Regulation of 1,25 (OH)2D synthesis in hypoparathyroidism and pseudohypoparathyroidism

1988 ◽  
Vol 255 (5) ◽  
pp. E730-E736
Author(s):  
N. A. Breslau ◽  
R. S. Weinstock
Keyword(s):  
Serum Phosphorus ◽  
Phosphorus Concentration ◽  
Parathyroid Hormone Receptor ◽  
Cyclic Monophosphate ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Complex Patients ◽  
Phosphorus Deprivation ◽  
Parathyroid Extract ◽  
Phosphorus Levels

We examined the regulation of 1,25-dihydroxyvitamin D [1,25(OH)2D] synthesis in patients with hypoparathyroidism (n = 5) and pseudohypoparathyroidism (n = 5) by administration of parathyroid extract (PTE) and N6,O2-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) and by phosphorus deprivation with antacids. In response to PTE, patients with hypoparathyroidism increased serum 1,25(OH)2D from 17 +/- 5 to 30 +/- 5 (SD) pg/ml (P less than 0.01). An approximate doubling of the 1,25(OH)2D concentration also occurred following dbcAMP infusion or phosphorus deprivation (serum phosphorus 4.4 +/- 0.5 to 2.6 +/- 1.1, P less than 0.01). Serum phosphorus and 1,25(OH)2D concentrations were inversely correlated (r = -0.73, P less than 0.001). Patients with pseudohypoparathyroidism had negligible responses to PTE with respect to urinary adenosine 3', 5'-cyclic monophosphate excretion, serum phosphorus concentration, or 1,25(OH)2D synthesis. They did show a rise in serum 1,25(OH)2D from 17 +/- 4 to 44 +/- 5 pg/ml (P less than 0.001) in response to dbcAMP infusion. During phosphorus deprivation, serum phosphorus decreased from 4.1 +/- 0.8 to 3.2 +/- 1.2 mg/dl (P less than 0.05), but there was no change in serum 1,25(OH)2D concentration or any correlation between serum phosphorus and 1,25(OH)2D levels. Although reduction in mean serum phosphorus levels was generally not as great in patients with pseudohypoparathyroidism, one such patient attained serum phosphorus of 1.2 mg/dl and still did not increase serum 1,25(OH)2D concentration. In addition to an abnormal parathyroid hormone receptor-adenylate cyclase complex, patients with pseudohypoparathyroidism appear to have an abnormal renal 1 alpha-hydroxylase, which does not respond appropriately to phosphate deprivation.

Role of Insulin in the Increase in Serum 1,25- Dihydroxyvitamin D Concentrations in Response Phosphorus Deprivation in Streptozotocin-Induced Diabetic Rats

Endocrinology ◽  
1986 ◽  
Vol 118 (4) ◽  
pp. 1440-1444 ◽  
Author(s):  
TOSHIO MATSUMOTO ◽  
YUMIKO KAWANOBE ◽  
IKUKO EZAWA ◽  
NAOHIKO SHIBUYA ◽  
KEISHI HATA ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Phosphorus Deprivation

scholarly journals Dipyridamole decreases renal phosphate leak and augments serum phosphorus in patients with low renal phosphate threshold.

1998 ◽  
Vol 9 (7) ◽  
pp. 1264-1269 ◽  
Author(s):  
D Prié ◽  
F B Blanchet ◽  
M Essig ◽  
J P Jourdain ◽  
G Friedlander
Keyword(s):  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Chronic Treatment ◽  
Serum Phosphorus ◽  
Calcium Excretion ◽  
Normal Range ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Renal Phosphate Reabsorption ◽  
A Prospective Study

It has been shown that an acute infusion of dipyridamole increased renal phosphate reabsorption in rats and humans. A prospective study was performed to determine whether chronic treatment by dipyridamole given orally could decrease renal phosphate leak and increase serum phosphorus in patients with idiopathic low renal phosphate threshold (TmPO4/GFR < 0.77 mM). Sixty-four patients with low TmPO4/GFR were included and treated with dipyridamole (75 mg, 4 times daily) for more than 12 mo. Serum phosphorus, TmPO4/GFR, parathyroid hormone, serum calcium, and 1,25-dihydroxyvitamin D were measured sequentially before treatment, and after 3, 6 to 9, and 12 mo of treatment. Under chronic treatment with dipyridamole, TmPO4/GFR and serum phosphorus significantly increased in 80% of patients within 3 mo, with maximal values reached within 9 mo. This improvement persisted after 12 mo of treatment. In 28 patients, 1,25-dihydroxyvitamin D concentrations were above the normal range (> 42 pg/ml) and normalized in parallel with the increase of serum phosphorus. The 24-h calcium excretion (which was initially increased in patients with high vitamin D concentrations) and urolithiasis decreased under treatment. Ionized serum calcium and parathyroid hormone remained unchanged. After 2 yr, treatment was discontinued in three patients; serum phosphorus and TmPO4/GFR decreased within 1 mo after discontinuation. Dipyridamole at a dose of 75 mg 4 times daily increases low TmPO4/GFR and improves hypophosphatemia in patients with renal phosphate losses and can be used to treat these patients.

