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Biomolecules Apr 202322q11.2 deletion syndrome (22q11.2DS) is associated with a high risk of developing various psychiatric and developmental disorders, including schizophrenia and...
22q11.2 deletion syndrome (22q11.2DS) is associated with a high risk of developing various psychiatric and developmental disorders, including schizophrenia and early-onset Parkinson's disease. Recently, a mouse model of this disease, Del(3.0Mb)/+, mimicking the 3.0 Mb deletion which is most frequently found in patients with 22q11.2DS, was generated. The behavior of this mouse model was extensively studied and several abnormalities related to the symptoms of 22q11.2DS were found. However, the histological features of their brains have been little addressed. Here we describe the cytoarchitectures of the brains of Del(3.0Mb)/+ mice. First, we investigated the overall histology of the embryonic and adult cerebral cortices, but they were indistinguishable from the wild type. However, the morphologies of individual neurons were slightly but significantly changed from the wild type counterparts in a region-specific manner. The dendritic branches and/or dendritic spine densities of neurons in the medial prefrontal cortex, nucleus accumbens, and primary somatosensory cortex were reduced. We also observed reduced axon innervation of dopaminergic neurons into the prefrontal cortex. Given these affected neurons function together as the dopamine system to control animal behaviors, the impairment we observed may explain a part of the abnormal behaviors of Del(3.0Mb)/+ mice and the psychiatric symptoms of 22q11.2DS.
Topics: Animals; Mice; DiGeorge Syndrome; Schizophrenia; Brain; Parkinson Disease; Prefrontal Cortex
PubMed: 37238632
DOI: 10.3390/biom13050763 -
Endocrine Feb 2017Restoration of the euparathyroid state is associated with improvement of bone dynamics both in hypoparathyroidism and primary hyperparathyroidism. To date, no study has...
Restoration of the euparathyroid state is associated with improvement of bone dynamics both in hypoparathyroidism and primary hyperparathyroidism. To date, no study has directly compared these two groups following correction of parathyroid hormone excess or deficiency. The study was designed to investigate changes in bone mineral density and trabecular bone score with restoration of the euparathyroid state by parathyroidectomy in primary hyperparathyroidism or recombinant parathyroid hormone [rhPTH(1-84)] replacement in hypoparathyroidism. This was a 2-year prospective intervention study in which we evaluated areal bone mineral density by DXA and trabecular bone score in 52 hypoparathyroid patients on rhPTH(1-84) replacement and 27 patients with primary hyperparathyroidism who underwent parathyroidectomy. We evaluated changes in areal bone mineral density by DXA and trabecular bone score at baseline, 6, 12, 18, and 24 months. After parathyroidectomy, areal bone mineral density increased from baseline at the lumbar spine and total hip at 6 months and at the femoral neck at 12 months, while there were no changes at the distal 1/3 radius. Treatment with rhPTH(1-84) was associated with significant increases in lumbar spine and decreases in distal 1/3 radius areal bone mineral density by 18 months in hypoparathyroid patients. At this time point, hypoparathyroid subjects demonstrated a significant increase in trabecular bone score from baseline, while there were no significant changes in trabecular bone score following parathyroidectomy. Bone mineral density increases both with administration of parathyroid hormone in a state of parathyroid hormone deficiency or removal of parathyroid hormone in a state of parathyroid hormone excess. However, only hypoparathyroid patients on rhPTH(1-84) appeared to have improvements in micro-architectural pattern as assessed by trabecular bone score.
Topics: Absorptiometry, Photon; Adult; Aged; Bone Density; Female; Hormone Replacement Therapy; Humans; Hyperparathyroidism, Primary; Hypoparathyroidism; Male; Middle Aged; Parathyroid Hormone; Parathyroidectomy; Recombinant Proteins; Treatment Outcome
PubMed: 27757772
DOI: 10.1007/s12020-016-1101-8 -
Case Reports in Endocrinology 2023Brachymetacarpia and brachymetatarsia are unique clinical entities associated with numerous rare conditions. Primary hypoparathyroidism is distinct from...
Brachymetacarpia and brachymetatarsia are unique clinical entities associated with numerous rare conditions. Primary hypoparathyroidism is distinct from pseudohypoparathyroidism and pseudopseudohypoparathyroidism by lacking skeletal changes such as short metacarpals or metatarsals. Here, we present a case of a 64-year-old patient with brachymetacarpia and brachymetatarsia presented with hypocalcemic symptoms and signs, bilateral cataracts, and basal ganglia calcifications, subsequently diagnosed with idiopathic primary hypoparathyroidism. This is a rare case describing such an infrequent observation of brachymetacarpia and brachymetatarsia in primary idiopathic hypoparathyroidism.
