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Endocrinology and Metabolism Clinics of... Dec 2021Calcium plays a key role in skeletal mineralization and several intracellular and extracellular homeostatic networks. It is an essential element that is only available... (Review)
Review
Calcium plays a key role in skeletal mineralization and several intracellular and extracellular homeostatic networks. It is an essential element that is only available to the body through dietary sources. Daily acquisition of calcium depends, in addition to the actual intake, on the hormonally regulated state of calcium homeostasis through three main mechanisms: bone turnover, intestinal absorption, and renal reabsorption. These procedures are regulated by a group of interacting circulating hormones and their key receptors. This includes parathyroid hormone (PTH), PTH-related peptide, 1,25-dihydroxyvitamin D, calcitonin, fibroblast growth factor 23, the prevailing calcium concentration itself, the calcium-sensing receptor, as well as local processes in the bones, gut, and kidneys.
Topics: Bone and Bones; Calcium; Calcium, Dietary; Homeostasis; Humans; Parathyroid Hormone; Vitamin D
PubMed: 34774235
DOI: 10.1016/j.ecl.2021.07.005 -
Journal of Bone and Mineral Research :... Jan 2023Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone... (Randomized Controlled Trial)
Randomized Controlled Trial
Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double-blind, placebo-controlled, 26-week, phase 3 PaTHway trial assessed the efficacy and safety of PTH replacement therapy for hypoparathyroidism individuals with the investigational drug TransCon PTH (palopegteriparatide). Participants (n = 84) were randomized 3:1 to once-daily TransCon PTH (initially 18 μg/d) or placebo, both co-administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin-adjusted serum calcium levels (8.3-10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. Other outcomes of interest included health-related quality of life measured by the 36-Item Short Form Survey (SF-36), hypoparathyroidism-related symptoms, functioning, and well-being measured by the Hypoparathyroidism Patient Experience Scale (HPES), and urinary calcium excretion. At week 26, 79% (48/61) of participants treated with TransCon PTH versus 5% (1/21) wiplacebo met the composite primary efficacy endpoint (p < 0.0001). TransCon PTH treatment demonstrated a significant improvement in all key secondary endpoint HPES domain scores (all p < 0.01) and the SF-36 Physical Functioning subscale score (p = 0.0347) compared with placebo. Additionally, 93% (57/61) of participants treated with TransCon PTH achieved independence from conventional therapy. TransCon PTH treatment normalized mean 24-hour urine calcium. Overall, 82% (50/61) treated with TransCon PTH and 100% (21/21) wiplacebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred. In conclusion, TransCon PTH maintained normocalcemia while permitting independence from conventional therapy and was well-tolerated in individuals with hypoparathyroidism. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Parathyroid Hormone; Calcium; Quality of Life; Hypoparathyroidism; Vitamin D; Hormone Replacement Therapy; Calcium, Dietary; Minerals
PubMed: 36271471
DOI: 10.1002/jbmr.4726 -
The Journal of Clinical Endocrinology... Jun 2020Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia and low or undetectable levels of parathyroid hormone. (Review)
Review
BACKGROUND
Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia and low or undetectable levels of parathyroid hormone.
METHODS
This review is an evidence-based summary of hypoparathyroidism in terms of relevant pathophysiological, clinical, and therapeutic concepts.
RESULTS
Many clinical manifestations of hypoparathyroidism are due to the lack of the physiological actions of parathyroid hormone on its 2 major target organs: the skeleton and the kidney. The skeleton is inactive, accruing bone without remodeling it. The kidneys lose the calcium-conserving actions of parathyroid hormone and, thus, excrete a greater fraction of calcium. Biochemical manifestations, besides hypocalcemia and low or undetectable levels of parathyroid hormone, include hyperphosphatemia and low levels of 1,25-dihydroxyvitamin D. Calcifications in the kidney, brain, and other soft tissues are common. Removal of, or damage to, the parathyroid glands at the time of anterior neck surgery is, by far, the most likely etiology. Autoimmune destruction of the parathyroid glands and other genetic causes represent most of the other etiologies. Conventional treatment with calcium and active vitamin D can maintain the serum calcium level but high doses may be required, adding to the risk of long-term soft tissue calcifications. The advent of replacement therapy with recombinant human PTH(1-84) represents a major step in the therapeutics of this disease.
CONCLUSIONS
Advances in our knowledge of hypoparathyroidism have led to greater understanding of the disease itself and our approach to it.
