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The Journal of Clinical Endocrinology... Apr 2022Multiglandular and familial parathyroid disease constitute important fractions of primary hyperparathyroidism (PHPT). Germline missense variants of GCM2, a regulator of...
CONTEXT
Multiglandular and familial parathyroid disease constitute important fractions of primary hyperparathyroidism (PHPT). Germline missense variants of GCM2, a regulator of parathyroid development, were observed in familial isolated hyperparathyroidism and sporadic PHPT. However, as these previously reported GCM2 variants occur at relatively high frequencies in the population, understanding their potential clinical utility will require both additional penetrance data and functional evidence relevant to tumorigenicity.
OBJECTIVE
Determine the frequency of GCM2 variants of interest among patients with sporadic multigland or familial parathyroid disease and assess their penetrance.
DESIGN AND PATIENTS
DNA-encoding PHPT-associated GCM2 germline variants were polymerase chain reaction-amplified and sequenced from 107 patients with either sporadic multigland or suspected/confirmed familial parathyroid tumors.
RESULTS
GCM2 variants were observed in 9 of 107 cases (8.4%): Y282D in 4 patients (6.3%) with sporadic multigland disease; Y394S in 2 patients (11.1%) with familial PHPT and 3 (4.8%) with sporadic multigland disease. Compared with the general population, Y282D was enriched 5.9-fold in multigland disease, but its penetrance was very low (0.02%). Y394S was enriched 79-fold in sporadic multigland disease and 93-fold in familial PHPT, but its penetrance was low (1.33% and 1.04%, respectively).
CONCLUSIONS
Observed in vitro-activating GCM2 variant alleles are significantly overrepresented in PHPT patients with multiglandular or familial disease compared to the general population, yet penetrance values are very low; that is, most individuals with these variants in the population have a very low risk of developing PHPT. The potential clinical utility of detecting these GCM2 variants requires further investigation, including assessing their possible role as pathogenic/low-penetrance alleles.
Topics: Germ-Line Mutation; Humans; Hyperparathyroidism, Primary; Nuclear Proteins; Parathyroid Neoplasms; Transcription Factors
PubMed: 34967908
DOI: 10.1210/clinem/dgab929 -
Annals of African Medicine 2022The standard gold treatment of primary hyperparathyroidism (PHP) is parathyroidectomy. Imaging in particular, cervical ultrasound (US) and technetium-99 m-...
INTRODUCTION
The standard gold treatment of primary hyperparathyroidism (PHP) is parathyroidectomy. Imaging in particular, cervical ultrasound (US) and technetium-99 m- méthoxyisobutylisonitrileparathyroid scintigraphy using the single-photon emission computed tomography (TC-99 m-MIBI-SPECT) are always indicated prior to parathyroid surgery, allowing the location of parathyroid adenomas. The objective of our study is to evaluate the contribution of TC-99 m-MIBI-SPECT and US in the preoperative topographic diagnosis of PHP.
MATERIALS AND METHODS
this is a descriptive and analytical retrospective study, conducted in our department of Endocrinology, Diabetology and Metabolic Diseases in Hassan II University Hospital of Fez between 2009 and 2018. All patients who received a para-thyroidectomy for PHP were recruited. All patients had received a cervical US and a TC-99 m-MIBI-SPECT. We compared imaging data before surgery with data from intraoperative exploration and anatomopathological findings of surgical samples.
RESULTS
Forty-eight patients were collected. US correctly identified parathyroid adenoma in 85.40% of patients with PHP versus 89.50% in TC-99 m-MIBI-SPECT. US correctly predicted surgical outecomes in 97.60% of patients and TC-99 m-MIBI-SPECT in 97.72% of cases. Their combination had better results in sensitivity and positive predictive value.
CONCLUSION
TC-99 m-MIBI-parathyroid scintigraphy SPECT had a higher probability for solitary parathyroid adenoma compared to cervical US. Its use coupled with the TC-99 m-MIBI-parathyroid scintigraphy SPECT allows reliable preoperative tracking.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Parathyroidectomy; Retrospective Studies; Sensitivity and Specificity; Technetium Tc 99m Sestamibi
PubMed: 35848650
DOI: 10.4103/aam.aam_73_20 -
Asian Journal of Surgery Jan 2022Primary hyperparathyroidism (pHPT) caused by a single benign parathyroid adenoma is a common endocrine disorder that is affected by regional differences. Living in...
Association of biochemical and clinical parameters with parathyroid adenoma weight. Turkish-Bulgarian endocrine and breast surgery study group, hyperparathyroidism registry study.
