of its frequent overexpression have remained mostly elusive. In this study, we explored a potential tumorigenic mechanism that could increase cyclin D1 stability through a defect in molecules responsible for its degradation.

Methods

We examined two tumor suppressor genes known to modulate cyclin D1 ubiquitination, PRKN and FBXO4 (FBX4), for evidence of classic two-hit tumor suppressor inactivation within a cohort of 82 PTA cases. We examined the cohort for intragenic inactivating and splice site mutations by Sanger sequencing and for locus-associated loss of heterozygosity (LOH) by microsatellite analysis.

Results

We identified no evidence of bi-allelic tumor suppressor inactivation of PRKN or FBXO4 via inactivating mutation or splice site perturbation, neither in combination with nor independent of LOH. Among the 82 cases, we encountered previously documented benign single nucleotide polymorphisms (SNPs) in 35 tumors at frequencies similar to those reported in the germlines of the general population. Eight cases exhibited intragenic LOH at the PRKN locus, in some cases extending to cover at least an additional 1.7 Mb of chromosome 6q25-26. FBXO4 was not affected by LOH.

Conclusion:

The absence of evidence for specific bi-allelic inactivation in PRKN and FBXO4 in this sizeable cohort suggests that these genes only rarely, if ever, serve as classic driver tumor suppressors responsible for the growth of PTAs.

Open access
Laura J Reid Edinburgh Centre for Endocrinology and Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK

Search for other papers by Laura J Reid in
Google Scholar
PubMed
Close
,
Bala Muthukrishnan Edinburgh Centre for Endocrinology and Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK

Search for other papers by Bala Muthukrishnan in
Google Scholar
PubMed
Close
,
Dilip Patel Department of Radiology, Royal Infirmary of Edinburgh, Edinburgh, UK

Search for other papers by Dilip Patel in
Google Scholar
PubMed
Close
,
Mike S Crane Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, UK

Search for other papers by Mike S Crane in
Google Scholar
PubMed
Close
,
Murat Akyol Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK

Search for other papers by Murat Akyol in
Google Scholar
PubMed
Close
,
Andrew Thomson Department of Pathology, Royal Infirmary of Edinburgh, Edinburgh, UK

Search for other papers by Andrew Thomson in
Google Scholar
PubMed
Close
,
Jonathan R Seckl Edinburgh Centre for Endocrinology and Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK
Centre for Cardiovascular Science, Queen’s Medical Research Unit, University of Edinburgh, Edinburgh, UK

Search for other papers by Jonathan R Seckl in
Google Scholar
PubMed
Close
, and
Fraser W Gibb Edinburgh Centre for Endocrinology and Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK

Search for other papers by Fraser W Gibb in
Google Scholar
PubMed
Close

Objective

Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT.

Design

Retrospective cohort study.

Patients

PHPT assessed between 2006 and 2014 (n = 611) in a university hospital.

Measurements

Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes.

Results

Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralisation was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035).

Conclusions

Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.

Open access
Xiao-Ping Qi Department of Oncologic and Urologic Surgery, The 117th PLA Hospital, Wenzhou Medical University, Hangzhou, Zhejiang Province, China

Search for other papers by Xiao-Ping Qi in
Google Scholar
PubMed
Close
,
Jian-Zhong Peng Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou, Zhejiang Province, China

Search for other papers by Jian-Zhong Peng in
Google Scholar
PubMed
Close
,
Xiao-Wei Yang Department of Pediatrics, The First People’s Hospital of Wenling City, Wenling, Zhejiang Province, China

Search for other papers by Xiao-Wei Yang in
Google Scholar
PubMed
Close
,
Zhi-Lie Cao Department of Oncologic and Urologic Surgery, The 117th PLA Hospital, Wenzhou Medical University, Hangzhou, Zhejiang Province, China