Topics: Humans; Hypocalcemia; Hypoparathyroidism; Parathyroid Hormone; Prognosis
PubMed: 32322899
DOI: 10.1210/clinem/dgaa113 -
La Clinica Terapeutica May 2021Tertiary hyperparathyroidism (HPT III) occurs when an excess of parathyroid hormone (PTH) is secreted by parathyroid glands, usually after longstanding secondary... (Review)
Review
Tertiary hyperparathyroidism (HPT III) occurs when an excess of parathyroid hormone (PTH) is secreted by parathyroid glands, usually after longstanding secondary hyperparathyroidism. Some authorities reserve the term for secondary hyperparathyroidism that persists after successful renal transplantation. Long-standing chronic kidney disease (CKD) is associated with several metabolic disturbances that lead to increased secretion of PTH, including hyperphosphatemia, calcit-riol deficiency, and hypocalcaemia. Hyperphosphatemia has a direct stimulatory effect on the parathyroid gland cell resulting in nodular hyperplasia and increased PTH secretion. Prolonged hypocalcaemia also causes parathyroid chief cell hyperplasia and excess PTH. Af-ter correction of the primary disorder CKD by renal transplant, the hypertrophied parathyroid tissue fails to resolute, enlarge over and continues to oversecrete PTH, despite serum calcium levels that are within the reference range or even elevated. They also may become resistant to calcimimetic treatment. The main indication for treatment is persistent hypercalcemia and/or an increased PTH, and the primary treatment is surgery. Three procedures are commonly performed: total parathyroidectomy with or without autotransplantation, subtotal parathyroidectomy, and limited parathyroidectomy. It is important to remove superior parts of thymus as well. The most appropriate surgical procedure, whether it be total, subtotal, or anything less than subtotal including "limited" or "focused" parathyroidectomies, continues to be unclear and controversial. Surgical complications are rare, and para-thyroidectomy appears to be a safe and feasible treatment option for HPT III.
Topics: Humans; Hyperparathyroidism, Secondary; Hyperphosphatemia; Hyperplasia; Hypocalcemia; Kidney Transplantation; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Renal Insufficiency, Chronic; Transplantation, Autologous
PubMed: 33956045
DOI: 10.7417/CT.2021.2322 -
Endokrynologia Polska 2020Primary hyperparathyroidism is an endocrine disorder that results in overproduction of parathyroid hormone by overactivated parathyroid gland leading to a significant... (Review)
Review
Primary hyperparathyroidism is an endocrine disorder that results in overproduction of parathyroid hormone by overactivated parathyroid gland leading to a significant rise in blood serum calcium. It results in hypercalcaemia, which has a significant impact mainly on the kidneys and bones and results in a variety of signs and symptoms. Primary hyperparathyroidism should be treated because, if left without any therapy, it can lead even to death. Surgery is considered as the best and only successful therapy, with very low risk of recurrence and relatively low complication rate. The aim of this review is to present clinical basis, aetiology, diagnostic possibilities, and treatment opportunities.
Topics: Female; Humans; Hyperparathyroidism, Primary; Male; Parathyroid Hormone; Parathyroidectomy
PubMed: 32797471
DOI: 10.5603/EP.a2020.0028 -
Biochemical Pharmacology Oct 2021Parathyroid hormone (PTH) is an 84-amino-acid peptide hormone that is secreted by the parathyroid gland. It has different administration modes in bone tissue through... (Review)
Review
Parathyroid hormone (PTH) is an 84-amino-acid peptide hormone that is secreted by the parathyroid gland. It has different administration modes in bone tissue through which it promotes bone formation (intermittent administration) and bone resorption (continuous administration) and has great potential for application in sbone defect repair. PTH regulates bone metabolism by binding to PTH1R. PTH plays an osteogenic role by acting directly on mesenchymal stem cells, cells with an osteoblastic lineage, osteocytes, and T cells. It also participates as an osteoclast by indirectly acting on osteoclast precursor cells and osteoclasts and directly acting on T cells. In these cells, PTH activates the Wnt signaling, cAMP/PKA, cAMP/PKC, and RANKL/RANK/OPG pathways and other signaling pathways. Although PTH(1-34), also known as teriparatide, has been used clinically, it still has some disadvantages. Developing improved PTH-related peptides is a potential solution to teriparatide's shortcomings. The action mechanism of these PTH-related peptides is not exactly the same as that of PTH. Thus, the mechanisms of PTH and PTH-related peptides in bone metabolism were reviewed in this paper.
