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Canadian Family Physician Medecin de... Feb 2012To provide family physicians with an evidence-based approach to the diagnosis and management of hypocalcemia. Quality of evidence MEDLINE and EMBASE articles from 2000... (Review)
Review
OBJECTIVE
To provide family physicians with an evidence-based approach to the diagnosis and management of hypocalcemia. Quality of evidence MEDLINE and EMBASE articles from 2000 to 2010 were searched, with a focus on the diagnosis and management of hypocalcemia. Levels of evidence (I to III) were cited where appropriate, with most studies providing level II or III evidence. References of pertinent papers were also searched for relevant articles. Main message Chronic hypocalcemia is commonly due to inadequate levels of parathyroid hormone or vitamin D, or due to resistance to these hormones. Treatment focuses on oral calcium and vitamin D supplements, as well as magnesium if deficiency is present. Treatment can be further intensified with thiazide diuretics, phosphate binders, and a low-salt and low-phosphorus diet when treating hypocalcemia secondary to hypoparathyroidism. Acute and life-threatening calcium deficit requires treatment with intravenous calcium.The current treatment recommendations are largely based on expert clinical opinion and published case reports,as adequately controlled clinical trial data are not currently available. Complications of current therapies for hypoparathyroidism include hypercalciuria, nephrocalcinosis, renal impairment, and soft tissue calcification. Current therapy is limited by serum calcium fluctuations. Although these complications are well recognized, the effects of therapy on overall well-being, mood, cognition, and quality of life, as well as the risk of complications,have not been adequately studied.
CONCLUSION
Family physicians play a crucial role in educating patients about the long-term management and complications of hypocalcemia. Currently, management is suboptimal and marked by fluctuations in serum calcium and a lack of approved parathyroid hormone replacement therapy for hypoparathyroidism.
Topics: Calcium; Chronic Disease; Diet Therapy; Dietary Supplements; Humans; Hypocalcemia; Magnesium; Primary Health Care; Vitamin D; Vitamins
PubMed: 22439169
DOI: No ID Found -
Nature Reviews. Endocrinology Dec 2018The Ca-sensing receptor (CaSR) is a dimeric family C G protein-coupled receptor that is expressed in calcitropic tissues such as the parathyroid glands and the kidneys... (Comparative Study)
Comparative Study Review
The Ca-sensing receptor (CaSR) is a dimeric family C G protein-coupled receptor that is expressed in calcitropic tissues such as the parathyroid glands and the kidneys and signals via G proteins and β-arrestin. The CaSR has a pivotal role in bone and mineral metabolism, as it regulates parathyroid hormone secretion, urinary Ca excretion, skeletal development and lactation. The importance of the CaSR for these calcitropic processes is highlighted by loss-of-function and gain-of-function CaSR mutations that cause familial hypocalciuric hypercalcaemia and autosomal dominant hypocalcaemia, respectively, and also by the fact that alterations in parathyroid CaSR expression contribute to the pathogenesis of primary and secondary hyperparathyroidism. Moreover, the CaSR is an established therapeutic target for hyperparathyroid disorders. The CaSR is also expressed in organs not involved in Ca homeostasis: it has noncalcitropic roles in lung and neuronal development, vascular tone, gastrointestinal nutrient sensing, wound healing and secretion of insulin and enteroendocrine hormones. Furthermore, the abnormal expression or function of the CaSR is implicated in cardiovascular and neurological diseases, as well as in asthma, and the CaSR is reported to protect against colorectal cancer and neuroblastoma but increase the malignant potential of prostate and breast cancers.
Topics: Calcimimetic Agents; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Hypercalcemia; Hypercalciuria; Hypocalcemia; Hypoparathyroidism; Incidence; Male; Mutation; Nephrolithiasis; Prognosis; Receptors, Calcium-Sensing; Risk Assessment; Treatment Outcome
PubMed: 30443043
DOI: 10.1038/s41574-018-0115-0 -
Current Allergy and Asthma Reports Apr 2023This review focuses on immunologic findings, relationships among immunologic findings and associated conditions of autoimmunity and atopy, and management of immunologic... (Review)
Review
PURPOSE OF REVIEW
This review focuses on immunologic findings, relationships among immunologic findings and associated conditions of autoimmunity and atopy, and management of immunologic disease in chromosome 22q11.2 deletion syndrome (22q11.2DS, historically known as DiGeorge syndrome).
RECENT FINDINGS
The implementation of assessment of T cell receptor excision circles (TRECs) in newborn screening has led to increased detection of 22q11.2 deletion syndrome. While not yet applied in clinical practice, cell-free DNA screening for 22q11.2DS also has the potential to improve early detection, which may benefit prompt evaluation and management. Multiple studies have further elucidated phenotypic features and potential biomarkers associated with immunologic outcomes, including the development of autoimmune disease and atopy. The clinical presentation of 22q11.2DS is highly variable particularly with respect to immunologic manifestations. Time to recovery of immune system abnormalities is not well-defined in current literature. An understanding of the underlying causes of immunologic changes found in 22q11.2DS, and the progression and evolution of immunologic changes over the lifespan have expanded over time and with improved survival. An included case highlights the variability of presentation and potential severity of T cell lymphopenia in partial DiGeorge syndrome and demonstrates successful spontaneous immune reconstitution in partial DiGeorge syndrome despite initial severe T cell lymphopenia.
