Basal ganglia calcification is associated with local and systemic metabolic mechanisms in adult hypoparathyroidism

2021 ◽  
Author(s):  
Guido Zavatta ◽  
Peter J Tebben ◽  
Cynthia H McCollough ◽  
Lifeng Yu ◽  
Thomas Vrieze ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Calcium Phosphate ◽  
Serum Calcium ◽  
Serum Phosphorus ◽  
Basal Ganglia Calcification ◽  
Ct Head ◽  
Nonsurgical Patients ◽  
The Brain ◽  
Chronic Hypoparathyroidism ◽  
Low Serum

Abstract Context Hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone, which may be associated with soft tissue calcification in the basal ganglia of the brain. Objective To assess the prevalence and factors involved in the pathophysiology of basal ganglia calcification (BGC) in the brain in chronic hypoparathyroidism, and to evaluate proposed pathophysiologic mechanisms. Design Case-control study with retrospective review of medical records over 20 years. Setting Single academic medical center. Patients 142 patients with chronic hypoparathyroidism and CT head scans followed between 1/1/2000 and 7/9/2020, and 426 age- and sex-matched controls with CT head scans over the same interval. Interventions None. Main Outcome Measures Demographic, biochemical, and CT head imaging findings, with semi-quantitative assessment of volumetric BGC. Results The study found that 25.4% of 142 patients followed for a median of 17 years after diagnosis of chronic hypoparathyroidism had BGC, which developed at a younger age than in controls. BGC was 5.1-fold more common in nonsurgical patients, and less common in postsurgical patients. Low serum calcium and low calcium/phosphate ratio correlated with BGC. Neither serum phosphorus nor calcium x phosphate product predicted BGC. Lower serum calcium was associated with greater volume of BGC. The extent of BGC varied widely, with nonsurgical patients generally having a greater volume and distribution of calcification. Conclusions BGC is associated with low serum calcium and low serum calcium/phosphate ratio, which may be related to severity of the disease, its etiology, or duration of treatment.

scholarly journals Basal Ganglia Calcification in Hypoparathyroidism Is Associated With Low Serum Calcium/Phosphate Ratio

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A255-A256
Author(s):  
Guido Zavatta ◽  
Peter J Tebben ◽  
Bart Lyman Clarke
Keyword(s):  
Risk Factors ◽  
Basal Ganglia ◽  
Calcium Phosphate ◽  
Serum Calcium ◽  
Weighted Average ◽  
Ct Scans ◽  
Basal Ganglia Calcification ◽  
Head Ct ◽  
Time Weighted Average ◽  
Low Serum

Abstract Background: Basal ganglia calcification (BGC) is a well-known complication of hypoparathyroidism. It is currently thought that increased serum phosphate or calcium x phosphate product may be major risk factors. However, the pathophysiology of BGC is still unclear, since the literature is largely based on limited case series or case reports. Methods: We identified a large cohort of patients with hypoparathyroidism diagnosed between 2000 and 2020 and evaluated those with head CT scans performed over this interval. Etiology and date of onset of hypoparathyroidism were determined by medical records review. All head CT scan images were reviewed to confirm radiology reports reporting BGC. We retrieved laboratory data within 10 years before the first head CT that showed incident BGC. Three age- and sex- matched controls with head CT scans were selected for each patient, and compared to the patients with hypoparathyroidism. Results: Of 1014 unique patients with a verified diagnosis of hypoparathyroidism, 142 had a head CT scan performed between 2000 and 2020. Head CT scans were performed for reasons unrelated to hypoparathyroidism in 96.5% of patients. In this cohort, 80.3% of patients (n=114) had post-surgical hypoparathyroidism. Age at which the first head CT in patients was done was 62±20.6 (range 11–97), and duration of hypoparathyroidism at the time of first head CT was 11.0±14.4 years (0–71). Prevalence of BGC in patients with hypoparathyroidism was 25.4% (n=36), as compared with 7.3% in the control group (31/426) (P<0.001). Patients and controls were similar in terms of cardiovascular risk factors (diabetes, hypertension, dyslipidemia, alcohol consumption, smoking status and BMI). In patients with non-surgical hypoparathyroidism (n=28), prevalence of BGC was 71.4% vs. 14.0% in the postsurgical cohort (OR 15.4; 95% CI 5.8–40, P<0.001). Compared to patients with hypoparathyroidism without BGC, those with BGC had lower time-weighted average serum calcium (8.4±0.8 vs. 8.8±0.8, P=0.002; normal range, 8.6–10.2 mg/dL), and lower time-weighted average calcium/phosphate ratio (Ca/P) (1.83±0.52 vs. 2.13±0.47, P=0.007). Conclusions: Basal ganglia calcification in hypoparathyroidism is associated with low serum calcium and low Ca/P ratio. This may allow increased bioavailability of phosphate in the extracellular space, leading to calcium phosphate crystal formation within the basal ganglia. Assessing Ca/P ratio may be useful to identify patients at risk for BGC. Prevalence of BGC is significantly higher in patients with non-surgical hypoparathyroidism.