Topics: Animals; Bone Density; Bone Resorption; Humans; Osteoclasts; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Receptor, Parathyroid Hormone, Type 1; Teriparatide
PubMed: 34224692
DOI: 10.1016/j.bcp.2021.114669 -
Archives of Endocrinology and Metabolism Nov 2022Primary hyperparathyroidism (PHPT) is an endocrine disorder resulting from the hyperfunction of one or more parathyroid glands, with hypersecretion of parathyroid... (Review)
Review
Primary hyperparathyroidism (PHPT) is an endocrine disorder resulting from the hyperfunction of one or more parathyroid glands, with hypersecretion of parathyroid hormone (PTH). It can be managed by parathyroidectomy (PTX) or non-surgically. Medical therapy with pharmacological agents is an alternative for those patients with asymptomatic PHPT who meet guidelines for surgery but are unable or unwilling to undergo PTX. In this review, we focus upon these non-surgical aspects of PHPT management. We emphasize the most studied and widely used pharmacological alternatives: bisphosphonates, denosumab, cinacalcet and hormone therapy, in addition to combined therapy. We also address the relevant aspects of perioperative management.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroidectomy; Cinacalcet; Parathyroid Hormone; Parathyroid Glands
PubMed: 36382758
DOI: 10.20945/2359-3997000000558 -
Frontiers in Endocrinology 2022Secondary hyperparathyroidism (SHPT) and tertiary hyperparathyroidism (THPT) are common and complicated clinical endocrine diseases. The parathyroid glands maintain... (Review)
Review
Secondary hyperparathyroidism (SHPT) and tertiary hyperparathyroidism (THPT) are common and complicated clinical endocrine diseases. The parathyroid glands maintain endocrine homeostasis by secreting parathyroid hormone to regulate blood calcium levels. However, structural alterations to multiple organs and systems occur throughout the body due to hyperactivity disorder in SHPT and THPT. This not only decreases the patients' quality of life, but also affects mortality. Since current treatments for these diseases remains unclear, we aimed to develop a comprehensive review of advances in the treatment of SHPT and THPT according to the latest relevant researches.
Topics: Humans; Hyperparathyroidism, Secondary; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Quality of Life
PubMed: 36561571
DOI: 10.3389/fendo.2022.1059828 -
Neuron Jun 2023Parathyroid hormone (PTH) is one of the most important hormones for bone turnover and calcium homeostasis. It is unclear how the central nervous system regulates PTH....
Parathyroid hormone (PTH) is one of the most important hormones for bone turnover and calcium homeostasis. It is unclear how the central nervous system regulates PTH. The subfornical organ (SFO) lies above the third ventricle and modulates body fluid homeostasis. Through retrograde tracing, electrophysiology, and in vivo calcium imaging, we identified the SFO as an important brain nucleus that responds to serum PTH changes in mice. Chemogenetic stimulation of GABAergic neurons in SFO induces decreased serum PTH followed by a decrease in trabecular bone mass. Conversely, stimulation of glutamatergic neurons in the SFO promoted serum PTH and bone mass. Moreover, we found that the blockage of different PTH receptors in the SFO affects peripheral PTH levels and the PTH's response to calcium stimulation. Furthermore, we identified a GABAergic projection from the SFO to the paraventricular nucleus, which modulates PTH and bone mass. These findings advance our understanding of the central neural regulation of PTH at cellular and circuit level.
Topics: Animals; Mice; Parathyroid Hormone; Subfornical Organ; Calcium; Body Fluids; GABAergic Neurons
PubMed: 37084721
DOI: 10.1016/j.neuron.2023.03.030 -
Advances in Clinical Chemistry 2021Parathyroid hormone is an essential regulator of extracellular calcium and phosphate. PTH enhances calcium reabsorption while inhibiting phosphate reabsorption in the...
Parathyroid hormone is an essential regulator of extracellular calcium and phosphate. PTH enhances calcium reabsorption while inhibiting phosphate reabsorption in the kidneys, increases the synthesis of 1,25-dihydroxyvitamin D, which then increases gastrointestinal absorption of calcium, and increases bone resorption to increase calcium and phosphate. Parathyroid disease can be an isolated endocrine disorder or part of a complex syndrome. Genetic mutations can account for diseases of parathyroid gland formulation, dysregulation of parathyroid hormone synthesis or secretion, and destruction of the parathyroid glands. Over the years, a number of different options are available for the treatment of different types of parathyroid disease. Therapeutic options include surgical removal of hypersecreting parathyroid tissue, administration of parathyroid hormone, vitamin D, activated vitamin D, calcium, phosphate binders, calcium-sensing receptor, and vitamin D receptor activators to name a few. The accurate assessment of parathyroid hormone also provides essential biochemical information to properly diagnose parathyroid disease. Currently available immunoassays may overestimate or underestimate bioactive parathyroid hormone because of interferences from truncated parathyroid hormone fragments, phosphorylation of parathyroid hormone, and oxidation of amino acids of parathyroid hormone.
Topics: Bicarbonates; Bone Development; Bone and Bones; Calcium; Gene Expression Regulation; Homeostasis; Humans; Hyperparathyroidism; Hypoparathyroidism; Parathyroid Hormone; Phosphates; Receptor, Parathyroid Hormone, Type 1
PubMed: 33706890
DOI: 10.1016/bs.acc.2020.06.005