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Comprehensive Physiology Mar 2016PTH and Vitamin D are two major regulators of mineral metabolism. They play critical roles in the maintenance of calcium and phosphate homeostasis as well as the... (Review)
Review
PTH and Vitamin D are two major regulators of mineral metabolism. They play critical roles in the maintenance of calcium and phosphate homeostasis as well as the development and maintenance of bone health. PTH and Vitamin D form a tightly controlled feedback cycle, PTH being a major stimulator of vitamin D synthesis in the kidney while vitamin D exerts negative feedback on PTH secretion. The major function of PTH and major physiologic regulator is circulating ionized calcium. The effects of PTH on gut, kidney, and bone serve to maintain serum calcium within a tight range. PTH has a reciprocal effect on phosphate metabolism. In contrast, vitamin D has a stimulatory effect on both calcium and phosphate homeostasis, playing a key role in providing adequate mineral for normal bone formation. Both hormones act in concert with the more recently discovered FGF23 and klotho, hormones involved predominantly in phosphate metabolism, which also participate in this closely knit feedback circuit. Of great interest are recent studies demonstrating effects of both PTH and vitamin D on the cardiovascular system. Hyperparathyroidism and vitamin D deficiency have been implicated in a variety of cardiovascular disorders including hypertension, atherosclerosis, vascular calcification, and kidney failure. Both hormones have direct effects on the endothelium, heart, and other vascular structures. How these effects of PTH and vitamin D interface with the regulation of bone formation are the subject of intense investigation.
Topics: Animals; Calcium; Fibroblast Growth Factor-23; Humans; Parathyroid Diseases; Parathyroid Hormone; Receptors, Calcitriol; Receptors, Parathyroid Hormone; Vitamin D; Vitamin D Deficiency
PubMed: 27065162
DOI: 10.1002/cphy.c140071 -
F1000Research 2020Secondary hyperparathyroidism is a complex pathology that develops as chronic kidney disease progresses. The retention of phosphorus and the reductions in calcium and... (Review)
Review
Secondary hyperparathyroidism is a complex pathology that develops as chronic kidney disease progresses. The retention of phosphorus and the reductions in calcium and vitamin D levels stimulate the synthesis and secretion of parathyroid hormone as well as the proliferation rate of parathyroid cells. Parathyroid growth is initially diffuse but it becomes nodular as the disease progresses, making the gland less susceptible to be inhibited. Although the mechanisms underlying the pathophysiology of secondary hyperparathyroidism are well known, new evidence has shed light on unknown aspects of the deregulation of parathyroid function. Secondary hyperparathyroidism is an important feature of chronic kidney disease-mineral and bone disorder and plays an important role in the development of bone disease and vascular calcification. Thus, part of the management of chronic kidney disease relies on maintaining acceptable levels of mineral metabolism parameters in an attempt to slow down or prevent the development of secondary hyperparathyroidism. Here, we will also review the latest evidence regarding several aspects of the clinical and surgical management of secondary hyperparathyroidism.
Topics: Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Hyperparathyroidism, Secondary; Parathyroid Hormone; Phosphorus; Renal Insufficiency, Chronic; Vitamin D
PubMed: 32913635
DOI: 10.12688/f1000research.22636.1 -
Frontiers in Endocrinology 2023Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures,... (Review)
Review
Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures, and cardiovascular diseases. Treatment for SHPT has changed radically with the advent of calcimimetics; however, parathyroidectomy (PTx) remains one of the most important treatments. For successful PTx, removing all parathyroid glands (PTGs) without complications is essential to prevent persistent or recurrent SHPT. Preoperative imaging studies for the localization of PTGs, such as ultrasonography, computed tomography, and Tc-Sestamibi scintigraphy, and intraoperative evaluation methods to confirm the removal of all PTGs, including, intraoperative intact parathyroid hormone monitoring and frozen section diagnosis, are useful. Functional and anatomical preservation of the recurrent laryngeal nerves can be confirmed intraoperative nerve monitoring. Total or subtotal PTx with or without transcervical thymectomy and autotransplantation can also be performed. Appropriate operative methods for PTx should be selected according to the patients' need for kidney transplantation. In the case of persistent or recurrent SHPT after the initial PTx, localization of the causative PTGs with autotransplantation is challenging as causative PTGs can exist in the neck, mediastinum, or autotransplanted areas. Additionally, the efficacy and cost-effectiveness of calcimimetics and PTx are increasingly being discussed. In this review, medical and surgical treatments for SHPT are described.
Topics: Humans; Parathyroidectomy; Hyperparathyroidism, Secondary; Parathyroid Glands; Parathyroid Hormone; Neck
PubMed: 37152972
DOI: 10.3389/fendo.2023.1169793 -
The Quarterly Journal of Nuclear... Jun 2022Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical...
Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical treatment of pHPT mainly consists of minimally invasive parathyroidectomy (MIP), as a single adenoma represents the most common cause of this endocrine disorder. Successful surgery requires an experienced surgeon and relies on the correct preoperative detection and localization of hyperfunctioning parathyroid glands. Failure to preoperatively identify the culprit parathyroid gland by imaging may entail a more invasive surgical approach, including bilateral open neck exploration, with higher morbidity compared to minimally invasive parathyroidectomy. Parathyroid imaging may be also useful before surgery in case of secondary hyperparathyroidism (sHPT) or hereditary disorders (MEN 1, 2, 4) as it enables correct localization of typically located parathyroid glands, detection of ectopic as well as supernumerary glands. It is now accepted by most surgeons experienced in parathyroid surgery that preoperative imaging plays a key role in their patients' management. Recently, the European Association of Nuclear Medicine (EANM) issued an updated version of its Guidelines on parathyroid imaging. Its aim is to precise the role and the advantages and drawbacks of the various imaging modalities proposed or well established in the preoperative imaging strategy. It also aims to favor high performance in indicating, performing, and interpreting those examinations. The objective of the present article is to offer a summary of those recent EANM Guidelines and their originality among other Guidelines in this domain issued by societies of nuclear medicine physicians or other disciplines.
Topics: Humans; Nuclear Medicine; Parathyroid Glands; Parathyroid Neoplasms; Parathyroidectomy; Radionuclide Imaging; Technetium Tc 99m Sestamibi
PubMed: 35166093
DOI: 10.23736/S1824-4785.22.03427-6 -
Frontiers in Endocrinology 2021Regulation of the serum calcium level in humans is achieved by the endocrine action of parathyroid glands working in concert with vitamin D and a set of critical target... (Review)
Review
Regulation of the serum calcium level in humans is achieved by the endocrine action of parathyroid glands working in concert with vitamin D and a set of critical target cells and tissues including osteoblasts, osteoclasts, the renal tubules, and the small intestine. The parathyroid glands, small highly vascularized endocrine organs located behind the thyroid gland, secrete parathyroid hormone (PTH) into the systemic circulation as is needed to keep the serum free calcium concentration within a tight physiologic range. Primary hyperparathyroidism (HPT), a disorder of mineral metabolism usually associated with abnormally elevated serum calcium, results from the uncontrolled release of PTH from one or several abnormal parathyroid glands. Although in the vast majority of cases HPT is a sporadic disease, it can also present as a manifestation of a familial syndrome. Many benign and malignant sporadic parathyroid neoplasms are caused by loss-of-function mutations in tumor suppressor genes that were initially identified by the study of genomic DNA from patients who developed HPT as a manifestation of an inherited syndrome. Somatic and inherited mutations in certain proto-oncogenes can also result in the development of parathyroid tumors. The clinical and genetic investigation of familial HPT in kindreds found to lack germline variants in the already known HPT-predisposition genes represents a promising future direction for the discovery of novel genes relevant to parathyroid tumor development.
Topics: Calcium; Genetic Predisposition to Disease; Humans; Hyperparathyroidism; Mutation; Parathyroid Glands; Parathyroid Hormone
PubMed: 33716975
DOI: 10.3389/fendo.2021.623667 -
Osteoporosis International : a Journal... Jan 2017The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its... (Review)
Review
The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of "Hyperparathyroidism. Primary" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized.
Topics: Humans; Hypercalcemia; Hyperparathyroidism, Primary; Incidence; Magnetic Resonance Imaging; Nephrolithiasis; Parathyroidectomy; Prevalence; Radionuclide Imaging; Tomography, X-Ray Computed
PubMed: 27613721
DOI: 10.1007/s00198-016-3716-2 -
American Family Physician Mar 2022Parathyroid disorders are most often identified incidentally by abnormalities in serum calcium levels when screening for renal or bone disease or other conditions....
Parathyroid disorders are most often identified incidentally by abnormalities in serum calcium levels when screening for renal or bone disease or other conditions. Parathyroid hormone, which is released by the parathyroid glands primarily in response to low calcium levels, stimulates osteoclastic bone resorption and serum calcium elevation, reduces renal calcium clearance, and stimulates intestinal calcium absorption through synthesis of 1,25-dihydroxyvitamin D. Primary hyperparathyroidism, in which calcium levels are elevated without appropriate suppression of parathyroid hormone levels, is the most common cause of hypercalcemia and is often managed surgically. Indications for parathyroidectomy in primary hyperparathyroidism include presence of symptoms, age 50 years or younger, serum calcium level more than 1 mg per dL above the upper limit of normal, osteoporosis, creatinine clearance less than 60 mL per minute per 1.73 m2, nephrolithiasis, nephrocalcinosis, and hypercalciuria. Secondary hyperparathyroidism is caused by alterations in calcium, phosphate, and vitamin D regulation that result in elevated parathyroid hormone levels. It most commonly occurs with chronic kidney disease and vitamin D deficiency, and less commonly with gastrointestinal conditions that impair calcium absorption. Secondary hyperparathyroidism can be managed with calcium and vitamin D replacement and reduction of high phosphate levels. There is limited evidence for the use of calcimimetics and vitamin D analogues for persistently elevated parathyroid hormone levels. Hypoparathyroidism, which is most commonly caused by iatrogenic surgical destruction of the parathyroid glands, is less common and results in hypocalcemia. Multiple endocrine neoplasia types 1 and 2A are rare familial syndromes that can result in primary hyperparathyroidism and warrant genetic testing of family members, whereas parathyroid cancer is a rare finding in patients with hyperparathyroidism.
