-
Journal of Bone and Mineral Research :... Dec 2022
Topics: Humans; Hypoparathyroidism; Parathyroid Hormone
PubMed: 36375811
DOI: 10.1002/jbmr.4671 -
Vitamins and Hormones 2022Nine mutations have been discovered in the parathyroid hormone (PTH) gene since it was initially sequenced in 1983. An autosomal dominant C18R mutation in the signal...
Nine mutations have been discovered in the parathyroid hormone (PTH) gene since it was initially sequenced in 1983. An autosomal dominant C18R mutation in the signal peptide was first reported in 1990, followed by an exon skipping mutation, leading to loss of exon 2 in 1992; the latter mutation prevents PTH biosynthesis, as exon 2 contains the initiation codon. The S23P and S23X mutations affecting the same residue were reported in 1999 and 2012, respectively, while in 2008, the somatic mutation, R83X, was detected in a parathyroid adenoma tissue sample from a patient with overt hyperparathyroidism. In 2013, the heterozygous p.Met1_Asp6del mutation was discovered incidentally in a case-control study, while another heterozygous mutation, M14K, was detected in the signal peptide 4 years later. In 2015, a homozygous R56C mutation was reported, and was the first hypoparathyroidism-causing mutation identified that affects the mature bioactive portion of PTH; this mutation has significantly contributed to the understanding of the molecular mechanisms involved in signal transduction through the PTH receptor. Recently, a novel homozygous S32P mutation was identified, which is also situated in the bioactive portion of PTH. The discovery of these nine mutations in the PTH gene and determination of the molecular mechanisms underlying their effects has provided deep insights into the synthesis, processing, and secretion of PTH. Future attempts to discover other such mutations will help elucidate as yet unknown functions of PTH, with potential clinical implications.
Topics: Case-Control Studies; Humans; Mutation; Parathyroid Glands; Parathyroid Hormone; Protein Sorting Signals
PubMed: 35953118
DOI: 10.1016/bs.vh.2022.04.004 -
Vitamins and Hormones 2021Falls result in multiple adverse health outcomes including mortality in older persons. Impaired balance is known to increase the risk of falls. Numerous factors play a...
Falls result in multiple adverse health outcomes including mortality in older persons. Impaired balance is known to increase the risk of falls. Numerous factors play a role in the etiology of balance disturbance. Among the calciotropic hormones, the role of vitamin D in falls risk has been extensively studied. There is evolving interest in the role of parathyroid hormone (PTH) in this area. Elevated PTH hormone levels have been associated with age-related syndromes such as frailty, osteoporosis, and sarcopenia. Among the existing studies, most have focused on muscle strength with few studies evaluating its role in balance disturbances. In this chapter, we will summarize the aspects of PTH and aging, its biological effects on muscle, and the known associations between PTH and balance.
Topics: Accidental Falls; Aged; Aged, 80 and over; Aging; Humans; Osteoporosis; Parathyroid Hormone; Vitamin D
PubMed: 33706948
DOI: 10.1016/bs.vh.2020.12.009 -
Vitamins and Hormones 2022A parathyroid adenoma comprises 80-85% as a cause of primary hyperparathyroidism. The clonal origin of most parathyroid adenomas suggests a defect at the level of the...
A parathyroid adenoma comprises 80-85% as a cause of primary hyperparathyroidism. The clonal origin of most parathyroid adenomas suggests a defect at the level of the gene controlling growth of the parathyroid cell or the expression of parathyroid hormone (PTH). Two genes, MEN1 and CCND1, a tumor suppressor and a proto-oncogene respectively, have been solidly established as primary tumorigenic drivers in parathyroid adenomas. As well, germline and somatic mutation of other genes involved in cell cycle regulation or PTH regulation have been discovered in parathyroid adenomas. Moreover, comparative genomic studies between parathyroid adenomas and normal parathyroid tissues have suggested more complex genetic landscape. Microarray analysis have revealed differential expression profiles of genes involved in cell cycle regulation, growth factors, apoptotic pathway, or PTH synthesis or regulation pathway such as CASR, GCM2 and KL (Klotho). Furthermore, recent next-generation sequencing analysis reconfirmed previous finding or revealed novel finding, suggesting signal peptidase complex subunit (SPCS2), ribosomal proteins (RPL23, RPL26, RPN1, RPS25), the endoplasmic reticulum membrane (SEC11C, SEC11A, SEC61G), Klotho, cyclin D1, β-catenin, VDR, CaSR and GCM2 may be important factors contributing to the parathyroid adenoma.