scholarly journals Primary hypoparathyroidism presenting as basal ganglia calcification secondary to extreme hypocalcemia

2018 ◽  
Author(s):  
Edite Marques Mendes ◽  
Lúcia Meireles-Brandão ◽  
Carla Meira ◽  
Nuno Morais ◽  
Carlos Ribeiro ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Basal Ganglia ◽  
Serum Calcium ◽  
Rare Condition ◽  
High Serum ◽  
Surgical Removal ◽  
Complete Work ◽  
Extensive Calcification ◽  
Cerebral Computed Tomography ◽  
Low Serum

Hypoparathyroidism is a rare endocrine disorder characterized by low serum calcium and parathyroid hormone levels. The most common cause is parathyroid iatrogenic surgical removal. However, innumerous and rarer conditions can cause hypoparathyroidism. The authors describe a 27-year-old man that presented in emergency department with confusion, amnesia and decreased attention span. A cerebral computed tomography revealed bilateral extensive calcification in the basal ganglia. A complete work-up revealed low serum calcium, high serum phosphorus and low parathyroid hormone, leading to the diagnosis of idiopathic primary hypoparathyroidism. Initial intravenous therapy with calcium gluconate and calcitriol was administered, with clinical and analytical improvement. The authors describe a rare condition, with an exuberant cerebral presentation and extreme hypocalcemia, which did not directly correlate to the severity of symptoms. Not only this is a treatable disorder that may have catastrophic results if overlooked but also its symptoms may be completely reversed with prompt treatment.

scholarly journals Recurrent Seizure: An Uncommon Presentation of Post Thyroidectomy Hypoparathyroidism

2015 ◽  
Vol 16 (1) ◽  
pp. 56-58
Author(s):  
Abdul Wadud Chowdhury ◽  
Sabbiha Nadia Majumder ◽  
Md Gaffar Amin ◽  
Kazi Nazrul Islam ◽  
Mohammed Abaye Deen Saleh ◽  
...  
Keyword(s):  
White Matter ◽  
Basal Ganglia ◽  
Total Thyroidectomy ◽  
Subcortical White Matter ◽  
Recurrent Seizure ◽  
Lentiform Nucleus ◽  
Basal Ganglia Calcification ◽  
Uncommon Presentation ◽  
Chronic Hypoparathyroidism ◽  
Matter Detection