Search for other papers by Zhi-Lie Cao in
Google Scholar
PubMed
Close
,
Xiu-Hua Yu Department of Oncologic and Urologic Surgery, The 117th PLA Hospital, Wenzhou Medical University, Hangzhou, Zhejiang Province, China

Search for other papers by Xiu-Hua Yu in
Google Scholar
PubMed
Close
,
Xu-Dong Fang Department of Oncologic and Urologic Surgery, The 117th PLA Hospital, Wenzhou Medical University, Hangzhou, Zhejiang Province, China

Search for other papers by Xu-Dong Fang in
Google Scholar
PubMed
Close
,
Da-Hong Zhang Department of Urologic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province, China

Search for other papers by Da-Hong Zhang in
Google Scholar
PubMed
Close
, and
Jian-Qiang Zhao Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China

Search for other papers by Jian-Qiang Zhao in
Google Scholar
PubMed
Close

Background

Cutaneous lichen amyloidosis (CLA) has been reported in some multiple endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical manifestation in ‘MEN 2A with CLA’, one of four variants of MEN 2A, which was strictly located in the scapular region of the upper back.

Patient Findings

This study reports a large south-eastern Chinese pedigree with 17 individuals carrying the MEN 2A-harboring germline C611Y (c.1832G>A) RET mutation by Sanger sequencing. One individual presented MEN 2A-related clinical features, including typical CLA in the interscapular region; another individual exhibited neurological pruritus and scratching in the upper back but lacked CLA skin lesions. Both subjects presented with CLA or pruritic symptoms several years before the onset of medullary thyroid carcinoma (MTC) and/or pheochromocytoma. The remaining 15 RET mutation carriers did not exhibit CLA; of these, one presented with MTC and pheochromocytoma, nine with MTC only, two with elevated serum calcitonin and three younger subjects with normal serum calcitonin levels. This family’s clinical data revealed a later diagnosis of MTC (mean age, 45.9 (range: 23–73) years), a lower penetrance of pheochromocytoma (2/17, 11.8%) and CLA (1/17, 5.9%). However, no hyperparathyroidism and Hirschsprung disease were reported in this family.

Summary and Conclusions

This is the first description of a family with MEN 2A-related CLA due to a germline RET C611Y mutation, which might exhibit a novel and diversified genotype–phenotype spectrum in MEN 2A.

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

Search for other papers by Bekir Cakir in
Google Scholar
PubMed
Close
,
F Neslihan Cuhaci Seyrek Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by F Neslihan Cuhaci Seyrek in
Google Scholar
PubMed
Close
,
Oya Topaloglu Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Oya Topaloglu in
Google Scholar
PubMed
Close
,
Didem Ozdemir Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Didem Ozdemir in
Google Scholar
PubMed
Close
,
Ahmet Dirikoc Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Ahmet Dirikoc in
Google Scholar
PubMed
Close
,
Cevdet Aydin Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Cevdet Aydin in
Google Scholar
PubMed
Close
,
Sefika Burcak Polat Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Sefika Burcak Polat in
Google Scholar
PubMed
Close
,
Berna Evranos Ogmen Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Berna Evranos Ogmen in
Google Scholar
PubMed
Close
,
Ali Abbas Tam Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Ali Abbas Tam in
Google Scholar
PubMed
Close
,
Husniye Baser Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Husniye Baser in
Google Scholar
PubMed
Close
,
Aylin Kilic Yazgan Department of Pathology, Ankara Ataturk Education and Research Hospital, Ankara, Turkey

Search for other papers by Aylin Kilic Yazgan in
Google Scholar
PubMed
Close
,
Mehmet Kilic Department of General Surgery, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Mehmet Kilic in
Google Scholar
PubMed
Close
,
Afra Alkan Department of Biostatistics, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Afra Alkan in
Google Scholar
PubMed
Close
, and
Reyhan Ersoy Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Search for other papers by Reyhan Ersoy in
Google Scholar
PubMed
Close

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.

