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Primary and secondary hyperparathyroidism present different expressions of calcium-sensing receptor.BMC Surgery Feb 2023Decreased calcium-sensing receptor (CaSR) has been observed in hyperparathyroidism (HPT) without a known mechanism. The purpose of this study was to evaluate the...
BACKGROUND
Decreased calcium-sensing receptor (CaSR) has been observed in hyperparathyroidism (HPT) without a known mechanism. The purpose of this study was to evaluate the expression of CaSR in primary (PHPT) and secondary (SHPT) subtypes.
METHODS
Immunohistochemical (IHC) staining and quantitative real-time PCR (qRT-PCR) assay were used to measure the differences in expression of CaSR protein and gene in PHPT and SHPT human samples, compared to matched controls.
RESULTS
CaSR protein was differentially downregulated in SHPT and PHPT compared to normal parathyroid tissues (2.42 ± 0.5 vs. 3.2 ± 0.62, P < 0.05; 1.8 ± 0.83 vs. 3.2 ± 0.62, P < 0.05, respectively). Furthermore, SHPT tissues exhibited significantly higher levels of CaSR mRNA (0.29 ± 0.23 vs. 0.01 ± 0.12, P < 0.05) and protein (2.42 ± 0.5 vs. 1.8 ± 0.83, P < 0.05) than those in PHPT tissue samples.
CONCLUSION
Depressed CaSR expression was a critical pathological hallmark of HPT. We found a differential decline of CaSR, in terms of both mRNA and protein levels, in PHPT and SHPT human samples. We think that CaSR dysregulation occurred at the very beginning of disease onset in PHPT, while a similar pathological scenario appeared at the later stage of SHPT. Future studies should be directed to dissect the mechanistic involvement of CaSR in PHPT and SHPT in order to bring treatment precisions in HPT management.
Topics: Humans; Hyperparathyroidism, Primary; Hyperparathyroidism, Secondary; Parathyroid Glands; Receptors, Calcium-Sensing; RNA, Messenger
PubMed: 36755240
DOI: 10.1186/s12893-023-01928-5 -
Pediatric Endocrinology, Diabetes, and... 2022Primary hyperparathyroidism (PHPT) is a rare disease in children and adolescents. Early recognition of this disease is important to prevent significant morbidity and...
INTRODUCTION
Primary hyperparathyroidism (PHPT) is a rare disease in children and adolescents. Early recognition of this disease is important to prevent significant morbidity and mortality.
MATERIAL AND METHODS
We included 10 consecutive patients with PHPT aged 14 to 19 years of age and followed-up prospectively upto one year after parathyroidectomy.
RESULTS
Our cohort included 6 females and 4 males. The mean age of the patients was 16.7 ±1.8 years. The symptoms at presentation were musculoskeletal pain (90%), bone deformity (50%), fracture (30%), proximal myopathy (40%), renal stones (50%), reflux symptoms (40%), and pancreatitis (30%). The mean serum calcium was 3.1 ±0.5 mmol/l, mean serum inorganic phosphorus was 0.9 ±0.3 mmol/l and median serum alkaline phosphatase (ALP) was 1911.5 IU/l (IQR: 522.7-5702.3). The median serum intact parathyroid hormone was 133.5 pmol/l (IQR: 69.5 -178.7) while serum 25(OH)D was 47.7 nmol/l (IQR: 23.7-72.7). Hypercalciuria was observed in 7 patients. Hungry bone syndrome was observed in 4 (40%) patients after surgery. Typical parathyroid adenoma was found in 9 (90%) patients while one patient had atypical adenoma with high mitotic index. After one year of surgery, all patients had significant improvement in clinical and biochemical parameters with persistence of residual bone deformities.
CONCLUSIONS
Our study showed the spectrum of manifestations of PHPT in children and adolescents and outcomes of parathyroidectomy till one year. Long-term follow-up studies with bigger cohorts are required to understand the true nature of the disease in children and adolescents.
Topics: Adolescent; Alkaline Phosphatase; Bone Diseases; Calcium; Child; Female; Humans; Hyperparathyroidism, Primary; Male; Parathyroid Hormone; Phosphorus; Young Adult
PubMed: 35942826
DOI: 10.5114/pedm.2022.118315 -
Endocrine Jan 2017
Topics: Asymptomatic Diseases; Dietary Supplements; Food, Fortified; Humans; Hyperparathyroidism, Primary; Nutritional Status; Polymorphism, Single Nucleotide; Severity of Illness Index; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein
PubMed: 27858283
DOI: 10.1007/s12020-016-1169-1 -
Journal of Bone and Mineral Research :... Sep 2023Primary hyperparathyroidism (PHPT) includes sporadic PHPT and hereditary PHPT. However, until now, there have been no exact data on the proportion and composition of...