Basal ganglia calcification is associated with chronic hypoparathyroidism. We report a case of 37 year old lady with long standing iatrogenic hypoparathyroidism following total thyroidectomy. The clinical evaluation revealed neurological symptoms but without any neurological deficit. The CT scan of head showed calcification in caudate nucleus and part of lentiform nucleus of basal ganglia and in the cortical and subcortical white matter. Detection of brain calcinosis in patient’s who had total thyroidectomy can guide clinicians to further investigation for possible hypoparathyroidism.DOI: http://dx.doi.org/10.3329/jom.v16i1.22406 J MEDICINE 2015; 16 : 56-58

scholarly journals MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor

2021 ◽  
Vol 7 (1) ◽  
pp. e548
Author(s):  
Andreea Ilinca ◽  
Elisabet Englund ◽  
Sofie Samuelsson ◽  
Katarina Truvé ◽  
Efthymia Kafantari ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Small Vessel Disease ◽  
Large Family ◽  
Vascular Endothelial ◽  
Basal Ganglia Calcification ◽  
Whole Exome ◽  
Heterozygous Variant ◽  
Skin Biopsies ◽  
Endothelial Growth Factor ◽  
The Brain

ObjectiveTo describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke.MethodsWe studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole-genome sequencing (WGS) and intrafamilial cosegregation analyses.ResultsFifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family. MAP3K6 has known functions in angiogenesis and affects vascular endothelial growth factor expression, which may be implicated in cerebrovascular disease.ConclusionsOur data strongly suggest the MAP3K6 variant to be causative for this novel disease phenotype, but the absence of functional data and the present lack of additional families with this disease and MAP3K6 mutations still limit the formal evidence for the variant's pathogenicity.

scholarly journals Fahr's Disease Presenting with Aneurysmal Subarachnoid Hemorrhage

2012 ◽  
Vol 2 ◽  
pp. 27 ◽  
Author(s):  
Hosam Al-Jehani ◽  
Abdulrazag Ajlan ◽  
David Sinclair
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Basal Ganglia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Rare Disorder ◽  
Basal Ganglia Calcification ◽  
Fahr’S Disease ◽  
Acute Presentation ◽  
Fahr's Disease ◽  
Idiopathic Basal Ganglia Calcification ◽  
The Brain

Fahr's disease is a rare disorder of slowly progressive cognitive, psychiatric, and motor decline associated with idiopathic basal ganglia calcification (IBGC) and widespread calcification in the brain and cerebellum. Acute presentation of IBGC is most often as a seizure disorder; however, we present a case of an acute IBCG presentation in which the cause of the deterioration was an aneurysmal subarachnoid hemorrhage.

scholarly journals Primary familial brain calcification: a clinical case

2019 ◽  
Vol 4 (3) ◽  
pp. 128-132
Author(s):  
Yu. A. Malyshenko ◽  
I. V. Soroko ◽  
D. V. Kober ◽  
R. S. Bogachev ◽  
A. E. Mityukov
Keyword(s):  
Computed Tomography ◽  
Basal Ganglia ◽  
Multislice Computed Tomography ◽  
Endocrine Disorders ◽  
Efficient Treatment ◽  
Basal Ganglia Calcification ◽  
Primary Familial Brain Calcification ◽  
Brain Calcification ◽  
Proper Diagnosis ◽  
The Brain

Primary familial brain calcification (familial idiopathic basal ganglia calcification, Fahr’s disease) is a rare neurodegenerative syndrome characterised by a symmetrical bilateral calcification in the basal ganglia, dentate nucleus, cerebral cortex, and other regions of the brain. The widespread use of multislice computed tomography and magnetic resonance imaging increased the number of diagnosed cases, yet neither causes nor efficient treatment of this disease are known to date. Due to variable symptoms, primary familial brain calcification can resemble multiple neurological, mental, and endocrine disorders. Here we describe a case of a 38-year-old woman where timely multislice computed tomography led to the proper diagnosis and successful treatment.

