scholarly journals Familial Hypocalciuric Hypercalcemia: The Challenge of Diagnosis

2021 ◽  
Author(s):  
David Taïeb ◽  
Adele Lasbleiz ◽  
Nunzia Cinzia Paladino ◽  
Pauline Romanet ◽  
Frédéric Castinetti ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Elevated Serum ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Clearance Ratio ◽  
Molecular Alterations ◽  
Genes Encoding ◽  
High Level ◽  
Inactivating Mutation ◽  
Very High

Abstract Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant genetic disorder classically characterized by lifelong mild-to-moderate asymptomatic hypercalcemia with inappropriately normal to elevated serum parathyroid hormone (PTH) concentrations and hypocalciuria, best expressed by a urine calcium-to-creatinine clearance ratio (CCCR)<0.01[1,2]. FHH prevalence is estimated between 1:10 000 to 1:100 000[3,4]. In 60% of cases, FHH is due to CASR inactivating mutation[5]. More rarely FHH is due to AP2S1 or GNA11 inactivating mutation, both genes encoding for proteins involved downstream of CASR activation[6]. These molecular alterations are found in all parathyroid cells, explaining disease persistence following partial parathyroidectomy and the ineffective surgical management of these patients. FHH phenotypes could however overlap with primary hyperparathyroidism (PHPT). Indeed, even if patients with FHH are currently asymptomatic, some of them present chondrocalcinosis, kidney stones or bone fracture and very high level of PTH or calcemia[7]. Nonetheless, the distinction has to be adressed since the therapeutic approach significantly differs between these two conditions. Surgery is usually recommended for PHPT[8] while follow-up is preferred in the latter case[9,10]. We report and discuss 7 cases, 6 out 7 being operated for a presumed PHPT.

scholarly journals Familial Hypocalciuric Hypercalcemia in an Index Male: Grey Zones of the Differential Diagnosis From Primary Hyperparathyroidism in a 13-Year Clinical Follow up

2020 ◽  
pp. S321-S328
Author(s):  
K. ZAJÍČKOVÁ ◽  
M. DVOŘÁKOVÁ ◽  
J. MORAVCOVÁ ◽  
J. VČELÁK ◽  
D. GOLTZMAN
Keyword(s):  
Differential Diagnosis ◽  
Family History ◽  
Primary Hyperparathyroidism ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Clearance Ratio ◽  
Japanese Family ◽  
Casr Gene ◽  
History Of ◽  
Inactivating Mutation

Familial hypocalciuric hypercalcemia (FHH) type 1, caused by a heterozygous inactivating mutation of the gene encoding the calcium-sensing receptor (CaSR), is characterized by mild to moderate hypercalcemia, hypocalciuria and inappropriately normal or elevated parathyroid hormone (PTH). FHH must be differentiated from primary hyperparathyroidism (PHPT) because parathyroidectomy is ineffective in the former. Herein, we report a 39-year-old male patient with a 13-year history of asymptomatic PTH-dependent hypercalcemia (mean calcium of 2.88 mmol/l; reference range 2.15-2.55 mmol/l) and calcium-to-creatinine clearance ratio (Ca/Cr) ranging from 0.007 to 0.0198, which is consistent with either FHH or PHPT. Although a family history of hypercalcemia was negative, and PET-CT with fluorocholine was suggestive of a parathyroid adenoma, genetic analysis of the CaSR gene identified a heterozygous inactivating mutation NM_000388.4:c.1670G>A p. (Gly557Glu) in exon 6 and a polymorphism NM_000388.4:c.1192G>A p. (Asp398Asn) in exon 4. The G557E mutation has been previously reported in a Japanese family in which all family members with the mutation had Ca/Cr below 0.01 consistent with FHH. The biochemical profile of FHH and PHPT may overlap. Our FHH patient with a G557E CaSR mutation illustrates that the differential diagnosis can be difficult in an index case with no family history, (false) positive parathyroid imaging and higher calciuria than expected for FHH. Calcium intake, vitamin D status and bone resorption might have contributed to the Ca/Cr variations over a 13-year clinical follow up. This case thus emphasizes the irreplaceable role of genetic testing of the CaSR gene when clinical evaluation is inconclusive.

