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1.
Recombinant parathyroid hormone for hypoparathyroidism in children: a narrative review.
Dayal, D, Gupta, A, Gupta, S, Dutta, A
Pediatric endocrinology, diabetes, and metabolism. 2019;(4):194-201
Abstract
The conventional management of hypoparathyroidism in children involves the use of calcium and vitamin D analogs. This therapy effec-tively increases the serum calcium levels but worsens hypercalciuria and its consequences such as nephrocalcinosis and renal insuffi-ciency. Although replacement with the missing parathyroid hormone (PTH) is ideal and available for more than 2 decades, the reported concerns of osteosarcoma prohibited its use in children with open epiphyses. Nevertheless, the data accumulated over the past several years suggests that the fears of bone malignancies were probably overstated. With an aim to review the available data on recombinant PTH (rhPTH) use, we performed a literature search using international databases and identified 15 studies involving approximately 70 children with hypoparathyroidism due to various etiologies who received rhPTH1-34 for durations between 1 day and 13.5 years. All the studies appear to indicate that rhPTH1-34 therapy is an effective short and long-term strategy for treatment of hypoparathyroidism with better metabolic control, lesser effects on renal function and improved quality of life as compared to conventional therapy. A more significant conclusion is the safety of long-term use of rhPTH1-34 with no observed adverse skeletal effects so far. However, all studies mention the importance of a continued surveillance for adverse effects in the treated patients. This narrative review discusses the experi-ence of rhPTH1-34 use exclusively in children.
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2.
The effectiveness and safety of parathyroid hormone in fracture healing: A meta-analysis.
Hong, H, Song, T, Liu, Y, Li, J, Jiang, Q, Song, Q, Deng, Z
Clinics (Sao Paulo, Brazil). 2019;:e800
Abstract
The very large economic and social burdens of fracture-related complications make rapid fracture healing a major public health goal. The role of parathyroid hormone (PTH) in treating osteoporosis is generally accepted, but the effect of PTH on fracture healing is controversial. This meta-analysis was designed to investigate the efficacy and safety of PTH in fracture healing. The EMBASE, PubMed, and Cochrane Library databases were systematically searched from the inception dates to April 26, 2018. The primary randomized clinical trials comparing PTH treatment for fracture healing with placebo or no treatment were identified. We did not gain additional information by contacting the authors of the primary studies. Two reviewers independently extracted the data and evaluated study quality. This meta-analysis was executed to determine the odds ratio, mean difference, standardized mean difference, and 95% confidence intervals with random-effects models. In total, 8 randomized trials including 524 patients met the inclusion criteria. There were significant differences in fracture healing time, pain relief and function improvement. There were no significant differences in the fracture healing rate or adverse events, including light-headedness, hypercalcemia, nausea, sweating and headache, except for slight bruising at the injection site. We determined that the effectiveness and safety of PTH in fracture healing is reasonably well established and credible.
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3.
Secondary Hyperparathyroidism: Pathogenesis and Latest Treatment.
Mizobuchi, M, Ogata, H, Koiwa, F
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2019;(4):309-318
Abstract
The classic pathogenesis of secondary hyperparathyroidism (SHPT) began with the trade-off hypothesis based on parathyroid hormone hypersecretion brought about by renal failure resulting from a physiological response to correct metabolic disorder of calcium, phosphorus, and vitamin D. In dialysis patients with failed renal function, physiological mineral balance control by parathyroid hormone through the kidney fails and hyperparathyroidism progresses. In this process, many significant genetic findings have been established. Abnormalities of Ca-sensing receptor and vitamin D receptor are associated with the pathogenesis of SHPT, and fibroblast growth factor 23 has also been shown to be involved in the pathogenesis. Vitamin D receptor activators (VDRAs) are widely used for treatment of SHPT. However, VDRAs have calcemic and phosphatemic effects that limit their use to a subset of patients, and calcimimetics have been developed as alternative drugs for SHPT. Hyperphosphatemia also affects progression of SHPT, and control of hyperphosphatemia is, therefore, thought to be fundamental for control of SHPT. Currently, a combination of a VDRA and a calcimimetic is recognized as the optimal strategy for SHPT, and for other outcomes such as reduced cardiovascular disease and improved survival. The latest findings on the pathogenesis and treatment of SHPT are summarized in this review.
