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Therapeutic Advances in Chronic Disease Jan 2018In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the... (Review)
Review
In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the classification system for osteogenesis imperfecta (OI) and the resultant increase in therapeutic options available for management of OI. Bisphosphonates remain the most widely used intervention for OI, although the effect on fracture rate reduction is equivocal. We review the other therapies showing promising results, including denosumab, teriparatide, sclerostin, transforming growth factor β inhibition and gene targeted approaches. X-linked hypophosphataemia (XLH) is the most common heritable form of osteomalacia and rickets caused by a mutation in the phosphate regulating endopeptidase gene resulting in elevated serum fibroblast growth factor 23 (FGF23) and decreased renal phosphate reabsorption. The traditional treatment is phosphate replacement. We discuss the development of a human anti-FGF23 antibody (KRN23) as a promising development in the treatment of XLH. The current management of primary hypoparathyroidism is replacement with calcium and active vitamin D. This can be associated with under or over replacement and its inherent complications. We review the use of recombinant parathyroid hormone (1-84), which can significantly reduce the requirements for calcium and vitamin D resulting in greater safety and quality of life for individuals with hypoparathyroidism. The use of receptor activator of nuclear factor κB ligand infusions in the treatment of a particular form of osteopetrosis and enzyme replacement therapy for hypophosphatasia are also discussed.
PubMed: 29344330
DOI: 10.1177/2040622317739538 -
International Journal of Molecular... Feb 2023DiGeorge syndrome (DGS) is a rare genetic disease caused by microdeletions of the 22q11.2 region (DGS1). A haploinsufficiency at 10p level has been proposed also as a... (Review)
Review
DiGeorge syndrome (DGS) is a rare genetic disease caused by microdeletions of the 22q11.2 region (DGS1). A haploinsufficiency at 10p level has been proposed also as a DGS cause (DGS2). Clinical manifestations are variable. The most frequent features are thymic hypoplasia or aplasia with consequent immune deficiency, cardiac malformations, hypoparathyroidism, facial and palatine abnormalities, variable degrees of cognitive impairment and psychiatric disorders. The specific aim of this descriptive report is to discuss the correlation between oxidative stress and neuroinflammation in DGS patients with microdeletions of the 22q11.2 region. The deleted chromosomic region maps various genes involved in mitochondrial metabolisms, such as DGCR8 and TXNRD2, that could lead to reactive oxygen species (ROS) increased production and antioxidant depletion. Furthermore, increased levels of ROS in mitochondria would lead to the destruction of the projection neurons in the cerebral cortex with consequent neurocognitive impairment. Finally, the increase in modified protein belonging to the family of sulfoxide compounds and hexoses, acting as inhibitors of the IV and V mitochondria complex, could result in direct ROS overproduction. Neuroinflammation in DGS individuals could be directly related to the development of the syndrome's characteristic psychiatric and cognitive disorders. In patients with psychotic disorders, the most frequent psychiatric manifestation in DGS, Th-17, Th-1 and Th-2 cells are increased with consequent elevation of proinflammatory cytokine IL-6 and IL1β. In patients with anxiety disorders, both CD3 and CD4 are increased. Some patients with autism spectrum disorders (ASDs) have an augmented level of proinflammatory cytokines IL-12, IL-6 and IL-1β, while IFNγ and the anti-inflammatory cytokine IL-10 seem to be reduced. Other data proposed that altered synaptic plasticity could be directly involved in DGS cognitive disorders. In conclusion, the use of antioxidants for restoring mitochondrial functionality in DGS could be a useful tool to protect cortical connectivity and cognitive behavior.
Topics: Humans; DiGeorge Syndrome; Reactive Oxygen Species; Neuroinflammatory Diseases; Interleukin-6; MicroRNAs; RNA-Binding Proteins; Oxidative Stress
PubMed: 36835652
DOI: 10.3390/ijms24044242 -
JAMA Network Open May 2024Hypoparathyroidism following thyroid surgery is a serious complication that occurs frequently when surgery is performed by low-volume thyroid surgeons without experience...
IMPORTANCE
Hypoparathyroidism following thyroid surgery is a serious complication that occurs frequently when surgery is performed by low-volume thyroid surgeons without experience in parathyroid surgery.
