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The Quarterly Journal of Nuclear... Jun 2023Primary hyperparathyroidism is a hard-to-diagnose condition that can run without symptoms for many years without causing symptoms; yet, it can cause dire long-term... (Review)
Review
Primary hyperparathyroidism is a hard-to-diagnose condition that can run without symptoms for many years without causing symptoms; yet, it can cause dire long-term consequences, such as osteoporosis and renal impairment. First-line diagnostic methods include ultrasound and parathyroid scintigraphy, which provide unsatisfactory results in terms of detection rate. Second-line imaging methods include [F]F-Choline PET/CT, 4D-CT, and their combination. These methods have shown a great detection rate and sensitivity; however, they are to this day less widespread than the first-line ones. Both the two methods (PET and 4D-CT) have their specific advantages and field of application, as well as their specific limitations. In this narrative review, we will describe the advantages and disadvantages of the two techniques extensively. Moreover, we will try to identify whether the combined examination can play a role and how relevant this role is. Finally, we will try to define the specific clinical situation in which each method can provide the best contribution to diagnosing parathyroid tissue hyperfunction.
Topics: Humans; Positron Emission Tomography Computed Tomography; Hyperparathyroidism, Primary; Four-Dimensional Computed Tomography; Choline; Parathyroid Glands; Technetium Tc 99m Sestamibi
PubMed: 37232932
DOI: 10.23736/S1824-4785.23.03514-8 -
Pediatric Nephrology (Berlin, Germany) Feb 2022The causes of hypercalcaemia in the neonate and infant are varied, and often distinct from those in older children and adults. Hypercalcaemia presents clinically with a... (Review)
Review
The causes of hypercalcaemia in the neonate and infant are varied, and often distinct from those in older children and adults. Hypercalcaemia presents clinically with a range of symptoms including failure to thrive, poor feeding, constipation, polyuria, irritability, lethargy, seizures and hypotonia. When hypercalcaemia is suspected, an accurate diagnosis will require an evaluation of potential causes (e.g. family history) and assessment for physical features (such as dysmorphology, or subcutaneous fat deposits), as well as biochemical measurements, including total and ionised serum calcium, serum phosphate, creatinine and albumin, intact parathyroid hormone (PTH), vitamin D metabolites and urinary calcium, phosphate and creatinine. The causes of neonatal hypercalcaemia can be classified into high or low PTH disorders. Disorders associated with high serum PTH include neonatal severe hyperparathyroidism, familial hypocalciuric hypercalcaemia and Jansen's metaphyseal chondrodysplasia. Conditions associated with low serum PTH include idiopathic infantile hypercalcaemia, Williams-Beuren syndrome and inborn errors of metabolism, including hypophosphatasia. Maternal hypocalcaemia and dietary factors and several rare endocrine disorders can also influence neonatal serum calcium levels. This review will focus on the common causes of hypercalcaemia in neonates and young infants, considering maternal, dietary, and genetic causes of calcium dysregulation. The clinical presentation and treatment of patients with these disorders will be discussed.
Topics: Calcium; Creatinine; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Infant; Infant, Newborn; Parathyroid Hormone; Phosphates
PubMed: 33990852
DOI: 10.1007/s00467-021-05082-z -
The Journal of Clinical Endocrinology... Nov 2023Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism caused by germline inactivating mutations in CDC73 encoding...
CONTEXT
Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism caused by germline inactivating mutations in CDC73 encoding parafibromin and is associated with an increased risk of parathyroid cancer. There is little evidence to guide the management of patients with the disease.
OBJECTIVE
(1) Characterize the natural history of HPT-JT, (2) correlate genotype and histology of parathyroid tumors with parafibromin immunostaining, (3) understand molecular changes downstream to CDC73 loss.
DESIGN
Retrospective study of patients with HPT-JT syndrome (genetically confirmed or affected first-degree relatives). Independent review of uterine tumor from 2 patients and staining for parafibromin on parathyroid tumors from 19 patients (13 adenomas, 6 carcinomas) was performed. RNA-sequencing was performed in 21 parathyroid samples (8 HPT-JT-related adenomas, 6 HPT-JT-related carcinomas, and 7 sporadic carcinomas with wild-type CDC73).
RESULTS
We identified 68 patients from 29 kindreds with HPT-JT with median age at last follow-up of 39 [interquartile range, 29-53] years. A total of 55/68 (81%) developed primary hyperparathyroidism; 17/55 (31%) had parathyroid carcinoma. Twelve of 32 (38%) females developed uterine tumors. Of the 11 patients who had surgical resection for uterine tumors, 12/24 (50%) tumors were rare mixed epithelial mesenchymal polypoid lesions. Four of 68 patients (6%) developed solid kidney tumors; 3/4 had a CDC73 variant at p.M1 residue. Parafibromin staining of parathyroid tumors did not correlate with tumor histology or genotype. RNA-sequencing showed a significant association of HPT-JT-related parathyroid tumors with transmembrane receptor protein tyrosine kinase signaling pathway, mesodermal commitment pathway, and cell-cell adhesion.
