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Endocrine-related Cancer Jan 2016Five syndromes share predominantly hyperplastic glands with a primary excess of hormones: neonatal severe primary hyperparathyroidism, from homozygous mutated CASR,... (Review)
Review
Five syndromes share predominantly hyperplastic glands with a primary excess of hormones: neonatal severe primary hyperparathyroidism, from homozygous mutated CASR, begins severely in utero; congenital non-autoimmune thyrotoxicosis, from mutated TSHR, varies from severe with fetal onset to mild with adult onset; familial male-limited precocious puberty, from mutated LHR, expresses testosterone oversecretion in young boys; hereditary ovarian hyperstimulation syndrome, from mutated FSHR, expresses symptomatic systemic vascular permeabilities during pregnancy; and familial hyperaldosteronism type IIIA, from mutated KCNJ5, presents in young children with hypertension and hypokalemia. The grouping of these five syndromes highlights predominant hyperplasia as a stable tissue endpoint and as their tissue stage for all of the hormone excess. Comparisons were made among this and two other groups of syndromes, forming a continuum of gland staging: predominant oversecretions express little or no hyperplasia; predominant hyperplasias express little or no neoplasia; and predominant neoplasias express nodules, adenomas, or cancers. Hyperplasias may progress (5 of 5) to neoplastic stages while predominant oversecretions rarely do (1 of 6; frequencies differ P<0.02). Hyperplasias do not show tumor multiplicity (0 of 5) unlike neoplasias that do (13 of 19; P<0.02). Hyperplasias express mutation of a plasma membrane-bound sensor (5 of 5), while neoplasias rarely do (3 of 14; P<0.002). In conclusion, the multiple distinguishing themes within the hyperplasias establish a robust pathophysiology. It has the shared and novel feature of mutant sensors in the plasma membrane, suggesting that these are major contributors to hyperplasia.
Topics: Adenoma; Adult; Child; Endocrine Glands; Female; Hormones, Ectopic; Humans; Hyperplasia; Hyperthyroidism; Male; Parathyroid Glands; Parathyroid Neoplasms; Pregnancy; Puberty, Precocious
PubMed: 26407873
DOI: 10.1530/ERC-15-0171 -
Physiological Research Apr 2022Inconclusive preoperative imaging is a strong predictor of multiglandular parathyroid disease (MGD) in patients with primary hyperparathyroidism (PHPT). MGD was...
Inconclusive preoperative imaging is a strong predictor of multiglandular parathyroid disease (MGD) in patients with primary hyperparathyroidism (PHPT). MGD was investigated in a cohort of 17 patients with PHPT (mean age 64.9 years, total calcium 2.75 mmol/l and parathyroid hormone (PTH) 113.3 ng/l) who underwent 18F-fluorocholine PET/CT (FCH) imaging before surgery. The initial MIBI SPECT scintigraphy (MIBI) and/or neck ultrasound were not conclusive or did not localize all pathological parathyroid glands, and PHPT persisted after surgery. Sporadic MGD was present in 4 of 17 patients with PHPT (24 %). In 3 of 4 patients with MGD, FCH correctly localized 6 pathological parathyroid glands and surgery was successful. Excised parathyroid glands were smaller (p <0.02) and often hyperplastic in MGD than in single gland disease. In two individuals with MGD, excision of a hyperplastic parathyroid gland led to a false positive decline in intraoperative PTH and/or postoperative serum calcium. Although in one patient it was associated with partial false negativity, parathyroid imaging with FCH seemed to be superior to neck ultrasound and/or MIBI scintigraphy in MGD.
Topics: Aged; Calcium; Humans; Hyperparathyroidism, Primary; Middle Aged; Parathyroid Glands; Positron Emission Tomography Computed Tomography; Technetium Tc 99m Sestamibi
PubMed: 35275696
DOI: 10.33549/physiolres.934851 -
Diagnostic and Interventional Imaging May 2022The purpose of this study was to assess the diagnostic capabilities of preoperative conventional imaging (Tc-MIBI scintigraphy, cervical ultrasonography [CUS]) and...
PURPOSE
The purpose of this study was to assess the diagnostic capabilities of preoperative conventional imaging (Tc-MIBI scintigraphy, cervical ultrasonography [CUS]) and F-fluorocholine PET/CT (FCH PET/CT) in the detection of hyperfunctioning parathyroid gland in patients with primary hyperparathyroidism (PHPT) used alone or as a single imaging set.
MATERIALS AND METHODS
A total of 51 consecutive patients (6 men, 45 women; mean age, 62 ± 11.6 [SD] years; age range: 28-86 years) with biochemically confirmed PHPT who underwent CUS, single-tracer dual phase Tc-MIBI scintigraphy and FCH PET/CT were retrospectively included. Tc-MIBI scintigraphy were performed immediately after CUS and interpreted by the same operators. FCH PET/CT examinations were interpreted independently by two nuclear medicine physicians. An additional reading session integrating the three imaging modalities read in consensus as a combined imaging set was performed.
