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Endokrynologia Polska 2021It is difficult to differentiate benign and malignant lesions just by histopathological evaluation due to lack of clear criteria of diagnosis. Moreover, the group of...
INTRODUCTION
It is difficult to differentiate benign and malignant lesions just by histopathological evaluation due to lack of clear criteria of diagnosis. Moreover, the group of benign pathologies of parathyroids is not homogenous, and recurrence of symptoms of hyperparathyroidism after surgical management was also noted in this group. This complication is not always due to inappropriate surgical technique. The goal of this work was to find the relationship between cellular ploidy and proliferative activity of adenomas and hyperplasia of parathyroids and preoperative levels of calcium and parathormone in the serum of patients surgically treated for primary hyperparathyroidism.
MATERIAL AND METHODS
A total of 98 parathyroid glands were tested, of which 81 (82.7%) were from female patients and 17 (17.3%) from male; the age of the patients was from 22 to 82 years, with an average of 58 years.
RESULTS
In resected glands pathological evaluation showed the following results: in 53 (54.1%) adenoma was present, and in 45 (45.9%) there was hyperplasia. Sixty-seven of the samples (68.4%) were characterised as diploid and 31 (31.6%) as aneuploid. There is important positive correlation (r = 0.34595; p = 0.011) between the percentage of S-phase cells (% SPF) and calcium levels measured prior to surgical resection of adenoma. The further analysis of patients with adenoma characterised by aneuploidy proved a statistically valid, positive correlation between %SPF and ionised calcium levels in blood serum of patients both before (r = 0.7189; p = 0.003) and after the surgical treatment (r = 0.6313; p = 0.012).
CONCLUSIONS
1. Benign lesions of parathyroid with ploidy indicates their heterogeneity. 2. In aneuploid benign adenomas of parathyroid glands an increased percentage of cells in S phase (% SPF) correlates with a high level of calcium in serum pre- and post-parathyroidectomy.
Topics: Adenoma; Adult; Aged; Aged, 80 and over; DNA, Neoplasm; Female; Humans; Hyperparathyroidism; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms; Young Adult
PubMed: 33125694
DOI: 10.5603/EP.a2020.0076 -
The Quarterly Journal of Nuclear... Jun 2023During the past decade, F-fluorocholine (FCH) PET/CT has been continuously performed at Tenon Hospital (Paris, France) for the detection of hyperfunctioning parathyroid...
BACKGROUND
During the past decade, F-fluorocholine (FCH) PET/CT has been continuously performed at Tenon Hospital (Paris, France) for the detection of hyperfunctioning parathyroid glands (PT).
METHODS
A cohort of 401 patients, deliberately referred for HPT since September 2012, has been analyzed. The aim of this real-life retrospective study was to determine the diagnostic utility of FCH in this setting, overall and in subgroups according to the type of hyperparathyroidism (HPT), the context of FCH in the imaging work-up and in the patient's history: initial imaging or persistence or recurrence after previous parathyroidectomy (PTX). The influence of the histologic type of resected PTs, hyperplasia or adenoma, on the preoperatory detection on FCH PET/CT has been studied as well.
RESULTS
Four hundred one FCH PET/CTs were included in the cohort, performed in 323 patients with primary HPT (pHPT), including 18 with familial HPT (fHPT), and in 78 patients with secondary renal HPT (rHPT). The overall positivity rate in the 401 FCH PET/CTs was 73%. The PTX rate was twice greater in patients whose FCH PET/CT was positive than negative (73% vs. 35%). Abnormal PT(s) were pathology proven in 214 patients: only hyperplastic gland(s) in 75 cases and at least one adenoma in 136 cases; FCH PET/CT sensitivity was 89% and 92%, respectively. Similarly, there was no significant difference in patient-based sensitivity whether FCH PET/CT was performed as 1 line or later in the imaging work-up, or indicated for initial imaging or for suspicion of persistent or recurrent HPT. Gland-based sensitivity was significantly lower for hyperplasia than for adenoma (72% and 86%, respectively). The lowest gland-based sensitivity value was 65%, observed in case of hyperplasia and when FCH was performed late in the imaging work-up. FCH PET/CT correctly showed multiglandular HPT (MGD) in 36/61 proven cases, 59%. Results of ultrasonography (US) and Tc-sestaMIBI (MIBI) imaging were available in 346 and 178 patients, respectively. For both modalities, the corresponding sensitivity values were significantly less than those of FCH PET/CT (e.g., overall gland-based sensitivity 78% for FCH, 45% for US, 30% for MIBI) and MGD was detected in 32% of cases by US and 15% by MIBI.