Primary hyperparathyroidism (PHPT) includes sporadic PHPT and hereditary PHPT. However, until now, there have been no exact data on the proportion and composition of hereditary PHPT in the Chinese PHPT population. This study aimed to clarify the proportion and composition of hereditary PHPT in patients at a large academic center in Beijing, China, and to analyze genotype-phenotype characteristics. A total of 394 newly diagnosed Han PHPT patients who consented to genetic screening were enrolled. Targeted next-generation sequencing (T-NGS) (including for MEN1, RET, CDKN1B, CaSR, HRPT2/CDC73, GNA11, AP2S1, GCM2), combined with MEN1-multiplex ligation-dependent probe amplification (MLPA) and CDC73-MLPA, was used for genetic screening. Diagnosis of hereditary PHPT was based on clinical manifestations, family history, and genetic screening. Thirty-seven pathogenic (P)/likely pathogenic (LP) variants were detected in 41 patients via T-NGS, and three patients carried long-range deletions of MEN1 or CDC73 detected by MLPA, with a variant detection rate of 11.2% (44/394). In total, 30 patients were clinically diagnosed with MEN1. Combined with genetic and clinical screening, the rate of hereditary PHPT in this study was 18.8% (74/394). For purposes of comparison, the rate of unequivocal nonhereditary PHPT was 66.5% (262/394); 14.7% (58/394) did not exhibit the clinical features of hereditary PHPT but carried variants of uncertain clinical significance and so could not be clearly categorized. Both the age at hospital visit (43.6 ± 14.0 versus 53.7 ± 14.9 years) and age at onset (35.4 ± 13.8 versus 50.6 ± 14.8 years) in the hereditary group (n = 74) were significantly lower than those in the nonhereditary group (n = 262). Higher levels of ionized calcium and serum β-CTX were observed in the hereditary group; proportions of parathyroid hyperplasia and multigland involvement were also higher. In addition to multigland disease and positive family history, it is recommended that patients with an age of onset less than 38 should be screened for hereditary forms. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Adult; Middle Aged; Aged; Hyperparathyroidism, Primary; East Asian People; Genetic Testing; Multiple Endocrine Neoplasia Type 1; Calcium; Transcription Factors
PubMed: 37449924
DOI: 10.1002/jbmr.4883 -
Journal of the Chinese Medical... Sep 2012Primary hyperparathyroidism (PHPT) is a common endocrine disorder in adults in whom the typical presentation is incidentally discovered as asymptomatic hypercalcemia.... (Review)
Review
Primary hyperparathyroidism (PHPT) is a common endocrine disorder in adults in whom the typical presentation is incidentally discovered as asymptomatic hypercalcemia. PHPT is much less common in children and adolescents, but has greater morbidity in this age group, as most young patients with PHPT will have symptomatic hypercalcemia or complications such as kidney stones, abdominal pain, and skeletal fragility. An important feature of PHPT in younger patients is the relatively high prevalence of germline inactivating mutations of the CASR gene, which encodes the calcium-sensing receptor. Biallelic CASR mutations cause neonatal severe hyperparathyroidism, a life-threatening condition that presents within days of life with marked hypercalcemia, respiratory distress, failure to thrive, and skeletal demineralization. By contrast, more common heterozygous CASR mutations are generally associated with a benign variant of PHPT termed familial hypocalciuric hypercalcemia. Appropriate management of PHPT in children and adolescents requires distinction between familial hypocalciuric hypercalcemia, which generally requires no specific treatment, and other forms of PHPT that are best treated by parathyroidectomy.
Topics: Adolescent; Child; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Male; Mutation; Receptors, Calcium-Sensing
PubMed: 22989537
DOI: 10.1016/j.jcma.2012.06.012 -
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 -
Diagnostic and Interventional Imaging May 2022The purpose of this study was to assess the diagnostic capabilities of preoperative conventional imaging (Tc-MIBI scintigraphy, cervical ultrasonography [CUS]) and...
PURPOSE
The purpose of this study was to assess the diagnostic capabilities of preoperative conventional imaging (Tc-MIBI scintigraphy, cervical ultrasonography [CUS]) and F-fluorocholine PET/CT (FCH PET/CT) in the detection of hyperfunctioning parathyroid gland in patients with primary hyperparathyroidism (PHPT) used alone or as a single imaging set.
MATERIALS AND METHODS
A total of 51 consecutive patients (6 men, 45 women; mean age, 62 ± 11.6 [SD] years; age range: 28-86 years) with biochemically confirmed PHPT who underwent CUS, single-tracer dual phase Tc-MIBI scintigraphy and FCH PET/CT were retrospectively included. Tc-MIBI scintigraphy were performed immediately after CUS and interpreted by the same operators. FCH PET/CT examinations were interpreted independently by two nuclear medicine physicians. An additional reading session integrating the three imaging modalities read in consensus as a combined imaging set was performed.
RESULTS
At surgery, 74 lesions were removed (32 parathyroid adenomas, 38 parathyroid hyperplasia and 4 subnormal glands). Thirty-six patients (71%) had single-gland disease and 15 patients (29%) had multiglandular disease at histopathological analysis. On a patient basis, sensitivity and accuracy of FCH PET/CT, CUS and Tc-MIBI scintigraphy for the detection of abnormal parathyroid glands were 76% (95% CI: 63-87%) and 76% (95% CI: 63-87%), 71% (95% CI: 56-83%) and 71% (95% CI: 56-83%), 33% (95% CI: 21-48%) and 33% (95% CI: 21-48%), respectively. The sensitivity of the combined imaging set was 94% (95% CI: 84-99%) and greater than the sensitivity of each individual imaging technique (P ≤ 0.001 for all).
