title: Cardiometabolic phenotyping of patients with familial hypocalcuric hypercalcemia.
abstract: BACKGROUND
  Heterozygous inactivating mutations of the calcium-sensing receptor (CaSR) gene cause alterations in calcium metabolism [familial hypocalciuric hypercalcemia (FHH)]. In addition, calcium-sensing receptor is expressed in the myocardium and endocrine cells including pancreatic islets, enteroendocrine cells, and adipose tissue.
  
  
  OBJECTIVE
  To discern whether FHH is associated with cardiometabolic alterations of clinical significance, endocrine responses to systemic calcium stimulation and oral glucose tolerance tests were performed. Ectopic lipid deposition and heart function were assessed using magnetic resonance spectroscopy/imaging.
  
  
  METHODS
  Eight FHH patients and nine controls matched for anthropometric characteristics (age 45 ± 18 y; body mass index 29 ± 4 vs 29 ± 6 kg/m(2)) were studied to determine cardiac function, ectopic and visceral lipid content, and insulin sensitivity and secretion.
  
  
  RESULTS
  Insulin sensitivity (clamp-like index: 4.5 ± 0.6 vs 4.3 ± 0.4 mg/kg · min), basal (insulin secretion rate: 266 ± 33 vs 218 ± 25 pmol/min), and glucose-stimulated β-cell function (adaptation index: 180.2 ± 12.2 vs 176.2 ± 17.4) as well as calcium-stimulated insulin secretion were comparable between FHH and controls, respectively. Ectopic lipid content in liver [3.75% (1.4%; 34%) vs 4.18% (0.9%; 28%)], soleus muscle (1.07% ± 0.38% vs 1.02% ± 0.56 %), and myocardium (0.39% ± 0.3% vs 0.32% ± 0.1 %), visceral and sc adipose tissue distribution (0.51 ± 0.16 vs 0.47 ± 0.17) as well as heart function (ejection fraction: 71.5% ± 8% vs 72.8% ± 8 %; E to A ratio: 1.4% ± 0.6% vs 1.3% ± 0.7%) were not different between the groups.
  
  
  CONCLUSIONS
  Despite comprehensive cardiometabolic phenotyping, no alterations in myocardial function, lipid distribution, or glucose metabolism were observed in FHH. Thus, FHH might reflect a laboratory finding without any relevant cardiometabolic alterations.
authors.affiliation: Department of Internal Medicine III, and High Field MR-Centre (M.Krs., I.J.K., S.T.), Division of Endocrinology and Metabolism (P.W., M.Krs., Y.W., C.-H.A., A.G., A.L., S.B.-P., M.Kre.), Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria; Metabolic Unit (C.-H.A.), Institute of Biomedical Engineering, National Research Council, I-35127 Padova, Italy; Mariahilf Community Pharmacy (C.-H.A.), A-9601 Arnoldstein, Austria; Medical Direction (C.-H.A.), Specialized Hospital Complex Agathenhof, A-9322 Micheldorf, Austria; and Ludwig Boltzman Institute of Osteology (E.Z.), Hanusch Hospital of the Vienna Regional Health Insurance Fund and Austrian Workers' Compensation Board Trauma Center, 1100 Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
authors.forename: Martin
authors.initials: M
authors.lastname: Krššák
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Winhofer
authors.forename: Christian-Heinz
authors.initials: CH
authors.lastname: Anderwald
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Zwettler
authors.forename: Ivica
authors.initials: I
authors.lastname: Just Kukurová
authors.forename: Alois
authors.initials: A
authors.lastname: Gessl
authors.forename: Siegfried
authors.initials: S
authors.lastname: Trattnig
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Sabina
authors.initials: S
authors.lastname: Baumgartner-Parzer
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D006321:Heart / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D006934:Hypercalcemia / Q000151:congenital* / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D044169:Receptors, Calcium-Sensing / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing; D002118:Calcium