scholarly journals Eosinophils May Serve as CEA-Secreting Cells for ABPA Patients

2020 ◽  
Author(s):  
Yang yanfei ◽  
Gao qiqi ◽  
Jin yangyi ◽  
Qi mengdie ◽  
Lu guohua ◽  
...  
Keyword(s):  
Pearson Correlation ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Elevated Serum ◽  
Endobronchial Ultrasound ◽  
Normal Lung ◽  
Serum Cea ◽  
Pearson Correlation Analysis ◽  
High Level ◽  
The Relationship

Abstract Background Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterized by an exaggerated response of the immune system to the fungus Aspergillus. This study aimed to assess the relationship between carcinoembryonic antigen (CEA) and eosinophils in ABPA patients.Methods: We describes a case of a 50-year-old patient who was diagnosed with ABPA presenting with high level of CEA and eosinophils. Besides,we used immunohistochemistry and immunofluorescence to identify eosinophils and CEA in sections which were obtained by Endobronchial ultrasound-guided transbronchial lung biopsy aspiration (EBUS-TBLB). The sections were then visualized using confocal microscopy. We also retrospectively analyzed a cohort of 37 ABPA patients between January 2013 and December 2019 in our hospital.Results: We found the patient whose serum CEA levels were consistent with eosinophils during the follow-up(r=0.929,P=0.022). The positive expression of CEA and abnormal expression of eosinophils was higher in the ABPA tissue compared to the normal lung tissue. The co-localization was represented as pixels containing both red and green color in the image (with various shades of orange and yellow) which signified that eosinophils were immunohistochemically positive for CEA. Patients with higher levels of eosinophils had higher levels of CEA in the serum (P<0.001). The results of Pearson correlation analysis showed that the levels of eosinophils were positively correlated with serum CEA levels(r=0.459 and r=0.506，P=0.004 and P=0.001). Conclusion: Serum CEA level is elevated in ABPA patients. The elevated serum CEA level was shown to be normalized after treatment. Increased CEA levels in ABPA patients may be positively correlated with eosinophil levels, and eosinophils may be served as CEA-secreting cells in patients with ABPA.

scholarly journals Concomitant familial hypocalciuric hypercalcemia and single parathyroid adenoma: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Simone Diedrichsen Marstrand ◽  
Charlotte Landbo Tofteng ◽  
Anne Jarløv ◽  
Line Borgwardt ◽  
Peter Schwarz
Keyword(s):  
Parathyroid Adenoma ◽  
Correct Diagnosis ◽  
Elevated Serum ◽  
Parathyroid Scintigraphy ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Clearance Ratio ◽  
Gene Encoding ◽  
Calcium Sensing ◽  
Severe Hypercalcemia ◽  
The Right

Abstract Background Primary hyperparathyroidism (PHPT) is a common endocrine disorder and the most frequent benign cause of hypercalcemia. PHPT is characterized by autonomous hypersecretion of parathyroid hormone (PTH), regardless of serum calcium levels. Familial hypocalciuric hypercalcemia (FHH) is a rare, benign syndrome only affecting the regulation of calcium metabolism. FHH is an autosomal-dominant genetic disease with high penetrance, caused by an inactivating variant in the CASR gene encoding the calcium-sensing receptor (CaSR). We present a unique case of concomitant PHPT and FHH without clinically actionable variants in MEN1. Case presentation A 47-year-old Caucasian man with severe hypercalcemia, genetic FHH, and initially normal parathyroid scintigraphy was referred for endocrine evaluation due to nonspecific symptoms. Biochemical evaluation showed elevated serum ionized calcium and PTH. The calcium–creatinine clearance ratio was low. All other biochemical measures were normal, including kidney function. Genetic evaluation was redone and confirmed FHH. A new parathyroid scintigraphy showed a significant single adenoma corresponding to the lower left gland. The patient underwent parathyroidectomy, and a parathyroid adenoma was removed. A reduced level of hypercalcemia persisted due to FHH. Conclusions The correct diagnosis of the underlying cause of hypercalcemia is important to ensure the right treatment. Patients with FHH should avoid operative treatment, and PHPT should be differentiated from MEN1 to determine whether surgery should include parathyroidectomy with removal of one adenoma or 3.5 hyperplastic parathyroid glands.