CONCLUSIONS
Although FCH PET/CT has been performed since 2017 as 1 line imaging for HPT at Tenon Hospital (Paris, France), a large majority of patients underwent prior US and/or MIBI in their preoperative work-up. Therefore, a selection bias is very likely, as most patients referred to FCH PET/CT had non-conclusive or discordant results of US and MIBI, explaining the low performance of those modalities in the present cohort compared to published results. Nevertheless, the superiority of FCH PET/CT over US and MIBI in detecting abnormal PTs reported in various comparative studies is definitely confirmed in this larger real-life cohort. The detection with FCH PET/CT of hyperplastic PTs was somewhat lower than that of adenomas but was better than using US or MIBI. The present results lead to recommend FCH PET/CT as the first line imaging modality in HPT when it is widely available or, if less available, at least in HPT with predominance of hyperplasia and/or MGD.
Topics: Humans; Positron Emission Tomography Computed Tomography; Parathyroid Glands; Retrospective Studies; Hyperplasia; Hyperparathyroidism, Primary; Choline; Technetium Tc 99m Sestamibi; Adenoma
PubMed: 36995286
DOI: 10.23736/S1824-4785.23.03513-6 -
European Journal of Pharmacology Aug 2009Calcimimetics and vitamin D sterols reduce serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism receiving dialysis, a disease state associated...
Calcimimetics and vitamin D sterols reduce serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism receiving dialysis, a disease state associated with parathyroid hyperplasia, vascular calcification, bone disease, and increased mortality. The aim of this study was to determine the effects of the research calcimimetic AMG 641 (Amgen, Inc., Thousand Oaks, CA) or calcitriol (Sigma Aldrich Corporation, St. Louis, MO) on vascular calcification in a rodent model of progressive uremia with accompanying secondary hyperparathyroidism induced by dietary adenine. Treatment effects on parathyroid gland hyperplasia and bone loss were also investigated. Rats were treated daily with vehicle, calcitriol (10 ng), AMG 641 (3 mg/kg), or no treatment during the 4 week period the animals were fed adenine. The uremia-induced increases in serum PTH levels were significantly attenuated by both AMG 641 (>90%) and calcitriol (approximately 50%). AMG 641 significantly reduced calcium-phosphorus product (CaxP) and significantly attenuated the development of both parathyroid hyperplasia and vascular calcification. In addition, AMG 641 prevented the defects in trabecular bone volume, trabecular number, and bone mineralization, as well as increases in trabecular spacing in this rodent model of secondary hyperparathyroidism. Calcitriol (10 ng/rat) decreased osteoid surface/bone surface, but had no effects on other bone parameters, or parathyroid hyperplasia (likely due to the lower PTH suppressive effect of calcitriol at the dose used in this study). However, this dose of calcitriol significantly exacerbated vascular calcification. These results suggest that calcimimetics can reduce the development of vascular calcification, parathyroid hyperplasia and bone abnormalities associated with secondary hyperparathyroidism.
Topics: Adenine; Animals; Biomimetic Materials; Biphenyl Compounds; Bone and Bones; Calcinosis; Calcium; Cinacalcet; Dose-Response Relationship, Drug; Hyperplasia; Male; Molecular Weight; Naphthalenes; Organ Size; Parathyroid Glands; Parathyroid Hormone; Phenethylamines; Rats; Rats, Sprague-Dawley; Uremia
PubMed: 19470383
DOI: 10.1016/j.ejphar.2009.05.013 -
Diagnostics (Basel, Switzerland) Dec 2019This study evaluates the diagnostic value of two-dimensional shear wave elastography (2 D-SWE) technique in the evaluation of hyperplastic parathyroid glands in cases...
