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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 -
Head and Neck Pathology Sep 2021Parathyromatosis is displaced parathyroid tissue in the neck and mediastinum related to prior surgery. Parathyromatosis can be difficult to distinguish from atypical...
Parathyromatosis is displaced parathyroid tissue in the neck and mediastinum related to prior surgery. Parathyromatosis can be difficult to distinguish from atypical adenoma and parathyroid carcinoma. The aim of this study is to evaluate clinical and morphologic features that may differentiate parathyromatosis, atypical adenoma, and parathyroid carcinoma. Cases of parathyromatosis, atypical adenoma, and parathyroid carcinoma were identified. Index cases were reviewed by consensus for histologic features, including stromal, cytologic/architectural, and invasive features. Ki67 was performed on index cases and scored using the Adsay method. Clinical information was gathered from the electronic medical record. 4 parathyromatosis, 17 atypical adenoma, and 6 parathyroid carcinoma were included. Parathyroid carcinomas were more likely to display coarse chromatin with nucleoli (P = 0.04), infiltrative invasion (P < 0.01), and metastasis (P < 0.01). Only parathyromatosis showed circumscribed invasion. Infiltrative invasion was more common in cases with progression (P = 0.046) and metastasis (P < 0.001). Necrosis and perineural invasion were only present in cases with progression and were more frequent in cases with metastasis (P = 0.079 and P = 0.19, respectively). There were no differences in presence of a fibrous capsule, capsular invasion, intralesional fibrous bands, random endocrine atypia, solid growth, Ki67 index, gland size/weight, serum PTH/calcium levels, and locoregional recurrence rates. There is overlap in the histologic features in parathyromatosis, atypical adenoma, and parathyroid carcinoma. While perineural, vascular, and infiltrative soft tissue invasion should remain diagnostic of malignancy, other atypical features such as solid growth, coarse chromatin with nucleoli, and necrosis should raise concern for recurrence and/or metastasis, and can be present in parathyroid lesions with and without recurrence.
Topics: Adenoma; Choristoma; Diagnosis, Differential; Humans; Mediastinum; Neck; Parathyroid Glands; Parathyroid Neoplasms
PubMed: 33394375
DOI: 10.1007/s12105-020-01281-6 -
Clinical and Experimental Nephrology May 2023Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease-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-mineral and bone disorder (CKD-MBD). Both hormones increase as kidney function declines, presumably as a response to maintain normal phosphate balance, but when patients reach kidney failure, PTH and FGF23 fail to exert their phosphaturic effects, leading to hyperphosphatemia and further elevations in PTH and FGF23. In patients with kidney failure, the major target organ for PTH is the bone, but elevated PTH is also associated with mortality presumably through skeletal and nonskeletal mechanisms. Indeed, accumulated evidence suggests improved survival with PTH-lowering therapies, and a more recent study comparing parathyroidectomy and calcimimetic treatment further suggests a notion of "the lower, the better" for PTH control. Emerging data suggest that the link between SHPT and mortality could in part be explained by the action of PTH to induce adipose tissue browning and wasting. In the absence of a functioning kidney, the classical target organ for FGF23 is the parathyroid gland, but FGF23 loses its hormonal effect to suppress PTH secretion owing to the depressed expression of parathyroid Klotho. In this setting, experimental data suggest that FGF23 exerts adverse nontarget effects, but it remains to be confirmed whether FGF23 directly contributes to multiple organ injury in patients with kidney failure and whether targeting FGF23 can improve patient outcomes. Further efforts should be made to determine whether intensive control of SHPT improves clinical outcomes and whether nephrologists should aim at controlling FGF23 levels just as with PTH levels.
Topics: Humans; Bone and Bones; Fibroblast Growth Factors; Parathyroid Glands; Parathyroid Hormone; Renal Insufficiency
PubMed: 36977891
DOI: 10.1007/s10157-023-02336-y -
Stem Cell Reports Nov 2022Parathyroid diseases are characterized by dysregulation of calcium homeostasis and alterations in parathyroid hormone (PTH) excretion. The development of...
Parathyroid diseases are characterized by dysregulation of calcium homeostasis and alterations in parathyroid hormone (PTH) excretion. The development of parathyroid-targeted treatment and imaging tracers could benefit from in vitro models. Therefore, we aim to establish a patient-derived parathyroid organoid model representing human parathyroid tissue. Hyperplastic parathyroid tissue was dispersed, and parathyroid organoids (PTOs) were cultured and characterized. PTO-derived cells exhibited self-renewal over several passages, indicative of the presence of putative stem cells. Immunofluorescence and RNA sequencing confirmed that PTOs phenocopy hyperplastic parathyroid tissue. Exposure of PTOs to increasing calcium concentrations and PTH-lowering drugs resulted in significantly reduced PTH excretion. PTOs showed specific binding of the imaging tracers C-methionine and Tc-sestamibi. These data show the functionality of PTOs resembling the parathyroid. This PTO model recapitulates the originating tissue on gene and protein expression and functionality, paving the way for future physiology studies and therapeutic target and tracer discovery.
