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World Journal of Clinical Cases Apr 2023Primary hyperparathyroidism (pHPT) is the third most common endocrine disease. The surgical procedure aims for permanent cure, but recurrence has been reported in 4%-10%... (Review)
Review
Primary hyperparathyroidism (pHPT) is the third most common endocrine disease. The surgical procedure aims for permanent cure, but recurrence has been reported in 4%-10% of pHPT patients. Preoperative localization imaging is highly valuable. It includes ultrasound, computed tomography (CT), single-photon-emission CT, sestamibi scintigraphy and magnetic resonance imaging. The operation has been defined as successful when postoperative continuous eucalcemia exists for more than the first six months. Ongoing hypercalcemia during this period is defined as persistence, and recurrence is defined as hypercalcemia after six months of normocalcemia. Vitamin D is a crucial factor for a good outcome. Intraoperative parathyroid hormone (PTH) monitoring can safely predict the outcomes and should be suggested. PTH ≤ 40 pg/mL or the traditional decrease ≥ 50% from baseline minimizes the likelihood of persistence. Risk factors for persistence are hyperplasia and normal parathyroid tissue on histopathology. Risk factors for recurrence are cardiac history, obesity, endoscopic approach and low-volume center (at least 31 cases/year). Cases with double adenomas or four-gland hyperplasia have a greater likelihood of persistence/ recurrence. A 6-mo calcium > 9.7 mg/dL and eucalcemic parathyroid hormone elevation at 6 mo may be associated with recurrence necessitating long-term follow-up. 18F-fluorocholine positron emission tomography and 4-dimensional CT in persistent and recurrent cases can be valuable before reoperation. With these novel advances in preoperative imaging and localization as well as intraoperative PTH measurement, the recurrence rate has dropped to 2.5%-5%. Six-month serum calcium ≥ 9.8 mg/dL and parathyroid hormone ≥ 80 pg/mL indicate a risk of recurrence. Negative sestamibi scintigraphy, diabetes and elevated osteocalcin levels are predictors of multiglandular disease, which brings an increased risk of persistence and recurrence. Bilateral neck exploration was considered the gold-standard diagnostic method. Minimally invasive parathyroidectomy and neck exploration are both effective surgical techniques. Multidisciplinary diagnostic and surgical management is required to prevent persistence and recurrence. Long-term follow-up, even up to 10 years, is necessary.
PubMed: 37122518
DOI: 10.12998/wjcc.v11.i10.2213 -
Nature Communications Feb 2022Parathyroid hormone (PTH) plays crucial role in maintaining calcium and phosphorus homeostasis. In the progression of secondary hyperparathyroidism (SHPT), expression of...
Parathyroid hormone (PTH) plays crucial role in maintaining calcium and phosphorus homeostasis. In the progression of secondary hyperparathyroidism (SHPT), expression of calcium-sensing receptors (CaSR) in the parathyroid gland decreases, which leads to persistent hypersecretion of PTH. How to precisely manipulate PTH secretion in parathyroid tissue and underlying molecular mechanism is not clear. Here, we establish an optogenetic approach that bypasses CaSR to inhibit PTH secretion in human hyperplastic parathyroid cells. We found that optogenetic stimulation elevates intracellular calcium, inhibits both PTH synthesis and secretion in human parathyroid cells. Long-term pulsatile PTH secretion induced by light stimulation prevented hyperplastic parathyroid tissue-induced bone loss by influencing the bone remodeling in mice. The effects are mediated by light stimulation of opsin expressing parathyroid cells and other type of cells in parathyroid tissue. Our study provides a strategy to regulate release of PTH and associated bone loss of SHPT through an optogenetic approach.
Topics: Bone and Bones; Calcium; Homeostasis; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary; Hyperplasia; Optogenetics; Parathyroid Glands; Parathyroid Hormone; Receptors, Calcium-Sensing
PubMed: 35140213
DOI: 10.1038/s41467-022-28472-9 -
Endocrine Pathology Sep 2020Parathyroid gland excision specimens are common and sometimes underestimated cases that many surgical pathologists encounter regularly. In the vast majority of cases,... (Review)
Review
Parathyroid gland excision specimens are common and sometimes underestimated cases that many surgical pathologists encounter regularly. In the vast majority of cases, these will be spot diagnoses of sporadic primary parathyroid adenomas or, perhaps, hyperplasias commonly in the setting of renal failure. However, a small but significant number of parathyroid gland excisions may be due to heritable disease. In most cases, hereditary disease is suspected by the referring clinicians. Nevertheless, a subset of these are undetected which is significant, particularly in the setting of the multiple endocrine neoplasia (MEN), and the hyperparathyroidism jaw tumour (HPT-JT) syndromes. There have been recent advances in recognition of the morphological and immunohistochemical characteristics of these tumours and hyperplasias. While hereditary kindreds are over-represented at specialist referral centres, with awareness of the characteristic clinical and morphological features, the general surgical pathologist is frequently able to suggest the possibility of hereditary parathyroid disease. We therefore provide a succinct guide for pathologists to increase the recognition of hereditary parathyroid disease.
