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BioRxiv : the Preprint Server For... Jun 2023The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup...
The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup of skeletal stem cells that contribute to the formation of columnar chondrocytes. The PTHrP-indian hedgehog (Ihh) feedback regulation is essential for sustaining growth plate activities; however, molecular mechanisms regulating cell fates of PTHrP resting chondrocytes and their eventual transformation into osteoblasts remain largely undefined. Here, in a mouse model, we utilized a tamoxifen-inducible line with ( ) floxed and tdTomato reporter alleles to specifically activate Hedgehog signaling in PTHrP resting chondrocytes and trace the fate of their descendants. Hedgehog-activated PTHrP chondrocytes formed large concentric clonally expanded cell populations within the resting zone (' ') and generated significantly wider columns of chondrocytes, resulting in hyperplasia of the growth plate. Interestingly, Hedgehog-activated PTHrP cell-descendants migrated away from the growth plate and eventually transformed into trabecular osteoblasts in the diaphyseal marrow space in the long term. Therefore, Hedgehog activation drives resting zone chondrocytes into transit-amplifying states as proliferating chondrocytes and eventually converts these cells into osteoblasts, unraveling a novel Hedgehog-mediated mechanism that facilitates osteogenic cell fates of PTHrP skeletal stem cells.
PubMed: 37398296
DOI: 10.1101/2023.05.31.543069 -
Radiology Case Reports Aug 2023Four-dimensional computed tomography (4DCT) is one of the preoperative imaging modalities that can be used to localize a parathyroid adenoma in primary...
Four-dimensional computed tomography (4DCT) is one of the preoperative imaging modalities that can be used to localize a parathyroid adenoma in primary hyperparathyroidism patients however, sensitivity differs in literature and could be improved especially for multiglandular hyperplasia or double adenomas. The most robust feature on the 4DCT for the differentiation between parathyroid adenoma and thyroid gland tissue is arterial enhancement. To make this better visible, we have developed a subtraction map that shows arterial enhancement as a color scale to increase sensitivity for 4DCT. In this report of 3 cases, we present the usefulness of this subtraction map in a 54-year-old male, a 57-year-old female and a 51-year-old male. Subtraction maps may increase sensitivity for 4DCT, especially for multiglandular hyperplasia or double adenomas.
PubMed: 37388258
DOI: 10.1016/j.radcr.2023.05.019 -
The Journal of Clinical Endocrinology... Oct 2023Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid... (Meta-Analysis)
Meta-Analysis
CONTEXT
Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia.
OBJECTIVE
The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD).
METHODS
A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting.
RESULTS
Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed.
CONCLUSION
This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD.
Topics: Humans; Calcifediol; Calcium; Ergocalciferols; Hyperparathyroidism, Secondary; Network Meta-Analysis; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic
PubMed: 37235771
DOI: 10.1210/clinem/dgad289 -
Indian Journal of Endocrinology and... 2023Primary hyperparathyroidism (PHPT) can occur due to a neoplastic process or hyperplasia. While the disease presentation is predominantly asymptomatic in developed...
CONTEXT
Primary hyperparathyroidism (PHPT) can occur due to a neoplastic process or hyperplasia. While the disease presentation is predominantly asymptomatic in developed countries, this is not the case yet in India. Differentiation of the type of lesion can only be done based on histomorphology but has its own challenges. Immunohistochemical markers like Ki-67 have been studied to aid in diagnosis but data on this is sparse from India.
AIMS
The aim of this study is to assess the clinical, biochemical and pathological profile of PHPT and to analyse the differences in immunohistochemical marker Ki-67 among the various lesions.
SETTING AND DESIGN
A descriptive study was carried out on 38 PHPT patients who were treated at our institute from January 2011 to March 2021.
MATERIALS AND METHODS
Post-surgery, the causative lesions were categorised as adenoma (31), hyperplasia (5) and carcinoma (2). Clinical, biochemical, radiological and histopathological features of all lesions were collected and analysed. Ki-67 proliferation index was calculated. The various parameters were compared across the three groups of lesions and correlated with Ki-67 index.
RESULTS
Out of 38 patients, 37 were symptomatic with skeletal symptoms being the most common followed by renal symptoms. There was no difference in clinical or biochemical parameters among the three types of lesions. Significant negative correlation was seen between serum iPTH and serum 25-OH Vitamin D levels ( The median Ki-67 index was found to be 0.40% in hyperplasia, 0.49% in adenoma and 5.84% in carcinoma.
CONCLUSION
PHPT still presents as an overtly symptomatic disease in India. Diagnosis of the nature of lesion depends on the accurate application of morphological criteria. A high Ki-67 index was not found to be an absolute marker of carcinoma, as it was also seen in a small proportion of atypical adenomas.