OBJECTIVE
To evaluate the occurrence of hypoparathyroidism following total thyroidectomy after the introduction of autofluorescence in low-volume, nonparathyroid institutions.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, multicenter cohort study, with a follow-up period of up to 1 year, was conducted in Denmark at 2 low-volume nonparathyroid institutions between January 2021 and November 2023. All adult patients referred for total thyroidectomy were assessed for eligibility (n = 90). Only patients with no history of thyroid surgery were considered (n = 89). Patients who only underwent lobectomy (n = 6) or declined to participate (n = 5) were excluded. All included patients completed follow-up. The prospective cohort was compared with a historical cohort of successive patients undergoing primary total thyroidectomy from 2016 to 2020 (before autofluorescence was available).
INTERVENTION
Included patients underwent autofluorescence-guided total thyroidectomy.
MAIN OUTCOMES AND MEASURES
Rate of hypoparathyroidism. Immediate hypoparathyroidism was defined as the need for active vitamin D postoperatively, whereas permanent hypoparathyroidism was considered when there still was a need for active vitamin D 1 year after surgery.
RESULTS
Seventy-eight patients underwent autofluorescence-guided surgery (mean [SD] age, 55.6 [13.1] years; 67 [86%] female) and were compared with 89 patients in the historical cohort (mean [SD] age, 49.7 [12.8] years; 78 [88%] female). The rate of immediate hypoparathyroidism decreased from 37% (95% CI, 27%-48%) to 19% (95% CI, 11%-30%) after the introduction of autofluorescence (P = .02). Permanent hypoparathyroidism rates decreased from 32% (95% CI, 22%-42%) to 6% (95% CI, 2%-14%) (P < .001), reaching 0% at the end of the study. More parathyroid glands were identified with autofluorescence (75% [95% CI, 70%-80%] vs 61% [95% CI, 56%-66%]) (P < .001) and less parathyroid glands were inadvertently excised (4% [95% CI, 1%-11%] vs 21% [95% CI, 13%-31%]) (P = .001).
CONCLUSIONS AND RELEVANCE
In this cohort study of autofluorescence-guided thyroid surgery in low-volume, nonparathyroid institutions, the use of autofluorescence was associated with a significant decrease in both immediate and permanent hypoparathyroidism. When autofluorescence was used, hypoparathyroidism rates were comparable with those of high-volume surgeons who also perform parathyroid surgery.
Topics: Humans; Thyroidectomy; Hypoparathyroidism; Female; Male; Middle Aged; Prospective Studies; Postoperative Complications; Adult; Denmark; Optical Imaging; Aged; Surgery, Computer-Assisted
PubMed: 38748422
DOI: 10.1001/jamanetworkopen.2024.11384 -
Journal of Clinical Medicine Feb 2021The coronavirus disease, COVID-19, has caused widespread and sustained disruption to healthcare, not only in the delivery of emergency care, but knock-on consequences... (Review)
Review
The coronavirus disease, COVID-19, has caused widespread and sustained disruption to healthcare, not only in the delivery of emergency care, but knock-on consequences have resulted in major delays to the delivery of elective care, including surgery. COVID-19 has accelerated novel pathways for delivering clinical services, many of which have an increased reliance on technology. COVID-19 has impacted care for patients with both hypoparathyroidism and hyperparathyroidism. The role of vitamin D in the prevention of severe COVID-19 infection has also been widely debated. Severe hypocalcemia can be precipitated by infection in patients with hypoparathyroidism. With this in mind, compliance with medical management, including calcium and vitamin D supplementation, is crucial. Technology in the form of text message reminders and smartphone apps may have a key role in ensuring this. Furthermore, clinicians should ensure that patients are educated on the symptoms of hypocalcemia and the steps needing to be taken should these symptoms be experienced. Patients with primary hyperparathyroidism (PHPT) should be educated on the symptoms of hypercalcemia, as well as the importance of remaining adequately hydrated. In addition, patients should be reassured that the postponement of parathyroidectomy is likely to have negligible impact on their condition; for those with symptomatic hypercalcemia, cinacalcet can be considered as an interim measure.
