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Journal of Bone and Mineral Research :... Nov 2022The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new... (Review)
Review
The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new insights into epidemiology, pathophysiology, diagnosis, measurements, genetics, outcomes, presentations, new imaging modalities, target and other organ systems, pregnancy, evaluation, and management. Advances in all these areas are demonstrated by the reference list in which the majority of listings were published after the last set of guidelines. It was thus, timely to convene an international group of over 50 experts to review these advances in our knowledge. Four Task Forces considered: 1. Epidemiology, Pathophysiology, and Genetics; 2. Classical and Nonclassical Features; 3. Surgical Aspects; and 4. Management. For Task Force 4 on the Management of PHPT, Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology addressed surgical management of asymptomatic PHPT and non-surgical medical management of PHPT. The findings of this systematic review that applied GRADE methods to randomized trials are published as part of this series. Task Force 4 also reviewed a much larger body of new knowledge from observations studies that did not specifically fit the criteria of GRADE methodology. The full reports of these 4 Task Forces immediately follow this summary statement. Distilling the essence of all deliberations of all Task Force reports and Methodological reviews, we offer, in this summary statement, evidence-based recommendations and guidelines for the evaluation and management of PHPT. Different from the conclusions of the last workshop, these deliberations have led to revisions of renal guidelines and more evidence for the other recommendations. The accompanying papers present an in-depth discussion of topics summarized in this report. © 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; Hyperparathyroidism, Primary
PubMed: 36245251
DOI: 10.1002/jbmr.4677 -
Archives of Endocrinology and Metabolism Nov 2022Normocalcemic primary hyperparathyroidism (PHPT) is a newer phenotype of PHPT defined by elevated PTH concentrations in the setting of normal serum calcium levels. It is... (Review)
Review
Normocalcemic primary hyperparathyroidism (PHPT) is a newer phenotype of PHPT defined by elevated PTH concentrations in the setting of normal serum calcium levels. It is increasingly being diagnosed in the setting of evaluation for nephrolithiasis or metabolic bone diseases. It is important to demonstrate that PTH values remain consistently elevated and to measure ionized calcium levels to make the diagnosis. A diagnosis of normocalcemic disease is one of exclusion of secondary forms of hyperparathyroidism, including vitamin D deficiency, renal failure, medications, malabsorption, and hypercalciuria. Lack of rigorous diagnostic criteria and selection bias of the studied populations may explain the different rates of bone and renal complications. The natural history still remains unknown. Caution should be used in recommending surgery, unless clearly indicated. Here we will review the diagnostic features, epidemiology, clinical presentation, natural history, medical and surgical management of normocalcemic PHPT.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Hormone; Calcium; Bone Diseases, Metabolic; Vitamin D Deficiency
PubMed: 36382756
DOI: 10.20945/2359-3997000000556 -
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 -
Journal of Bone and Mineral Research :... Nov 2022In this narrative review, we present data gathered over four decades (1980-2020) on the epidemiology, pathophysiology and genetics of primary hyperparathyroidism (PHPT).... (Review)
Review
In this narrative review, we present data gathered over four decades (1980-2020) on the epidemiology, pathophysiology and genetics of primary hyperparathyroidism (PHPT). PHPT is typically a disease of postmenopausal women, but its prevalence and incidence vary globally and depend on a number of factors, the most important being the availability to measure serum calcium and parathyroid hormone levels for screening. In the Western world, the change in presentation to asymptomatic PHPT is likely to occur, over time also, in Eastern regions. The selection of the population to be screened will, of course, affect the epidemiological data (ie, general practice as opposed to tertiary center). Parathyroid hormone has a pivotal role in regulating calcium homeostasis; small changes in extracellular Ca++ concentrations are detected by parathyroid cells, which express calcium-sensing receptors (CaSRs). Clonally dysregulated overgrowth of one or more parathyroid glands together with reduced expression of CaSRs is the most important pathophysiologic basis of PHPT. The spectrum of skeletal disease reflects different degrees of dysregulated bone remodeling. Intestinal calcium hyperabsorption together with increased bone resorption lead to increased filtered load of calcium that, in addition to other metabolic factors, predispose to the appearance of calcium-containing kidney stones. A genetic basis of PHPT can be identified in about 10% of all cases. These may occur as a part of multiple endocrine neoplasia syndromes (MEN1-MEN4), or the hyperparathyroidism jaw-tumor syndrome, or it may be caused by nonsyndromic isolated endocrinopathy, such as familial isolated PHPT and neonatal severe hyperparathyroidism. DNA testing may have value in: confirming the clinical diagnosis in a proband; eg, by distinguishing PHPT from familial hypocalciuric hypercalcemia (FHH). Mutation-specific carrier testing can be performed on a proband's relatives and identify where the proband is a mutation carrier, ruling out phenocopies that may confound the diagnosis; and potentially prevention via prenatal/preimplantation diagnosis. © 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: Infant, Newborn; Female; Humans; Hyperparathyroidism, Primary; Calcium; Hypercalcemia; Receptors, Calcium-Sensing; Parathyroid Hormone
PubMed: 36245271
DOI: 10.1002/jbmr.4665 -
The Journal of Clinical Endocrinology... Nov 2018Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women. The clinical presentation of PHPT has... (Review)
Review
BACKGROUND
Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women. The clinical presentation of PHPT has evolved over the past 40 years to include three distinct clinical phenotypes, each of which has been studied in detail and has led to evolving concepts about target organ involvement, natural history, and management.