PubMed: 37215275
DOI: 10.4103/ijem.ijem_208_22 -
BMC Endocrine Disorders May 2023Parathyroid carcinoma is a rare disease with a frequency of 0.005% of all malignancies [1, 2]. Various aspects of its pathogenesis, diagnosis, and treatment remain...
BACKGROUND
Parathyroid carcinoma is a rare disease with a frequency of 0.005% of all malignancies [1, 2]. Various aspects of its pathogenesis, diagnosis, and treatment remain poorly understood. Furthermore, cases with secondary hyperparathyroidism are fewer. In this case report, we describe a case of left parathyroid carcinoma with secondary hyperparathyroidism.
CASE PRESENTATION
The patient was a 54-year-old woman who had been on hemodialysis since the age of 40 years. At 53 years of age, her calcium levels were high, and she was diagnosed with drug-resistant secondary hyperparathyroidism and was referred to our hospital for surgical treatment. Blood tests revealed calcium levels of 11.4 mg/dL and intact parathyroid hormone (PTH) levels of 1007 pg/mL. Neck ultrasonography revealed a 22-mm large round hypoechoic mass, partially indistinct margins, and D/W ratio > 1 at the left thyroid lobe. Computed tomography scans revealed a 20-mm nodule at the left thyroid lobe. No enlarged lymph nodes or distant metastases were noted. Tc-hexakis-2-methoxyisobutylisonitrile scintigraphy revealed an accumulation at the superior pole of the left thyroid lobe. Laryngeal endoscopy revealed paralysis of the left vocal cord, signifying recurrent nerve palsy due to parathyroid carcinoma. Based on these results, a diagnosis of secondary hyperparathyroidism and suspected left parathyroid carcinoma was made, and the patient underwent surgery. Pathology results revealed hyperplasia in the right upper and lower parathyroid glands. The left upper parathyroid gland showed capsular and venous invasion, and the diagnosis was left parathyroid carcinoma. At 4 months post-surgery, calcium levels improved to 8.7 mg/dL and intact PTH levels to 20 pg/mL, with no signs of recurrence.
CONCLUSIONS
We report a case of left parathyroid carcinoma associated with secondary hyperparathyroidism. Concomitant secondary hyperparathyroidism may cause mild hypercalcemia compared to parathyroid carcinoma alone due to the added modification of dialysis. Although our patient also presented with mild hypercalcemia, a D/W ratio > 1 on preoperative echocardiography and presence of recurrent nerve palsy on laryngoscopy led to the suspicion and treatment of parathyroid carcinoma preoperatively.
Topics: Humans; Female; Adult; Middle Aged; Parathyroid Neoplasms; Hypercalcemia; Calcium; Hyperparathyroidism, Secondary; Paralysis; Parathyroid Hormone
PubMed: 37193977
DOI: 10.1186/s12902-023-01370-x -
Diagnostics (Basel, Switzerland) Apr 2023Hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) includes secondary (sHPT) and tertiary hyperparathyroidism (tHPT). Considering that the role of...
Hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) includes secondary (sHPT) and tertiary hyperparathyroidism (tHPT). Considering that the role of preoperative imaging in the clinical setting is controversial, in the present study we have retrospectively compared pre-surgical diagnostic performances of F-Fluorocholine (F-FCH) PET/CT, cervical ultrasonography (US), parathyroid scintigraphy, and 4D-CT in a group of 30 patients with CKD and HPT (18/12 sHPT/tHPT), 21 CKD G5 including 18 in dialysis, and 9 kidney transplant recipients. All patients underwent F-FCH, and 22 had cervical US, 12 had parathyroid scintigraphy, and 11 had 4D-CT. Histopathology was the gold standard. Seventy-four parathyroids were removed: 65 hyperplasia, 6 adenomas, and 3 normal glands. In the whole population, in a analysis, F-FCH PET/CT was significantly more sensitive and accurate (72%, 71%) than neck US (25%, 43%), parathyroid scintigraphy (35%, 47%), and 4D-CT (40%, 47%). The specificity of F-FCH PET/CT (69%) was lower than that of neck US (95%) and parathyroid scintigraphy (90%), without, however, achieving significance. F-FCH PET/CT was more accurate than all other diagnostic techniques when sHPT and tHPT patients were considered separately. F-FCH PET/CT sensitivity was significantly higher in tHPT (88%) than in sHPT (66%). Three ectopic hyperfunctioning glands (in three different patients) were all detected by F-FCH PET/CT, two by parathyroid scintigraphy, and none by cervical US and 4D-CT. Our study confirms that F-FCH PET/CT is an effective preoperative imaging option in patients with CKD and HPT. These findings may be of greater importance in patients with tHPT (who could benefit from minimally invasive parathyroidectomy) than in patients with sHPT, who often undergo bilateral cervicotomy. In these cases, preoperative F-FCH PET/CT may be helpful in locating ectopic glands and may guide the surgical choice for gland preservation.