Open access
Elizaveta Mamedova Department of Neuroendocrinology and Bone Diseases, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Elizaveta Mamedova in
Google Scholar
PubMed
Close
,
Natalya Mokrysheva Department of Parathyroid Diseases, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Natalya Mokrysheva in
Google Scholar
PubMed
Close
,
Evgeny Vasilyev Department and Laboratory of Inherited Endocrine Disorders, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Evgeny Vasilyev in
Google Scholar
PubMed
Close
,
Vasily Petrov Department and Laboratory of Inherited Endocrine Disorders, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Vasily Petrov in
Google Scholar
PubMed
Close
,
Ekaterina Pigarova Department of Neuroendocrinology and Bone Diseases, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Ekaterina Pigarova in
Google Scholar
PubMed
Close
,
Sergey Kuznetsov Department of Surgery, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Sergey Kuznetsov in
Google Scholar
PubMed
Close
,
Nikolay Kuznetsov Department of Surgery, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Nikolay Kuznetsov in
Google Scholar
PubMed
Close
,
Liudmila Rozhinskaya Department of Neuroendocrinology and Bone Diseases, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Liudmila Rozhinskaya in
Google Scholar
PubMed
Close
,
Galina Melnichenko I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
Institute of Clinical Endocrinology, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Galina Melnichenko in
Google Scholar
PubMed
Close
,
Ivan Dedov Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Ivan Dedov in
Google Scholar
PubMed
Close
, and
Anatoly Tiulpakov Department and Laboratory of Inherited Endocrine Disorders, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Anatoly Tiulpakov in
Google Scholar
PubMed
Close

Background

Primary hyperparathyroidism (PHPT) is a relatively rare disorder among children, adolescents and young adults. Its development at an early age is suspicious for hereditary causes, though the need for routine genetic testing remains controversial.

Objective

To identify and describe hereditary forms of PHPT in patients with manifestation of the disease under 40 years of age.

Design

We enrolled 65 patients with PHPT diagnosed before 40 years of age. Ten of them had MEN1 mutation, and PHPT in them was the first manifestation of multiple endocrine neoplasia type 1 syndrome.

Methods

The other fifty-five patients underwent next-generation sequencing (NGS) of a custom-designed panel of genes, associated with PHPT (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D). In cases suspicious for gross CDC73 deletions multiplex ligation-dependent probe amplification was performed.

Results

NGS revealed six pathogenic or likely pathogenic germline sequence variants: four in CDC73 c.271C>T (p.Arg91*), c.496C>T (p.Gln166*), c.685A>T (p.Arg229*) and c.787C>T (p.Arg263Cys); one in CASR c.3145G>T (p.Glu1049*) and one in MEN1 c.784-9G>A. In two patients, MLPA confirmed gross CDC73 deletions. In total, 44 sporadic and 21 hereditary PHPT cases were identified. Parathyroid carcinomas and atypical parathyroid adenomas were present in 8/65 of young patients, in whom CDC73 mutations were found in 5/8.

Conclusions

Hereditary forms of PHPT can be identified in up to 1/3 of young patients with manifestation of the disease at <40 years of age. Parathyroid carcinomas or atypical parathyroid adenomas in young patients are frequently associated with CDC73 mutations.

Open access
Elena Pardi Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Elena Pardi in
Google Scholar
PubMed
Close
,
Stefano Mariotti Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Stefano Mariotti in
Google Scholar
PubMed
Close
,
Natalia S Pellegata Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Natalia S Pellegata in
Google Scholar
PubMed
Close
,
Katiuscia Benfini Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Katiuscia Benfini in
Google Scholar
PubMed
Close
,
Simona Borsari Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Simona Borsari in
Google Scholar
PubMed
Close
,
Federica Saponaro Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Federica Saponaro in
Google Scholar
PubMed
Close
,
Liborio Torregrossa Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Liborio Torregrossa in
Google Scholar
PubMed
Close
,
Antonello Cappai Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Antonello Cappai in
Google Scholar
PubMed
Close
,
Chiara Satta Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Chiara Satta in
Google Scholar
PubMed
Close
,
Marco Mastinu Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Marco Mastinu in
Google Scholar
PubMed
Close
,
Claudio Marcocci Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Claudio Marcocci in
Google Scholar
PubMed
Close
, and
Filomena Cetani Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Filomena Cetani in
Google Scholar
PubMed
Close