METHODS
In the present review, I provide an evidence-based summary of this disorder as it has been studied worldwide, citing key concepts and data that have helped to shape our concepts about this disease.
RESULTS
PHPT is now recognized to include three clinical phenotypes: overt target organ involvement, mild asymptomatic hypercalcemia, and high PTH levels with persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is used, vitamin D deficiency is present, and whether parathyroid hormone levels are routinely measured in the evaluation of low bone density or frank osteoporosis. Guidelines for parathyroidectomy apply to all three clinical forms of the disease. If surgical guidelines are not met, parathyroidectomy can also be an appropriate option if no medical contraindications are present. If either the serum calcium or bone mineral density is of concern and surgery is not an option, pharmacological approaches are available and effective.
CONCLUSIONS
Advances in our knowledge of PHPT have guided new concepts in diagnosis and management.
Topics: Bone Density; Bone Density Conservation Agents; Calcimimetic Agents; Calcium; Evidence-Based Medicine; Feeding Behavior; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Male; Osteoporosis; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Postmenopause; Practice Guidelines as Topic; Sex Factors; Vitamin D Deficiency
PubMed: 30060226
DOI: 10.1210/jc.2018-01225 -
Nature Reviews. Endocrinology Feb 2018In this Review, we describe the pathogenesis, diagnosis and management of primary hyperparathyroidism (PHPT), with a focus on recent advances in the field. PHPT is a... (Review)
Review
In this Review, we describe the pathogenesis, diagnosis and management of primary hyperparathyroidism (PHPT), with a focus on recent advances in the field. PHPT is a common endocrine disorder that is characterized by hypercalcaemia and elevated or inappropriately normal serum levels of parathyroid hormone. Most often, the presentation of PHPT is asymptomatic in regions of the world where serum levels of calcium are routinely measured. In addition to mild hypercalcaemia, PHPT can manifest with osteoporosis and hypercalciuria as well as with vertebral fractures and nephrolithiasis, both of which can be asymptomatic. Other clinical forms of PHPT, such as classical disease and normocalcaemic PHPT, are less common. Parathyroidectomy, the only curative treatment for PHPT, is recommended in patients with symptoms and those with asymptomatic disease who are at risk of progression or have subclinical evidence of end-organ sequelae. Parathyroidectomy results in an increase in BMD and a reduction in nephrolithiasis. Various medical therapies can increase BMD or reduce serum levels of calcium, but no single drug can do both. More data are needed regarding the neuropsychological manifestations of PHPT and the pathogenetic mechanisms leading to sporadic PHPT, as well as on risk factors for complications of the disorder. Future work that advances our knowledge in these areas will improve the management of the disorder.
Topics: Disease Management; Disease Progression; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Osteoporosis; Parathyroid Hormone; Parathyroidectomy
PubMed: 28885621
DOI: 10.1038/nrendo.2017.104 -
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 -
Best Practice & Research. Clinical... Oct 2018Familial hypocalciuric hypercalcemia (FHH) causes hypercalcemia by three genetic mechanisms: inactivating mutations in the calcium-sensing receptor, the G-protein... (Review)
Review
Familial hypocalciuric hypercalcemia (FHH) causes hypercalcemia by three genetic mechanisms: inactivating mutations in the calcium-sensing receptor, the G-protein subunit α, or adaptor-related protein complex 2, sigma 1 subunit. While hypercalcemia in other conditions causes significant morbidity and mortality, FHH generally follows a benign course. Failure to diagnose FHH can result in unwarranted treatment or surgery for the mistaken diagnosis of primary hyperparathyroidism (PHPT), given the significant overlap of biochemical features. Determinations of urinary calcium excretion greatly aid in distinguishing PHPT from FHH, but overlap still exists in certain cases. It is important that 24-h urine calcium and creatinine be included in the initial workup of hypercalcemia. FHH should be considered if low or even low normal urinary calcium levels are found in what is typically an asymptomatic hypercalcemic patient. The calcimimetic cinacalcet has been used to treat hypercalcemia in certain symptomatic causes of FHH.
Topics: Adaptor Protein Complex 2; GTP-Binding Protein alpha Subunits, Gq-G11; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Kidney Diseases; Mutation; Receptors, Calcium-Sensing
PubMed: 30449544
DOI: 10.1016/j.beem.2018.05.004 -
Journal of Bone and Mineral Research :... Nov 2022
Topics: Humans; Hyperparathyroidism, Primary
PubMed: 36245277
DOI: 10.1002/jbmr.4670 -
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