PubMed: 37189475
DOI: 10.3390/diagnostics13081374 -
Renal Failure Dec 2023The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one...
BACKGROUND
The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one year after kidney transplantation (KT) and identify the influencing factors of MBD.
METHODS
A total of 95 KTRs in our center were enrolled. The changes in bone mineral density (BMD) and bone metabolism biochemical markers, including serum calcium (Ca), phosphorus(P), 25-hydroxyvitamin D(25(OH)vitD), intact parathyroid hormone (iPTH), bone alkaline phosphatase, osteocalcin (OC), type I collagen N-terminal peptide and type I collagen C-terminal peptide (CTx), over one year after KT were assessed. The possible influencing factors of BMD were analyzed. The relationships between bone metabolism biochemical markers were evaluated. The indicators between groups with or without iPTH normalization were also compared.
RESULTS
MBD after KT was manifested as an increased prevalence of hypophosphatemia and bone loss, persistent 25(OH)vitD deficiency, and partially decreased PTH and bone turnover markers (BTMs). Femoral neck BMD was positively correlated with body mass index (BMI) and postoperative 25(OH)vitD, and negatively correlated with postoperative PTH. Lumbar spine BMD was positively correlated with BMI and preoperative TG, and negatively correlated with preoperative OC and CTx. BMD loss was positively associated with glucocorticoid accumulation. Preoperative and postoperative iPTH was negatively correlated with postoperative serum P and 25(OH)vitD, and positively correlated with postoperative Ca and BTMs. The recipients without iPTH normalization, who accounted for 41.0% of all KTRs, presented with higher Ca, lower P, higher BTMs, advanced age, and a higher prevalence of preoperative parathyroid hyperplasia.
CONCLUSIONS
MBD persisted after KT, showing a close relationship with hyperparathyroidism, high bone turnover, and glucocorticoid accumulation.
Topics: Humans; Biomarkers; Bone Density; Bone Remodeling; Cohort Studies; Collagen Type I; Glucocorticoids; Kidney Transplantation; Parathyroid Hormone; Peptides; Hyperparathyroidism; Chronic Kidney Disease-Mineral and Bone Disorder; Osteoporosis
PubMed: 37183797
DOI: 10.1080/0886022X.2023.2210231 -
Endokrynologia Polska 2023Not required for Clinical Vignette.
Not required for Clinical Vignette.
Topics: Humans; Parathyroid Neoplasms; Adenoma; Multiple Endocrine Neoplasia; Hyperplasia; Parathyroid Glands
PubMed: 37155305
DOI: 10.5603/EP.a2023.0033 -
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 -
Frontiers in Endocrinology 2023We evaluated the difference in parathyroid visualization on F-FCH PET/CT images obtained at 5 and 60 min, and quantitatively analyzed the mode of FCH uptake at...
OBJECTIVE
We evaluated the difference in parathyroid visualization on F-FCH PET/CT images obtained at 5 and 60 min, and quantitatively analyzed the mode of FCH uptake at different time points, to determine the best imaging time for FCH PET/CT.
METHODS
This retrospective study included 73 patients with hyperparathyroidism (HPT) who underwent F-FCH PET/CT imaging between December 2017 and December 2021. The diagnostic efficiency of 5- and 60-min dual time point imaging for the diagnosis of hyperparathyroidism and parathyroid adenoma and hyperplasia, were compared using visual and quantitative analyses.
RESULTS
Dual-time F-FCH PET/CT imaging visual analysis had diagnostic value for HPT. The receiver operating characteristic curve of PET/CT quantitative parameters for the diagnosis of HPT and lesions showed that the parathyroid/thyroid SUVmax ratio for 60-min imaging had a higher sensitivity and specificity (based on patient, sensitivity: 90.90% and specificity: 85.71%; based on focus, sensitivity: 83.06% and specificity: 85.71%) compared to that for 5-min imaging. PET/CT quantitative parameters can distinguish parathyroid adenoma and hyperplasia. The 60-min parathyroid SUVmax value had the highest diagnostic value (cutoff: 3.945; area under the curve: 0.783).
CONCLUSION
The quantitative parameters of 60min F-FCH PET/CT have more advantages in aiding in the pathologica diagnosis and clinical treatment of HPT.
Topics: Humans; Positron Emission Tomography Computed Tomography; Parathyroid Neoplasms; Retrospective Studies; Hyperplasia; Choline; Hyperparathyroidism
PubMed: 37113486
DOI: 10.3389/fendo.2023.1100056