PubMed: 33652905
DOI: 10.3390/jcm10050920 -
Clinical Endocrinology Oct 2022Disorders of calcium homeostasis are the most frequent metabolic bone and mineral disease encountered by endocrinologists. These disorders usually manifest as primary... (Review)
Review
Disorders of calcium homeostasis are the most frequent metabolic bone and mineral disease encountered by endocrinologists. These disorders usually manifest as primary hyperparathyroidism (PHPT) or hypoparathyroidism (HP), which have a monogenic aetiology in 5%-10% of cases, and may occur as an isolated endocrinopathy, or as part of a complex syndrome. The recognition and diagnosis of these disorders is important to facilitate the most appropriate management of the patient, with regard to both the calcium-related phenotype and any associated clinical features, and also to allow the identification of other family members who may be at risk of disease. Genetic testing forms an important tool in the investigation of PHPT and HP patients and is usually reserved for those deemed to be an increased risk of a monogenic disorder. However, identifying those suitable for testing requires a thorough clinical evaluation of the patient, as well as an understanding of the diversity of relevant phenotypes and their genetic basis. This review aims to provide an overview of the genetic basis of monogenic metabolic bone and mineral disorders, primarily focusing on those associated with abnormal calcium homeostasis, and aims to provide a practical guide to the implementation of genetic testing in the clinic.
Topics: Calcium; Calcium, Dietary; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Phenotype; Receptors, Calcium-Sensing
PubMed: 34935164
DOI: 10.1111/cen.14644 -
Problemy Endokrinologii Aug 2021Hypoparathyroidism is a rare disorder characterized by the absent or inappropriately decreased serum parathyroid hormone in the parathyroid glands, which is accompanied... (Review)
Review
Hypoparathyroidism is a rare disorder characterized by the absent or inappropriately decreased serum parathyroid hormone in the parathyroid glands, which is accompanied by impaired calcium-phosphorus metabolism.The main etiology of hypoparathyroidism remains damage or removal of the parathyroid glands during neck surgery. In view of the incidence of thyroid cancer, primary hyperparathyroidism and other pathologies of the neck organs, which radical treatment can lead to the parathyroid gland impairment, an increased number of patients with hypoparathyroidism is expected. Autoimmune hypoparathyroidism is the second most common form of the disease, usually occurring as part of type 1 autoimmune polyglandular syndrome. Autoimmune hypoparathyroidism usually occurs in childhood and is characterized by a severe course of the disease, especially in the case of concomitant malabsorption syndrome.Chronic hypoparathyroidism of any etiology requires lifelong multicomponent therapy, as well as careful monitoring and an individual approach to choose the optimal treatment strategy. In the absence of adequate follow-up, the risks of long-term complications significantly increase, particularly in the renal, cardiovascular systems; in the soft tissues and in the brain, it could lead to visual disturbances; pathology of the musculoskeletal system with a decreased bone remodeling and a potential risk of fractures, as well as to the neurocognitive disorders and an impaired health-related quality of life.Timely diagnosis, rational medical therapy and management strategy may reduce the risks of short-term and long-term complications, frequency of hospitalizations and disability of patients, as well as improve the prognosis.This review covers the main issues of Russian guidelines for the management of chronic hypoparathyroidism, approved in 2021, including laboratory and instrumental evaluation, treatment approaches and follow-up. This guidelines also include the recommendations for special groups of patients: with acute hypocalcemia, hypoparathyroidism during pregnancy.
Topics: Humans; Hypocalcemia; Hypoparathyroidism; Parathyroid Glands; Parathyroid Hormone; Quality of Life
PubMed: 34533015
DOI: 10.14341/probl12800 -
World Journal of Gastroenterology Sep 2011The parathyroid glands are the main regulator of plasma calcium and have a direct influence on the digestive tract. Parathyroid disturbances often result in unknown... (Review)
Review
The parathyroid glands are the main regulator of plasma calcium and have a direct influence on the digestive tract. Parathyroid disturbances often result in unknown long-standing symptoms. The main manifestation of hypoparathyroidism is steatorrhea due to a deficit in exocrine pancreas secretion. The association with celiac sprue may contribute to malabsorption. Hyperparathyroidism causes smooth-muscle atony, with upper and lower gastrointestinal symptoms such as nausea, heartburn and constipation. Hyperparathyroidism and peptic ulcer were strongly linked before the advent of proton pump inhibitors. Nowadays, this association remains likely only in the particular context of multiple endocrine neoplasia type 1/Zollinger-Ellison syndrome. In contrast to chronic pancreatitis, acute pancreatitis due to primary hyperparathyroidism is one of the most studied topics. The causative effect of high calcium level is confirmed and the distinction from secondary hyperparathyroidism is mandatory. The digestive manifestations of parathyroid malfunction are often overlooked and serum calcium level must be included in the routine workup for abdominal symptoms.
