-
Clinical Case Reports Jan 2021During operative exploration of the neck for parathyroid surgery, the surgeon should always consider possible ectopic locations of the glands and have a reasonable...
During operative exploration of the neck for parathyroid surgery, the surgeon should always consider possible ectopic locations of the glands and have a reasonable surgical strategy for locating these ectopic glands.
PubMed: 33505697
DOI: 10.1002/ccr3.3476 -
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 -
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 -
Gland Surgery Feb 2020Clinical or subclinical primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders in the world. Parathyroidectomy is the treatment of choice in... (Review)
Review
Clinical or subclinical primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders in the world. Parathyroidectomy is the treatment of choice in symptomatic patients, stabilizing the progression of complications caused by the destruction activity of parathyroid hormone (PTH). Parathyroid surgical techniques have evolved over the years from bilateral neck exploration, to minimally invasive single parathyroid gland exploration, to minimally invasive video-assisted parathyroidectomy. Localization of the abnormal parathyroid gland before surgery is crucial for the operation to be effective. Increased incidences of reoperations of the parathyroid glands and the rapid development of minimally invasive methods led to the development of new localization techniques. The noninvasive studies include ultrasound (US), computed tomography (CT), magnetic resonance (MR) and Tc-methoxyisobutylisonitrile (MIBI) scintigraphy combined with single-photon emission CT (SPECT/CT). Among the latest technologies, the four-dimensional (4D)-CT scan, positron emission tomography (PET)/CT and PET/MR are very promising, and are going to have surgical implications in the future.
PubMed: 32175249
DOI: 10.21037/gs.2019.11.10 -
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 -
Medicina (Kaunas, Lithuania) Dec 2021: preoperative differentiation of enlarged parathyroid glands may be challenging in conventional B-mode ultrasound. The aim of our study was to analyse qualitative and...
: preoperative differentiation of enlarged parathyroid glands may be challenging in conventional B-mode ultrasound. The aim of our study was to analyse qualitative and quantitative characteristics of parathyroid gland lesions, using multiparametric ultrasound protocol-B-mode, Colour Doppler (CD), and contrast-enhanced ultrasound (CEUS)-and to evaluate correlation with morphology in patients with hyperparathyroidism (HPT). : consecutive 75 patients with 88 parathyroid lesions and biochemically confirmed HPT prior to parathyroidectomy were enrolled in the prospective study. B-mode ultrasound, CD, and CEUS were performed with the subsequent qualitative and quantitative evaluation of acquired data. We used 1 mL or 2 mL of intravenous ultrasound contrast agent during the CEUS examination. Correlation with post-surgical morphology was evaluated. seventy parathyroid adenomas were hypoechoic and well contoured with increased central echogenicity (44.3%), peripheral-central vascularization (47%), and polar feeding vessel (100%). Twelve hyperplasias presented with similar ultrasound appearance and were smaller in volume ( = 0.036). Hyperplasias had a tendency for homogenous, marked intense enhancement vs. peripherally enhanced adenomas with central wash-out in CEUS after quantitative analysis. No significant difference was observed in contrasting dynamics, regardless of contrast media volume use (1 mL vs. 2 mL). We achieved 90.9% sensitivity and 72.7% specificity, 93% positive predictive value (PPV), 87.3% negative predictive value (NPV), and 87.3% accuracy in the differentiation of parathyroid lesions prior to post-processing. In a quantitative lesion analysis, our sensitivity increased up to 98%, specificity 80%, PPV 98%, and NPV 80% with an accuracy of 96.4%. CEUS of parathyroid lesions shows potential in the differentiation of adenoma from hyperplasia, regardless of the amount of contrast media injected. The quantitative analysis improved the sensitivity and specificity of differentiation between parathyroid lesions. Hyperplasia was characterized by homogeneous enhancement, fast uptake, and homogeneous wash-out appearance; adenoma-by peripheral uptake, central wash-out, and reduced hemodynamics. The use of CEUS quantification methods are advised to improve the ultrasound diagnostic role in suspected parathyroid lesions.
Topics: Contrast Media; Humans; Parathyroid Glands; Prospective Studies; Sensitivity and Specificity; Ultrasonography
PubMed: 35056309
DOI: 10.3390/medicina58010002 -
Journal of the American Society of... Sep 2022Secondary hyperparathyroidism (SHP) is a common complication of CKD that increases morbidity and mortality. In experimental SHP, increased parathyroid hormone (PTH)...
BACKGROUND
Secondary hyperparathyroidism (SHP) is a common complication of CKD that increases morbidity and mortality. In experimental SHP, increased parathyroid hormone (PTH) expression is due to enhanced mRNA stability, mediated by changes in its interaction with stabilizing AUF1 and destabilizing KSRP. The isomerase Pin1 leads to KSRP dephosphorylation, but in SHP parathyroid Pin1 activity is decreased and hence phosphorylated KSRP fails to bind mRNA, resulting in high mRNA stability and levels. The up- and downstream mechanisms by which CKD stimulates the parathyroid glands remain elusive.
METHODS
Adenine-rich high-phosphate diets induced CKD in rats and mice. Parathyroid organ cultures and transfected cells were incubated with Pin1 inhibitors for their effect on PTH expression. Mass spectrometry was performed on both parathyroid and mRNA pulled-down proteins.
RESULTS
CKD led to changes in rat parathyroid proteome and phosphoproteome profiles, including KSRP phosphorylation at Pin1 target sites. Furthermore, both acute and chronic kidney failure led to parathyroid-specific Pin1 Ser16 and Ser71 phosphorylation, which disrupts Pin1 activity. Pharmacologic Pin1 inhibition, which mimics the decreased Pin1 activity in SHP, increased PTH expression in parathyroid glands in culture and in transfected cells through the mRNA-protein interaction element and KSRP phosphorylation.
CONCLUSIONS
Kidney failure leads to loss of parathyroid Pin1 activity by inducing Pin1 phosphorylation. This predisposes parathyroids to increase PTH production through impaired mRNA decay that is dependent on KSRP phosphorylation at Pin1-target motifs. Pin1 and KSRP phosphorylation and the Pin1-KSRP- mRNA axis thus drive SHP.
Topics: Rats; Mice; Animals; Parathyroid Glands; RNA, Messenger; Phosphorylation; Hyperparathyroidism, Secondary; Parathyroid Hormone; Kidney Failure, Chronic; Renal Insufficiency
PubMed: 35961788
DOI: 10.1681/ASN.2022020197