Topics: Calcium; Humans; Hyperparathyroidism, Primary; Hyperparathyroidism, Secondary; Middle Aged; Parathyroid Diseases; Parathyroid Hormone; Phosphates; Vitamin D
PubMed: 35289573
DOI: No ID Found -
Nutrients Mar 2023Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism.... (Review)
Review
Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism. Moreover, people with CKD are at a higher risk of multifactorial VD deficiency, which has been extensively associated with poor outcomes, including bone disease, cardiovascular disease, and higher mortality. Evidence is abundant in terms of the association of negative outcomes with low levels of VD, but recent studies have lowered previous high expectations regarding the beneficial effects of VD supplementation in the general population. Although controversies still exist, the diagnosis and treatment of VD have not been excluded from nephrology guidelines, and much data still supports VD supplementation in CKD patients. In this narrative review, we briefly summarize evolving controversies and useful clinical approaches, underscoring that the adverse effects of VD derivatives must be balanced against the need for effective prevention of progressive and severe secondary hyperparathyroidism. Guidelines vary, but there seems to be general agreement that VD deficiency should be avoided in CKD patients, and it is likely that one should not wait until severe SHPT is present before cautiously starting VD derivatives. Furthermore, it is emphasized that the goal should not be the complete normalization of parathyroid hormone (PTH) levels. New developments may help us to better define optimal VD and PTH at different CKD stages, but large trials are still needed to confirm that VD and precise control of these and other CKD-MBD biomarkers are unequivocally related to improved hard outcomes in this population.
Topics: Humans; Vitamin D; Renal Insufficiency, Chronic; Vitamins; Kidney; Bone Diseases; Hyperparathyroidism, Secondary; Vitamin D Deficiency; Parathyroid Hormone; Minerals
PubMed: 37049415
DOI: 10.3390/nu15071576 -
Archives of Endocrinology and Metabolism Nov 2022Primary hyperparathyroidism (PHPT) is a hypercalcemic disorder that occurs when one or more parathyroid glands produces excessive parathyroid hormone (PTH). PHPT is... (Review)
Review
Primary hyperparathyroidism (PHPT) is a hypercalcemic disorder that occurs when one or more parathyroid glands produces excessive parathyroid hormone (PTH). PHPT is typically treated with surgery, and it remains the only definitive therapy, whose techniques have evolved over previous decades. Advances in preoperative localization exams and the intraoperative PTH monitoring have become the cornerstones of recent parathyroidectomy techniques, as minimally invasive techniques are appropriate for most patients. Nevertheless, these techniques, are not suitable for PHPT patients who are at risk for multiglandular disease, especially in those who present with familial forms of PHPT that require bilateral neck exploration. This manuscript also explores other conditions that warrant special consideration during surgical treatment for PHPT: normocalcemic primary hyperparathyroidism, pregnancy, reoperation for persistent or recurrent PHPT, parathyroid carcinoma, and familial and genetic forms of hyperparathyroidism.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroidectomy; Parathyroid Neoplasms; Parathyroid Hormone; Parathyroid Glands
PubMed: 36382757
DOI: 10.20945/2359-3997000000557 -
Journal of Endocrinological... Jun 2023Parathyroid diseases are related to parathyroid hormone (PTH) dysregulation by parathyroid cells or alteration of PTH function. They include hyperparathyroidism (PTH... (Review)
Review
PURPOSE
Parathyroid diseases are related to parathyroid hormone (PTH) dysregulation by parathyroid cells or alteration of PTH function. They include hyperparathyroidism (PTH excess), hypoparathyroidism (PTH deficiency) and pseudohypoparathyroidism (PTH resistance). Little is known about correlation between parathyroid diseases and metabolic syndrome (MetS).
METHODS
An electronic-based search using PubMed was performed until October 2022 and articles were selected based on relevance of title, abstract, English language and publication in peer-reviewed journals.
RESULTS
Possible association between PTH alterations and the diverse manifestation of MetS have been proposed and it could be supposed that MetS may negatively influence parathyroid diseases. Available data show significant association for hyperparathyroidism and pseudohypoparathyroidism.
CONCLUSIONS
This review highlights the possible implications between MetS and parathyroid diseases. Given the increasing MetS global prevalence and the higher parathyroid diseases awareness and diagnosis, it may be interesting to further explore the possible role of alterations in parathyroid homeostasis in the development of MetS components with dedicated prospective studies.
Topics: Humans; Metabolic Syndrome; Prospective Studies; Parathyroid Diseases; Parathyroid Hormone; Hypoparathyroidism; Pseudohypoparathyroidism; Hyperparathyroidism
PubMed: 36773188
DOI: 10.1007/s40618-023-02018-2