title: Reduced parathyroid hormone-stimulated 1,25-dihydroxyvitamin d production in vitamin d sufficient postmenoposual women with low bone mass and idiopathic secondary hyperparathyroidism.
abstract: OBJECTIVE
  Distinguishing secondary hyperparathyroidism (sHPT) from eucalcemic primary hyperparathyroidism (EC-pHPT) is important. The objective of this study was to measure parathyroid hormone (PTH)-stimulated production of 1α,25-dihydroxyvitamin D (1,25[OH]2D) in early postmenopausal patients with idiopathic sHPT, who also fit the criteria for EC-pHPT, compared to age-matched controls.
  
  
  METHODS
  In this pilot case-control study, postmenopausal women aged 44 to 55 years with normal serum calcium (Ca), glomerular filtration rate (GFR) ≥65 mL/min, and 25-hydroxyvitamin D (25[OH]D) ≥75 nmol/L (30 ng/mL) were given an 8 hour infusion of PTH(1-34), 12 pmol/kg/h. Patients (n = 5) had elevated PTH, normal 1,25(OH)2D, and no hypercalciuria. Controls (n = 5) had normal PTH. At baseline, 4, and 8 hours, serum Ca, creatinine (Cr), phosphorus (P), 1,25(OH)2D, fibroblast growth factor (FGF23), and 24,25(OH)2D as well as urine Ca, P, Cr, and cAMP/GFR were measured. The fractional excretion of calcium (FeCa) and tubular reabsorption of phosphorus (TMP)/GFR were calculated.
  
  
  RESULTS
  Patients had lower 1,25(OH)2D levels (± SD) than controls at 4 (39.8 ± 6.9 versus 58.8 ± 6.7; P = .002) and 8 hours (56.4 ± 9.2 versus 105 ± 2.3; P = .003) of PTH infusion, attenuated after adjusting for higher body mass index (BMI) in patients (P = .05, .04), respectively. The 24,25(OH)2D levels were lower in patients than controls (1.9 ± 0.6 versus 3.4 ± 0.6, respectively; P = .007). No differences were seen in serum Ca or P, urine cAMP/GFR, TRP/GFR, FeCa, or PTH suppression at 8 hours (patients 50%, controls 64%).
  
  
  CONCLUSIONS
  Vitamin D sufficient patients who fit the criteria for EC-pHPT had reduced PTH-stimulated 1,25(OH)2D compared to controls, partially attributable to their higher BMI. Other causes of reduced 1,25(OH)2D production ruled out were excessive catabolism of vitamin D metabolites, elevated FGF23, and CYP27B1 mutation. Elevated BMI and idiopathic reduced PTH-stimulated 1,25(OH)2D production should be considered in the differential of sHPT.
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD 21201, USA. estreete@medicine.umaryland.edu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Streeten
authors.forename: Amy S
authors.initials: AS
authors.lastname: Rogstad
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Flammer
authors.forename: Kiarash
authors.initials: K
authors.lastname: Zarbalian
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ryan
authors.forename: Mara
authors.initials: M
authors.lastname: Horwitz
authors.forename: Michael F
authors.initials: MF
authors.lastname: Holick
authors.forename: John
authors.initials: J
authors.lastname: Shelton
mesh_terms: D000328:Adult; D015519:Bone Density / Q000502:physiology*; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000097:blood / Q000175:diagnosis*; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000175:diagnosis*; D008875:Middle Aged; D010281:Parathyroid Hormone; D010865:Pilot Projects; D017698:Postmenopause / Q000097:blood*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23