Topics: Adenoma; Humans; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Peptide Hydrolases; SEC Translocation Channels; Transcriptome
PubMed: 35953114
DOI: 10.1016/bs.vh.2022.04.003 -
Clinical Chemistry Jul 2022
Topics: Calcium; Humans; Hypocalcemia; Parathyroid Hormone
PubMed: 36103325
DOI: 10.1093/clinchem/hvac022 -
Endocrine Practice : Official Journal... Jan 2022Patients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly...
OBJECTIVE
Patients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly stimulate PTH secretion. Either adrenalectomy or mineralocorticoid receptor blockers could reduce PTH levels in patients with PA. The aim of this study was to assess the relationship between aldosterone levels and parathyroid hormone (PTH)-vitamin D-calcium axis in a cohort of patients with PA, compared with patients with nonsecreting adrenocortical tumors in conditions of vitamin D sufficiency.
METHODS
We enrolled a series of 243 patients retrospectively, of whom 66 had PA and 177 had nonsecreting adrenal tumors, and selected those with full mineral metabolism evaluation and 25(OH) vitamin D levels >20 ng/mL at the time of initial endocrine screening. The final cohort was composed of 26 patients with PA and 39 patients, used as controls, with nonsecreting adrenal tumors. The relationships between aldosterone, PTH levels, and biochemistries of mineral metabolism were assessed.
RESULTS
Aldosterone was positively associated with PTH levels (r = 0.260, P < .05) in the whole cohort and in the PA cohort alone (r = 0.450; P = .02). In the multivariate analysis, both aldosterone concentrations and urinary calcium excretion were significantly related to PTH levels, with no effect of 25(OH) vitamin D or other parameters of bone metabolism.
CONCLUSION
PTH level is associated with aldosterone, probably independent of 25(OH) vitamin D levels and urinary calcium. Whether aldosterone interacts directly with the parathyroid glands remains to be established.
Topics: Adrenal Cortex Neoplasms; Aldosterone; Calcium; Humans; Hyperaldosteronism; Parathyroid Hormone; Retrospective Studies; Vitamin D
PubMed: 34508903
DOI: 10.1016/j.eprac.2021.09.002 -
Endocrinology Jul 2021Secondary hyperparathyroidism (SHPT) in uremic patients is characterized by parathyroid gland (PTG) hyperplasia and parathyroid hormone (PTH) elevation. Previously, we...
Secondary hyperparathyroidism (SHPT) in uremic patients is characterized by parathyroid gland (PTG) hyperplasia and parathyroid hormone (PTH) elevation. Previously, we demonstrated that NF-κB activation contributed to parathyroid cell proliferation in rats with chronic kidney disease. Although vitamin D inhibits inflammation and ameliorates SHPT, the contribution of vitamin D deficiency to SHPT via local NF-κB activation remains to be clarified. PTGs collected from 10 uremic patients with advanced SHPT were used to test the expressions of vitamin D receptor (VDR), NF-κB, and proliferating cell nuclear antigen (PCNA). Freshly excised PTG tissues were incubated for 24 hours in vitro with VDR activator (VDRA) calcitriol or NF-κB inhibitor pyrrolidine thiocarbamate (PDTC). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate the regulation of PTH transcription by NF-κB. We found higher levels of activated NF-κB and lower expression of VDR in nodular hyperplastic PTGs than in diffuse hyperplasia. In cultured PTG tissues, treatment with VDRA or PDTC inhibited NF-κB activation and PCNA expression, and downregulated preproPTH mRNA and intact PTH levels. ChIP assays demonstrated the presence of NF-κB binding sites in PTH promoter. Furthermore, in luciferase reporter assays, addition of exogenous p65 significantly increased PTH luciferase activity by 2.4-fold (P < 0.01), while mutation of NF-κB binding site at position -908 of the PTH promoter suppressed p65-induced PTH reporter activity (P < 0.01). In summary, local NF-κB activation contributes to SHPT and mediates the transcriptional activation of PTH directly in uremic patients. Vitamin D deficiency may be involved in SHPT via the activation of NF-κB pathway.
Topics: Calcitriol; Female; Humans; Hyperparathyroidism, Secondary; Hyperplasia; Male; Middle Aged; NF-kappa B; Parathyroid Glands; Parathyroid Hormone; Proliferating Cell Nuclear Antigen; Pyrrolidines; Receptors, Calcitriol; Thiocarbamates; Tissue Culture Techniques; Transcription Factor RelA; Transcription, Genetic; Uremia
PubMed: 33912936
DOI: 10.1210/endocr/bqab084 -
The American Surgeon May 2022Intraoperative parathyroid hormone (iPTH) testing is often used to confirm successful removal of hypersecreting parathyroid glands during parathyroidectomy....
BACKGROUND
Intraoperative parathyroid hormone (iPTH) testing is often used to confirm successful removal of hypersecreting parathyroid glands during parathyroidectomy. Unfortunately, the iPTH test can be a time-consuming and highly variable process that occurs while the patient is under anesthesia. We set out to improve iPTH lab efficiency and variability.