Effect of aging on the metabolism of phosphorus and 1,25-dihydroxyvitamin D in healthy men

1996 ◽  
Vol 270 (3) ◽  
pp. E483-E490
Author(s):  
A. A. Portale ◽  
B. P. Halloran ◽  
R. C. Morris ◽  
E. T. Lonergan
Keyword(s):  
Time Course ◽  
Young Men ◽  
Normal Serum ◽  
Serum Phosphorus ◽  
Serum Concentrations ◽  
Elderly Men ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Healthy Elderly ◽  
Dietary Phosphorus

We tested the hypothesis that aging alters physiological regulation of the serum concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] by inorganic phosphorus. In seven elderly men [age 71 +/- 1 (SE) yr] and 9 young men (29 +/- 2 yr), dietary phosphorus was first normal, then increased and decreased within its normal range. At each intake of phosphorus, serum concentrations of 1,25(OH)2D in the elderly did not differ from those in young men, but fasting and 24-h mean serum concentrations of phosphorus were lower in elderly men. With phosphorus restriction, in each group serum 1,25(OH)2D increased by 47%, and 24-h mean serum phosphorus decreased by 0.6 +/- 0.1 mg/dl. Serum concentrations of 1,25(OH)2D varied inversely with 24-h mean serum phosphorus (R= -0.92, P<0.0001). Thus, in healthy elderly men in whom glomerular filtration rate is normal or near normal, serum concentrations of 1,25(OH)2D increase when dietary phosphorus is restricted; the magnitude of response at steady state is unaffected by aging, but the time course of response is delayed. At any level of serum phosphorus, serum 1,25(OH)2D is lower than that in young men, as reflected by a lower intercept of regression of serum 1,25(OH)2D on 24-h mean phosphorus.

Regulation of Renal Parathyroid Hormone Receptor Expression by 1,25-Dihydroxyvitamin D3 and Retinoic Acid

1998 ◽  
Vol 8 (5) ◽  
pp. 261-277 ◽  
Author(s):  
W. Bruce Sneddon ◽  
Elizabeth L.R. Barry ◽  
Bonita A. Coutermarsh ◽  
Frank A. Gesek ◽  
Fengming Liu ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Parathyroid Hormone ◽  
Hormone Receptor ◽  
Receptor Expression ◽  
Parathyroid Hormone Receptor ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Hormone Receptor Expression

Effect of Parathyroid Hormone on Vitamin D Metabolism in Osteopetrosis

PEDIATRICS ◽  
1981 ◽  
Vol 68 (1) ◽  
pp. 109-112
Author(s):  
Dagfinn Aarskog ◽  
Lage Aksnes ◽  
Trond Markestad
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Serum Levels ◽  
Target Cells ◽  
Normal Range ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Basal Serum ◽  
Parathyroid Extract

Indices of vitamin D metabolism were studied before and after infusion of bovine parathyroid hormone extract in three children with osteopetrosis. Basal serum concentrations of calcium, alkaline phosphatase, and 25-hydroxyvitamin D tended to be low. Serum immunoreactive parathyroid hormone levels were in the upper normal range in two patients. A marked increase in urinary cyclic adenosine 3': 5'-monophosphate(cAMP) in all patients was solely due to an increase in the nephrogenous cAMP. The basal concentration of 1,25-dihydroxyvitamin D was clearly more than the upper limit of normal range in all three patients and increased after parathyroid extract infusion in one patient. The basal serum levels of 24,25-dihydroxyvitamin D were within normal limits and tended to decrease after parathyroid extract infusion in two of the patients. Parathyroid hormone and 1,25-dihydroxyvitamin D act in concert to increase calcium resorption from bone, and the increased serum levels of both these factors may reflect lack, or unresponsiveness, of target cells in bone.