This study evaluates the diagnostic value of two-dimensional shear wave elastography (2 D-SWE) technique in the evaluation of hyperplastic parathyroid glands in cases with secondary and tertiary hyperparathyroidism. A total of 59 patients (end-stage renal disease, under supplemental dialysis program) with visible parathyroid hyperplastic glands on ultrasound, confirmed by biochemical assay and scintigraphy, were enrolled; they were examined on grayscale ultrasound and 2 D shear wave elastography. We determined the elasticity index (EI) in the parathyroid gland, thyroid parenchyma and surrounding muscles, and the elasticity ratio of hyperplastic parathyroid glands compared to muscle, specifically sternocleidomastoid muscle. Patients presented fibrocystic bone disease with secondary hyperparathyroidism induced by end-stage chronic kidney disease; being on prolonged chronic dialysis therapy, they had positive sestamibi scintigraphy and high values of serum parathormone (1141.04 pg/mL). Nodules placed posterior to the thyroid capsule that were cystic, had a hypoechoic aspect, and were homogenous with an independent afferent artery were found. Mean EI in the parathyroid gland was 7.83 kPa, the median value in thyroid parenchyma was 13.76 kPa, and mean muscle EI value was 15.78 kPa. The observed mean parathyroid/muscle SWE ratio was 0.5356 and the value for parathyroid/normal thyroid parenchyma was 0.5995. Using receiver operating characteristic (ROC) analysis, we found that EI below 9.74 kPa correctly identifies parathyroid tissue, with a sensitivity of 94.8%, specificity of 90.7%, and accuracy of 92.26% when compared to normal thyroid tissue. Compared with the muscle tissue, we identified that EI below 9.98 kPa has a sensitivity, specificity, and accuracy of 93.8%, 90.7%, and 91.75%, respectively. Ultrasound elastography is a helpful tool in identifying parathyroid hyperplasia in patients with chronic kidney disease. A cutoff value of 9.98 kPa can be used in 2 D-SWE for accurate diagnosis of parathyroid disease.
PubMed: 31817421
DOI: 10.3390/diagnostics9040213 -
World Journal of Surgery Feb 2018Lithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of...
BACKGROUND
Lithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of bipolar patients (BP) with and without concomitant lithium treatment and to study surgical outcomes for lithium-associated hyperparathyroidism.
METHODS
Retrospective data, including laboratory results, surgical outcomes and medications, were collected from 313 BP treated with lithium from two psychiatric outpatient units in central Sweden. In addition, data were collected from 148 BP without lithium and a randomly selected control population of 102 individuals. Logistic regression was used to compare odds of hypercalcemia in these respective populations.
RESULTS
The prevalence of lithium-associated hypercalcemia was 26%. Mild hypercalcemia was detected in 87 out of 563 study participants. The odds of hypercalcemia were significantly higher in BP with lithium treatment compared with BP unexposed to lithium (adjusted OR 13.45; 95% CI 3.09, 58.55; p = 0.001). No significant difference was detected between BP without lithium and control population (adjusted OR 2.40; 95% CI 0.38, 15.41; p = 0.355). Seven BP with lithium underwent surgery where an average of two parathyroid glands was removed. Parathyroid hyperplasia was present in four patients (57%) at the initial operation. One patient had persistent disease after the initial operation, and six patients had recurrent disease at follow-up time which was on average 10 years.
CONCLUSION
The high prevalence of LAH justifies the regular monitoring of calcium homeostasis, particularly in high-risk groups. If surgery is necessary, bilateral neck exploration should be considered in patients on chronic lithium treatment. Prospective studies are needed.