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4.
Clinical Guidelines and PTH Measurement: Does Assay Generation Matter?
Smit, MA, van Kinschot, CMJ, van der Linden, J, van Noord, C, Kos, S
Endocrine reviews. 2019;(6):1468-1480
Abstract
PTH is an important regulator of calcium and phosphate homeostasis and bone remodeling. It is metabolized into PTH fragments, which are measured to a different extent by PTH assays of different generations because of differences in fragments recognized and lack of assay standardization. PTH is measured in the workup of several conditions, and clinical guidelines provide recommendations concerning these measurements. This review provides an overview of the impact of differences between PTH assays, applying distinct clinical guidelines for primary and secondary hyperparathyroidism and perioperative use of PTH measurements. Guidelines deal with PTH measurement in different ways, recommending either trend monitoring, the use of a fold increase of the upper reference limit, or an absolute PTH cutoff value. For classic primary hyperparathyroidism (PHPT), the type of PTH assay used will not affect diagnosis or management because the precise concentration of PTH is less relevant. In chronic kidney disease, the guideline recommends treating secondary hyperparathyroidism above a twofold to ninefold PTH increase, which will result in different clinical decisions depending on the assay used. For patients after bariatric surgery, guidelines state absolute cutoff values for PTH, but the impact of different generation assays is unknown because direct comparison of PTH assays has never been performed. During parathyroid surgery, PTH measurements with a third-generation assay reflect treatment success more rapidly than second-generation assays. Increased awareness among clinicians regarding the complexity of PTH measurements is warranted because it can affect clinical decisions.
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5.
Genetic hypercalcemia.
Cormier, C
Joint bone spine. 2019;(4):459-466
Abstract
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.
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6.
Parathyroid Hormone and Cardiac Electrophysiology: A Review.
Palmeri, NO, Walker, MD
Cardiology in review. 2019;(4):182-188
Abstract
Calcium has long been known to be essential to cardiac electrical activity. Parathyroid hormone (PTH) is the main regulator of serum calcium and is central to calcium homeostasis. Although there are significant data linking parathyroid disease states with changes in cardiac electrophysiology, most data have focused on how PTH modulates serum calcium to produce these effects. Close scrutiny of early literature demonstrates that the relationship between PTH and electrocardiographic changes is not straightforward, and numerous studies have linked PTH to arrhythmia. Basic science research has demonstrated that there is a basis for a direct role of PTH on cardiac electrophysiology outside of its effect on serum calcium. Later studies in secondary hyperparathyroidism indicate that PTH disturbances could have important implications for broad categories of patients with cardiovascular disease. The current review summarizes the existing literature on PTH and electrophysiology based on clinical and basic science studies of various parathyroid states, providing directions for future study.
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7.
Update on hypoparathyroidism.
Cusano, NE, Bilezikian, JP
Current opinion in rheumatology. 2019;(4):381-387
Abstract
PURPOSE OF REVIEW Hypoparathyroidism is a rare endocrine disorder characterized by low or insufficient parathyroid hormone (PTH) concentrations leading to hypocalcemia, hyperphosphatemia, and markedly reduced bone turnover. Despite being a rare disease, hypoparathyroidism has a profound impact on affected patients. RECENT FINDINGS Recent epidemiologic surveys demonstrate a prevalence of between 5.3 and 40/100 000, confirming the orphan status of this disease. There is a female predominance, and anterior neck surgery is the most common etiology. Recent studies have better elucidated the chronic manifestations of the disease, impacting quality of life and multiple organ systems including the renal, cardiovascular, and skeletal systems. There are now data on longer term use of parathyroid hormone (PTH) and PTH analogs. SUMMARY This review focuses on recent contributions to the literature on the prevalence and epidemiology of the disease, risk of chronic manifestations, and treatment with PTH(1-34) and rhPTH(1-84). Further research is needed to determine the pathophysiology of complications in hypoparathyroidism and whether interventions can decrease future risk of these complications. In addition, further data are needed with regards to more physiologic dosing regimens and long-term treatment with PTH and PTH analogs.
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8.