RESULTS
At surgery, 74 lesions were removed (32 parathyroid adenomas, 38 parathyroid hyperplasia and 4 subnormal glands). Thirty-six patients (71%) had single-gland disease and 15 patients (29%) had multiglandular disease at histopathological analysis. On a patient basis, sensitivity and accuracy of FCH PET/CT, CUS and Tc-MIBI scintigraphy for the detection of abnormal parathyroid glands were 76% (95% CI: 63-87%) and 76% (95% CI: 63-87%), 71% (95% CI: 56-83%) and 71% (95% CI: 56-83%), 33% (95% CI: 21-48%) and 33% (95% CI: 21-48%), respectively. The sensitivity of the combined imaging set was 94% (95% CI: 84-99%) and greater than the sensitivity of each individual imaging technique (P ≤ 0.001 for all).
CONCLUSION
Our results suggest that CUS, Tc-MIBI scintigraphy and FCH PET/CT interpreted as a single imaging set could be the ideal practice to precisely localize parathyroid lesion in patients with PHPT before surgery.
Topics: Adult; Aged; Aged, 80 and over; Choline; Female; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Parathyroid Glands; Positron Emission Tomography Computed Tomography; Retrospective Studies; Technetium Tc 99m Sestamibi
PubMed: 35039246
DOI: 10.1016/j.diii.2021.12.005 -
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 -
PloS One 2020Ultrasonographic examination of the normal thyroid and parathyroid glands has been described for humans and many animal species. However, similar reports for goats are...
Ultrasonographic examination of the normal thyroid and parathyroid glands has been described for humans and many animal species. However, similar reports for goats are still missing. The aim of the study was to present ultrasound features of the normal thyroid and internal parathyroid glands in goats with the determination of their dimensions and volume, followed by a comparison of the results to the gross examination. Seventy-two goats were used in the study. The echostructure and echogenicity of the thyroid and parathyroid glands were assessed. The length, width and height of the thyroid and the length and width of the parathyroid glands were measured. The thyroid volume was calculated using the ellipsoid formula, basing on the ultrasonographic dimensions. Size and volume of the dissected thyroid glands were established grossly, followed by a histological examination. In order to accurately describe the anatomy of the thyroid, new anatomical terminology characterizing this gland was proposed. The mean dimensions of the thyroid lobes were 30.2 x 10.5 x 6.3 mm. There were no statistically significant differences between the right and left lobe. Parathyroid glands measured an average of 3.6 x 2.4 mm. The percentage Root Mean Square Error between the results of ultrasonographic and gross examination was 16.73%, 20.65% and 17.01% for thyroid length, width and height, respectively, and 46.30% for volume. In order to obtain more precise calculation of the thyroid volume, a modified correction factor for the ellipsoid formula was introduced. For the first time, the normal ultrasonographic characteristics and dimensions of the caprine thyroid and internal parathyroid glands were presented. The results may serve as a radiological reference and be the basis for further research.
Topics: Animals; Female; Goats; Parathyroid Glands; Thyroid Gland; Ultrasonography
PubMed: 32470047
DOI: 10.1371/journal.pone.0233685 -
International Journal of Molecular... Jun 2020Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that correlates with morbidity and mortality in uremic patients. It is... (Review)
Review
Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that correlates with morbidity and mortality in uremic patients. It is characterized by high serum parathyroid hormone (PTH) levels and impaired bone and mineral metabolism. The main mechanisms underlying SHP are increased PTH biosynthesis and secretion as well as increased glandular mass. The mechanisms leading to parathyroid cell proliferation in SHP are not fully understood. Reduced expressions of the receptors for calcium and vitamin D contribute to the disinhibition of parathyroid cell proliferation. Activation of transforming growth factor-α-epidermal growth factor receptor (TGF-α-EGFR), nuclear factor kappa B (NF-kB), and cyclooxygenase 2- prostaglandin E2 (Cox2-PGE2) signaling all correlate with parathyroid cell proliferation, underlining their roles in the development of SHP. In addition, the mammalian target of rapamycin (mTOR) pathway is activated in parathyroid glands of experimental SHP rats. Inhibition of mTOR by rapamycin prevents and corrects the increased parathyroid cell proliferation of SHP. Mice with parathyroid-specific deletion of all miRNAs have a muted increase in serum PTH and fail to increase parathyroid cell proliferation when challenged by CKD, suggesting that miRNA is also necessary for the development of SHP. This review summarizes the current knowledge on the mechanisms of parathyroid cell proliferation in SHP.
