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Nephrology, Dialysis, Transplantation :... May 2023The situation of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients not on dialysis (ND-CKD) is probably best characterised by the Kidney Disease:...
The situation of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients not on dialysis (ND-CKD) is probably best characterised by the Kidney Disease: Improving Global Outcomes Chronic Kidney Disease-Mineral and Bone Disorder Update 2017 guideline 4.2.1 stating that the optimal parathyroid hormone levels are not known in these stages. Furthermore, new caution became recommended with regard to the routine use of active vitamin D analogues in early CKD stages and moderate SHPT phenotypes, due to their potential risks for hypercalcaemia and hyperphosphataemia aggravation. Nevertheless, there is still a substantial clinical need to prevent the development of parathyroid gland autonomy, with its associated consequences of bone and vascular damage, including fracture risks and cardiovascular events. Therefore we now attempt to review the current guideline-based and clinical practice management of SHPT in ND-CKD, including their strengths and weaknesses, favouring individualised approaches respecting calcium and phosphate homeostasis. We further comment on extended-release calcifediol (ERC) as a new differential therapeutic option now also available in Europe and on a potentially novel understanding of a required vitamin D saturation in more advanced CKD stages. There is no doubt, however, that knowledge gaps will remain unless powerful randomised controlled trials with hard and meaningful endpoints are performed.
Topics: Humans; Renal Dialysis; Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic; Vitamin D; Chronic Kidney Disease-Mineral and Bone Disorder; Parathyroid Hormone
PubMed: 35977397
DOI: 10.1093/ndt/gfac236 -
Journal of the American Veterinary... Feb 2020
Topics: Animals; Cat Diseases; Cats; Female; Lymphoma, B-Cell; Parathyroid Diseases; Renal Insufficiency, Chronic
PubMed: 31961272
DOI: 10.2460/javma.256.3.319 -
Journal of Visceral Surgery Oct 2010Primary hyperparathyroidism (HPT1) is a common endocrine disorder, which is asymptomatic in 80% of cases. The diagnosis is ordinarily easily made, based on an... (Review)
Review
Primary hyperparathyroidism (HPT1) is a common endocrine disorder, which is asymptomatic in 80% of cases. The diagnosis is ordinarily easily made, based on an inappropriately elevated parathormone level (PTH) in the face of hypercalcemia. In 85% of cases, HPT1 is due to hormone secretion from a single parathyroid gland (uniglandular disease) and the remaining patients have multiglandular disease. The best localization study is MIBI scintigraphy (methoxy isobutyl isonitrile) coupled with the results of a neck ultrasound exam (sensitivity >95%). Other investigations are reserved for patients with persistent or recurrent HPT1 post-surgery. Surgery is the only cure. The surgical approach may include a bilateral cervical exploration, a unilateral approach under local anesthesia, or focused minimally invasive (video-assisted or totally endoscopic) approaches. A decrease in PTH level measured intraoperatively of greater than 50% is predictive of cure in more than 97% of cases. Surgery is recommended even for moderate HPT1 and for very elderly patients because improvement in both the quality of life and bone density have been proven in these situations. The role of medical treatment is limited. Persistent or recurrent HPT1 requires a meticulous diagnostic approach and management in surgical centers with expertise. Persistent elevation of PTH postoperatively without hypercalcemia does not mandate further exploration. The prognosis of normocalcemic patients with elevated postoperative PTH levels remains uncertain.
Topics: Algorithms; Decision Trees; Humans; Hyperparathyroidism, Primary; Recurrence; Severity of Illness Index
PubMed: 20888315
DOI: 10.1016/j.jviscsurg.2010.08.018 -
Nature Communications Feb 2022Parathyroid hormone (PTH) plays crucial role in maintaining calcium and phosphorus homeostasis. In the progression of secondary hyperparathyroidism (SHPT), expression of...
Parathyroid hormone (PTH) plays crucial role in maintaining calcium and phosphorus homeostasis. In the progression of secondary hyperparathyroidism (SHPT), expression of calcium-sensing receptors (CaSR) in the parathyroid gland decreases, which leads to persistent hypersecretion of PTH. How to precisely manipulate PTH secretion in parathyroid tissue and underlying molecular mechanism is not clear. Here, we establish an optogenetic approach that bypasses CaSR to inhibit PTH secretion in human hyperplastic parathyroid cells. We found that optogenetic stimulation elevates intracellular calcium, inhibits both PTH synthesis and secretion in human parathyroid cells. Long-term pulsatile PTH secretion induced by light stimulation prevented hyperplastic parathyroid tissue-induced bone loss by influencing the bone remodeling in mice. The effects are mediated by light stimulation of opsin expressing parathyroid cells and other type of cells in parathyroid tissue. Our study provides a strategy to regulate release of PTH and associated bone loss of SHPT through an optogenetic approach.
Topics: Bone and Bones; Calcium; Homeostasis; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary; Hyperplasia; Optogenetics; Parathyroid Glands; Parathyroid Hormone; Receptors, Calcium-Sensing
PubMed: 35140213
DOI: 10.1038/s41467-022-28472-9 -
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 -
Annals of Surgery Oct 1976Recurrent hyperparathyroidism occurred in 11 of 295 patients from 10 months to 34 years after an initially successful operation. Seven patients with recurrent...