Inactivating germline mutations of the CDKN1B gene encoding the nuclear cyclin-dependent kinase inhibitor P27kip1 protein have been reported in patients with multiple endocrine neoplasia type 4 (MEN4), a MEN1-like phenotype without MEN1 mutations. The aim of this study was to characterize in vitro the germline CDKN1B mutation c.374_375delCT (S125X) we detected in a patient with MEN4. The proband was affected by primary hyperparathyroidism due to multiglandular parathyroid involvement and gastro–entero–pancreatic tumors. We carried out subcellular localization experiments by transfection with plasmid vectors expressing the WT or mutant CDKN1B cDNA into the eukaryotic human cervix adenocarcinoma (HeLa) and GH3 cell lines. Results from western blotting studies indicated that fusion proteins were expressed at equal levels. The mutated protein was shorter compared with the WT protein and lacked the highly conserved C-terminal domain, which includes the bipartite nuclear localization signal at amino acids 152/153 and 166/168. In HeLa and GH3 cells, WT P27 localized in the nucleus, whereas the P27_S125X protein was retained in the cytoplasm, predicting the loss of tumor-suppressive function. The proband's tumoral parathyroid tissue did not show allelic loss, because both WT and mutant alleles were determined to be present by sequencing the somatic DNA. Immunohistochemistry revealed a complete loss of nuclear expression of P27 in a parathyroid adenoma, which had been removed by the second surgery in the patient. In conclusion, our results confirm the pathogenic role of the c.374_375delCT CDKN1B germline mutation in a patient with MEN4.

Open access
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

Search for other papers by Felix Haglund in
Google Scholar
PubMed
Close
,
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

Search for other papers by Gustaf Rosin in
Google Scholar
PubMed
Close
,
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

Search for other papers by Inga-Lena Nilsson in
Google Scholar
PubMed
Close
,
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

Search for other papers by C Christofer Juhlin in
Google Scholar
PubMed
Close
,
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

Search for other papers by Ylva Pernow in
Google Scholar
PubMed
Close
,
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

Search for other papers by Sophie Norenstedt in
Google Scholar
PubMed
Close
,
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

Search for other papers by Andrii Dinets in
Google Scholar
PubMed
Close
,
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

Search for other papers by Catharina Larsson in
Google Scholar
PubMed
Close
,
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

Search for other papers by Johan Hartman in
Google Scholar
PubMed
Close
, and
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

Search for other papers by Anders Höög in
Google Scholar
PubMed
Close

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.

Open access
Daniel Bell Department of Pharmacy, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

Search for other papers by Daniel Bell in
Google Scholar
PubMed
Close
,
Julia Hale Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

Search for other papers by Julia Hale in
Google Scholar
PubMed
Close
,
Cara Go Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

Search for other papers by Cara Go in
Google Scholar
PubMed
Close
,
Ben G Challis Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

Search for other papers by Ben G Challis in
Google Scholar
PubMed
Close
,
Tilak Das Department of Radiology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

Search for other papers by Tilak Das in
Google Scholar
PubMed
Close
,
Brian Fish Department of Head and Neck Surgery, Cambridge University NHS Foundation Trust, Cambridge, UK

Search for other papers by Brian Fish in
Google Scholar
PubMed
Close
, and
Ruth T Casey Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
Department of Medical Genetics, Cambridge University, Cambridge, UK