CONCLUSION
Our results suggest that CUS, Tc-MIBI scintigraphy and FCH PET/CT interpreted as a single imaging set could be the ideal practice to precisely localize parathyroid lesion in patients with PHPT before surgery.
Topics: Adult; Aged; Aged, 80 and over; Choline; Female; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Parathyroid Glands; Positron Emission Tomography Computed Tomography; Retrospective Studies; Technetium Tc 99m Sestamibi
PubMed: 35039246
DOI: 10.1016/j.diii.2021.12.005 -
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 -
Frontiers in Endocrinology 2023Cardiovascular diseases (CVD) and metabolic disorders (MD) have retained leading positions in the structure of morbidity and mortality for many years. Primary...
INTRODUCTION
Cardiovascular diseases (CVD) and metabolic disorders (MD) have retained leading positions in the structure of morbidity and mortality for many years. Primary hyperparathyroidism (PHPT) is also associated with a greater incidence of CVD and MD. The aim of the present study was to describe the prevalence and structure of CVD and MD in hospitalized patients with PHPT and to search for possible associations between these pathologies.
METHODS
838 patients with a verified PHPT were included in the study. The studied cohort was divided into 2 groups according to their age at the time of admission: patients aged 18 to 49 years (group A, n = 150); patients aged 50 years and older (group B, n = 688).
RESULTS
There were no significant differences between two groups in parameters of calcium-phosphorus metabolism. Obesity was diagnosed in 24.2% of patients in group A and in 35.9% in group B. Type 2 diabetes mellitus was more common in older patients (14.4% in group B vs. 2.6% in group A). Arterial hypertension, ischemic heart disease, chronic heart failure and brachiocephalic arteries atherosclerosis were more frequent in older patients, occurring in 79.1%, 10.8%, 8.4%, and 84% of cases respectively. The cutoff points that increased the risk of CVD detection turned out to be age above 56 years, eGFR below 92 ml/min/1.73m2, BMI above 28.3 kg/m2.
DISCUSSION
The present study demonstrated a high incidence of some CVD, as well as disorders of lipid, carbohydrate and purine metabolism in patients with PHPT.
Topics: Humans; Middle Aged; Aged; Hyperparathyroidism, Primary; Diabetes Mellitus, Type 2; Risk Factors; Hypertension; Cardiovascular Diseases
PubMed: 37842310
DOI: 10.3389/fendo.2023.1266728 -
JAMA Otolaryngology-- Head & Neck... Mar 2022Primary hyperparathyroidism (pHPT) is a common endocrine disorder with many diagnostic and treatment challenges. Despite high-quality guidelines, care is variable, and...
IMPORTANCE
Primary hyperparathyroidism (pHPT) is a common endocrine disorder with many diagnostic and treatment challenges. Despite high-quality guidelines, care is variable, and there is low adherence to evidence-based treatment pathways.
OBJECTIVE
To develop quality indicators (QIs) to evaluate the diagnosis and treatment of pHPT that could measure, improve, and optimize quality of care and outcomes for patients with this disease.
DESIGN, SETTING, AND PARTICIPANTS
This quality improvement study used a guideline-based approach to develop QIs that were ranked by a Canadian 9-member expert panel of 3 endocrinologists, 3 otolaryngologists, and 3 endocrine surgeons. Data were analyzed between September 2020 and May 2021.
MAIN OUTCOMES AND MEASURES
Candidate indicators (CIs) were extracted from published primary hyperparathyroidism guidelines and summarized with supporting evidence. The 9-member expert panel rated each CI on the validity, reliability, and feasibility of measurement. Final QIs were selected from CIs using the modified RAND-University of California, Los Angeles appropriateness methodology. All panelists were then asked to rank the top 5 QIs for primary, endocrine, and surgical care.
RESULTS
Forty QIs were identified and evaluated by the expert panel. After 2 rounds of evaluations and discussion, a total of 18 QIs were selected as appropriate measures of high-quality care. The top 5 QIs for primary, endocrine, and surgical care were selected following panelist rankings.
CONCLUSIONS AND RELEVANCE
This quality improvement study proposes 18 QIs for the diagnosis and management of pHPT. Furthermore, the top 5 QIs applicable to physicians commonly treating pHPT, including general physicians, internists, endocrinologists, otolaryngologists, and surgeons, are included. These QIs not only assess the quality of care to guide the process of improvement, but also can assess the implementation of evidence-based guideline recommendations. Using these indicators in clinical practice and health system registries can improve quality and cost-effectiveness of care for patients with pHPT.
Topics: Canada; Humans; Hyperparathyroidism, Primary; Quality Improvement; Quality Indicators, Health Care; Reproducibility of Results
PubMed: 34989783
DOI: 10.1001/jamaoto.2021.3858