Pro-FHH: A Risk Equation to Facilitate the Diagnosis of Parathyroid-Related Hypercalcemia

Bertocchio, Jean‐Philippe; Tafflet, Muriel; Koumakis, Eugénie; Maruani, Gérard; Vargas‐Poussou, Rosa; Silve, Caroline; Nissen, Peter H.; Baron, Stéphanie; Prot-Bertoye, Caroline; Courbebaisse, Marie; Souberbielle, Jean‐Claude; Rejnmark, Lars; Cormier, Catherine; Houillier, Pascal

doi:10.1210/jc.2017-02773

Cited by 35 publications

(22 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FHH could have a very similar clinical presentation to primary hyperparathyroidism, and, despite proposed scores and algorithms, it remains difficult to have a precise clinical diagnosis. 13 It is therefore recommended in these cases to exclude a diagnosis of FHH before committing to parathyroidectomy, which is inappropriate in FHH. 14 We were able to analyze the data of 86 patients for whom a genetic diagnosis of FHH was excluded and follow-up information was available.…”

Section: Discussionmentioning

confidence: 99%

High-throughput sequencing contributes to the diagnosis of tubulopathies and familial hypercalcemia hypocalciuria in adults

Hureaux

Ashton

Dahan

et al. 2019

Kidney International

Self Cite

View full text Add to dashboard Cite

I nherited renal tubulopathies are rare diseases often diagnosed in children, particularly those with autosomal recessive transmission. Although some tubulopathies are diagnosed in adulthood, including recessive diseases with potentially mild presentation (e.g., Gitelman syndrome), slowly progressive dominant diseases (e.g., autosomal dominant tubulointerstitial kidney disease), and diseases with variable severity (e.g., Dent disease), the prevalence of tubulopathies in adults remains mostly unknown. 1-3 In addition, the clinical presentation may be atypical or insidious, complicating and delaying the diagnosis of tubular dysfunction. 4 Advances in understanding renal tubular solute transport systems has been achieved through the elucidation of

show abstract

Section: Discussionmentioning

confidence: 99%

High-throughput sequencing contributes to the diagnosis of tubulopathies and familial hypercalcemia hypocalciuria in adults

Hureaux

Ashton

Dahan

et al. 2019

Kidney International

Self Cite

View full text Add to dashboard Cite

show abstract

“…This is higher than previous estimates of 20‐30%, emphasizing the challenges in getting the diagnosis of hypercalcemic patients correct. In recent studies, additional clinical tools have been suggested to assist the correct diagnosis, for example the Pro‐FHH equation that calculates the probability of PHPT using plasma calcium, osteocalcin, PTH and the 24‐CCCR . Hannan et al developed an algorithm to differentiate between FHH3, caused by variants in codon 15 of the AP2S1 gene, and FHH1 and FHH2, by calculating the CMCR index that uses plasma values of calcium and magnesium and the CCCR .…”

Section: Discussionmentioning

confidence: 99%

“…In recent studies, additional clinical tools have been suggested to assist the correct diagnosis, for example the Pro-FHH equation that calculates the probability of PHPT using plasma calcium, osteocalcin, PTH and the 24-CCCR. 26 Hannan et al developed an algorithm to differentiate between FHH3, caused by variants in codon 15 of the AP2S1 gene, and FHH1 and FHH2, by calculating the CMCR index that uses plasma values of calcium and magnesium and the CCCR. 27 The goal of these new clinical tools is to reduce the number of genetic tests performed.…”

Section: Discussionmentioning

confidence: 99%

Expanding the spectrum of genetic variants in the calcium‐sensing receptor (CASR) gene in hypercalcemic individuals

