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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 -
Journal of Feline Medicine and Surgery May 2015Hyperparathyroidism exists in primary and secondary forms. Primary hyperparathyroidism has typically been considered a disease that uncommonly affects cats, but this... (Review)
Review
PRACTICAL RELEVANCE
Hyperparathyroidism exists in primary and secondary forms. Primary hyperparathyroidism has typically been considered a disease that uncommonly affects cats, but this condition is more prevalent than previous diagnoses would suggest. Secondary hyperparathyroidism may be caused by either nutritional influences (ie, nutritional secondary hyperparathyroidism) or chronic kidney disease (ie, renal secondary hyperparathyroidism). Tertiary hyperparathyroidism has yet to be documented in veterinary medicine, but it is possible that this condition occurs in some cats following longstanding renal secondary hyperparathyroidism.
CLINICAL CHALLENGES
Diagnosis of this group of calcium metabolic disorders presents a number of challenges for the clinician. For example, clinical signs can be non-specific and, especially in the case of primary hyperparathyroidism, there is often a low index of suspicion for the disease; careful sample handling is required for testing of parathyroid hormone (PTH) and ionized calcium levels; and there is currently no feline-specific assay for PTH, which has implications for test sensitivity and interpretation of results.
AIMS
This article briefly outlines PTH and calcium physiology by way of introduction to a review of PTH measurement and interpretation. Various forms of feline hyperparathyroidism are then described, encompassing diagnosis and treatment options.
Topics: Animals; Calcium; Cat Diseases; Cats; Hyperparathyroidism, Primary; Hyperparathyroidism, Secondary; Parathyroid Hormone; Veterinary Medicine
PubMed: 25896242
DOI: 10.1177/1098612X15581134 -
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 -
Joint Bone Spine Jul 2019A genetic disorder should be suspected in patients with hypercalcemia, notably those who are young; have family members with hypercalcemia; or have had a tumor of the... (Comparative Study)
Comparative Study Review
A genetic disorder should be suspected in patients with hypercalcemia, notably those who are young; have family members with hypercalcemia; or have had a tumor of the endocrine pancreas, thyroid, pituitary, adrenal gland, or jaw bone. All forms of hypercalcemia should be interpreted according to the serum level of parathyroid hormone (PTH). Genetic forms are thus classified as related or unrelated to a parathyroid gland disorder. When the PTH level is elevated or is not depressed despite the hypercalcemia, findings that suggest family history of hypercalcemia due to a genetic cause include syndromic manifestations in the patient or family members, parathyroid cancer (either suspected before surgery or confirmed during parathyroidectomy), multiple or recurrent parathyroid tumors, a family history of primary hyperparathyroidism, and the onset of primary hyperthyroidism before 50 years of age. In patients with moderate hypercalcemia, a normal PTH level, and relative hypocalciuria, the first hypothesis is a mutation in the calcium-sensing receptor gene, which is often difficult to distinguish from primary hyperparathyroidism, particularly when there is no known family history of hyperparathyroidism, as is often the case. A low PTH level suggests non-parathyroid hypercalcemia due to a genetic defect in patients with no evidence of other conditions associated with hypercalcemia and low PTH levels and in those whose calcitriol levels are elevated or normal (instead of depressed as expected when PTH is elevated). Patients with hypercalciuria but no evidence of conditions such as granulomatous diseases should be evaluated for increased vitamin D sensitivity due to a CYP 4A1 mutation. Other very rare causes include hypophosphatasia due to ALPL mutations, which is characterized by a low alkaline phosphatase level; and renal phosphate wasting due to an NPT2A mutation, in which serum phosphate levels are low. A thorough analysis of the clinical and laboratory data can point toward a genetic disorder in patients with hypercalcemia. The diagnosis is then confirmed by obtaining genetic tests tailored to the clinical and laboratory test abnormalities. The current development of diagnostic genetic testing is shedding new light on the phenotypes, thereby improving their management.
Topics: Cytochrome P-450 CYP4A; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Genetic Testing; Humans; Hypercalcemia; Hyperparathyroidism; Incidence; Male; Mutation; Parathyroid Hormone; Prognosis; Receptors, Calcium-Sensing; Risk Assessment
PubMed: 30300686
DOI: 10.1016/j.jbspin.2018.10.001 -
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 -
Frontiers of Hormone Research 2019The regulation of plasma calcium levels is essential for the normal physiologic function of every cell. Parathyroid hormone (PTH) is the principal regulator of serum... (Review)
Review
The regulation of plasma calcium levels is essential for the normal physiologic function of every cell. Parathyroid hormone (PTH) is the principal regulator of serum calcium and phosphate homeostasis. PTH is synthesized and secreted by the parathyroid chief cells in the parathyroid glands primarily in response to a decline in serum calcium levels. The causes of hypocalcemia can be broadly classified as inadequate PTH or vitamin D production, PTH resistance, or miscellaneous causes. The term "hypoparathyroidism" refers to a metabolic disorder in which hypocalcemia and hyperphosphatemia occur either from a failure of the parathyroid glands to secrete sufficient amounts of biologically active PTH, or from an inability of PTH to appropriately induce a biological response in its target tissues. The most common cause of acquired hypoparathyroidism is surgery, accounting for 75% of all cases. Nonsurgical causes of hypoparathyroidism include autoimmune, genetic variants, infiltrative, metastatic, radiation, mineral deposition, magnesium deficiency or excess or idiopathic. The objective of this chapter is to provide a comprehensive review of the physiology of calcium homeostasis, the causes of hypocalcemia, and the epidemiology of hypoparathyroidism. It is very important to determine the underlying cause of the hypoparathyroidism in order to effectively treat our patients and improve quality of life.