Topics: Cell Proliferation; Down-Regulation; Fibroblast Growth Factor-23; Humans; Hyperparathyroidism, Secondary; Parathyroid Glands; Receptors, Calcitriol; Receptors, Calcium-Sensing; Renal Insufficiency, Chronic
PubMed: 32570711
DOI: 10.3390/ijms21124332 -
Archives of Endocrinology and Metabolism Jun 2021
Topics: Cicatrix; Humans; Parathyroid Glands; Thyroid Gland; Thyroidectomy
PubMed: 34191416
DOI: 10.20945/2359-3997000000381 -
Journal of Biophotonics Jun 2021During thyroid surgeries, it is important for surgeons to accurately identify healthy parathyroid glands and assess their vascularity to preserve their function...
During thyroid surgeries, it is important for surgeons to accurately identify healthy parathyroid glands and assess their vascularity to preserve their function postoperatively, thus preventing hypoparathyroidism and hypocalcemia. Near infrared autofluorescence detection enables parathyroid identification, while laser speckle contrast imaging allows assessment of parathyroid vascularity. Here, we present an imaging system combining the two techniques to perform both functions, simultaneously and label-free. An algorithm to automate the segmentation of a parathyroid gland in the fluorescence image to determine its average speckle contrast is also presented, reducing a barrier to clinical translation. Results from imaging ex vivo tissue samples show that the algorithm is equivalent to manual segmentation. Intraoperative images from representative procedures are presented showing successful implementation of the device to identify and assess vascularity of healthy and diseased parathyroid glands.
Topics: Diagnostic Imaging; Optical Imaging; Parathyroid Glands; Parathyroidectomy; Thyroid Gland; Thyroidectomy
PubMed: 33583122
DOI: 10.1002/jbio.202100008 -
Human Pathology May 2022Intraoperative consultation for assessment of parathyroid tissue is a controversial area of endocrine pathology. This assessment often follows historical institutional... (Review)
Review
Intraoperative consultation for assessment of parathyroid tissue is a controversial area of endocrine pathology. This assessment often follows historical institutional and individual surgical practitioner practices rather than documented utility data and adjuvant intraoperative testing data, including intraoperative parathyroid hormone level testing by clinical pathologists and the use of Oil Red O vital stain on frozen tissue sections by anatomic pathologists, as a means of conferring etiology of parathyroid disease. The American Association of Endocrine Surgeons (AAES), in 2016, proposed guidelines for the management of primary hyperparathyroidism, including recommendations for intraoperative consultation, recommending against the use of intraoperative frozen section to determine parathyroid functional status but in support for its use for parathyroid identification. In this series, we review a one-year, retrospective cohort of consecutive parathyroid surgeries at Massachusetts General Hospital, including over 200 cases meeting inclusion criteria for which primary hyperparathyroidism was the indication for surgery, discussing outcomes, compliance with AAES guidelines, and overall utility of intraoperative consultation and adjuvant testing.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Retrospective Studies
PubMed: 35196527
DOI: 10.1016/j.humpath.2022.02.012 -
Physiological Reports Apr 2019Altered parathyroid gland biology in patients with chronic kidney disease (CKD) is a major contributor to chronic kidney disease-mineral bone disorder (CKD-MBD). This...
Altered parathyroid gland biology in patients with chronic kidney disease (CKD) is a major contributor to chronic kidney disease-mineral bone disorder (CKD-MBD). This disorder is associated with an increased risk of bone disorders, vascular calcification, and cardiovascular events. Parathyroid hormone (PTH) secretion is primarily regulated by the ionized calcium concentration as well as the phosphate concentration in the extracellular fluid and vitamin D. The metabolic disturbances in patients with CKD lead to alterations in the parathyroid gland biology. A hallmark of CKD is secondary hyperparathyroidism, characterized by an increased production and release of PTH, reduced expression of calcium-sensing and vitamin D receptors on the surface of parathyroid cells, and hyperplasia and hypertrophy of these cells. These alterations happen on different timescales and influence each other, thereby triggering a cascade of negative and positive feedback loops in a highly complex manner. Due to this complexity, mathematical models are a useful tool to break down the patterns of the multidimensional cascade of processes enabling the detailed study of subsystems. Here, we introduce a comprehensive mathematical model that includes the major adaptive mechanisms governing the production, secretion, and degradation of PTH in patients with CKD on hemodialysis. Combined with models for medications targeting the parathyroid gland, it provides a ready-to-use tool to explore treatment strategies. While the model is of particular interest for use in hemodialysis patients with secondary hyperparathyroidism, it has the potential to be applicable to other clinical scenarios such as primary hyperparathyroidism or hypo- and hypercalcemia.
Topics: Calcium; Humans; Hyperparathyroidism, Secondary; Models, Theoretical; Parathyroid Glands; Parathyroid Hormone; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 30927339
DOI: 10.14814/phy2.14045