Project description:ObjectiveTo investigate the association between imaging findings and histopathological characteristics of parathyroid glands in patients with secondary hyperparathyroidism (SHPT).MethodsSeventy-four glands from 21 patients with SHPT who underwent parathyroidectomy were evaluated for their pathological characteristics. The detection rates of parathyroid glands using ultrasound (US) and 99Tc-MIBI-SPECT/CT (MIBI) were compared. Glands were classified as either US-positive or US-negative, and MIBI-positive or MIBI-negative. Morphological and pathological differences between the positive and negative groups were systematically analysed.ResultsThe detection rates for parathyroid glands were 71% with US, 65% with MIBI, and 82% when combining both methods. US and MIBI showed similar localization accuracy in SHPT (P = .38). MIBI-positive glands had significantly larger oxyphil nodules compared with MIBI-negative glands (area: 10.92 mm² vs 3.09 mm², P < .01; area proportion: 61% vs 30%, P = .002), while no significant differences were found in chief nodules. The US-positive group had fewer and smaller chief nodules (number: 2 vs 9, P = .005; area: 1.53 mm² vs 11.08 mm², P = .033) and a higher percentage of oxyphil nodules (74% vs 33%, P = .003) compared with the US-negative group. Thirteen glands undetected by both US and MIBI had smaller oxyphil nodule areas (3.59 vs 13.24 mm²) and lower oxyphil nodule area percentages (25% vs 68%). These pathological features, including adipose infiltration, intra-gland haemorrhage, cyst formation, and calcification, showed no correlation with the gland's imaging results.ConclusionUS and MIBI had similar value in preoperative localization of SHPT. Parathyroid glands with more and larger oxyphil nodules were more likely to be detected by both MIBI and US.
Project description: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.
Project description:IntroductionNodular hyperplasia of parathyroid glands (PG) is the most probable cause of medical treatment failure in secondary hyperparathyroidism (sHPT). This prospective cohort study is located at the interface of medical and surgical consideration of sHPT treatment options and identifies risk-factors for nodular hyperplasia of PG.Material and methodsOne-hundred-eight resected PG of 27 patients with a broad spectrum of sHPT severity were classified according to the degree of hyperplasia by histopathology. Twenty routinely gathered parameters from medical history, ultrasound findings of PG and laboratory results were analyzed for their influence on nodular hyperplasia of PG by risk-adjusted multivariable binary regression. A prognostic model for non-invasive assessment of PG was developed and used to weight the individual impact of identified risk-factors on the probability of nodular hyperplasia of single PG.ResultsIndependent risk-factors for nodular hyperplasia of single PG were duration of dialysis in years, PG volume in mm3 determined by ultrasound and serum level of parathyroid hormone in pg/mL. Multivariable analyses computed a model with an Area Under the Receiver Operative Curve of 0.857 (95%-CI:0.773-0.941) when predicting nodular hyperplasia of PG. Theoretical assessment of risk-factor interaction revealed that the duration of dialysis had the strongest influence on the probability of nodular hyperplasia of single PG.ConclusionsThe three identified risk-factors (duration of dialysis, PG volume determined by ultrasound and serum level of parathyroid hormone) can be easily gathered in daily routine and could be used to non-invasively assess the probability of nodular hyperplasia of PG. This assessment would benefit from periodically collected data sets of PG changes during the course of sHPT, so that the choice of medical or surgical sHPT treatment could be adjusted more to the naturally changing type of histological PG lesion on an individually adopted basis in the future.
Project description:The parathyroid glands are essential for regulating calcium homeostasis in the body. The genetic programs that control parathyroid fate specification, morphogenesis, differentiation, and survival are only beginning to be delineated, but are all centered around a key transcription factor, GCM2. Mutations in the Gcm2 gene as well as in several other genes involved in parathyroid organogenesis have been found to cause parathyroid disorders in humans. Therefore, understanding the normal development of the parathyroid will provide insight into the origins of parathyroid disorders.