scholarly journals FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1

2009 ◽  
Vol 297 (2) ◽  
pp. F282-F291 ◽  
Author(s):  
Jyothsna Gattineni ◽  
Carlton Bates ◽  
Katherine Twombley ◽  
Vangipuram Dwarakanath ◽  
Michael L. Robinson ◽  
...  
Keyword(s):  
Fibroblast Growth Factor 23 ◽  
Serum Phosphorus ◽  
Minor Role ◽  
Metanephric Mesenchyme ◽  
Fgf Receptor ◽  
Targeted Deletion ◽  
Dihydroxyvitamin D ◽  
A Minor ◽  
Phosphorus Levels

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone that contributes to several hypophosphatemic disorders by reducing the expression of the type II sodium-phosphate cotransporters (NaPi-2a and NaPi-2c) in the kidney proximal tubule and by reducing serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels. The FGF receptor(s) mediating the hypophosphatemic action of FGF23 in vivo have remained elusive. In this study, we show that proximal tubules express FGFR1, −3, and −4 but not FGFR2 mRNA. To determine which of these three FGFRs mediates FGF23's hypophosphatemic actions, we characterized phosphate homeostasis in FGFR3−/− and FGFR4−/− null mice, and in conditional FGFR1−/− mice, with targeted deletion of FGFR1 expression in the metanephric mesenchyme. Basal serum phosphorus levels and renal cortical brush-border membrane (BBM) NaPi-2a and NaPi-2c expression were comparable between FGFR1−/−, FGFR3−/−, and FGFR4−/− mice and their wild-type counterparts. Administration of FGF23 to FGFR3−/− mice induced hypophosphatemia in these mice (8.0 ± 0.4 vs. 5.4 ± 0.3 mg/dl; p ≤ 0.001) and a decrease in renal BBM NaPi-2a and NaPi-2c protein expression. Similarly, in FGFR4−/− mice, administration of FGF23 caused a small but significant decrease in serum phosphorus levels (8.7 ± 0.3 vs. 7.6 ± 0.4 mg/dl; p ≤ 0.001) and in renal BBM NaPi-2a and NaPi-2c protein abundance. In contrast, injection of FGF23 into FGFR1−/− mice had no effects on serum phosphorus levels (5.6 ± 0.3 vs. 5.2 ± 0.5 mg/dl) or BBM NaPi-2a and NaPi-2c expression. These data show that FGFR1 is the predominant receptor for the hypophosphatemic action of FGF23 in vivo, with FGFR4 likely playing a minor role.

scholarly journals Variable Clinical Presentation of Children With Hereditary Hypophosphatemic Rickets With Hypercalciuria: A Case Series

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A708-A708
Author(s):  
Stephanie Christensen ◽  
Peter J Tebben ◽  
David Sas ◽  
Ana Creo
Keyword(s):  
Vitamin D ◽  
Sodium Phosphate ◽  
Serum Phosphorus ◽  
Hypophosphatemic Rickets ◽  
Urinary Stones ◽  
Dihydroxyvitamin D ◽  
Presenting Symptoms ◽  
Renal Tubular Cells ◽  
1,25 Dihydroxyvitamin D ◽  
Low Serum

Abstract Background: Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) is a rare condition of phosphate wasting due to variants in the SLC34A3 gene, encoding the sodium-phosphate cotransporter 2c (NaPi2c) at the brush border of proximal renal tubular cells (1). While labs are characterized by low serum phosphorus, high 1,25 dihydroxyvitamin D and inappropriately high levels of urine phosphate and calcium, the presenting symptoms can vary widely. Little remains known about specific phenotype-genotype correlations, especially in children. Clinical Cases: We report three new cases of HHRH in an unrelated 12 year-old male, 9 year-old female and 14 year-old male. All three patients were found to have low serum phosphorus for age (2.9-3.2 mg/dL), normocalcemia (9.4-9.9 mg/dL), low to low-normal parathyroid hormone (7-15 pg/mL), elevated 1,25 dihydroxyvitamin D (91-178 pg/mL), and hypercalciuria (4.5-7.6 mg/kg/day). Urine phosphorus was inappropriately elevated given the degree of their hypophosphatemia. Despite having similar lab findings, however, their clinical presentations were varied. The 12 year-old male presented with lower extremity pain, which was previously ascribed to patellofemoral pain syndrome. He had no history of renal symptoms, though a renal ultrasound later identified stones bilaterally. Conversely, the 9 year-old female and 14 year-old male presented with recurrent urinary stones and no bone symptoms. Genetic analyses identified 4 novel SLC34A3 gene mutations. Of interest, the 12 year-old male and 9 year-old female each shared a variant (c.575C-T (p.Ser192Leu)) despite having disparate symptoms. All three patients were treated with phosphorus supplementation and were advised to discontinue Vitamin D, if this had previously been prescribed. Conclusion: These three cases highlight the variability of presenting signs and symptoms among individuals with HHRH. Obtaining an accurate diagnosis is critical, as the addition of Vitamin D can seriously worsen symptoms in HHRH though it is a commonly used treatment for other disorders of phosphate wasting and bone demineralization. To aid in clinical decision making, we present a stepwise approach to the diagnosis of hypophosphatemic diseases. References: (1) Lorenz-Depiereux, B., Benet-Pages, A., Eckstein, G., Tenenbaum-Rakover, Y., Wagenstaller, J., Tiosano, D., Gershoni-Baruch, R., Albers, N., Lichtner, P., Schnabel, D., Hochberg, Z., Strom, T. Hereditary Hypophosphatemic Rickets with Hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am. J. Hum. Genetic. 2006;78:193-201.

