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%).

Conclusion: 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.

Figures

Fig. 1

Unadjusted 1α,25-dihydroxyvitamin D (1,25[OH]2D) levels during parathyroid hormone (PTH) (1-34) infusion in patients and controls. For the unadjusted difference between patients and controls at 4 hours (P = .002) and 8 hours (P = .003). After adjusting for body mass index (BMI), the difference between groups was attenuated (4 hours [P = .05] and 8 hours [P = .04]).

Fig. 2

Correlations of body mass index (BMI) with parathyroid hormone (PTH) levels and 1α,25-dihydroxyvitamin D (1,25[OH]2D). A. 1,25(OH)2D after 8 hours of PTH infusion versus BMI in patients and controls. B. Baseline PTH levels versus BMI in patients. Patients are notated as open squares and controls are notated as closed diamonds. n=5 in each group.