METHODS
We performed a retrospective review of 85 patients who underwent parathyroidectomy at our institution from October 2017 to October 2019. Each step of the iPTH lab reporting process was recorded and analyzed. Three simulations were performed of the entire process. We then established interventions to modify inefficiencies in the process and studied 21 patients who underwent parathyroidectomy at our institution from November 2019 to March 2020.
RESULTS
Twenty-five minutes of time inherent to the process were identified. Four critical steps were identified as modifiable steps in the process:1. Operating room (OR) blood draw ---> lab receipt.2. Lab receipt ---> placement on centrifuge.3. Removal from centrifuge ---> placement on PTH machine.4. PTH machine result ---> OR verbal report.We improved iPTH lab efficiency by 19%, decreasing the average lab result from 45 to 36 minutes ( = .001). We improved iPTH lab variability by 62%, decreasing the standard deviation from 21 to 8 minutes ( = .001).
DISCUSSION
Utilizing a team-based approach to identify and expedite critical steps in the iPTH lab process can make a significant improvement in iPTH lab efficiency, improving patient care by decreasing total anesthesia time.
Topics: Humans; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Retrospective Studies
PubMed: 34841912
DOI: 10.1177/00031348211054556 -
Cartilage Dec 2022To characterize the effects of parathyroid hormone (PTH) and alendronate (Alend) on the osteochondral tissue of temporomandibular joint (TMJ).
OBJECTIVE
To characterize the effects of parathyroid hormone (PTH) and alendronate (Alend) on the osteochondral tissue of temporomandibular joint (TMJ).
MATERIALS AND METHODS
Ninety-six male and female transgenic reporter mice, 4 to 5 weeks old were divided into 6 groups: (1) Control group: Saline was injected daily for 14 days; (2) PTH: PTH was injected daily for 14 days; (3) Alend: Alend was injected every alternate days for 14 days; (4) Combined PTH and Alend: PTH was injected daily and Alend injected every alternate days for 14 days; (5) PTH then Alend: PTH was injected daily for 14 days followed by Alend injections in alternate days for 14 days; and (6) PTH wait Alend: PTH was injected daily for 14 days. There was a waiting period of 1 week before administration of Alend in alternate days for 14 days. Mice were injected with 5-ethnyl-2'-deoxyuridine (EdU), 48 and 24 hours prior to euthanization.
RESULTS
There was significant increase in bone volume and decrease in osteoclastic activity in groups in which Alend was administered after PTH in both gender. There was significant increase in cartilage thickness with PTH or Alend alone in females, whereas in males, PTH alone led to increase in cartilage thickness. Chondrocyte apoptosis was significantly decreased with PTH or Alend alone in both male and female. Matrix metallopeptidase 13, and aggreganase-2 (ADAMTS5) expression were significantly decreased with PTH and Alend alone in both gender.
CONCLUSION
PTH and Alend administration causes anabolic effects in the osteochondral tissue of TMJ.
Topics: Male; Female; Mice; Animals; Alendronate; Parathyroid Hormone; Chondrocytes; Cartilage; Temporomandibular Joint
PubMed: 36239576
DOI: 10.1177/19476035221109229 -
Archives of Gerontology and Geriatrics 2020To systematically estimate the association between elevated parathyroid hormone (PTH) levels and cognitive function.
OBJECTIVE
To systematically estimate the association between elevated parathyroid hormone (PTH) levels and cognitive function.
METHODS
This review was conducted on ten papers identified through database searches from inception to 31 October 2018. The quality of studies was assessed using the Downs and Black checklist.
RESULTS
There is a low volume of data reporting on the impact of elevated PTH levels on cognitive impairment. The quality of the identified studies ranged from poor (37 %) to good (76 %). Although the results from studies were mixed, one cross-sectional study and one prospective study suggested a link between elevated PTH levels and a decrease in the Mini-Mental State Examination (MMSE) score. Three cross-sectional studies that assessed other cognitive domain in specific domains, such as language, memory and executive function provided mixed results for an association between elevated PTH levels and cognitive function. Two studies showed mixed evidence for a link between elevated PTH levels and poor executive function. One prospective study, one cross-sectional study and three case-control studies provide mixed evidence for an association between higher PTH levels and Alzheimer´s disease (AD). Two studies showed limited evidence for an association between elevated PTH levels and vascular dementia.
CONCLUSION
This review presented that the level of evidence available to support an association between elevated PTH levels and cognitive function was generally weak and inconsistent. Future studies with more better methodological quality are needed.
Topics: Cognition; Cognitive Dysfunction; Executive Function; Humans; Memory; Parathyroid Hormone
PubMed: 31770681
DOI: 10.1016/j.archger.2019.103985