Calcium Mediates the Phosphaturia in Hypercalcemia of Malignancy
Bibliographic record
Abstract
Background: Humoral hypercalcemia of malignancy (HHM) is claimed to be caused by circulating parathyroid hormone like peptide (PTHrP) that shares several of the cardinal biochemical and skeletal histological features with hyperparathyroidism (HPT). Both syndromes are characterized by hypercalcemia from increased renal tubular reabsorption of filtered calcium, increased urinary cyclic AMP, renal phosphate wasting and hypophosphatemia, in contrast to low 1,25(OH)2D levels, metabolic alkalosis, and uncoupled bone formation-resorption rate in HHM. The aim of the study was to reassess if phosphaturia of HHM can be attributed to hypercalcemia rather than to humoral effect of PTHrP. Methods: A prospective study was conducted at Mount Sinai Services at Queens Hospital Center, NY. Results: Nine (four females and five males) out of 20 patients with hypercalcemia of malignancy documented having elevated PTHrP, normal renal function, and low PTH levels were finalized for the study. Serum calcium, phosphate, creatinine, albumin, and PTHrP concentration were determined. On the initiation of hydration, 24 h urine for creatinine, calcium and phosphorous were also collected. Blood and urine tests were repeated after serum calcium levels had been decreased by at least 1.5 mg/dL. All patients received vigorous intravenous hydration with normal saline at 200 cc/h. After the first 24 h, small doses of furosemide were given to two out of nine patients for 48 - 72 h. Hydration has shown statistically significant decrease in serum calcium concentration (13.9 ± 2.1 to 10.8 ± 1.48 mg/dL; P < 0.001) and increase in tubular reabsorption of phosphate (TRP) (69.54±8.16% to 77.85±12.24%; P < 0.01). However, PTHrP levels have shown no statistically significant difference on hydration therapy. Conclusion: Improvement of hypercalcemia by hydration reverses phosphaturia without reducing PTHrP levels. It is being proposed that in HHM, PTHrP can lead to hypercalcemia from uncoupled bone formation-resorption rate through a local autocrine or paracrine action produced by bony micrometastases that could not be demonstrated radiologically, rather than from PTHrP’s humoral effect. J Endocrinol Metab. 2017;7(2):55-60 doi: https://doi.org/10.14740/jem402w
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".