scholarly journals Eosinophils may serve as CEA-secreting cells for allergic bronchopulmonary aspergillosis (ABPA) patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yanfei Yang ◽  
qiqi Gao ◽  
Yangyi Jin ◽  
Mengdie Qi ◽  
Guohua Lu ◽  
...  
Keyword(s):  
Pearson Correlation ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Elevated Serum ◽  
Endobronchial Ultrasound ◽  
Normal Lung ◽  
Serum Cea ◽  
Pearson Correlation Analysis ◽  
High Level ◽  
The Relationship

AbstractAllergic bronchopulmonary aspergillosis (ABPA) is a condition characterized by an exaggerated response of the immune system to the fungus Aspergillus. This study aimed to assess the relationship between carcinoembryonic antigen (CEA) and eosinophils in ABPA patients. We describes a case of a 50-year-old patient who was diagnosed with ABPA presenting with high level of CEA and eosinophils. Besides,we used immunohistochemistry and immunofluorescence to identify eosinophils and CEA in sections which were obtained by Endobronchial ultrasound-guided transbronchial lung biopsy aspiration (EBUS-TBLB). The sections were then visualized using confocal microscopy. We also retrospectively analyzed a cohort of 37 ABPA patients between January 2013 and December 2019 in our hospital. We found the patient whose serum CEA levels were consistent with eosinophils during the follow-up (r = 0.929, P = 0.022). The positive expression of CEA and abnormal expression of eosinophils was higher in the ABPA tissue compared to the normal lung tissue. The co-localization was represented as pixels containing both red and green color in the image (with various shades of orange and yellow) which signified that eosinophils were immunohistochemically positive for CEA. Patients with higher levels of eosinophils had higher levels of CEA in the serum (P < 0.001). The results of Pearson correlation analysis showed that the levels of eosinophils were positively correlated with serum CEA levels (r = 0.459 and r = 0.506, P = 0.004 and P = 0.001). Serum CEA level is elevated in ABPA patients. The elevated serum CEA level was shown to be normalized after treatment. Increased CEA levels in ABPA patients may be positively correlated with eosinophil levels, and eosinophils may be served as CEA-secreting cells in patients with ABPA.

scholarly journals Fear Avoidance Beliefs and Risk of Long-Term Sickness Absence: Prospective Cohort Study among Workers with Musculoskeletal Pain

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Kenneth Jay ◽  
Sannie Vester Thorsen ◽  
Emil Sundstrup ◽  
Ramon Aiguadé ◽  
Jose Casaña ◽  
...  
Keyword(s):  
Physical Activity ◽  
Sickness Absence ◽  
Musculoskeletal Pain ◽  
Occupational Physical Activity ◽  
Fear Avoidance ◽  
Fear Avoidance Beliefs ◽  
High Level ◽  
Very High

Background and Objective. Musculoskeletal pain is common in the population. Negative beliefs about musculoskeletal pain and physical activity may lead to avoidance behavior resulting in absence from work. The present study investigates the influence of fear avoidance beliefs on long-term sickness absence. Methods. Workers of the general working population with musculoskeletal pain (low back, neck/shoulder, and/or arm/hand pain; n = 8319) from the Danish Work Environment Cohort Study were included. Long-term sickness absence data were obtained from the Danish Register for Evaluation and Marginalization (DREAM). Time-to-event analyses (cox regression) controlled for various confounders estimated the association between fear avoidance beliefs (very low, low, moderate [reference category], high, and very high) at baseline and long-term sickness absence (LTSA; ≥6 consecutive weeks) during a 2-year follow-up. Results. During the 2-year follow-up, 10.2% of the workers experienced long-term sickness absence. In the fully adjusted model, very high-level fear avoidance increased the risk of LTSA with hazard ratio (HR) of 1.48 (95% CI 1.15-1.90). Similar results were seen analyses stratified for occupational physical activity, i.e., sedentary workers (HR 1.72 (95% CI 1.04-2.83)) and physically active workers (HR 1.48 (95% CI 1.10-2.01)). Conclusion. A very high level of fear avoidance is a risk factor for long-term sickness absence among workers with musculoskeletal pain regardless of the level of occupational physical activity. Future interventions should target fear avoidance beliefs through information and campaigns about the benefits of staying active when having musculoskeletal pain.