Project description:PurposeThe anatomy of parathyroid glands (PTG) is highly variable in the population. The aim of this study was to conduct a systematic analysis on the prevalence and location of PTG in healthy and hyperparathyroidism (HPT) patients.MethodsAn extensive search of the major electronic databases was conducted to identify all studies that reported relevant data on the number of PTG per patient and location of PTG. The data was extracted from the eligible studies and pooled into a meta-analysis.ResultsThe overall analysis of 26 studies (n = 7005 patients; n = 23,519 PTG) on the number of PTG showed that 81.4% (95% CI 65.4-85.8) of patients have four PTG. A total of 15.9% of PTG are present in ectopic locations, with 11.6% (95% CI 5.1-19.1) in the neck and 4.3% (95% CI 0.7-9.9) in mediastinum. The subgroup analysis of ectopic PTG showed that 51.7% of ectopic PTG in the neck are localized in retroesophageal/paraesophageal space or in the thyroid gland. No significant differences were observed between the healthy and HPT patients and cadaveric and intraoperative studies.ConclusionsKnowledge regarding the prevalence, location, and anatomy of PTG is essential for surgeons planning for and carrying out parathyroidectomies, as any unidentified PTG, either supernumerary or in ectopic location, can result in unsuccessful treatment and need for reoperation.
Project description:BackgroundNeck ultrasound (US) is a widely used and accessible operator-dependent technique that helps characterize thyroid nodules and pathologic parathyroid glands (PPGs). However, thyroid nodules may sometimes be confused with PPGs. PARATH-US study aims at identifying US characteristics to differentiate PPGs from thyroid nodules, as there is no study, at present, which directly compares the US features of these two common neoplasms.MethodsPARATH-US is a single-center study that was conducted at a tertiary referral center, including consecutive lesions from patients undergoing neck US examination from 2016 to 2022.Findings176 PPGs (158 patients: serum calcium levels 2.91 [IQR 2.74-3.05] mmol/L, PTH levels 173 [112-296] ng/L) were compared to 232 size- and volume-matched thyroid nodules (204 age- and sex-matched patients). The morphologic patterns, echoic content and vascular status were all different between PPGs and thyroid neoplasms (p < 0.01 for all comparisons). The combined parameters maximally discriminated PPGs from thyroid nodules (OR, 7.6; 95% CI: 3.4, 17.1, p < 0.0001). When applying risk stratification systems developed for thyroid malignancies, 58-63% of PPGs were classified as high-risk lesions. Parathyroid adenomas had larger sizes and volumes than hyperplasias (p = 0.013 and p = 0.029). Serum calcium and PTH levels were significantly correlated with PPG size and volume (p < 0.0001 for all comparisons).InterpretationWe demonstrate the presence of distinct US characteristics in PPGs, which help differentiate them from thyroid nodules. When mistaken for thyroid nodules, PPGs bear high-risk US features. When dealing with high-risk cervical lesions detected on US, a PPG should be suspected, and an assessment of calcium levels recommended to avoid unnecessary invasive procedures.FundingCYTO-TRAIN, C2022DOSRH053, funded by the French Regional Health Agency.
Project description:ContextThe glial cells missing 2 (GCM2) gene functions as a transcription factor that is essential for parathyroid gland development, and variants in this gene have been associated with 2 parathyroid diseases: isolated hypoparathyroidism in patients with homozygous germline inactivating variants and primary hyperparathyroidism in patients with heterozygous germline activating variants. A recurrent germline activating missense variant of GCM2, p.Y394S, has been reported in patients with familial primary hyperparathyroidism.ObjectiveTo determine whether the GCM2 p.Y394S missense variant causes overactive and enlarged parathyroid glands in a mouse model.MethodsCRISPR/Cas9 gene editing technology was used to generate a mouse model with the germline heterozygous Gcm2 variant p.Y392S that corresponds to the human GCM2 p.Y394S variant. Wild-type (Gcm2+/+) and germline heterozygous (Gcm2+/Y392S) mice were evaluated for serum biochemistry and parathyroid gland morphology.ResultsGcm2 +/Y392S mice did not show any change compared to Gcm2+/+ mice in serum calcium and parathyroid hormone levels, parathyroid gland histology, cell proliferation, or parathyroid gland size.ConclusionThe mouse model of the p.Y392S variant of Gcm2 shows that this variant is tolerated in mice, as it does not increase parathyroid gland cell proliferation and circulating calcium or PTH levels. Further investigation of Gcm2+/Y392S mice to study the effect of this variant of Gcm2 on early events in parathyroid gland development will be of interest.
