Efficacy of calcium excretion and calcium/creatinine clearance ratio in the differential diagnosis of familial hypocalciuric hypercalcemia and primary hyperparathyroidism

Bhangu, Jagdeep Singh; Selberherr, Andreas; Brammen, Lindsay; Scheuba, Christian; Riss, Philipp

doi:10.1002/hed.25568

Cited by 18 publications

(14 citation statements)

References 20 publications

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“…On the other hand, the pathogenic variant detection rate for FHH (types 1 and 3) was 32% in those with a CCCR ≤ 0.01 and 19% in those with CCCR < 0.02. Similarly, others have also found that CCCR was not reliable in distinguishing between PHPTH and FHH and in one large cohort, nearly two thirds of patients with a CCCR < 0.02 had surgically confirmed PHPTH 18,19 …”

Section: Discussionmentioning

confidence: 87%

Genetic testing for hereditary hyperparathyroidism and familial hypocalciuric hypercalcaemia in a large UK cohort

Mariathasan

Andrews

Thompson

et al. 2020

Clinical Endocrinology

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Background Primary hyperparathyroidism (PHPTH) is a common endocrine disorder and an estimated 10% of cases are hereditary, related to syndromes including; multiple endocrine neoplasia (MEN) type 1, MEN type 4, MEN2A and hereditary hyperparathyroidism‐jaw tumour syndrome. Establishing the underlying genetic cause for PHPTH allows for personalized and cost‐effective management. Familial hypocalicuric hypercalcaemia (FHH) is a benign disorder of hypercalcaemia associated with an inappropriately low urinary calcium excretion, which is quantified by the calcium creatinine clearance ratio (CCCR). Recent NHS England National Genomic Test Directory testing criteria for familial hyperparathyroidism state testing patients presenting with PHPTH and CCCR > 0.02 presenting (i) <35 years of age, or (ii) <45y with one of (a) multiglandular disease, or (b) hyperplasia on histology, or (c) ossifying fibroma(s) of the maxilla and/ or mandible, or (d) a family history of unexplained PHPTH. The testing criterion for FHH is a CCCR < 0.02. Aims and Methods A retrospective review of patients referred for genetic testing over a 4 year period for suspected hereditary HPTH was performed. Genetic analysis was performed by next‐generation sequencing of the following genes; MEN1, CDC73, CASR, CDKN1A, CDKN1B, CDKN2B, CDKN2C, RET, GCM2, GNA11, and AP2S1 in NHS‐accredited Regional Genetic laboratories. Aims of this study were to better define testing criteria for suspected hereditary PHPTH in a UK cohort. Results A total of 121 patients were included in this study (92 female) with a mean age of 41 years (SD 17). A pathogenic germline variant was identified in 16% (n = 19). A pathogenic variant was identified in the PHPTH genes CDC73 in a single patient and MEN1 in six patients (6% of total), in the FHH genes, CASR in 11 patients and AP2S1 in a single paediatric case (10% of total). A variant of uncertain significance (VUS) was identified in eight patients (6%) but over the course of this study familial segregation studies and computational analysis enabled re‐classification of four of the variants, with two VUS’s in the CASR gene being upgraded to likely pathogenic variants. Age at diagnosis and multiglandular disease as sole risk factors were not predictive of a pathogenic germline variant in this cohort but a positive family history was strongly predictive (P = .0002). A significant difference in the mean calcium creatinine clearance ratio (CCCR) in those patients with an identified CASR pathogenic variant versus those without (P = .0001) was demonstrated in this study. Thirty‐three patients were aged over 50 years and the diagnostic rate of a pathogenic variant was 15.1% in those patients >50 years of age compared to 15.9% in those <50 years. Five patients >50 years and with a CCCR of <0.01, were diagnosed with a pathogenic variant in CASR. Conclusion Family history was the strongest predictor of hereditary PHPTH in this cohort. This study has highlighted the importance of re‐evaluating VUS’s in order to inform patient management a...