Search for other papers by Ruth T Casey in
Google Scholar
PubMed
Close

Primary hyperparathyroidism (pHPT) is a common endocrine disorder that can be cured by parathyroidectomy; patients unsuitable for surgery can be treated with cinacalcet. Availability of surgery may be reduced during COVID-19, and cinacalcet can be used as bridging therapy. In this single-centre retrospective analysis, we investigated the utility and safety of cinacalcet in patients with pHPT receiving cinacalcet between March 2019 and July 2020, including pre-parathyroidectomy bridging. We reviewed and summarised the published literature. Cinacalcet dosages were adjusted by endocrinologists to achieve target calcium < 2.70 mmol/L. Eighty-six patients were identified, with the most achieving target calcium (79.1%) with a mean dose of 39.4 mg/day (±17.1 mg/day) for a median duration of 35 weeks (1–178 weeks). Calcium was normalised in a median time of 5 weeks. The majority of patients commenced cinacalcet of 30 mg/day (78 patients) with the remainder at 60 mg/day (8 patients). Forty-seven patients commencing lower dose cinacalcet (30 mg/day) achieved target calcium without requiring 60 mg/day. Baseline PTH was significantly higher in patients requiring higher doses of cinacalcet. 18.6% of patients reported adverse reactions and 4.7% discontinued cinacalcet. Patients treated with cinacalcet pre-parathyroidectomy required a higher dose and fewer achieved target calcium compared to medical treatment with cinacalcet alone. Post-operative calcium was similar to patients who were not given pre-parathyroidectomy cinacalcet. In summary, cinacalcet at an initial dose of 30 mg/day is safe and useful for achieving target calcium in patients with symptomatic or severe hypercalcaemia in pHPT, including those treated for pre-parathyroidectomy. We propose a PTH threshold of >30 pmol/L to initiate at a higher dose of 60 mg/day.

Open access
Mengting Yin Sichuan University West China Hospital, Chengdu, China

Search for other papers by Mengting Yin in
Google Scholar
PubMed
Close
,
Qianhui Liu Sichuan University West China Hospital, Chengdu, China

Search for other papers by Qianhui Liu in
Google Scholar
PubMed
Close
,
Qingzhong Wang Jintang First People’s Hospital, West China Hospital Sichuan University Jingtang Hospital, Chengdu, China

Search for other papers by Qingzhong Wang in
Google Scholar
PubMed
Close
,
Yong He Sichuan University West China Hospital, Chengdu, China

Search for other papers by Yong He in
Google Scholar
PubMed
Close
,
Haolan Song Sichuan University West China Hospital, Chengdu, China

Search for other papers by Haolan Song in
Google Scholar
PubMed
Close
,
Xin Nie Sichuan University West China Hospital, Chengdu, China

Search for other papers by Xin Nie in
Google Scholar
PubMed
Close
, and
Guixing Li Sichuan University West China Hospital, Chengdu, China

Search for other papers by Guixing Li in
Google Scholar
PubMed
Close

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.

Open access
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

Search for other papers by Yuan Liu in
Google Scholar
PubMed
Close
,
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

Search for other papers by Siyi Guo in
Google Scholar
PubMed
Close
,
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

Search for other papers by Jinsong Wu in
Google Scholar
PubMed
Close
,
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

Search for other papers by Rongai Wang in
Google Scholar
PubMed
Close
,
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

Search for other papers by Jinbo Liu in
Google Scholar
PubMed
Close
,
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

Search for other papers by Yan Liu in
Google Scholar
PubMed
Close
,
Bin Lv Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, China

Search for other papers by Bin Lv in
Google Scholar
PubMed
Close
,
Nan Liu Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, China

Search for other papers by Nan Liu in
Google Scholar
PubMed
Close
,
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

Search for other papers by Ling Jiang in
Google Scholar
PubMed
Close
, and
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

Search for other papers by Xiaoli Zhang in
Google Scholar
PubMed
Close

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