Effects of serum calcium and phosphorus on skeletal mineralization in vitamin D-deficient rats

1986 ◽  
Vol 251 (2) ◽  
pp. E234-E240 ◽  
Author(s):  
M. E. Holtrop ◽  
K. A. Cox ◽  
D. L. Carnes ◽  
M. F. Holick
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Volume Density ◽  
Normal Serum ◽  
Serum Phosphorus ◽  
Deficient Diet ◽  
Hydroxyvitamin D ◽  
Normal Serum Calcium ◽  
Calcium And Phosphorus ◽  
Low Serum

In the present study, we have evaluated the role of calcium and phosphorus concentrations in serum on the mineralization of bone in the absence of vitamin D. This was accomplished by feeding mother rats and subsequently their pups vitamin D-deficient diets varying in calcium, phosphorus, and lactose content. After 5-7 wk on these diets, serum concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-hydroxyvitamin D [1,25(OH)2D] were undetectable. Rats fed a vitamin D-deficient diet containing 0.44% calcium and 0.3% phosphorus showed a serum calcium of 4.9-5.9 mg/dl and a serum phosphorus of 7.3-8.2 mg/dl; rickets (wide epiphysial plates) had developed as well as osteomalacia (wide osteoid seams). Rats maintained on a vitamin D-deficient diet containing 3% calcium and 0.65% phosphorus had normal serum calcium, low serum phosphorus, and severe rickets, but osteomalacia was not seen. Rats fed a diet containing 20% lactose, 4% calcium, and 1% phosphorus showed normal serum calcium, somewhat low serum phosphorus, normal serum PTH, normal width of the epiphysial plate, normal volume density of trabecular bone, and normal volume density of osteoid seams. These data confirm the findings of others, using a different experimental model, that serum calcium and phosphorus concentrations are the determining factors in mineralization defects and not the absence of 25(OH)D or 1,25(OH)2D. In these rats thyroparathyroidectomy is well tolerated, which makes for an ideal model for the study of the effects of calcium-regulating hormones on bone histology, cytology, and biochemistry.

scholarly journals Mechanisms of calcification in Fahr disease and exposure of potential therapeutic targets

2019 ◽  
Vol 10 (5) ◽  
pp. 449-457
Author(s):  
Melissa E.M. Peters ◽  
Esther J.M. de Brouwer ◽  
Jonas W. Bartstra ◽  
Willem P.Th.M. Mali ◽  
Huiberdina L. Koek ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Autosomal Recessive ◽  
Gene Mutations ◽  
Autosomal Recessive Inheritance ◽  
Causative Gene ◽  
Basal Ganglia Calcification ◽  
Ectopic Mineralization ◽  
Fahr Disease ◽  
The Brain ◽  
Blood Brain Barrier Integrity

Purpose of reviewThere is growing interest in disorders involved in ectopic mineralization. Fahr disease or idiopathic basal ganglia calcification can serve as a model for ectopic mineralization in the basal ganglia, which is fairly common in the general population. In this review, we will focus on causative gene mutations and corresponding pathophysiologic pathways in Fahr disease.Recent findingsPatients with Fahr disease have a variability of symptoms, such as movement disorders, psychiatric signs, and cognitive impairment, but can also be asymptomatic. Fahr disease is mostly autosomal dominant inherited, and there are mutations found in 4 causative genes. Mutations in SLC20A2 and XPR1 lead to a disrupted phosphate metabolism involving brain-specific inorganic phosphate transporters. Mutations in PDGFB and PDGFRB are associated with disrupted blood-brain barrier integrity and dysfunctional pericyte maintenance. In addition, the MYORG gene has recently been discovered to be involved in the autosomal recessive inheritance of Fahr.SummaryKnowledge about the mutations and corresponding pathways may expose therapeutic opportunities for patients with Fahr disease and vascular calcifications in the brain in general.

scholarly journals FAHR'S Sy ndrome: A rare Neurodegenerative Disorder

2017 ◽  
Vol 29 (1) ◽  
pp. 39-41
Author(s):  
Md Abdul Ahad ◽  
SM Kamal ◽  
Umme Salma
Keyword(s):  
Basal Ganglia ◽  
Middle Age ◽  
Neurodegenerative Disorder ◽  
Neuropsychiatric Symptoms ◽  
Brain Vessels ◽  
Basal Ganglia Calcification ◽  
Fahr’S Syndrome ◽  
Fahr Disease ◽  
The Brain ◽  
Idiopathic Disease