Topics: Infant, Newborn; Humans; DiGeorge Syndrome; Chromosome Deletion; Neonatal Screening; Lymphopenia; Chromosomes
PubMed: 36897497
DOI: 10.1007/s11882-023-01071-4 -
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 -
Frontiers in Pediatrics 2021Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type-1 (APS-1), is a rare monogenic autoimmune... (Review)
Review
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type-1 (APS-1), is a rare monogenic autoimmune disease caused by loss-of-function mutations in the autoimmune regulator () gene. AIRE deficiency impairs immune tolerance in the thymus and results in the peripheral escape of self-reactive T lymphocytes and the generation of several cytokine- and tissue antigen-targeted autoantibodies. APECED features a classic triad of characteristic clinical manifestations consisting of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and primary adrenal insufficiency (Addison's disease). In addition, APECED patients develop several non-endocrine autoimmune manifestations with variable frequencies, whose recognition by pediatricians should facilitate an earlier diagnosis and allow for the prompt implementation of targeted screening, preventive, and therapeutic strategies. This review summarizes our current understanding of the genetic, immunological, clinical, diagnostic, and treatment features of APECED.
PubMed: 34790633
DOI: 10.3389/fped.2021.723532 -
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 -
Journal of Bone and Mineral Research :... Jan 2023Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone... (Randomized Controlled Trial)
Randomized Controlled Trial
Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double-blind, placebo-controlled, 26-week, phase 3 PaTHway trial assessed the efficacy and safety of PTH replacement therapy for hypoparathyroidism individuals with the investigational drug TransCon PTH (palopegteriparatide). Participants (n = 84) were randomized 3:1 to once-daily TransCon PTH (initially 18 μg/d) or placebo, both co-administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin-adjusted serum calcium levels (8.3-10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. Other outcomes of interest included health-related quality of life measured by the 36-Item Short Form Survey (SF-36), hypoparathyroidism-related symptoms, functioning, and well-being measured by the Hypoparathyroidism Patient Experience Scale (HPES), and urinary calcium excretion. At week 26, 79% (48/61) of participants treated with TransCon PTH versus 5% (1/21) wiplacebo met the composite primary efficacy endpoint (p < 0.0001). TransCon PTH treatment demonstrated a significant improvement in all key secondary endpoint HPES domain scores (all p < 0.01) and the SF-36 Physical Functioning subscale score (p = 0.0347) compared with placebo. Additionally, 93% (57/61) of participants treated with TransCon PTH achieved independence from conventional therapy. TransCon PTH treatment normalized mean 24-hour urine calcium. Overall, 82% (50/61) treated with TransCon PTH and 100% (21/21) wiplacebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred. In conclusion, TransCon PTH maintained normocalcemia while permitting independence from conventional therapy and was well-tolerated in individuals with hypoparathyroidism. © 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; Parathyroid Hormone; Calcium; Quality of Life; Hypoparathyroidism; Vitamin D; Hormone Replacement Therapy; Calcium, Dietary; Minerals
PubMed: 36271471
DOI: 10.1002/jbmr.4726 -
American Family Physician Aug 2013Disorders of the parathyroid glands most commonly present with abnormalities of serum calcium. Patients with primary hyperparathyroidism, the most common cause of... (Review)
Review
Disorders of the parathyroid glands most commonly present with abnormalities of serum calcium. Patients with primary hyperparathyroidism, the most common cause of hypercalcemia in outpatients, are often asymptomatic or may have bone disease, nephrolithiasis, or neuromuscular symptoms. Patients with chronic kidney disease may develop secondary hyperparathyroidism with resultant chronic kidney disease-mineral and bone disorder. Hypoparathyroidism most often occurs after neck surgery; it can also be caused by autoimmune destruction of the glands and other less common problems. Evaluation of patients with abnormal serum calcium levels includes a history and physical examination; repeat measurement of serum calcium level; and measurement of creatinine, magnesium, vitamin D, and parathyroid hormone levels. The treatment for symptomatic primary hyperparathyroidism is parathyroidectomy. Management of asymptomatic primary hyperparathyroidism includes monitoring symptoms; serum calcium and creatinine levels; and bone mineral density. Patients with hypoparathyroidism require close monitoring and vitamin D (e.g., calcitriol) replacement.
Topics: Absorptiometry, Photon; Asymptomatic Diseases; Bone Diseases, Metabolic; Calcitriol; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Hyperparathyroidism, Secondary; Hypocalcemia; Hypoparathyroidism; Parathyroid Diseases; Renal Insufficiency, Chronic
PubMed: 23944728
DOI: No ID Found -
Journal of Bone and Mineral Research :... Dec 2022
Topics: Humans; Hypoparathyroidism; Parathyroid Hormone
PubMed: 36375811
DOI: 10.1002/jbmr.4671