Topics: Celiac Disease; Gastrointestinal Diseases; Humans; Pancreas; Pancreatitis; Parathyroid Diseases; Steatorrhea; Zollinger-Ellison Syndrome
PubMed: 22039319
DOI: 10.3748/wjg.v17.i36.4063 -
Journal of Pediatric Endocrinology &... Feb 2023The past 50 years of research in pediatric bone and mineral metabolism have led to remarkable progress in the identification and characterization of disorders that... (Review)
Review
The past 50 years of research in pediatric bone and mineral metabolism have led to remarkable progress in the identification and characterization of disorders that affect the developing skeleton. Progress has been facilitated through advances in both technology and biology and this paper provides a brief description of some but not all of the key findings, including identification of the calcium sensing receptor and the polypeptides parathyroid hormone and parathyroid hormone-related protein as well as their shared receptor and signal generating pathways; the elucidation of vitamin D metabolism and actions; discovery of fibroblast growth factor 23 (FGF23), the sodium-phosphate co-transporters and the other components that regulate phosphate metabolism. Moreover, the past half-century of research has led to the delineation of the molecular bases for genetic forms of hypoparathyroidism, pseudohypoparathyroidism, and primary hyperparathyroidism as well as the determination of the genetic causes of osteogenesis imperfecta, osteopetrosis, hypophosphatasia, and other disorders of mineral/bone homeostasis. During the next decade we expect that many of these fundamental discoveries will lead to the development of innovative treatments that will improve the lives of children with these disorders.
Topics: Child; Adolescent; Humans; Bone and Bones; Parathyroid Hormone; Osteogenesis Imperfecta; Hypophosphatasia; Phosphates; Fibroblast Growth Factors; Calcium; Vitamin D
PubMed: 36636022
DOI: 10.1515/jpem-2022-0624 -
Proceedings of the Royal Society of... Dec 1964
Topics: Calcium; Calcium, Dietary; Child; Diagnosis; Dihydrotachysterol; Drug Therapy; Ergocalciferols; Humans; Hypoparathyroidism
PubMed: 14244887
DOI: No ID Found -
Experimental and Therapeutic Medicine May 2022Low levels of serum calcium, elevated levels of serum phosphorus and absent or abnormally low levels of serum parathyroid hormone characterize hypoparathyroidism, a rare...
Low levels of serum calcium, elevated levels of serum phosphorus and absent or abnormally low levels of serum parathyroid hormone characterize hypoparathyroidism, a rare endocrine deficiency illness. Hypoparathyroidism is caused by injury to the parathyroid gland as a result of surgery or autoimmune disease. In addition, hypoparathyroidism may develop due to genetic causes or infiltrative diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by multi-organ involvement, including the dysfunction of endocrine glands. Previous studies have demonstrated that SARS-CoV-2 infection induces endocrine tissue damage via various mechanisms, including direct cell damage from viral entry to the glands by binding to the angiotensin converting enzyme 2 receptors and replication, vasculitis, arterial and venous thrombosis, hypoxic cell damage, immune response and the cytokine storm. The effects of the new coronavirus, coronavirus disease 2019 (COVID-19) on the parathyroid glands have received limited attention. Hypoparathyroidism has been observed in a small number of individuals as a result of SARS-CoV-2 infection. The present study describes the case of a patient with primary hypoparathyroidism induced by COVID-19. Clinicians should also keep in mind that, despite the fact that SARS-CoV-2 has no known tropism for the parathyroid glands, it can result in primary hypoparathyroidism and decompensation of old primary hypoparathyroidism.
PubMed: 35401797
DOI: 10.3892/etm.2022.11276