Idiopathic Basal Ganglia Calcification, also known as Fahr disease or Fahr's Syndrome or Bilateral StriatoPallidoDentate Calcinosis (BSPDC) is a rare, genetically dominant, inherited neurological disorder characterized by abnormal deposits of calcium in areas of the brain that control movement, including the basal ganglia and the cerebral cortex. A rare idiopathic disease which manifests in middle age characterized by punctate areas of non-arteriosclerotic calcination in parts of the gray and dentate nuclei, particularly of smaller brain vessels. The symptoms include mental and growth retardation, dystonic movements, and athetosis. May be caused by a malfunction of the glandula parathyreoidea. The term Fahr triad consists of symmetrical calcification of the basal ganglia, neuropsychiatric symptoms, and hypofunction of the parathyroid gland. Treatment is directed toward minimizing symptoms. The prognosis for any individual with Fahr's Syndrome is variable and hard to predict. Progressive neurological deterioration generally results in disability and death.Medicine Today 2017 Vol.29(1): 39-41

Metabolism of 1,25-dihydroxyvitamin D3

1984 ◽  
Vol 64 (2) ◽  
pp. 478-504 ◽  
Author(s):  
R. Kumar
Keyword(s):  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Biliary Excretion ◽  
Extracellular Fluid ◽  
Serum Phosphorus ◽  
General Terms ◽  
Wide Range ◽  
Calcium Phosphorus ◽  
Calcium And Phosphorus ◽  
Low Serum

Synthesis of 1,25(OH)2D3 is controlled by numerous factors. The major ones, however, are the circulating amounts of parathyroid hormone (the secretion of which is stimulated by low serum calcium), serum or extracellular fluid phosphorus concentrations, circulating levels of 1,25(OH)2D3 itself, and perhaps serum calcium directly. Many of the other factors noted have effects in vitro only or effects that are observed inconsistently or in one species only. Thus, in low-calcium states, 1,25(OH)2D3 synthesis increases because of increased parathyroid hormone activity. Parathyroid hormone may stimulate 1,25(OH)2D3 synthesis directly or via alterations (a decrease) in serum phosphorus or both. Low serum phosphorus will stimulate 1,25(OH)2D3 synthesis independent of parathyroid hormone levels. Low serum calcium may directly stimulate 25(OH)D3 1 alpha-hydroxylase activity independently of parathyroid hormone. In general terms the vitamin D-endocrine system tends to correct abnormalities in calcium and phosphorus homeostasis. The further metabolism of 1,25(OH)2D3 to other metabolites appears to be mainly a degradative or excretory process. Currently there is no evidence that 1,25(OH)2D3 must itself be altered to other metabolites prior to inducing intestinal calcium transport or bone mobilization. The processes involved in the excretion of 1,25(OH)2D3, such as side-chain oxidation and biliary excretion, are not regulated by serum calcium, phosphorus, or 1,25(OH)2D3 levels. The biliary excretion pathway is also unsaturable over a very wide range and not regulated by calcium, phosphorus, or vitamin D3. Therefore these processes, which account for a large part of the metabolism of 1,25(OH)2D3, are largely unregulated by factors that control the synthesis of 1,25(OH)2D3 and regulate the formation of other calcium-controlling hormones. Other processes involved in the metabolism of 1,25(OH)2D3, such as 24-hydroxylation and 26-hydroxylation, occur in normocalcemic and normophosphatemic states. 24-Hydroxylation is also induced by 1,25(OH)2D3, which benefits the organism, because excessive 1,25(OH)2D3 in various tissues can be altered to a less active metabolite, 1,24,25(OH)3D3. Although there is still no evidence concerning the regulation of C-24 oxidation by dietary calcium and phosphorus levels, the fact that this process is induced by 1,25(OH)2D3 suggests that the metabolic pathway functions in much the same manner as the 24-hydroxylation pathway. The formation of 1,25(OH)2D3-26,23-lactone occurs in normocalcemic states and in situations in which 1,25(OH)2D3 has been administered.

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