Topics: Humans; Organoids; Calcium; Parathyroid Glands; Technetium Tc 99m Sestamibi; Hyperparathyroidism, Primary
PubMed: 36306782
DOI: 10.1016/j.stemcr.2022.09.015 -
International Journal of Molecular... Apr 2024Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established...
Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established findings in this respect with regard to TRPC6. Although the parathyroid gland is a crucial organ in calcium household regulation, little is known about the protein distribution of TRPC channels-especially TRPC3 and TRPC6-in this organ. Our aim was therefore to investigate the protein expression profile of TRPC3 and TRPC6 in healthy and diseased human parathyroid glands. Surgery samples from patients with healthy parathyroid glands and from patients suffering from primary hyperparathyroidism (pHPT) were investigated by immunohistochemistry using knockout-validated antibodies against TRPC3 and TRPC6. A software-based analysis similar to an H-score was performed. For the first time, to our knowledge, TRPC3 and TRPC6 protein expression is described here in the parathyroid glands. It is found in both chief and oxyphilic cells. Furthermore, the TRPC3 staining score in diseased tissue (pHPT) was statistically significantly lower than that in healthy tissue. In conclusion, TRPC3 and TRPC6 proteins are expressed in the human parathyroid gland. Furthermore, there is strong evidence indicating that TRPC3 plays a role in pHPT and subsequently in parathyroid hormone secretion regulation. These findings ultimately require further research in order to not only confirm our results but also to further investigate the relevance of these channels and, in particular, that of TRPC3 in the aforementioned physiological functions and pathophysiological conditions.
Topics: Humans; TRPC Cation Channels; Hyperparathyroidism, Primary; Parathyroid Glands; Female; Male; TRPC6 Cation Channel; Down-Regulation; Middle Aged; Aged; Adult; Immunohistochemistry; Parathyroid Hormone
PubMed: 38673977
DOI: 10.3390/ijms25084392 -
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 -
Frontiers in Endocrinology 2023More than 30,000 thyroid surgeries are performed annually in the Russian Federation. The surgeries are relatively safe because of the prevention methods for...
OBJECTIVE
More than 30,000 thyroid surgeries are performed annually in the Russian Federation. The surgeries are relatively safe because of the prevention methods for postoperative complications. Currently, there is no single effective method of postoperative hypoparathyroidism prevention. This complication is frequently reported and may be health and life-threatening.
AIM
We aimed to estimate the effectiveness of the intraoperative ICG-angiography and intrathyroid injection of Brilliant Green for the prevention of postoperative hypoparathyroidism.
MATERIAL AND METHODS
One hundred and forty-three thyroidectomies were performed. Patients were divided into three groups: intraoperative angiography was used in 24 cases; Brilliant Green was injected in 58 cases to identify parathyroid glands; the visual estimation of the parathyroid preservation was used in 61 cases. Calcium level was measured in all patients before and after surgery.
RESULTS
Calcium level in the serum before and after surgery was 2.37±0.14 and 2.27±0.17 in Group 1, 2.38±0.16 and 2.21±0.16 in Group 2, and 2.39±0.17 and 2.18±0.19 in Group 3. Postoperative hypocalcemia was more prominent in the group with the visually estimated PTG than in the two other groups. The differences in postoperative calcium levels in Groups 1 and 3 were statistically different. Pre- and postoperative Parathormone levels were 6.2±0.4 in Group 1, 5.6±0.57 in Group 2, and 3.5±0.32 in Group 3. Postoperative levels significantly differed in Groups 1 and 3 (p<0.01) and in Groups 2 and 3 (p<0.05).
CONCLUSIONS
ICG-angiography and intrathyroid injection of the Brilliant Green are safe methods of identification and sparing of the parathyroid glands. The severity of hypocalcemia and hypoparathormonemia in Group 3 shows the necessity of finding new methods in endocrine surgery to improve patient outcomes.
Topics: Humans; Hypocalcemia; Calcium; Hypoparathyroidism; Parathyroid Glands; Thyroidectomy
PubMed: 38027177
DOI: 10.3389/fendo.2023.1206881 -
Endocrine Regulations Jan 2023Hyperparathyroidism is a prevalent disease with parathyroid adenomas being the most common cause. Surgical excision remains the standard treatment for parathyroid...