CONCLUSIONS
Multiple, recurrent atypical adenomyomatous uterine polyps appear to be enriched in women with HPT-JT and appear characteristic of the disease. Patients with CDC73 variants at p.M1 residue appear predisposed to kidney tumors.
CLINICAL TRIAL NUMBER
NCT04969926.
Topics: Humans; Female; Adult; Middle Aged; Male; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Retrospective Studies; Jaw Neoplasms; Adenoma; Transcription Factors; Carcinoma; Uterine Neoplasms; Kidney Neoplasms; RNA
PubMed: 37339334
DOI: 10.1210/clinem/dgad368 -
Medicine Sep 2023The aim of this study was to perform a descriptive analysis of scientific articles about primary hyperparathyroidism (PHPT) using bibliometric approaches. By analyzing...
The aim of this study was to perform a descriptive analysis of scientific articles about primary hyperparathyroidism (PHPT) using bibliometric approaches. By analyzing the links between the various research components (authors, journals, institutions, countries) of the academic outputs, it was aimed to summarize the intellectual structure of PHPT, identify recent research trends, and determine the global productivity. Three thousand nine hundred fifty-four articles on PHPT published between 1980 and 2022 were pulled from the Web of Science database and analyzed using bibliometric approaches. Bibliometric network visualization maps were used to identify trending topics, citation analysis, and international collaborations. Spearman correlation coefficient was used for correlation analysis. The 3 most prolific authors are Bilezikian JP. (n = 87), Silverberg SJ. (n = 72) and Akerstrom G. (n = 57). The top 3 most productive institutions were Columbia University (n = 133), Udice French Research Universities (n = 127) and Uppsala University (n = 98). The top 3 most productive journals were Surgery (n = 216), Journal of Clinical Endocrinology and Metabolism (n = 201) and World Journal of Surgery (n = 148). The top 3 contributing countries to the PHPT literature were United States of America (n = 1062, 26.8%), Italy (346, 8.7%) and United Kingdom (274, 6.9%). The most studied topics from past to present are parathyroidectomy, hypercalcemia, parathyroid hormone/adenoma/glands, calcium/calcimimetics, scintigraphy/sestamibi, bone mineral density, ultrasound, vitamin D, osteoporosis, minimally invasive parathyroidectomy, brown tumor, nephrocalcinosis/nephrolithiasis, multiple endocrine neoplasia type 1, normocalcemia, pregnancy, imaging/preoperative imaging, parathyroid cancer/carcinoma, asymptomatic primary hyperparathyroidism, and cinacalcet. The trending topics in recent years were normocalcemic primary hyperparathyroidism, trabecular bone score, children, CDC73, microwave ablation, radiofrequency ablation, denosumab, cinacalcet, preoperative imaging, imaging, diagnosis, CT, PET, PET/CT, 4D/CT, SPECT/CT, F-18-fluorocholine, quality of life, fractures, and metabolic syndrome. We can say that there will be an increasing research trend on PHPT in the coming years. In addition to the Western countries such as the United States and European countries with large economies, Japan and Turkey were also identified as leading countries in the development of the PHPT literature. This study provides significant information about the intellectual structure and global productivity of PHPT to clinicians and other researchers interested on PHPT.
Topics: Child; Female; Pregnancy; Humans; Cinacalcet; Hyperparathyroidism, Primary; Positron Emission Tomography Computed Tomography; Quality of Life; Bibliometrics
PubMed: 37657020
DOI: 10.1097/MD.0000000000034622 -
Endocrinology and Metabolism (Seoul,... Oct 2022Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the... (Review)
Review
Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi-single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient's clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Tomography, Emission-Computed, Single-Photon; Radiopharmaceuticals; Parathyroid Glands
PubMed: 36327985
DOI: 10.3803/EnM.2022.1589 -
Predicting multigland disease in primary hyperparathyroidism using ultrasound and clinical features.Frontiers in Endocrinology 2023The identification of multigland disease (MGD) in primary hyperparathyroidism (PHPT) patients is essential for minimally invasive surgical decision-making.
BACKGROUND
The identification of multigland disease (MGD) in primary hyperparathyroidism (PHPT) patients is essential for minimally invasive surgical decision-making.
OBJECTIVE
To develop a nomogram based on ultrasound (US) findings and clinical factors to predict MGD in PHPT patients.
