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Published on: March 14, 2017
Effect of age on the response to parathyroid hormone
1Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201, USA.
Insights
Phosphate regulation by parathyroid hormone (PTH) shows age-dependent differences in healthy individuals and patients with hormonal disorders. Children exhibit a more pronounced phosphaturic response to PTH compared to adults.
Area of Science:
- Endocrinology
- Pediatric Nephrology
- Mineral Metabolism
Background:
- Serum phosphate (PO4) and tubular reabsorption thresholds are higher in children than adults.
- Parathyroid hormone (PTH) regulates phosphate homeostasis, but its age-dependent effects require further elucidation.
Purpose of the Study:
- To investigate the influence of age on the phosphaturic response to parathyroid hormone (PTH) infusion.
- To compare PTH response in healthy children and adults, and in patients with hypoparathyroidism (HP) and pseudohypoparathyroidism (PHP).
Main Methods:
- Administered PTH(1-34) infusion to healthy children (n=8), adults (n=12), HP patients (n=2), and PHP patients (n=6).
- Measured serum phosphate (PO4), tubular threshold for PO4 corrected for GFR (TP/GF), urinary cyclic AMP corrected for GFR (UcAMP/GF), and maximal fractional PO4 excretion (FEP).
- Analyzed correlations between these parameters and the effect of age on PTH response.
Main Results:
- In healthy subjects, baseline TP/GF correlated inversely with UcAMP/GF.
- PTH infusion increased UcAMP/GF, which correlated inversely with TP/GF and directly with FEP.
- The regression slopes of TP/GF and FEP with UcAMP/GF were steeper in children than adults, indicating a greater phosphaturic response.
- PHP patients showed a correlation between PTH-stimulated TP/GF and peak UcAMP/GF.
- PHP patients could be distinguished by low FEP or high TP/GF with low UcAMP/GF.
Conclusions:
- The phosphaturic response to PTH is linked to increased urinary cAMP and is age-dependent.
- Children exhibit a more significant decrease in TP/GF compared to adults following PTH stimulation.
- Distinctive biochemical profiles in PHP patients aid in their differentiation from healthy controls.
Abstract:
Serum phosphate (PO4) levels and the tubular threshold for PO4 corrected for glomerular filtration (TP/GF) are age-dependent, being higher in children than in adults. We evaluated the effect of age on the response to infusion of parathyroid hormone(1-34) (PTH) in healthy children (n = 8) and adults (n = 12). In addition, six patients with pseudohypoparathyroidism (PHP) and two with PTH deficiency (hypoparathyroidism [HP]) were also studied. At baseline, TP/GF in normal subjects was inversely correlated with urinary cyclic adenosine monophosphate corrected for glomerular filtration (UcAMP/GF) (P < .0359). After PTH administration in the controls, UcAMP/GF was inversely correlated with TP/GF (P < .0007) and directly correlated with maximal fractional extraction of PO4 (FEP) (P < .0002). The slope of the regression of TP/GF (P < .0076) and FEP (P < .0034) with UcAMP/GF was steeper in children than in adults. Two HP patients had high PTH-stimulated UcAMP/GF levels, but stimulated TP/GF and FEP were not changed commensurate with levels that would expected from the normative data. In six patients with PHP, PTH-stimulated TP/GF was also correlated with peak UcAMP/GF (r = .96, P < .002). PHP patients could be distinguished from normal controls based on the combination of low peak FEP or high TP/GF together with low peak UcAMP/GF. Thus, in normal subjects, the phosphaturic response to PTH is correlated with the increase in urinary cAMP and is age-dependent, with a greater decrease of TP/GF in children than in adults.
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