BACKGROUND
Primary hyperparathyroidism (pHPT) caused by a single benign parathyroid adenoma is a common endocrine disorder that is affected by regional differences. Living in different geographical regions reveals differences in the laboratory results and pathological findings, but studies on this subject are not sufficient. The article focuses on biochemical and pathological effects of geographical differences in parathyroid adenoma. In addition, the present study seeks to elaborate on treatment methods and effectiveness of screening in geographical area of Bulgaria and Turkey.
METHOD
In this prospective study, 159 patients were included from 16 centres. Demographic characteristics, symptoms, biochemical markers and pathologic characteristics were analysed and compared between 8 different regions.
RESULTS
Patients from Turkish Black Sea had the highest median serum calcium (Ca) level, whereas patients from Eastern Turkey had the lowest median serum phosphorus (P) level. On the other hand, there was no significant difference between Ca, parathormone (PTH) and P levels according to regions. Patients from Eastern Turkey had the highest adenoma weight, while patients from Bulgaria had the lowest adenoma weight. The weight of adenoma showed statistically significant differences between regions (p < 0.001). There was a correlation between adenoma weight and serum PTH level (p = 0.05) and Ca level (p = 0.035).
CONCLUSION
This study has provided a deeper insight into the effect of the regional differences upon clinicopathological changing and biochemical values of pHTP patients with adenoma. Awareness of regional differences will assist in biochemical screening and treatment of this patient group.
Topics: Breast Neoplasms; Bulgaria; Calcium; Female; Humans; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Parathyroidectomy; Prospective Studies; Registries; Retrospective Studies; Turkey
PubMed: 34353709
DOI: 10.1016/j.asjsur.2021.06.035 -
Cancer Genomics & Proteomics 2021The lack of specific parathyroid carcinoma (PC) biomarkers in clinical practice points out the importance of analyzing the proteomic signature of this cancer. We...
BACKGROUND/AIM
The lack of specific parathyroid carcinoma (PC) biomarkers in clinical practice points out the importance of analyzing the proteomic signature of this cancer. We performed a comparative proteomic analysis of PC and parathyroid adenoma (PA) co-existing in the same patient.
PATIENTS AND METHODS
PC and PA were taken from a 63-year-old patient. Using two-dimensional differential gel electrophoresis (2D-DIGE) coupled to mass spectrometry we examined the differences between PC and PA proteins. For validation, additional PC and PA samples were obtained from 10 patients. Western blot analysis was used to validate the difference of expression observed with 2D-DIGE analysis. Bioinfomatic analysis was performed using QIAGEN's Ingenuity Pathways Analysis (IPA) to determine the predominant canonical pathways and interaction networks involved.
RESULTS
Thirty-three differentially expressed proteins were identified in PC compared to PA. Among these, ubiquitin C-terminal hydrolase-L1 (UCH-L1) was highly overexpressed in PC. The result was confirmed by Western Blot analysis in additional PC samples.
CONCLUSION
Our comparative proteomic analysis of co-existing neoplasms allowed detecting specific and peculiar differences between PC and PA overcoming population biological variability.
Topics: Adenoma; Humans; Male; Middle Aged; Parathyroid Neoplasms; Proteomics
PubMed: 34697069
DOI: 10.21873/cgp.20297 -
Langenbeck's Archives of Surgery Oct 2023Despite advances in biochemical and radiological identification of parathyroid gland enlargement, primary hyperparathyroidism (PHPT) due to sporadic multigland... (Review)
Review
BACKGROUND
Despite advances in biochemical and radiological identification of parathyroid gland enlargement, primary hyperparathyroidism (PHPT) due to sporadic multigland parathyroid disease (MGPD) remains a perioperative diagnostic dilemma. Failure to recognise MGPD pre- or intraoperatively may negatively impact surgical cure rates and result in persistent PHPT and ongoing patient morbidity.
METHODS
We have conducted a comprehensive review of published literature in attempt to determine factors that could aid in reliably diagnosing sporadic MGPD pre- or intraoperatively. We discuss preoperative clinical features and examine pre- and intraoperative biochemical and imaging findings concentrating on those areas that give practicing surgeons and the wider multi-disciplinary endocrine team indications that a patient has MGDP. This could alter surgical strategy.
CONCLUSION
Biochemistry can provide diagnosis of PHPT but cannot reliably discriminate parathyroid pathology. Histopathology can aid diagnosis between MGPD and adenoma, but histological appearance can overlap. Multiple negative imaging modalities indicate that MGPD may be more likely than a single parathyroid adenoma, but the gold standard for diagnosis is still intraoperative identification during BNE. MGPD remains a difficult disease to both diagnose and treat.