Topics: Diagnosis, Differential; Diagnostic Techniques, Endocrine; Genetic Diseases, Inborn; Humans; Hyperparathyroidism, Primary; Immunohistochemistry; Parathyroid Diseases; Parathyroid Glands; Pathologists; Practice Patterns, Physicians'
PubMed: 32468209
DOI: 10.1007/s12022-020-09631-4 -
Polish Journal of Pathology : Official... 2021Advances in laboratory diagnostics and surgical treatment of primary hyperparathyroidism have ensured solid basis for research in parathyroid pathology in order to...
Advances in laboratory diagnostics and surgical treatment of primary hyperparathyroidism have ensured solid basis for research in parathyroid pathology in order to specify key molecules in pathogenesis and morphological diagnostics of difficult cases. The aim of this study was to assess the molecular landscape and its heterogeneity in primary parathyroid hyperplasia (PPH) and adenoma, compared to carcinoma and normal glands. In a retrospective analysis of 179 surgically removed parathyroid glands (102 adenomas; 27 PPH; 45 normal glands; 5 carcinomas), expression of Ki-67, p21, p27, p53, cyclin D1, Bcl-2 protein, vimentin, cytokeratin (CK) 19, E-cadherin, CD56, CD44 and parafibromin was detected by immunohistochemistry, followed by computer-assisted assessment of mean values and heterogeneity measures. Descriptive statistics and Kruskal-Wallis test were applied. Significant differences were disclosed regarding the mean and highest fraction of Ki-67 (both p < 0.001), p21 (both p < 0.001), cyclin D1 (p = 0.002) and p27-expressing cells (p = 0.010). Proliferative lesions (PPH, adenoma and carcinoma) showed statistically significantly up-regulated CK19 (p = 0.012), decreased E-cadherin levels and distinctive patterns of vimentin. CD44, CD56 and p53 were almost absent from parathyroid tissues. All carcinomas lacked parafibromin contrasting with invariable positivity in adenomas. Remarkable heterogeneity of cell cycle markers and intermediate filaments must be accounted for in scientific studies and elaboration of diagnostic cut-offs.
Topics: Adenoma; Carcinoma; Humans; Parathyroid Glands; Parathyroid Neoplasms; Retrospective Studies
PubMed: 34706517
DOI: 10.5114/pjp.2021.109513 -
Therapeutics and Clinical Risk... 2017Secondary hyperparathyroidism (SHPT), a very frequent, severe, and worsening complication of chronic kidney disease, is characterized by high serum parathyroid hormone... (Review)
Review
Secondary hyperparathyroidism (SHPT), a very frequent, severe, and worsening complication of chronic kidney disease, is characterized by high serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and disturbances in mineral metabolism. Clinically, SHPT shows renal osteodystrophy, vascular calcification, cardiovascular damage, and fatal outcome. Calcium-sensing receptor (CaSR) is the main physiological regulator of PTH secretion; its activation by calcium rapidly inhibits PTH. Another important player in regulating mineral metabolism is vitamin D receptor (VDR), which is under the influence of vitamin D and influences the intestinal absorption of calcium and phosphate, PTH gene expression, and bone calcium mobilization. Serum phosphate levels influence fibroblast growth factor 23 (FGF-23) production, a phosphatonin that modulates serum phosphate reabsorption, PTH synthesis, and vitamin D production. Current therapeutic approaches consist of 1) phosphate intake control by diet or phosphate binders, 2) vitamin D by VDR activation, and 3) calcimimetic agents that activate CaSR. Recently, a new long-acting peptide (etelcalcetide) belonging to the calcimimetics class was approved for intravenous use in hemodialysis patients with SHPT. Etelcalcetide binds directly to CaSR, by a sulfide bond, inhibiting the production and secretion of PTH by parathyroid glands. After intravenous administration in rats, etelcalcetide is quickly distributed to the tissues and eliminated by kidneys, while in uremic animals the nonrenal excretion is only 1.2%. In hemodialysis patients, the treatment itself is the main route of elimination. Etelcalcetide in hemodialysis patients with SHPT was more effective than placebo and cinacalcet, with a PTH reduction of >30% in 76% of patients with etelcalcetide versus 10% with placebo. Particular attention was paid to the safety of the drug; the most common adverse event was asymptomatic blood calcium reduction, similar to cinacalcet, while gastrointestinal symptoms were less frequent. This promising new drug available for better control of SHPT will, together with drugs already in use, optimize the treatment to normalize the biochemical parameters.
PubMed: 28615947
DOI: 10.2147/TCRM.S108490 -
Endocrinology and Metabolism (Seoul,... Jun 2024Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder.... (Review)
Review
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.