Project description:Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) and correlates with morbidity and mortality. In this study we profiled microRNAs (miRNA) in parathyroids from different experimental SHP models and uremic patients and studied the function of specific miRNA using antagonizing oligonucleotides (anti-miRs). miRNA profiles established by small RNA deep sequencing showed that human, rat and mouse parathyroids share the same most abundant miRNAs. Principal component analyses clearly segregated parathyroids from SHP rats from normal rats, based on their miRNA expression profiles. Similar findings were observed in hyperplastic parathyroids from CKD patients compared to normal parathyroids from patients without kidney disease. We identifed specific parathyroid miRNAs that were dysregulated in all experimental SHP models studied. let-7i was decreased and miR-141 and miR-148a were increased in the parathyroids of rats with prolonged CKD induced by an 8 w adenine high phosphorus diet. Down-regulation of let-7 by anti-miRs increased PTH secretion in normal and in CKD rats, as well as in parathyroid organ cultures. Anti-miR-148 prevented the increase in serum PTH in CKD rats and decreased secreted PTH in parathyroid organ cultures. Our findings characterized parathyroid miRNA profiles and demonstrated conservation of the abundant miRNAs in different species. The evolutionary conservation of abundant miRNAs and their regulation in SHP suggest that miRNAs are important for parathyroid function and the development of SHP. Down-regulation of let-7 and miR-148 affects PTH secretion in vivo and in vitro, suggesting a role for these miRNAs in SHP. We propose that let-7 restrains while miR-148 promotes PTH secretion. In CKD, the decrease in parathyroid let-7 and the increase in miR-148 miRNAs may contribute to the development of SHP.
Project description:The mechanisms of chronic kidney disease-associated secondary hyperparathyroidism are partially understood. In this project we aimed to gain new information and propose research hypotheses by proteome and phosphoproteome profiling of normal and hyperplastic rat parathyroid glands. Glands were microdissected from rats on normal control diet or CKD-inducing high adenine diet enriched with phosphorus to produce secondary hyperparathyroidism. Protein extracts were pooled from 4 glands (2 rats) for proteome profiling (3 normal and 3 CKD pools), and from 12 glands (6 rats) for phosphoproteome profiling (2 normal and 2 CKD pools).
Project description:PurposeSystematic identification of all 4 parathyroid glands has been recommended during total thyroidectomy (TT); however, it is unclear whether this strategy necessarily translates into optimized functional parathyroid preservation. We wished to investigate the association between number of parathyroids identified intraoperatively during TT, and incidence of incidental parathyroidectomy, and postoperative hypoparathyroidism.MethodsRetrospective review of prospectively maintained database of 511 consecutive patients undergoing TT at an academic teaching hospital. The association between number of parathyroid glands identified intraoperatively and incidence of biochemical hypocalcaemia (defined as any calcium < 2 mmol/L n first 48 h after surgery), symptomatic hypocalcaemia; permanent hypoparathyroidism (defined as any hypocalcaemia or need for calcium or vitamin D > 6 months after surgery), and incidental parathyroidectomy, was investigated. The association between number of parathyroid glands visualized and postoperative parathyroid hormone (PTH) levels was investigated in a subset of 454 patients.ResultsPatients in whom a greater number of parathyroids had been identified had a significantly higher incidence of biochemical and symptomatic hypocalcaemia, and significantly lower postoperative PTH levels, than patients with fewer glands identified. There were no significant differences in incidence of permanent hypoparathyroidism or incidental parathyroidectomy. On multivariate analysis, malignancy, Graves disease, and identification of 3-4 parathyroids were independent predictors of biochemical hypocalcaemia. For symptomatic hypocalcaemia, identification of 2-4 parathyroids, and identification of 3-4 parathyroids, were significant.ConclusionsSystematic identification of as many parathyroid glands as possible during TT is not necessary for functional parathyroid preservation.