Topics: Adult; Aged; Aged, 80 and over; Bipolar Disorder; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Hyperplasia; Lithium; Logistic Models; Male; Middle Aged; Parathyroid Glands; Prevalence; Prospective Studies; Retrospective Studies; Sweden; Young Adult
PubMed: 29260296
DOI: 10.1007/s00268-017-4328-5 -
Kidney International Dec 1998Renal osteodystrophy (ROD) is still one of the major long-term complications in end-stage renal disease leading to considerable morbidity. Despite some progress in... (Review)
Review
BACKGROUND
Renal osteodystrophy (ROD) is still one of the major long-term complications in end-stage renal disease leading to considerable morbidity. Despite some progress in understanding the pathogenesis of secondary hyperparathyroidism (sHPT) during recent years, prevention and treatment of ROD is still suboptimal, requiring surgical parathyroidectomy in 6 to 10% of all patients on dialysis after 10 years. In addition, the spectrum of bone lesions has changed, with non-aluminum-related adynamic bone disease (ABD) found in up to 43% of peritoneal dialysis (PD) patients.
METHODS
Current recommendations concerning prevention of ROD in PD based on the literature and personal recent data were reviewed. The focus is on (i) the importance of early prophylactic intervention to prevent parathyroid gland hyperplasia, (ii) the pathogenesis of ABD, and (iii) the role of metabolic acidosis in ROD.
RESULTS
There is ample evidence that sHPT starts early during the course of renal failure and results from both hypersecretion of PTH by parathyroid cells and glandular hyperplasia. As shown by experimental and clinical studies, established parathyroid cell hyperplasia is hardly reversible by pharmacological means, and therefore prevention of parathyroid cell proliferation needs to start early. Recent data from randomized trials document the efficacy and safety of low dose active vitamin D (0.125 to 0.25 microgram/day) and/or an oral calcium substitute to prevent progression of sHPT in patients with mild to moderate renal failure. Since little is known about the pathogenesis, natural course and clinical impact of ABD in PD, specific therapeutic concepts have not yet been generated. Diabetes and advanced age are established risk factors, whereas the role of calcium and vitamin D overtreatment or the type of dialysis (PD vs. HD) are still controversial. Currently no evidence for different functional behavior of the parathyroids in ABD and sHPT has been found. The role of circulating or local factors such as cytokines, growth factors or the presence of advanced glycation end-product (AGE)-modified matrix proteins for the pathogenesis of either type of ROD deserves further investigation. Avoiding oversuppression of parathyroid gland and the use of low calcium dialysate may help prevent ABD. There is growing evidence that a correction of metabolic acidosis will influence ROD by both direct effects on the bone and on parathyroid cell function. New dialysate composition for CAPD with a high HCO3 concentration will allow normalization of acid-based metabolism in PD patients. Their effects on ROD under long term conditions remain to be determined.
CONCLUSION
Therapeutic efforts should aim to prevent the development of parathyroid gland hyperplasia and sHPT early during the course of renal failure, and should include the use of low dose vitamin D therapy and oral calcium substitution as well as correction of metabolic acidosis. Concerning ABD, more information is needed regarding the causes and consequences of this type of bone lesion to develop a more specific therapy.
Topics: Acidosis; Bone Density; Bone Diseases; Cell Division; Chronic Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Hyperplasia; Parathyroid Glands; Peritoneal Dialysis; Uremia
PubMed: 9853289
DOI: 10.1046/j.1523-1755.1998.00182.x -
Medicine Jul 2020Tc-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has been used to help surgeons explore the location of parathyroid diseases,...
The Usefulness of Maximum Standardized Uptake Value at the Delayed Phase of Tc-99m sestamibi single-photon emission computed tomography/computed tomography for Identification of Parathyroid Adenoma and Hyperplasia.