scholarly journals Rickets with Alopecia Signals Vitamin D Dependent Rickets Type II

2016 ◽  
Vol 35 (2) ◽  
pp. 198-201
Author(s):  
Shankar Prasad Yadav ◽  
Nisha Keshary Bhatta
Keyword(s):  
Vitamin D ◽  
Serum Alkaline Phosphatase ◽  
Elevated Serum ◽  
Autosomal Recessive Disorder ◽  
Female Child ◽  
High Dose ◽  
Type Ii ◽  
25 Hydroxy Vitamin D ◽  
High Level ◽  
Very High

Vitamin D-dependent rickets type II is a rare autosomal recessive disorder. We report 27 months female child with classical rachitic changes, very high level of 25-hydroxy Vitamin D, 1,25 (OH)2D and markedly elevated serum Alkaline phosphatase. Very high dose of oral calcium and vitamin D3 was prescribed with minor improvement in skeletal features and alopecia. This case report hints the physician to diagnose and manage Vitamin D-dependent rickets type II, when rachitic changes are associated with alopecia.J Nepal Paediatr Soc 2015;35(2):198-201

scholarly journals Unassigned Geriatric Evaluation and Management Program: preventing sub-acute hospital admissions

2002 ◽  
Vol 25 (6) ◽  
pp. 164 ◽  
Author(s):  
Clare Heaney ◽  
Kwang Lim ◽  
Sharryn Lydall-Smith ◽  
Michael Dorevitch
Keyword(s):  
Hospital Admissions ◽  
Management Program ◽  
Community Case Management ◽  
Level Of Satisfaction ◽  
Extended Care ◽  
Geriatric Evaluation ◽  
High Level ◽  
Effective Service ◽  
Very High

The purpose of this study was to describe and evaluate the Unassigned Geriatric Evaluation and Management (UGEM) program recently developed at Bundoora Extended Care Centre (BECC). The UGEM program resembles a bed substitution service and aims to prevent hospital admissions by providing community case management services to clients who would otherwise require inpatient admission.Data was collected on 36 clients who had received UGEM services. Twenty-six clients/carers also took part in a follow-up telephone satisfaction interview.Overall, the evaluation indicates that the UGEM program is a flexible, valuable and effective service. Most UGEM clients could be maintained at home with services, and this suggests that the program succeeds in assisting many clients to avoid hospitalisation in crisis situations. Further, clients and carers displayed a very high level of satisfaction with the service. The ongoing funding of such programs is crucial in order to maintain the reduction in hospital admissions and hence the high costs associated with inpatient care.

التغير المناخي واثره في المقنن المائي لمحصول العنب في محافظة ديالى

2019 ◽  
Vol 1 (34) ◽  
pp. 391-422
Author(s):  
اشواق حسن حميد صالح
Keyword(s):  
Climate Change ◽  
Statistical Analysis ◽  
Wind Speed ◽  
Extreme Temperature ◽  
Solar Brightness ◽  
The Subject ◽  
Climate Station ◽  
The Times ◽  
High Level ◽  
Very High

Climate change and its impact on water resources is the problem of the times. Therefore, this study is concerned with the subject of climate change and its impact on the water ration of the grape harvest in Diyala Governorate. The study was based on the data of the Khanaqin climate station for the period 1973-2017, (1986-2017) due to lack of data at governorate level. The general trend of the elements of the climate and its effect on the water formula was extracted. The equation of change was extracted for the duration of the study. The statistical analysis was also used between the elements of the climate (actual brightness, normal temperature, micro and maximum degrees Celsius, wind speed m / s, relative humidity% The results of the statistical analysis confirm that the water ration for the study area is based mainly on the X7 evaporation / netting variable, which is affected by a set of independent variables X1 Solar Brightness X4 X5 Extreme Temperature Wind Speed ​​3X Minimal Temperature and Very High Level .

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