Recurrent hyperparathyroidism occurred in 11 of 295 patients from 10 months to 34 years after an initially successful operation. Seven patients with recurrent hyperparathyroidism had either multiple endocrine adenomatosis type I (MEA) or familial hyperparathyroidism (FHP), one patient had parathyroid cancer, and two patients had renal failure at the time of recurrence. Four of these patients ahd their initial operations elsewhere. Recurrence developed in 33% of patients with MEA or FHP but in only 0.4% of 242 patients without MEA or FHP. The presence of MEA or FHP was known before parathyroid exploration in 18 (86%) of the 21 patients. In patients with MEA or FHP, subtotal parathyroidectomy should be performed if there is more than one gland involved. Other patients should be treated by selective removal of an adenoma because recurrence is rare. Subtotal parathyroidectomy should be reserved for patients with diffuse hyperplasia.
Topics: Adenoma; Adolescent; Adult; Aged; California; Female; Follow-Up Studies; Humans; Hyperparathyroidism; Hypocalcemia; Male; Middle Aged; Parathyroid Diseases; Recurrence
PubMed: 1015886
DOI: 10.1097/00000658-197610000-00001 -
Endocrine-related Cancer Jun 2016Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the... (Review)
Review
Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential.
Topics: Endocrine Gland Neoplasms; Humans; Hyperparathyroidism; Syndrome
PubMed: 27207564
DOI: 10.1530/ERC-16-0059 -
The Journal of Clinical Endocrinology... Sep 2012PTHrP was identified as a cause of hypercalcemia in cancer patients 25 yr ago. In the intervening years, we have learned that PTHrP and PTH are encoded by related genes... (Review)
Review
PTHrP was identified as a cause of hypercalcemia in cancer patients 25 yr ago. In the intervening years, we have learned that PTHrP and PTH are encoded by related genes that are part of a larger "PTH gene family." This evolutionary relationship permits them to bind to the same type 1 PTH/PTHrP receptor, which explains why humoral hypercalcemia of malignancy resembles hyperparathyroidism. This review will outline basic facts about PTHrP biology and its normal physiological functions, with an emphasis on new findings of the past 5-10 yr. The medical and research communities first became aware of PTHrP because of its involvement in a common paraneoplastic syndrome. Now, research into the basic biology of PTHrP has suggested previously unrecognized connections to a variety of disease states such as osteoporosis, osteoarthritis, and breast cancer and has highlighted how PTHrP itself might be used in therapy for osteoporosis and diabetes. Therefore, the story of this remarkable protein is a paradigm for translational research, having gone from bedside to bench and now back to bedside.
Topics: Animals; Cell Nucleus; Humans; Parathyroid Diseases; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Protein Conformation; Receptors, Parathyroid Hormone
PubMed: 22745236
DOI: 10.1210/jc.2012-2142 -
Toxins Feb 2020Cardiovascular (CV) disease is highly prevalent in the population with chronic kidney disease (CKD), where the risk of CV death in early stages far exceeds the risk of... (Review)
Review
Cardiovascular (CV) disease is highly prevalent in the population with chronic kidney disease (CKD), where the risk of CV death in early stages far exceeds the risk of progression to dialysis. The presence of chronic kidney disease-mineral and bone disorder (CKD-MBD) has shown a strong correlation with CV events and mortality. As a non-atheromatous process, it could be partially explained why standard CV disease-modifying drugs do not provide such an impact on CV mortality in CKD as observed in the general population. We summarize the potential association of CV comorbidities with the older (parathyroid hormone, phosphate) and newer (FGF23, Klotho, sclerostin) CKD-MBD biomarkers.
Topics: Animals; Avitaminosis; Biomarkers; Cardiovascular Diseases; Cardiovascular System; Chronic Kidney Disease-Mineral and Bone Disorder; Comorbidity; Fibroblast Growth Factor-23; Humans; Parathyroid Hormone; Phosphates; Risk Factors
PubMed: 32106499
DOI: 10.3390/toxins12030140 -
Jornal Brasileiro de Nefrologia 2022Hypoparathyroidism (HP) is a rare metabolic disorder and causes hypocalcemia because parathyroid hormone secretion is inadequate to mobilize calcium from bone and...
Hypoparathyroidism (HP) is a rare metabolic disorder and causes hypocalcemia because parathyroid hormone secretion is inadequate to mobilize calcium from bone and reabsorb calcium from kidney and gut. Anterior neck surgery is the most common cause of acquired HP and autoimmune HP is the next most common form in adults. The duration, severity, and rate of development of hypocalcemia determine the clinical presentation. A variety of organs can be affected by calcification, more frequently kidneys, but also joints, eyes, skin, vasculature, and other organ systems and, although rarely seen, intracerebral calcifications. We report four cases of bilateral basal ganglia calcifications (BGC) also known as Fahr's syndrome related to hypoparathyroidism. Fahr's syndrome is characterized by bilateral symmetrical calcification of areas of the brain that control movements including basal ganglia, thalamus, and others; it is a rare inherited or sporadic neurological disorder with a prevalence of less than 1/1.000.000. Main symptoms related to bilateral BGC include extra-pyramidal and cerebellar disorders, cognitive impairment, epileptic seizures, and psychiatric changes. BGC has been established as a possible outcome of HP. Its prevalence, demonstrated in the HP cohorts, varied significantly from 12 up to 74%. Currently, computed tomography (CT) is the most valuable method for diagnosis. The treatment include symptomatic support and identification of causes, but there is no specific treatment limiting the progression of calcification in the basal ganglia. Especially in HP, an early treatment can prevent calcification and neurophysiological disorders.
Topics: Adult; Humans; Calcium; Hypocalcemia; Basal Ganglia Diseases; Hypoparathyroidism
PubMed: 34224552
DOI: 10.1590/2175-8239-JBN-2020-0243