MATERIALS AND METHODS
Patients with PHPT who had surgery between March 2021 and January 2022 were consecutively enrolled to this study. Biochemical and clinicopathological data were recorded. US images were analyzed to extract US features for prediction. Logistic regression analyses were used to identify MGD risk factors. A nomogram was constructed based on these factors and its performance evaluated by area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow tests, and decision curve analysis (DCA).
RESULTS
A total of 102 PHPT patients were included; 82 (80.4%) had single-gland disease (SGD) and 20 (19.6%) had MGD. Using multivariate analyses, MGD was positively correlated with age (odds ratio (OR) = 1.033, 95% confidence interval (CI): 0.190-4.047), PTH levels (OR = 1.001, 95% CI: 1.000-1.002), multiple endocrine neoplasia type 1 (MEN1) (OR = 29.730, 95% CI: 3.089-836.785), US size (OR = 1.198, 95% CI: 0.647-2.088), and US texture (cystic-solid) (OR = 5.357, 95% CI: 0.499-62.912). MGD was negatively correlated with gender (OR = 0.985, 95% CI: 0.190-4.047), calcium levels (OR = 0.453, 95% CI: 0.070-2.448), and symptoms (yes) (OR = 0.935, 95% CI: 0.257-13.365). The nomogram showed good discrimination with an AUC = 0.77 (0.68-0.85) and good agreement in predicting MGD in PHPT patients. Also, 65 points was recommended as a cut-off value, with specificity = 0.94 and sensitivity = 0.50.
CONCLUSION
US was useful in evaluating MGD. Combining US and clinical features in a nomogram showed good diagnostic performance for predicting MGD.
Topics: Humans; Hyperparathyroidism, Primary; Retrospective Studies; ROC Curve; Nomograms
PubMed: 37051192
DOI: 10.3389/fendo.2023.1088045 -
Journal of Endocrinological... Mar 2020There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy, but the mechanism of cognitive dysfunction has not been...
PURPOSE
There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy, but the mechanism of cognitive dysfunction has not been delineated. We assessed if cerebrovascular function is impaired in PHPT, improves post-parathyroidectomy and is associated with PTH level and cognitive dysfunction.
METHODS
This is an observational study of 43 patients with mild hypercalcemic or normocalcemic PHPT or goiter. At baseline, cerebrovascular function (dynamic cerebral autoregulation and vasomotor reactivity) by transcranial Doppler and neuropsychological function were compared between all three groups. A subset underwent parathyroidectomy or thyroidectomy, and was compared 6 months post-operatively.
RESULTS
Mean cerebrovascular and neuropsychological function was normal and no worse in PHPT compared to controls preoperatively. Higher PTH was associated with worse intracerebral autoregulation (r = - 0.43, p = 0.02) and worse cognitive performance on some tests. Post-parathyroidectomy, mood improved significantly, but changes did not differ compared to those having thyroidectomy (p = 0.84). There was no consistent improvement in cognition or change in vascular function in either surgical group.
CONCLUSIONS
Although higher PTH was associated with worse intracerebral autoregulation, cerebrovascular function, cognition and mood were normal in mild PHPT. PTX did not improve vascular or cognitive function. The observed improvement in mood cannot be clearly attributed to PTX. Notwithstanding the small sample size, the results do not support changing current criteria for parathyroidectomy to include cognitive complaints. However, the associations between PTH, cognition and cerebral autoregulation merit future studies in those with more severe hyperparathyroidism.
Topics: Aged; Aged, 80 and over; Cerebrovascular Circulation; Cognition; Female; Humans; Hyperparathyroidism, Primary; Middle Aged; Middle Cerebral Artery; Neuropsychological Tests; Parathyroidectomy; Treatment Outcome
PubMed: 31621051
DOI: 10.1007/s40618-019-01128-0 -
Clinical Endocrinology Oct 2022Disorders of calcium homeostasis are the most frequent metabolic bone and mineral disease encountered by endocrinologists. These disorders usually manifest as primary... (Review)
Review
Disorders of calcium homeostasis are the most frequent metabolic bone and mineral disease encountered by endocrinologists. These disorders usually manifest as primary hyperparathyroidism (PHPT) or hypoparathyroidism (HP), which have a monogenic aetiology in 5%-10% of cases, and may occur as an isolated endocrinopathy, or as part of a complex syndrome. The recognition and diagnosis of these disorders is important to facilitate the most appropriate management of the patient, with regard to both the calcium-related phenotype and any associated clinical features, and also to allow the identification of other family members who may be at risk of disease. Genetic testing forms an important tool in the investigation of PHPT and HP patients and is usually reserved for those deemed to be an increased risk of a monogenic disorder. However, identifying those suitable for testing requires a thorough clinical evaluation of the patient, as well as an understanding of the diversity of relevant phenotypes and their genetic basis. This review aims to provide an overview of the genetic basis of monogenic metabolic bone and mineral disorders, primarily focusing on those associated with abnormal calcium homeostasis, and aims to provide a practical guide to the implementation of genetic testing in the clinic.