Nissen

Rejnmark

2019

Clinical Endocrinology

Self Cite

View full text Add to dashboard Cite

Objective Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominantly inherited disorder with overlapping biochemistry profile with primary hyperparathyroidism (PHPT), making the correct diagnosis a challenge. The objective of the study was to evaluate the results of the clinical work‐up of a large group of hypercalcemic individuals. Design Cross‐sectional study. Patients Patients undergoing clinical work‐up of hypercalcemia. Measurements Molecular genetic analysis of the CASR gene and exon 2 of the AP2S1 gene. Plasma levels of ionized calcium and PTH as well as calcium creatinine clearance ratio (CCCR). Results A rare CASR variant was identified in 38 of 624 index patients (6.1%). A total of 18 CASR variants identified in this study were novel. No variants were identified in exon 2 of the AP2S1 gene. The majority of the variants (N = 16) were classified as likely pathogenic. The level of plasma calcium, plasma PTH and the CCCR was not affected by the type of variant (ie nonsense vs missense) (all P‐values >.05). The CCCR was found to be significantly lower for variants in the transmembrane domain compared with variants located in the extracellular domain (P < .05). Plasma levels of calcium and PTH were not associated with the location of the variant (P > .05). Conclusions We expanded the spectrum of CASR variants in hypercalcemia with 18 novel variants, and suggest that the location of the CASR variant may affect calcium excretion as determined by the CCCR.

show abstract

“…Comorbid vitamin D deficiency, as in this case, will increase PTH levels, and reduce urine CE, making interpretation of biochemistry more difficult. A new risk equation for FHH, Pro‐FHH, using calcium, PTH, urine CCCR, and bone remodeling markers, was recently published; however, it has not been validated in pregnancy . Nuclear medicine imaging is contraindicated during pregnancy, and neck US is operator‐dependent, with no known sensitivity and specificity for use during pregnancy .…”

Section: Discussionmentioning

confidence: 99%

Familial Hypocalciuric Hypercalcemia in Pregnancy: Diagnostic Pitfalls

et al. 2020

View full text Add to dashboard Cite

Familial hypocalciuric hypercalcemia (FHH) is a group of autosomal dominant disorders caused by dysfunction of the calcium sensing receptor (CaSR) and its downstream signaling proteins, leading to generally asymptomatic hypercalcemia. During pregnancy, distinguishing FHH from primary hyperparathyroidism (PHPT) is important, as the latter is associated with adverse outcomes and can be treated surgically during pregnancy, whereas the former is benign. This case report highlights the difficulties in diagnosing FHH during pregnancy. A 32‐year‐old woman was found to have asymptomatic hypercalcemia at 14‐weeks’ gestation. Investigations showed a corrected calcium (cCa) of 2.61 mmol/L (2.10 to 2.60), ionized Ca (iCa) of 1.40 mmol/L (1.15 to 1.28), 25OHD of 33 nmol/L (75 to 250), and PTH of 9.5 pmol/L (1.5 to 7.0). The patient was treated with 2000 IU cholecalciferol daily with normalization of 25OHD. The urine calcium / creatinine clearance ratio (CCCR) was 0.0071, and neck US did not visualize a parathyroid adenoma. Upon a retrospective review of the patient's biochemistry from 2 years prior, hypercalcemia was found that was not investigated. The patient was monitored with serial iCa levels and obstetric US. She delivered a healthy boy at 38‐weeks’ gestation. Postnatal iCa was 1.48 mmol/L and remained elevated. Her son had elevated iCa at birth of 1.46 mmol/L (1.15 to 1.33), which rose to 1.81 mmol/L by 2 weeks. He was otherwise well. Given the familial hypercalcemia, a likely diagnosis of FHH was made. Genetic testing of the son revealed a missense mutation, NM_000388.3(CASR):c.2446A > G, in exon 7 of the CaSR, consistent with FHH type 1. To our knowledge, there are only three existing reports of FHH in pregnancy. When differentiating between FHH and PHPT in pregnancy, interpretation of biochemistry requires an understanding of changes in Ca physiology, and urine CCCR may be unreliable. If the decision is made to observe, clinical symptoms, calcium levels, and fetal US should be monitored, with biochemistry and urine CCCR performed postpartum, once lactation is completed © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

show abstract

Pro-FHH: A Risk Equation to Facilitate the Diagnosis of Parathyroid-Related Hypercalcemia

Abstract: Pro-FHH effectively predicted whether a patient has PHPT. A prospective trial is necessary to assess its usefulness in a larger population and in patients with elevated PTH concentration.

Cited by 35 publications

References 33 publications

High-throughput sequencing contributes to the diagnosis of tubulopathies and familial hypercalcemia hypocalciuria in adults

High-throughput sequencing contributes to the diagnosis of tubulopathies and familial hypercalcemia hypocalciuria in adults

Expanding the spectrum of genetic variants in the calcium‐sensing receptor (CASR) gene in hypercalcemic individuals

Familial Hypocalciuric Hypercalcemia in Pregnancy: Diagnostic Pitfalls

Contact Info

Product

Resources

About