Tc-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has been used to help surgeons explore the location of parathyroid diseases, but quantitative parameters have not been systemically investigated for this purpose. We aimed to establish objective criteria for adenoma and hyperplasia using the standardized uptake value (SUV) in patients with hyperparathyroidism.Thirty-nine hyperparathyroid patients (male/female: 17/22, age: 58.33 ± 11.69 years) with at least 1 uptake-positive lesion of any degree by visual assessment in preoperative Tc-99m sestamibi quantitative SPECT/CT were included from Oct 2015 to Oct 2017. Pathologically, 44 lesions (32 adenomas and 12 hyperplasia) were identified. All patients experienced normalized levels of intact parathyroid hormone immediately after surgery. Quantitative SPECT/CT was performed at 10 minute and 2 hour post injection of Tc-99m sestabmibi (dose = 740 MBq), and maximum SUV (SUVmax) was measured for the parathyroid lesions. Experienced pathologists evaluated the percentage cellular proportions of chief cells, oxyphil cells, and clear cells.SUVmax (g/mL) of adenomas, hyperplasia, and reference thyroid tissue were 12.92 ± 6.68, 7.90 ± 5.49, and 7.01 ± 2.62 at 10min (early phase), decreasing to 7.46 ± 5.66, 4.65 ± 3.14, and 2.21 ± 1.07 at 2 hour (delayed phase), respectively. The adenomas showed significantly higher SUVmax than both the hyperplasia (P = .0131) and reference thyroid tissue (P < .0001) along the early and delayed phases, but the SUVmax of the hyperplasia did not differ from that of the reference thyroid tissue (P = .4196). The adenomas and hyperplasia were discriminated from the reference thyroid tissue using a cutoff SUVmax of 3.26 at the delayed phase. The adenomas had lower %proportions of oxyphil cells than the hyperplasia (P = .0054), but its SUVmax at the delayed phase was positively correlated with the %proportions of mitochondria-abundant oxyphil cells (rho = 0.418, P = .0173). The hyperplasia showed no correlation between SUVmax and cellular proportions.SUVmax at the delayed phase in the Tc-99m sestamibi quantitative SPECT/CT was useful for the identification and differentiation of parathyroid lesions causing hyperparathyroidism.
Topics: Adenoma; Adult; Aged; Diagnosis, Differential; Female; Humans; Hyperparathyroidism; Hyperplasia; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms; Radiopharmaceuticals; Retrospective Studies; Single Photon Emission Computed Tomography Computed Tomography; Technetium Tc 99m Sestamibi
PubMed: 32664158
DOI: 10.1097/MD.0000000000021176 -
British Medical Journal Jul 1971Twenty-eight members of a family over three generations were studied; six of them had hyperparathyroidism. Four of the six were siblings and one of these had suffered...
Twenty-eight members of a family over three generations were studied; six of them had hyperparathyroidism. Four of the six were siblings and one of these had suffered from recurrent hyperparathyroidism. No member of the family showed any other significant endocrine disturbance or active peptic ulceration.Attention is drawn to the prominent lack of symptoms despite dangerous levels of hypercalcaemia and advanced disease with the consequent need for estimation of serum calcium levels in all close relatives. Multiple gland involvement is common in familial hyperparathyroidism and is often coupled with a tendency to recurrence, necessitating long-term follow-up. Histological appearances vary considerably, and the risk of recurrence is not limited to cases showing primary chief cell hyperplasia, with the implication that resection of three parathyroid glands and part of the remaining gland may be the treatment of choice in all cases of familial hyperparathyroidism when multiple gland involvement is found.
Topics: Adenoma; Adolescent; Adult; Alkaline Phosphatase; Bone and Bones; Calcium; Female; Humans; Hyperparathyroidism; Hyperplasia; Male; Parathyroid Neoplasms; Pedigree; Phosphates; Recurrence
PubMed: 5090827
DOI: 10.1136/bmj.3.5766.87 -
European Journal of Endocrinology Dec 2017Inflammatory infiltrates are sometimes present in solid tumors and may be coupled to clinical behavior or etiology. Infectious viruses contribute to tumorigenesis in a... (Comparative Study)
Comparative Study
CONTEXT
Inflammatory infiltrates are sometimes present in solid tumors and may be coupled to clinical behavior or etiology. Infectious viruses contribute to tumorigenesis in a significant fraction of human neoplasias.