Topics: Calcium; Calcium, Dietary; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Phenotype; Receptors, Calcium-Sensing
PubMed: 34935164
DOI: 10.1111/cen.14644 -
Surgery Jan 2021The incidence of primary hyperparathyroidism has increased 300% in the United States in the past 30 years, and secondary hyperparathyroidism is almost universal in...
BACKGROUND
The incidence of primary hyperparathyroidism has increased 300% in the United States in the past 30 years, and secondary hyperparathyroidism is almost universal in patients with end-stage renal disease. We assessed the presence of environmental chemicals in human hyperplastic parathyroid tumors as possible contributing factors to this increase.
METHODS
Cryopreserved hyperplastic parathyroid tumors and normal human parathyroids were analyzed by gas chromatography and liquid chromatography coupled to ultra-high-resolution mass spectrometry, bioinformatics, and biostatistics.
RESULTS
Detected environmental chemicals included polychlorinated biphenyls, polybrominated diphenyl ethers, dichloro-diphenyl-trichloroethane derivatives, and other insecticides. A total of 99% had p,p'-dichlorodiphenyldichloroethylene. More than 50% contained other environmental chemicals, and many classified as endocrine disruptors. Polychlorinated biphenyl-28 and polychlorinated biphenyl-49 levels correlated positively with parathyroid tumor mass. Polybrominated diphenyl ether-47 concentrations in tumors were inversely correlated with patients' serum calcium levels. Cellular metabolites in pathways of purine and pyrimidine synthesis and mitochondrial energy production were associated with tumor growth and with p,p'-dichlorodiphenyldichloroethylene in primary hyperparathyroidism tumors. In normal parathyroids, p,p'-dichlorodiphenyldichloroethylene , polychlorinated biphenyl-28, polychlorinated biphenyl-74, and polychlorinated biphenyl-153, but not p,p'-dichlorodiphenyldichloroethylene or polychlorinated biphenyl-49, were detected.
CONCLUSION
Environmental chemicals are present in human parathyroid tumors and warrant detailed epidemiologic and mechanistic studies to test for causal links to the growth of human parathyroid tumors.
Topics: Causality; Endocrine Disruptors; Environmental Pollutants; Female; Gas Chromatography-Mass Spectrometry; Halogenated Diphenyl Ethers; Humans; Hyperparathyroidism, Primary; Hyperparathyroidism, Secondary; Incidence; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms; Parathyroidectomy; Polychlorinated Biphenyls; Retrospective Studies; United States
PubMed: 32771296
DOI: 10.1016/j.surg.2020.06.010 -
European Archives of... Oct 2021There is no consensus for management of Mild primary hyperparathyroidism (MILD-pHP). Specific management has been suggested by some authors. We have compared the...
INTRODUCTION
There is no consensus for management of Mild primary hyperparathyroidism (MILD-pHP). Specific management has been suggested by some authors. We have compared the surgical management of the patients with MILD-pHP to those with Classic primary hyperparathyroidism (C-pHP) treated by surgery according to The Fourth International Workshop on pHP.
MATERIALS AND METHODS
Data of 173 patients who underwent a parathyroidectomy were reviewed and retrospectively analysed. Management of 32 patients with MILD-pHPT (18.5%) patients were compared to that of 141 (81.5%) patients with C-pHPT.
RESULTS
MILD-pHP group was more often discovered after non-fractured osteoporosis (21.9% vs 7.1%, p = 0.02) and surgery for chondrocalcinosis was more often carried out (6.3% vs 0%, p = 0.03) in the MILD-pHP group. A Mini-Invasive Parathyroidectomy (MIP) was carried out in 81.3% of cases, and 87.5% of patients had a single adenoma. The rate of multiglandular pathology was not different. Same day discharge was significantly higher in MILD-pHP group (37.5% vs 17.7%, p = 0.01). Success was obtained in 87.5% in the MILD-pHP group, there was no significant difference with the C-pHP group (92.9%, p = 0.48). There was no significant difference in the imaging performances. Imaging discordance was observed in 18.8% of cases in MILD-pHP and 33.6% in C-pHP (p = 0.38) without correlation with surgical failure.
CONCLUSION
This study suggests that, by selecting patients on the basis of concordant imaging and international recommendations, there is no difference in outcome between MILD-pHP and C-pHP treated surgically.
Topics: Adenoma; Diagnostic Imaging; Humans; Hyperparathyroidism, Primary; Parathyroid Hormone; Parathyroidectomy; Retrospective Studies
PubMed: 34328555
DOI: 10.1007/s00405-021-06953-9