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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 -
American Journal of Kidney Diseases :... Oct 2021Osteoporosis is defined as a skeletal disorder of compromised bone strength predisposing those affected to an elevated risk of fracture. However, based on bone... (Review)
Review
Osteoporosis is defined as a skeletal disorder of compromised bone strength predisposing those affected to an elevated risk of fracture. However, based on bone histology, osteoporosis is only part of a spectrum of skeletal complications that includes osteomalacia and the various forms of renal osteodystrophy of chronic kidney disease-mineral and bone disorder (CKD-MBD). In addition, the label "kidney-induced osteoporosis" has been proposed, even though the changes caused by CKD do not qualify as osteoporosis by the histological diagnosis. It is clear, therefore, that such terminology may not be helpful diagnostically or in making treatment decisions. A new label, "CKD-MBD/osteoporosis" could be a more appropriate term because it brings osteoporosis under the official label of CKD-MBD. Neither laboratory nor noninvasive diagnostic investigations can discriminate osteoporosis from the several forms of renal osteodystrophy. Transiliac crest bone biopsy can make the diagnosis of osteoporosis by exclusion of other kidney-associated bone diseases, but its availability is limited. Recently, a classification of metabolic bone diseases based on bone turnover, from low to high, together with mineralization and bone volume, has been proposed. Therapeutically, no antifracture treatments have been approved by the US Food and Drug Administration for patients with kidney-associated bone disease. Agents that suppress parathyroid hormone (vitamin D analogues and calcimimetics) are used to treat hyperparathyroid bone disease. Antiresorptive and osteoanabolic agents approved for osteoporosis are being used off-label to treat CKD stages 3b-5 in high-risk patients. It has now been suggested that intermittent administration of parathyroid hormone as early as CKD stage 2 could be an effective management strategy. If confirmed in clinical trials, it could mitigate the retention of phosphorus and subsequently the rise in fibroblast growth factor 23 and may be beneficial for coexisting osteoporosis.
Topics: Anabolic Agents; Bone Diseases, Metabolic; Bone Remodeling; Chronic Kidney Disease-Mineral and Bone Disorder; Fibroblast Growth Factor-23; Humans; Hyperparathyroidism; Osteoporosis; Parathyroid Hormone; Vitamin D
PubMed: 33774081
DOI: 10.1053/j.ajkd.2020.12.024 -
Lancet (London, England) Jan 2018Primary hyperparathyroidism is a common endocrine disorder of calcium metabolism characterised by hypercalcaemia and elevated or inappropriately normal concentrations of... (Review)
Review
Primary hyperparathyroidism is a common endocrine disorder of calcium metabolism characterised by hypercalcaemia and elevated or inappropriately normal concentrations of parathyroid hormone. Almost always, primary hyperparathyroidism is due to a benign overgrowth of parathyroid tissue either as a single gland (80% of cases) or as a multiple gland disorder (15-20% of cases). Primary hyperparathyroidism is generally discovered when asymptomatic but the disease always has the potential to become symptomatic, resulting in bone loss and kidney stones. In countries where biochemical screening tests are not common, symptomatic primary hyperparathyroidism tends to predominate. Another variant of primary hyperparathyroidism has been described in which the serum calcium concentration is within normal range but parathyroid hormone is elevated in the absence of any obvious cause. Primary hyperparathyroidism can be cured by removal of the parathyroid gland or glands but identification of patients who are best advised to have surgery requires consideration of the guidelines that are regularly updated. Recommendations for patients who do not undergo parathyroid surgery include monitoring of serum calcium concentrations and bone density.
Topics: Humans; Hyperparathyroidism, Primary
PubMed: 28923463
DOI: 10.1016/S0140-6736(17)31430-7 -
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 -
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 -
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 -
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 -
Journal of Bone and Mineral Research :... Dec 2022Hypoparathyroidism (HypoPT) is a rare disorder characterized by hypocalcemia in the presence of a low or inappropriately normal parathyroid hormone level. HypoPT is most...
Hypoparathyroidism (HypoPT) is a rare disorder characterized by hypocalcemia in the presence of a low or inappropriately normal parathyroid hormone level. HypoPT is most commonly seen after neck surgery, which accounts for approximately 75% of cases, whereas approximately 25% have HypoPT due to nonsurgical causes. In both groups of patients, conventional therapy includes calcium and active vitamin D analogue therapy aiming to maintain serum calcium concentration in the low normal or just below the normal reference range and normalize serum phosphorus, magnesium concentrations, and urine calcium levels. The limitations of conventional therapy include wide fluctuations in serum calcium, high pill burden, poor quality of life, and renal complications. Parathyroid hormone (PTH) replacement therapy may improve the biochemical profile in those in whom conventional therapy proves unsatisfactory. Based on a systematic review and meta-analysis of the literature, the panel made a graded recommendation suggesting conventional therapy as first line therapy rather than administration of PTH (weak recommendation, low quality evidence). When conventional therapy is deemed unsatisfactory, the panel considers use of PTH. Because pregnancy and lactation are associated with changes in calcium homeostasis, close monitoring is required during these periods with appropriate adjustment of calcium and active vitamin D analogue therapy to ensure that serum calcium remains in the mid to low normal reference range in order to avoid maternal and fetal complications. Emerging therapies include molecules with prolonged PTH action as well as different mechanisms of action that may significantly enhance drug efficacy and safety. © 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: Female; Humans; Calcium; Calcium, Dietary; Hypoparathyroidism; Parathyroid Hormone; Quality of Life; Vitamin D; Practice Guidelines as Topic
PubMed: 36161671
DOI: 10.1002/jbmr.4716 -
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 -
European Journal of Endocrinology Feb 2022This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in...
European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders.
This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders (PARAT) in 2019, were discussed during two virtual workshops in 2021, and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosing to familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represent areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT, need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborns children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed for a broader clinical audience, and were developed with focus on endocrinologists in training.
Topics: Adult; Calcium; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Hypoparathyroidism; Infant, Newborn; Lactation; Parathyroid Diseases; Parathyroid Hormone; Pregnancy
PubMed: 34863037
DOI: 10.1530/EJE-21-1044