Topics: Humans; Parathyroid Hormone; Parathyroidectomy; Parathyroid Diseases; Parathyroid Glands; Parathyroid Neoplasms; Hyperparathyroidism, Primary; Retrospective Studies
PubMed: 37806985
DOI: 10.1007/s00423-023-03087-w -
Asian Journal of Surgery Oct 2021
Review
Topics: Humans; Hyperparathyroidism, Primary; Mediastinum; Parathyroid Neoplasms
PubMed: 34384676
DOI: 10.1016/j.asjsur.2021.06.053 -
Asian Pacific Journal of Cancer... Dec 2017Objective: Ultrasonography (US) and parathyroid scintigraphy (PS) with 99mTc-MIBI are common methods for preoperative localization of parathyroid adenomas but there... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparative Diagnostic Performance of Ultrasonography and 99mTc-Sestamibi Scintigraphy for Parathyroid Adenoma in Primary Hyperparathyroidism; Systematic Review and Meta- Analysis.
Objective: Ultrasonography (US) and parathyroid scintigraphy (PS) with 99mTc-MIBI are common methods for preoperative localization of parathyroid adenomas but there discrepancies exist with regard to diagnostic accuracy. The aim of the study was to compare PS and US for localization of parathyroid adenoma with a systematic review and meta-analysis of the literature. Methods: Pub Med, Scopus (EMbase), Web of Science and the reference lists of all included studies were searched up to 1st January 2016. The search strategy was according PICO characteristics. Heterogeneity between the studies was accounted by P < 0.1. Point estimates were pooled estimate of sensitivity, specificity and positive predictive value of SPECT and ultrasonography with 99% confidence intervals (CIs) by pooling available data. Data analysis was performed using Meta-DiSc software (version 1.4). Results: Among 188 studies and after deletion of duplicated studies (75), a total of 113 titles and abstracts were studied. From these, 12 studies were selected. The meta-analysis determined a pooled sensitivity for scintigraphy of 83% [99% confidence interval (CI) 96.358 -97.412] and for ultra-sonography of 80% [99% confidence interval (CI) 76-83]. Similar results for specificity were also obtained for both approache. Conclusion: According this meta- analysis, there were no significant differences between the two methods in terms of sensitivity and specificity. There were overlaps in 99% confidence intervals. Also features of the two methods are similar.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Prognosis; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Ultrasonography
PubMed: 29281866
DOI: 10.22034/APJCP.2017.18.12.3195 -
Acta Chirurgiae Orthopaedicae Et... 2021Skeletal deformation like genu valgum is reported to be rare in Primary hyperparathyroidism (PHPT). The solitary adenoma or hyperplasia of the parathyroid glands are the...
Skeletal deformation like genu valgum is reported to be rare in Primary hyperparathyroidism (PHPT). The solitary adenoma or hyperplasia of the parathyroid glands are the cause in 80-85% of the cases. We report 2 cases of girls on 12 years and 15 years of age, complaining from pain and genu valgum deformation of the lower extremities before the planned orthopaedic surgical correction. The first patient had complaints for 3 years and lost ability to walk independently, the second case lost normal gate for a period of 5 months. The paraclinical screening discovered hypercalcemia, hypophosphatemia, elevated alkaline phosphatase, normal creatinine, raised parathormone. In the first case the X-rays depicted fibrocystic osteodistrophy from a hyperparathyroid type with bone cysts, giant cell "brown tumors" and pathological bone reorganization, in the second case - coarse fibrous structure of the left knee joint with genu valgum with bone cysts in the distal metaphysis of the left femur. The ultrasound of the thyroid gland found oval hypoechoic formations with suspicious origin from the parathyroid glands. These findings were confirmed from the SPECT/CT pointing active adenomas in the parathyroid glands. Skeletal deformation like genu valgum is the reason to search for the primary diagnosis in our 2 cases. Investigation of the serum calcium and parathormone are diagnostic in 100%. The imaging diagnosis has a critical role for indicating surgical treatment of the parathyroid gland adenoma. Key words: genu valgum, hypercalcemia, paediatric parathyroid adenoma, ultrasound, SPECT/CT.
Topics: Adenoma; Child; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Ultrasonography
PubMed: 34738897
DOI: No ID Found -
Journal of Endocrinological... Jun 2023This study was designed to evaluate whether patients with ectopic parathyroid adenoma (EPA) have clinical predictors by comparing them with other patients operated on...