Growth hormone increases serum 1,25-dihydroxyvitamin D levels and decreases 24,25-dihydroxyvitamin D levels in children with growth hormone deficiency

1997 ◽  
Vol 136 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Shi Wei ◽  
Hiroyuki Tanaka ◽  
Toshihide Kubo ◽  
Taeko Ono ◽  
Susumu Kanzaki ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Vitamin D ◽  
Renal Tubules ◽  
Vitamin D Metabolites ◽  
Gh Therapy ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Igf I ◽  
Phosphorus Levels

Abstract The influence of growth hormone (GH) on calcium–phosphorus metabolism and modulation of vitamin D metabolism has been demonstrated, but the mechanism remains unclear. We investigated the effect of a 6-month course of GH therapy on vitamin D and mineral metabolism in twelve GH-deficient children. Before GH therapy, levels of vitamin D metabolites and other biochemistry data were within normal ranges. All patients responded to GH therapy with increased growth velocity. 1,25-Dihydroxyvitamin D levels increased after 1 month of treatment and remained at these higher levels, with a significant increase found at 3 months (P < 0·05), whereas 24,25-dihydroxyvitamin D levels were decreased at 1 and 3 months, the latter being a significant decrease (P < 0·05), and then returned to the baseline levels at 6 months. 25-Hydroxyvitamin D levels did not change significantly. A significant increase in serum insulin-like growth factor-I (IGF-I) levels occurred during the 6 months of treatment (1 month, P < 0·01; 3 and 6 months, P < 0·001). Serum parathyroid hormone (PTH) levels decreased significantly at 3 and 6 months (3 months, P < 0·01; 6 months, P < 0·05). Serum calcium and phosphorus levels did not change significantly. Significant increases were found in the urinary calcium/urinary creatinine ratio (3 and 6 months, P < 0·05) and the percent tubular reabsorption of phosphorus levels (1 and 3 months, P 0·05). The results of this study confirmed the actions of GH on renal tubules with increases in calcium excretion and phosphorus reabsorption, and indicate that the action of GH on modulating vitamin D metabolism may be IGF-I mediated, not PTH mediated. European Journal of Endocrinology 136 45–51

scholarly journals Risedronate, a Highly Effective Oral Agent in the Treatment of Patients with Severe Paget’s Disease1

1998 ◽  
Vol 83 (6) ◽  
pp. 1906-1910
Author(s):  
Frederick R. Singer ◽  
Thomas L. Clemens ◽  
Rachelle A. Eusebio ◽  
Pirow J. Bekker
Keyword(s):  
Serum Alkaline Phosphatase ◽  
Urinary Calcium ◽  
Oral Agent ◽  
Normal Range ◽  
Intact Pth ◽  
Urinary Hydroxyproline ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Percent Decrease ◽  
Phosphorus Levels

Thirteen patients with severe Paget’s disease of bone [mean serum alkaline phosphatase (SAP) level 17 times the upper limit of normal] were treated with 30 mg oral risedronate daily for 8 weeks. Patients were followed for 16 weeks without treatment. The change from baseline SAP was the primary end point. Those patients whose SAP levels did not reach the normal range were retreated with 30 mg for another 8 weeks. There was a mean percent decrease in SAP of 77% after the first course of risedronate treatment and 87% after the second course of treatment. All patients who completed the study had a decrease in SAP of at least 77% from the baseline. The urinary hydroxyproline/creatinine level was decreased by 64% and 79%, respectively, during the first and second treatment courses. There were transient asymptomatic decreases in serum calcium and phosphorus levels. The urinary calcium/creatinine ratio also decreased in these patients. Serum intact PTH and 1,25-dihydroxyvitamin D levels increased transiently during risedronate treatment. Oral risedronate was well tolerated by the patients. Only one patient discontinued treatment because of an adverse event (diarrhea) thought to be related to risedronate therapy.

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