Topics: Humans; Hypocalcemia; Hypoparathyroidism
PubMed: 30641528
DOI: 10.1159/000491042 -
Seminars in Pediatric Surgery Jun 2020Parathyroid glands are critical for calcium and phosphate homeostasis. Parathyroid disease is relatively rare in the pediatric population, but there are some important... (Review)
Review
Parathyroid glands are critical for calcium and phosphate homeostasis. Parathyroid disease is relatively rare in the pediatric population, but there are some important pediatric-specific considerations and conditions. This article reviews parathyroid physiology, disorders of hyper- and hypo- function, operative management, and uniquely pediatric diagnoses such as neonatal severe hyperparathyroidism. Advances in preoperative imaging, intra-operative gland identification, and management of post-thyroidectomy hypocalcemia are also presented in detail. This article combines a review of fundamentals with recent advances in care, emphasizing pediatric-specific publications.
Topics: Adolescent; Biomarkers; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Parathyroid Diseases; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Perioperative Care; Postoperative Complications
PubMed: 32571508
DOI: 10.1016/j.sempedsurg.2020.150923 -
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 -
Clinical Obstetrics and Gynecology Jun 2019Although uncommon in pregnancy, parathyroid dysfunction may produce significant perinatal and maternal morbidity and mortality. The prevalence of hyperparathyroidism is... (Review)
Review
Although uncommon in pregnancy, parathyroid dysfunction may produce significant perinatal and maternal morbidity and mortality. The prevalence of hyperparathyroidism is 0.5%. The most common cause of primary hyperparathyroidism in pregnancy is a single parathyroid adenoma, which is present in nearly 80% of cases. Surgery is the only definitive treatment for primary hyperparathyroidism, with a cure rate that is excellent. The most common etiology of hypoparathyroidism is damage to the parathyroid glands after surgery, with an incidence of 0.2%. Treatment of hypoparathyroidism is usually a high-calcium diet with vitamin D supplementation. Vitamin D deficiency is common, associated with perinatal morbidity and easily corrected.
Topics: Calcitriol; Calcium, Dietary; Female; Humans; Hyperparathyroidism; Hypocalcemia; Hypoparathyroidism; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Pregnancy Complications; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 30921001
DOI: 10.1097/GRF.0000000000000447 -
Seminars in Nuclear Medicine Jul 2023Primary hyperparathyroidism (1° HPT) is a relatively common endocrine disorder usually caused by autonomous secretion of parathormone by one or several parathyroid... (Review)
Review
Primary hyperparathyroidism (1° HPT) is a relatively common endocrine disorder usually caused by autonomous secretion of parathormone by one or several parathyroid adenomas. 1° HPT causing hypercalcemia, kidney stones and/or osteoporosis should be treated whenever possible by parathyroidectomy. Accurate preoperative location of parathyroid adenomas is crucial for surgery planning, mostly when performing minimally invasive surgery. Cervical ultrasonography (US) is usually performed to localize parathyroid adenomas as a first intention, followed by Tc- sestamibi scintigraphy with SPECT/CT whenever possible. 4D-CT is a possible alternative to Tc- sestamibi scintigraphy. Recently, F-fluorocholine positron emission tomography/computed tomography (F-FCH PET/CT) has made its way in the clinics as it is the most sensitive method for parathyroid adenoma detection. It can eventually be combined to 4D-CT to increase its diagnostic performance, although this results in higher dose exposure to the patient. Other forms of hyperparathyroidism consist in secondary (2° HPT) and tertiary hyperparathyroidism (3° HPT). As parathyroidectomy is not usually part of the management of patients with 2° HPT, parathyroid imaging is not routinely performed in these patients. In patients with 3° HPT, total or subtotal parathyroidectomy is often performed. Localization of hyperfunctional glands is an important aid to surgery planning. As F-FCH PET/CT is the most sensitive modality in multigland disease, it is the preferred imaging technic in 3° HPT patients, although its cost and availability may limit its widespread use in this setting.
Topics: Humans; Positron Emission Tomography Computed Tomography; Parathyroid Neoplasms; Parathyroid Glands; Hyperparathyroidism; Technetium Tc 99m Sestamibi; Radiopharmaceuticals
PubMed: 36922339
DOI: 10.1053/j.semnuclmed.2023.02.004