Amino-Terminal Form of Parathyroid Hormone (PTH) with Immunologic Similarities to hPTH(1–84) Is Overproduced in Primary and Secondary Hyperparathyroidism
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Bibliographic record
Abstract
BACKGROUND: To separate non-(1-84)parathyroid hormone [non-(1-84)PTH] from PTH(1-84), we developed new HPLC gradients and observed that the peak coeluting with hPTH(1-84) could be separated into two entities recognized by a cyclase-activating PTH (CA-PTH) assay that reacts with the first four amino acids of the PTH structure. METHODS: Sera from six healthy individuals and five patients with primary hyperparathyroidism, and eight pools of sera from patients in renal failure were fractionated by HPLC. A total (T)-PTH assay reacting with the (15-20) region, the CA-PTH assay, and a COOH-terminal (C)-PTH assay with a (65-84) structure requirement were used to measure basal and fractionated PTH values. RESULTS: T-PTH was higher than CA-PTH in all healthy controls [mean (SD), 3.13 (0.37) vs 2.29 (0.33) pmol/L; P <0.01] and in renal failure patients [47 (35.1) vs 33.4 (26.1) pmol/L; P <0.01]. By contrast, CA-PTH concentrations were similar to or higher than T-PTH in three of five patients with primary hyperparathyroidism [25.7 (26.1) vs 23.1 (24.2) pmol/L; not significant]. The CA-PTH assay reacted with the hPTH(1-84) peak and with a minor peak different from the non-(1-84) peak recognized by the T-PTH assay. This minor peak was not recognized by the T-PTH assay. It represented 8 (2)% of CA-PTH in controls, 25 (23)% in patients with primary hyperparathyroidism, and 22 (7)% in renal failure patients, assuming equimolar reactivity to hPTH(1-84) in the CA-PTH assay. It was not oxidized hPTH(1-84), which migrated differently on HPLC and reacted similarly in the CA and T-PTH assays. CONCLUSIONS: This new molecular form of PTH has structural integrity of the (1-4) region but presumably is modified in the region (15-20), which is usually recognized by the T-PTH assay. Its clinical implications remain to be defined.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it