OBJECTIVE
Characterize inflammatory infiltrates and possible viral transcription in primary hyperparathyroidism.
DESIGN
From the period 2007 to 2016, a total of 55 parathyroid tumors (51 adenomas and 4 hyperplasias) with prominent inflammatory infiltrates were identified from more than 2000 parathyroid tumors in the pathology archives, and investigated by immunohistochemistry for CD4, CD8, CD20 and CD45 and scored as +0, +1 or +2. Clinicopathological data were compared to 142 parathyroid adenomas without histological evidence of inflammation. Transcriptome sequencing was performed for 13 parathyroid tumors (four inflammatory, 9 non-inflammatory) to identify potential viral transcripts.
RESULTS
Tumors had prominent germinal center-like nodular (+2) lymphocytic infiltrates consisting of T and B lymphocytes (31%) and/or diffuse (+1-2) infiltrates of predominantly CD8+ T lymphocytes (84%). In the majority of cases with adjacent normal parathyroid tissue, the normal rim was unaffected by the inflammatory infiltrates (96%). Presence of inflammatory infiltrates was associated with higher levels of serum-PTH ( = 0.007) and oxyphilic differentiation ( = 0.002). Co-existent autoimmune disease was observed in 27% of patients with inflammatory infiltrates, which in turn was associated with oxyphilic differentiation ( = 0.041). Additionally, prescription of anti-inflammatory drugs was associated with lower serum ionized calcium ( = 0.037).
CONCLUSIONS
No evidence of virus-like sequences in the parathyroid tumors could be found by transcriptome sequencing, suggesting that other factors may contribute to attract the immune system to the parathyroid tumor tissue.
Topics: Adenoma; Antigens, CD20; B-Lymphocytes; Biomarkers; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cohort Studies; Female; Humans; Hyperparathyroidism, Primary; Hyperplasia; Immunohistochemistry; Leukocyte Common Antigens; Leukocytes; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms; RNA, Viral; Retrospective Studies; Transcription, Genetic; Viral Proteins; Virus Replication
PubMed: 28855268
DOI: 10.1530/EJE-17-0277 -
Kidney International Jun 2022The molecular circadian clock is an evolutionary adaptation to anticipate recurring changes in the environment and to coordinate variations in activity, metabolism and...
The molecular circadian clock is an evolutionary adaptation to anticipate recurring changes in the environment and to coordinate variations in activity, metabolism and hormone secretion. Parathyroid hyperplasia in uremia is a significant clinical challenge. Here, we examined changes in the transcriptome of the murine parathyroid gland over 24 hours and found a rhythmic expression of parathyroid signature genes, such as Casr, Vdr, Fgfr1 and Gcm2. Overall, 1455 genes corresponding to 6.9% of all expressed genes had significant circadian rhythmicity. Biological pathway analysis indicated that the circadian clock system is essential for the regulation of parathyroid cell function. To study this, a novel mouse strain with parathyroid gland-specific knockdown of the core clock gene Bmal1 (PTHcre;Bmal1) was created. Dampening of the parathyroid circadian clock rhythmicity was found in these knockdown mice, resulting in abrogated rhythmicity of regulators of parathyroid cell proliferation such as Sp1, Mafb, Gcm2 and Gata3, indicating circadian clock regulation of these genes. Furthermore, the knockdown resulted in downregulation of genes involved in mitochondrial function and synthesis of ATP. When superimposed by uremia, these PTHcre;Bmal1 mice had an increased parathyroid cell proliferative response, compared to wild type mice. Thus, our findings indicate a role of the internal parathyroid circadian clock in the development of parathyroid gland hyperplasia in uremia.
Topics: Animals; Cell Proliferation; Circadian Clocks; Circadian Rhythm; Gene Expression Regulation; Hyperplasia; Mice; Parathyroid Glands; Uremia
PubMed: 35276205
DOI: 10.1016/j.kint.2022.02.018