Hyperparathyroidism is a prevalent disease with parathyroid adenomas being the most common cause. Surgical excision remains the standard treatment for parathyroid adenoma. Successful preoperative localization of the parathyroid adenoma could facilitate the decision regarding the extent of surgical exploration. The aim of the current study was to assess the correlation between the preoperative values of parathyroid hormone and ionized calcium with the adenoma weight and volume in patient with primary hyperparathyroidism caused by single-gland adenoma. We did this retrospective review for all patients who were diagnosed with primary hyperparathyroidism due to a solitary parathyroid adenoma in our general surgery department over 4 years. SPSS software was used to get the correlation coefficient between the peak preoperative levels of calcium and parathyroid hormone with the parathyroid adenoma weight and volume. Ninety-nine patients were included into the study. The average age at surgery was 62.65±12.00 years. The correlation coefficient between the adenoma volume and weight with the preoperative ionized calcium level was weakly positive (r=0.329, p<0.01) and (r=0.281, p=0.019), respectively, while the correlation with the preoperative parathyroid hormone level was stronger (r=0.708, p<0.01) and (r=0.650, p<0.01), respectively. The strong positive relationship between the preoperative parathyroid hormone and calcium levels with the parathyroid adenoma size and weight can help the surgeon to predict the volume of the involved gland and avoid an unnecessary dissection.
Topics: Humans; Middle Aged; Aged; Parathyroid Glands; Calcium; Parathyroid Neoplasms; Hyperparathyroidism, Primary; Parathyroid Hormone; Parathyroidectomy; Adenoma; Retrospective Studies
PubMed: 36753663
DOI: 10.2478/enr-2023-0002 -
Physiological Research Dec 2023Multiglandular primary hyperparathyroidism (MGD) represents a rare form of primary hyperparathyroidism (PHPT). MGD is associated with hereditary PHPT, but the sporadic... (Review)
Review
Multiglandular primary hyperparathyroidism (MGD) represents a rare form of primary hyperparathyroidism (PHPT). MGD is associated with hereditary PHPT, but the sporadic MGD is more common and affects a similar patient profile as single gland parathyroid disease (SGD). The distinction between SGD and MGD is of great clinical importance, especially for the strategy of parathyroidectomy. Based on the limited knowledge available, MGD is likely to be a genetically heterogeneous disease resulting from the interaction of germline and somatic DNA mutations together with epigenetic alterations. Furthermore, these events may combine and occur independently in parathyroid tumors within the same individual with MGD. Gene expression profiling has shown that SGD and MGD may represent distinct entities in parathyroid tumorigenesis. We are waiting for studies to analyze exactly which genes are different in SGD and MGD in order to identify potential biomarkers that can distinguish between the two forms of the disease.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Hormone; Retrospective Studies; Parathyroid Glands; Molecular Biology
PubMed: 38116772
DOI: 10.33549/physiolres.935253 -
Current Medical Imaging 2021Embryologic developmental variants of the thyroid and parathyroid glands may cause cervical anomalies that are detectable in ultrasound examinations of the neck. For...
Embryologic developmental variants of the thyroid and parathyroid glands may cause cervical anomalies that are detectable in ultrasound examinations of the neck. For some of these developmental variants, molecular genetic factors have been identified. Ultrasound, as the first-line imaging procedure, has proven useful in detecting clinically relevant anatomic variants. The aim of this article was to systematically summarize the ultrasound characteristics of developmental variants of the thyroid and parathyroid glands as well as ectopic thymus and neck cysts. Quantitative measures were developed based on our findings and the respective literature. Developmental anomalies frequently manifest as cysts that can be detected by cervical ultrasound examinations. Median neck cysts are the most common congenital cervical cystic lesions, with a reported prevalence of 7% in the general population. Besides cystic malformations, developmental anomalies may appear as ectopic or dystopic tissue. Ectopic thyroid tissue is observed in the midline of the neck in most patients and has a prevalence of 1/100,000 to 1/300,000. Lingual thyroid accounts for 90% of cases of ectopic thyroid tissue. Zuckerkandl tubercles (ZTs) have been detected in 55% of all thyroid lobes. Prominent ZTs are frequently observed in thyroid lobes affected by autoimmune thyroiditis compared with normal lobes or nodular lobes (P = 0.006). The correct interpretation of the ultrasound characteristics of these variants is essential to establish the clinical diagnosis. In the preoperative assessment, the identification of these cervical anomalies via ultrasound examination is indispensable.
Topics: Humans; Neck; Parathyroid Glands; Thyroid Diseases; Ultrasonography
PubMed: 33504311
DOI: 10.2174/1573405617666210127162328