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Section: Discussionmentioning

confidence: 87%

Genetic testing for hereditary hyperparathyroidism and familial hypocalciuric hypercalcaemia in a large UK cohort

Mariathasan

Andrews

Thompson

et al. 2020

Clinical Endocrinology

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“…Each student solved 4 Bayesian cases, which consisted of different medical contexts from the field of clinical endocrinology: Cushing’s syndrome, 38 familial hypocalciuric hypercalcemia (FHH), 39 primary aldosteronism, 40 and thyroid cancer. 1…”

Section: Methodsmentioning

confidence: 99%

“…Material and medical context. Each student solved 4 Bayesian cases, which consisted of different medical contexts from the field of clinical endocrinology: Cushing's syndrome, 38 familial hypocalciuric hypercalcemia (FHH), 39 primary aldosteronism, 40 and thyroid cancer. 1 Endocrinology was selected because in this field of internal medicine, there is a great discrepancy between very frequent diseases in the population.…”

Section: Methodsmentioning

confidence: 99%

Improving Diagnostic Efficiency with Frequency Double-Trees and Frequency Nets in Bayesian Reasoning

Kunzelmann

Binder

Fischer³

et al. 2022

MDM Policy & Practice

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Background. Medical students often have problems with Bayesian reasoning situations. Representing statistical information as natural frequencies (instead of probabilities) and visualizing them (e.g., with double-trees or net diagrams) leads to higher accuracy in solving these tasks. However, double-trees and net diagrams (which already contain the correct solution of the task, so that the solution could be read of the diagrams) have not yet been studied in medical education. This study examined the influence of information format (probabilities v. frequencies) and visualization (double-tree v. net diagram) on the accuracy and speed of Bayesian judgments. Methods. A total of 142 medical students at different university medical schools (Munich, Kiel, Goettingen, Erlangen, Nuremberg, Berlin, Regensburg) in Germany predicted posterior probabilities in 4 different medical Bayesian reasoning tasks, resulting in a 3-factorial 2 × 2 × 4 design. The diagnostic efficiency for the different versions was represented as the median time divided by the percentage of correct inferences. Results. Frequency visualizations led to a significantly higher accuracy and faster judgments than did probability visualizations. Participants solved 80% of the tasks correctly in the frequency double-tree and the frequency net diagram. Visualizations with probabilities also led to relatively high performance rates: 73% in the probability double-tree and 70% in the probability net diagram. The median time for a correct inference was fastest with the frequency double tree (2:08 min) followed by the frequency net diagram and the probability double-tree (both 2:26 min) and probability net diagram (2:33 min). The type of visualization did not result in a significant difference. Discussion. Frequency double-trees and frequency net diagrams help answer Bayesian tasks more accurately and also more quickly than the respective probability visualizations. Surprisingly, the effect of information format (probabilities v. frequencies) on performance was higher in previous studies: medical students seem also quite capable of identifying the correct solution to the Bayesian task, among other probabilities in the probability visualizations. Highlights Frequency double-trees and frequency nets help answer Bayesian tasks not only more accurately but also more quickly than the respective probability visualizations. In double-trees and net diagrams, the effect of the information format (probabilities v. natural frequencies) on performance is remarkably lower in this high-performing sample than that shown in previous studies.

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“…Vor chirurgischen Eingriffen an den Nebenschilddrüsen sollte eine FHH deshalb ausgeschlossen werden, um unnötige Operationen zu vermeiden [10,11].…”

Section: äTiologieunclassified

Primärer Hyperparathyreoidismus

Scherkl

Tmava-Berisha

Amrein

2020

J. Klin. Endokrinol. Stoffw.

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Efficacy of calcium excretion and calcium/creatinine clearance ratio in the differential diagnosis of familial hypocalciuric hypercalcemia and primary hyperparathyroidism

Cited by 18 publications

References 20 publications

Genetic testing for hereditary hyperparathyroidism and familial hypocalciuric hypercalcaemia in a large UK cohort

Genetic testing for hereditary hyperparathyroidism and familial hypocalciuric hypercalcaemia in a large UK cohort

Improving Diagnostic Efficiency with Frequency Double-Trees and Frequency Nets in Bayesian Reasoning

Primärer Hyperparathyreoidismus

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