PubMed: 36895827
DOI: 10.1155/2023/4149677 -
Endocrine Journal Jan 2024Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and... (Review)
Review
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and pituitary irAEs are frequently observed, followed by primary adrenal insufficiency, insulin-dependent diabetes mellitus, and hypoparathyroidism. These conditions could lead to life-threatening consequences, such as adrenal crisis and diabetic ketoacidosis. On the other hand, several types of irAEs including thyroid and pituitary irAEs are reported to be associated with better overall survival. Therefore, it is important to understand and manage endocrine irAEs, which differ depending on the ICI regimen used. In this review, we describe the clinical features, potential biomarkers, management strategies, and possible mechanisms of thyroid and pituitary irAEs.
Topics: Humans; Thyroid Gland; Pituitary Gland; Pituitary Diseases; Biomarkers; Diabetes Mellitus, Type 1; Neoplasms
PubMed: 37940567
DOI: 10.1507/endocrj.EJ23-0524 -
Biomedicines Apr 2021Pregnancy and lactation are characterized by sophisticated adaptations of calcium homeostasis, aiming to meet fetal, neonatal, and maternal calcium requirements.... (Review)
Review
Pregnancy and lactation are characterized by sophisticated adaptations of calcium homeostasis, aiming to meet fetal, neonatal, and maternal calcium requirements. Pregnancy is primarily characterized by an enhancement of intestinal calcium absorption, whereas during lactation additional calcium is obtained through resorption from the maternal skeleton, a process which leads to bone loss but is reversible following weaning. These maternal adaptations during pregnancy and lactation may influence or confound the presentation, diagnosis, and management of parathyroid disorders such as primary hyperparathyroidism or hypoparathyroidism. Parathyroid diseases are uncommon in these settings but can be severe when they occur and may affect both maternal and fetal health. This review aims to delineate the changes in calcium physiology that occur with pregnancy and lactation, describe the disorders of calcium and parathyroid physiology that can occur, and outline treatment strategies for these diseases in the above settings.
PubMed: 33925967
DOI: 10.3390/biomedicines9050475 -
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 -
PloS One 2015Metabolic factors are increasingly recognized to play an important role in the pathogenesis of Alzheimer's disease and dementia. Abnormal parathyroid hormone (PTH)... (Review)
Review
BACKGROUND
Metabolic factors are increasingly recognized to play an important role in the pathogenesis of Alzheimer's disease and dementia. Abnormal parathyroid hormone (PTH) levels play a role in neuronal calcium dysregulation, hypoperfusion and disrupted neuronal signaling. Some studies support a significant link between PTH levels and dementia whereas others do not.
METHODS
We conducted a systematic review through January 2014 to evaluate the association between PTH and parathyroid conditions, cognitive function and dementia. Eleven electronic databases and citation indexes were searched including Medline, Embase and the Cochrane Library. Hand searches of selected journals, reference lists of primary studies and reviews were also conducted along with websites of key organizations. Two reviewers independently screened titles and abstracts of identified studies. Data extraction and study quality were performed by one and checked by a second reviewer using predefined criteria. A narrative synthesis was performed due to the heterogeneity of included studies.
RESULTS
The twenty-seven studies identified were of low and moderate quality, and challenging to synthesize due to inadequate reporting. Findings from six observational studies were mixed but suggest a link between higher serum PTH levels and increased odds of poor cognition or dementia. Two case-control studies of hypoparathyroidism provide limited evidence for a link with poorer cognitive function. Thirteen pre-post surgery studies for primary hyperparathyroidism show mixed evidence for improvements in memory though limited agreement in other cognitive domains. There was some degree of cognitive impairment and improvement postoperatively in observational studies of secondary hyperparathyroidism but no evident pattern of associations with specific cognitive domains.
CONCLUSIONS
Mixed evidence offers weak support for a link between PTH, cognition and dementia due to the paucity of high quality research in this area.
Topics: Alzheimer Disease; Calcium; Cognition; Humans; Memory; Neurons; Parathyroid Hormone
PubMed: 26010883
DOI: 10.1371/journal.pone.0127574 -
Journal of the Endocrine Society Apr 2018Endocrine disorders are common in individuals with mitochondrial disease. To develop evidence-based screening practices in this high-risk population, updated...
CONTEXT
Endocrine disorders are common in individuals with mitochondrial disease. To develop evidence-based screening practices in this high-risk population, updated age-stratified estimates of the prevalence of endocrine conditions are needed.
OBJECTIVE
To measure the point prevalence of selected endocrine disorders in individuals with mitochondrial disease.
DESIGN SETTING AND PATIENTS
The North American Mitochondrial Disease Consortium Patient Registry is a large, prospective, physician-curated cohort study of individuals with mitochondrial disease. Participants (n = 404) are of any age, with a diagnosis of primary mitochondrial disease confirmed by molecular genetic testing.
MAIN OUTCOME MEASURES
Age-specific prevalence of diabetes mellitus (DM), abnormal growth and sexual maturation (AGSM), hypoparathyroidism, and hypothyroidism.