Elevated parathyroid hormone levels after successful parathyroidectomy for primary hyperparathyroidism: a clinical review.
de la Plaza Llamas, R, Ramia Ángel, JM, Arteaga Peralta, V, García Amador, C, López Marcano, AJ, Medina Velasco, AA, González Sierra, B, Manuel Vázquez, A, Latorre Fragua, RA
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2018;(3):659-669
Abstract
INTRODUCTION Surgery for primary hyperparathyroidism (PHPT) is traditionally deemed to be successful if serum calcium levels return to normal 6 months after parathyroidectomy. Regular monitoring of serum calcium and parathyroid hormone (PTH) in the follow-up of patients after parathyroidectomy for PHPT has drawn attention to the presence of a normocalcemic group of patients with elevated PTH (NCePTH) during the post-operative period. The etiological factors and mechanisms underlying this condition, its consequences, and the possibility of treatment are the object of this study. MATERIALS AND METHODS We conducted an unlimited PubMed search updated on March 31, 2017, which yielded 1628 results. We selected 37 articles, 33 of which included cases of NCePTH in their series and 23 performed statistical studies to assess factors associated with NCePTH. RESULTS The maximum mean prevalence of NCePTH in the various series was 23.5%, ranging from 3 to 46%. Many factors were associated with NCePTH. The most important were higher pre-operative PTH, low pre-operative 25 (OH) D3, lower pre-operative creatinine clearance and greater adenoma weight. The origin of NCePTH may be multifactorial, since several factors were implicated in the etiology. NCePTH does not seem to be related to an increase in PHPT recurrence, although this possibility should not be dismissed. Vitamin D deficiency should be corrected. Treatment with calcium supplements seems to be clearly beneficial. CONCLUSION The prevalence of NCePTH is high. The causes of secondary hyperparathyroidism should be investigated carefully. Patients require treatment and long-term follow-up.
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9.
Metabolic Syndrome in Parathyroid Diseases.
Corbetta, S, Mantovani, G, Spada, A
Frontiers of hormone research. 2018;:67-84
Abstract
Parathyroid glands are the main regulator of body mineral metabolism through parathormone (PTH) actions on bone and kidney. Experimental evidence suggests that PTH may have non-classical target organs such as adipose tissue, arterial vascular wall, cardiac muscle cells, and adrenal cortex cells, where it may play a role in controlling body energy, blood pressure, and metabolism. Cardiometabolic features have been investigated in the wide spectrum of clinical parathyroid disorders, from hyperparathyroidism to pseudohypoparathyroidism and hypoparathyroidism. Indeed, in parathyroid disorders, besides altered PTH secretion, impaired serum calcium levels and vitamin D status occur. Both calcium and vitamin D have been shown to regulate metabolism and to be associated with cardiovascular diseases. However, despite the complexity of parathyroid disorders, features of metabolic syndrome, such as obesity, insulin resistance, and glucose intolerance, arterial blood hypertension, and dyslipidemia, are frequently diagnosed in primary and secondary hyperparathyroidism as well as in pseudohyperparathyroidism. Here, we reviewed the most consistent data highlighting challenges and providing clinical remarks.
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10.
Parathyroid hormone resistance syndromes - Inactivating PTH/PTHrP signaling disorders (iPPSDs).
Elli, FM, Pereda, A, Linglart, A, Perez de Nanclares, G, Mantovani, G
Best practice & research. Clinical endocrinology & metabolism. 2018;(6):941-954
Abstract
Metabolic disorders caused by impairments of the Gsα/cAMP/PKA pathway affecting the signaling of PTH/PTHrP lead to features caused by non-responsiveness of target organs, in turn leading to manifestations similar to the deficiency of the hormone itself. Pseudohypoparathyroidism (PHP) and related disorders derive from a defect of the α subunit of the stimulatory G protein (Gsα) or of downstream effectors of the same pathway, such as the PKA regulatory subunit 1A and the phosphodiesterase type 4D. The increasing knowledge on these diseases made the actual classification of PHP outdated as it does not include related conditions such as acrodysostosis (ACRDYS) or progressive osseous heteroplasia (POH), so that a new nomenclature and classification has been recently proposed grouping these disorders under the term "inactivating PTH/PTHrP signaling disorder" (iPPSD). This review will focus on the pathophysiology, clinical and molecular aspects of these rare, heterogeneous but closely related diseases.