PURPOSE
This study was designed to evaluate whether patients with ectopic parathyroid adenoma (EPA) have clinical predictors by comparing them with other patients operated on for primary hyperparathyroidism (PHPT) with uniglandular parathyroid adenomas in other localizations.
METHODS
The data of PHPT patients who underwent parathyroidectomy in our institution were assessed retrospectively. Abnormal gland localization was confirmed by operative and pathology reports as well as normocalcemia that lasted for at least 6 months postoperatively. The relationships of biochemical and clinical findings of patients with confirmed adenoma localizations were analyzed. In order to determine independent factors that can predict EPAs, binary logistic regression was used.
RESULTS
Among 421 patients (83.4% female, mean age 49 ± 13.2 years) enrolled in the study, the most common adenoma localization was the lower left parathyroid gland (36.1%; p < 0.001). Parathyroid adenomas were more common in lower localizations compared to upper localizations and were smaller in size (p < 0.001 and p = 0.004, respectively). In univariate analysis, serum intact parathyroid hormone and calcium levels were found to be higher (p = 0.004 and p = 0.002, respectively), moderate/severe hypercalcemia was more common (p = 0.024), phosphorus levels were lower (p = 0.04), and postoperative transient hypocalcemia was more common (p = 0.013) in cases of EPAs than other localizations. There was no significant difference in adenoma size between EPAs and other classical localizations. In multivariate analysis, only a high serum calcium level was an independent predictor of EPAs (OR 2.017, 95% CI 1.142-3.564, p = 0.016). Receiver-operating characteristic curve analysis yielded an optimal cutoff value of 12.25 mg/dL for serum calcium (88% sensitivity, 63% specificity, and area under the curve: 0.861).
CONCLUSION
EPAs can cause a more biochemically distinct PHPT picture compared to parathyroid adenomas in classical localizations. A high calcium level at diagnosis may be a clinical predictor for EPAs and may affect the clinical approach and imaging technique choices. Due to the increased risk of transient hypocalcemia in patients with EPAs, caution should be exercised in postoperative follow-up. Furthermore, in the event of negative preoperative imaging, starting the parathyroid exploration from the lower left region may be a good option for the surgeon.
Topics: Humans; Female; Adult; Middle Aged; Male; Parathyroid Neoplasms; Hypocalcemia; Calcium; Retrospective Studies; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Adenoma; Hyperparathyroidism, Primary
PubMed: 36510103
DOI: 10.1007/s40618-022-01986-1 -
Journal of Medical Case Reports Sep 2021Primary hyperparathyroidism (PHPT) is a common endocrine disorder and the most frequent benign cause of hypercalcemia. PHPT is characterized by autonomous hypersecretion...
BACKGROUND
Primary hyperparathyroidism (PHPT) is a common endocrine disorder and the most frequent benign cause of hypercalcemia. PHPT is characterized by autonomous hypersecretion of parathyroid hormone (PTH), regardless of serum calcium levels. Familial hypocalciuric hypercalcemia (FHH) is a rare, benign syndrome only affecting the regulation of calcium metabolism. FHH is an autosomal-dominant genetic disease with high penetrance, caused by an inactivating variant in the CASR gene encoding the calcium-sensing receptor (CaSR). We present a unique case of concomitant PHPT and FHH without clinically actionable variants in MEN1.
CASE PRESENTATION
A 47-year-old Caucasian man with severe hypercalcemia, genetic FHH, and initially normal parathyroid scintigraphy was referred for endocrine evaluation due to nonspecific symptoms. Biochemical evaluation showed elevated serum ionized calcium and PTH. The calcium-creatinine clearance ratio was low. All other biochemical measures were normal, including kidney function. Genetic evaluation was redone and confirmed FHH. A new parathyroid scintigraphy showed a significant single adenoma corresponding to the lower left gland. The patient underwent parathyroidectomy, and a parathyroid adenoma was removed. A reduced level of hypercalcemia persisted due to FHH.
CONCLUSIONS
The correct diagnosis of the underlying cause of hypercalcemia is important to ensure the right treatment. Patients with FHH should avoid operative treatment, and PHPT should be differentiated from MEN1 to determine whether surgery should include parathyroidectomy with removal of one adenoma or 3.5 hyperplastic parathyroid glands.
Topics: Calcium; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Male; Middle Aged; Parathyroid Hormone; Parathyroid Neoplasms
PubMed: 34556169
DOI: 10.1186/s13256-021-03051-6