Topics: Humans; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Parathyroid Hormone; Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary; Animals
PubMed: 38752265
DOI: 10.3803/EnM.2024.1978 -
Annals of Surgery Dec 2017We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid...
OBJECTIVE
We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms.
BACKGROUND
The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones.
METHODS
From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays.
RESULTS
Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline.
CONCLUSIONS
Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.
Topics: Adenoma; Animals; Cells, Cultured; Humans; Hyperparathyroidism; Hyperplasia; Immunohistochemistry; Leptin; Mice, Knockout; Microscopy, Confocal; Microscopy, Fluorescence; Microscopy, Immunoelectron; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Prospective Studies; RNA, Messenger; Receptors, Leptin
PubMed: 27611607
DOI: 10.1097/SLA.0000000000002004 -
Clinical Nuclear Medicine Nov 2022The coexistence of parathyroid hyperplasia and carcinoma is uncommon. Here we report findings of 99m Tc-sestamibi SPECT/CT study in a case of unilateral bifocal...
The coexistence of parathyroid hyperplasia and carcinoma is uncommon. Here we report findings of 99m Tc-sestamibi SPECT/CT study in a case of unilateral bifocal parathyroid carcinoma coexisting with parathyroid hyperplasia in a 49-year-old man. The images showed 4 foci of elevated activity around the thyroid. Histopathology confirmed the 2 lesions of the left side as parathyroid hyperplasia and the other 2 lesions of the right side as parathyroid carcinoma.
Topics: Adenoma; Humans; Hyperparathyroidism, Primary; Hyperplasia; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms; Technetium Tc 99m Sestamibi
PubMed: 35972509
DOI: 10.1097/RLU.0000000000004343 -
Journal of Clinical Medicine Jul 2023(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary...
(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary hyperparathyroidism (PHPT). The purpose of this study was to compare classical and functional/secreting cystic parathyroid lesions and identify risk factors for severe hypercalcemia; (2) Methods: A total of 17 patients with PHPT and parathyroid cysts (study group) were compared with the group of 100 patients with hyperparathyroidism caused by adenoma or hyperplasia (control group). In both groups the majority were women (88% vs. 12%, with gender ratio 7, 3:1). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium and phosphate serum and urine concentrations and calcidiol serum levels were assessed; (3) Results: Patients with parathyroid cyst had statistically higher PTH and calcium serum concentration, higher calciuria and lower serum phosphate concentration. There were no statistically significant differences in the concentration of creatine in serum and urine and tubular reabsorption of phosphorus (TRP); (4) Conclusions: Due to higher PTH and calcium levels, cystic parathyroid adenomas could be one of the rare risk factors for severe hypercalcemia and hypercalcemic crisis which can be life threatening.
PubMed: 37568342
DOI: 10.3390/jcm12154939 -
Cirugia Espanola Sep 2022Primary hyperparathyroidism is the third most common endocrine disease. The aim of our study was to determine long-term outcomes and risk factors for persistence in...
INTRODUCTION
Primary hyperparathyroidism is the third most common endocrine disease. The aim of our study was to determine long-term outcomes and risk factors for persistence in patients undergoing parathyroidectomy for primary hyperparathyroidism.
METHODS
Retrospective study including patients undergoing parathyroidectomy between 2009-2019. Cure was defined as reestablishment of normal calcium homeostasis lasting a minimum of 6 months. Persistence was defined by ongoing hypercalcemia more than 6 months after surgery. Recurrent PHTP was defined by recurrence of hypercalcemia after a normocalcemic interval at more than 6 months after surgery. A more detailed analysis was performed on patients with normocalcemia and persistently elevated PTH levels after surgery. Variables independently related to persistence were analyzed by multivariate analysis.
RESULTS
We included 212 patients. Mean age was 59 years and 83% were women. Cure was observed in 204 patients (96.2%), persistence in 8 (3.8%) and recurrence in 3 (1.4%). Four patients (1.9%) presented normocalcemia and persistently elevated PTH after surgery. All presented parathyroid pathology (2 adenomas and 2 hyperplasia). In follow-up we observed that adenoma subgroup presented one patient with CKD and one with vitamin D deficiency while in the hyperplasia subgroup two patients presented CKD. Persistence was independently associated with hyperplasia (Odds ratio = 12.6, IC95% = 1.28-124, p = 0.030) and normal parathyroid tissue (Odds ratio = 188, IC95% = 9.33-379, p = 0.001) on histopathological report.
CONCLUSION
Primary hyperparathyroidism is a safe procedure in terms of morbidity and long-term outcomes. Hyperplasia and normal parathyroid tissue on histopathological report are risk factors for persistence. An interdisciplinary diagnostic and therapeutic approach is required to prevent persistence.
Topics: Adenoma; Calcium; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Hyperplasia; Male; Middle Aged; Parathyroid Hormone; Parathyroid Neoplasms; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors
PubMed: 35504549
DOI: 10.1016/j.cireng.2022.04.008