RESULTS
The majority of our sample was pediatric (<18 years; 60.1%), female (56.9%), and white (85.9%). DM affected 2% of participants aged <18 years [95% confidence interval (CI): 0.4% to 5.7%] and 24.4% of adult participants (95% CI: 18.6% to 30.9%). DM prevalence was highest in individuals with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes syndrome (MELAS; 31.9%, of whom 86.2% had the m.3243A>G mutation). DM occurred more often with mitochondrial DNA defects (point mutations and/or deletions) than with nuclear DNA mutations (23.3% vs 3.7%, respectively; < 0.001). Other prevalence estimates were 44.1% (95% CI: 38.8% to 49.6%) for AGSM; 0.3% (95% CI: 0% to 1.6%) for hypoparathyroidism; and 6.3% (95% CI: 4% to 9.3%) for hypothyroidism.
CONCLUSION
DM and AGSM are highly prevalent in primary mitochondrial disease. Certain clinical mitochondrial syndromes (MELAS and Kearns-Sayre/Pearson syndrome spectrum disorders) demonstrated a higher burden of endocrinopathies. Clinical screening practices should reflect the substantial prevalence of endocrine disorders in mitochondrial disease.
PubMed: 29594260
DOI: 10.1210/js.2017-00434 -
Frontiers in Physiology 2016Extracellular calcium is essential for life and its concentration in the blood is maintained within a narrow range. This is achieved by a feedback loop that receives... (Review)
Review
Extracellular calcium is essential for life and its concentration in the blood is maintained within a narrow range. This is achieved by a feedback loop that receives input from the calcium-sensing receptor (CASR), expressed on the surface of parathyroid cells. In response to low ionized calcium, the parathyroids increase secretion of parathyroid hormone (PTH) which increases serum calcium. The CASR is also highly expressed in the kidneys, where it regulates the reabsorption of calcium from the primary filtrate. Autosomal dominant hypocalcemia (ADH) type 1 is caused by heterozygous activating mutations in the CASR which increase the sensitivity of the CASR to extracellular ionized calcium. Consequently, PTH synthesis and secretion are suppressed at normal ionized calcium concentrations. Patients present with hypocalcemia, hyperphosphatemia, low magnesium levels, and low or low-normal levels of PTH. Urinary calcium excretion is typically increased due to the decrease in circulating PTH concentrations and by the activation of the renal tubular CASR. Therapeutic attempts using CASR antagonists (calcilytics) to treat ADH are currently under investigation. Recently, heterozygous mutations in the alpha subunit of the G protein G11 (Gα11) have been identified in patients with ADH, and this has been classified as ADH type 2. ADH2 mutations lead to a gain-of-function of Gα11, a key mediator of CASR signaling. Therefore, the mechanism of hypocalcemia appears similar to that of activating mutations in the CASR, namely an increase in the sensitivity of parathyroid cells to extracellular ionized calcium. Studies of activating mutations in the CASR and gain-of-function mutations in Gα11 can help define new drug targets and improve medical management of patients with ADH types 1 and 2.
PubMed: 27803672
DOI: 10.3389/fphys.2016.00458 -
Kidney International. Supplement Dec 1999Recognizing the role of the extracellular calcium-sensing receptor (CaR) in mineral metabolism greatly improves our understanding of calcium homeostasis. The biology of... (Review)
Review
Recognizing the role of the extracellular calcium-sensing receptor (CaR) in mineral metabolism greatly improves our understanding of calcium homeostasis. The biology of the low affinity, G-protein-coupled CaR and the effects of its activation in various tissues are reviewed. Physiological roles include regulation of parathyroid hormone (PTH) secretion by small changes in ionized calcium (Ca2+) and control of urinary calcium excretion with small changes in blood Ca2+. The CaR also affects the renal handling of sodium, magnesium and water. Mutations affecting the CaR that make it either less or more sensitive to Ca2+ cause various clinical disorders; heterozygotes of mutations causing the CaR to be less sensitive to extracellular Ca2+ cause familial hypocalciuric hypercalcemia, while the homozygous form results in severe infantile hyperparathyroidism. Mutations causing increased sensitivity of the CaR to extracellular Ca2+ produce hereditary forms of hypoparathyroidism. Disorders, such as primary and secondary hyperparathyroidism, may exhibit acquired abnormalities of the CaR. Calcimimetic drugs, which amplify the sensitivity of the CaR to Ca2+, can suppress PTH levels, leading to a fall in blood Ca2+. Experiences with this agent in patients with secondary and primary hyperparathyroidism and parathyroid carcinoma are summarized. In animals and humans with hyperparathyroidism, this agent produces a dose-dependent fall in PTH and blood Ca2+, with larger doses causing more sustained effects. The treatment has been short-term except for one patient followed for more than 600 days for parathyroid carcinoma; nonetheless the drug did not cause major side-effects and appears to be safe. Further long-term controlled studies are needed with calcimimetic agents of this type.
Topics: Aniline Compounds; Animals; Calcium; Humans; Hyperparathyroidism; Kidney; Parathyroid Glands; Parathyroid Hormone; Phenethylamines; Propylamines; Receptors, Calcium-Sensing; Receptors, Cell Surface
PubMed: 10633465
DOI: 10.1046/j.1523-1755.1999.07303.x