Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Purpose To evaluate total and free vitamin D metabolites and hormone-to-prohormone [1,25(OH)(2)D/25(OH)D] "activation ratio" in PHPT patients with low or insufficient vitamin D status. Methods Thirty female patients with primary hyperparathyroidism (PHPT) and 30 age and body mass index (BMI) matched healthy controls were enrolled. Serum levels of calcium, intact parathyroid hormone (iPTH), vitamin D binding protein (DBP), albumin, total 25(OH)D and 1,25(OH)(2)D were measured. The activation ratio of vitamin D was calculated as total 1,25(OH)(2)D/25(OH)D. Calculated serum-free 25(OH)D and 1,25(OH)(2)D levels were also reported. Results Compared to the control subject, patients with PHPT had a lower total 25(OH)D and DBP levels (p < 0.001). The serum concentration of free 25(OH)D and total 1,25(OH)(2)D were similar between the two groups; but free 1,25(OH)(2)D levels were about 26% higher in the PHPT patients compared to controls (p < 0.001). PHPT patients had a significantly higher activation ratio (p < 0.01), although their total 25(OH)D were lower than controls. The free (but not total) 1,25(OH)(2)D level was inversely correlated with DBP (p < 0.01). Both free 1,25(OH)(2)D levels and activation ratio were positively correlated with iPTH and calcium levels (p < 0.01). The activation ratio was highly correlated with levels of total vitamin D stores and free vitamin D metabolites (p < 0.001). Conclusion Patients with PHPT had significantly higher free 1,25(OH)(2)D levels and activation ratio compared to control subjects. We suggest that levels of free vitamin D metabolites and vitamin D activation ratio may provide additional values for the diagnosis and therapeutic choices in these patient populations with compromised vitamin D status.

Conventional CRISPR approaches for precision genome editing rely on the introduction of DNA double-strand breaks (DSB) and activation of homology-directed repair (HDR), which is inherently genotoxic and inefficient in somatic cells. The development of base editing (BE) systems that edit a target base without requiring generation of DSB or HDR offers an alternative. Here, we describe a novel BE system called Pin-pointTM that recruits a DNA base-modifying enzyme through an RNA aptamer within the gRNA molecule. Pin-point is capable of efficiently modifying base pairs in the human genome with precision and low on-target indel formation. This system can potentially be applied for correcting pathogenic mutations, installing premature stop codons in pathological genes, and introducing other types of genetic changes for basic research and therapeutic development.

To investigate Klotho level and its association with biochemical indices of primary hyperparathyroidism (PHPT). Fifty PHPT patients and fifty-two age- and body mass index-(BMI) matched healthy control subjects were recruited. In addition, twenty-five PHPT patients underwent parathyroidectomy (PTX) and had 4-month follow-up visits. Intact parathyroid hormone (iPTH), 25-hydroxyvitamin D [25(OH)D], calcium, albumin, corrected calcium, and Klotho levels were determined. There was no significant difference in age and BMI between PHPT subjects and controls (p > 0.05). PHPT patients had Klotho levels (15.4 ± 1.2 ng/mL) about 23% higher compared with those of the controls (11.9 ± 0.8 ng/mL), but this difference was not significant (p = 0.063). However, postmenopausal PHPT patients had 45% higher Klotho levels (17.6 ± 1.5 ng/ml) compared with postmenopausal controls (12.1 ± 0.9 ng/mL, p = 0.008). For postmenopausal subjects, Klotho levels had positive correlation with levels of iPTH (r = 0.25, p = 0.026) and corrected calcium (r = 0.34, p = 0.003), but negative correlation with 25(OH)D (r = −0.23, p = 0.042). After PTX, levels of iPTH and corrected calcium decreased and 25(OH)D levels increased to normal range (p < 0.001). However, there was no significant change in Klotho levels after a 4-month follow-up. Serum Klotho levels are higher in postmenopausal PHPT patients than in healthy postmenopausal control subjects. The etiology of elevated Klotho level and its clinical significance requires further investigation.

To evaluate the measured free 25-hydroxyvitamin D [25(OH)D] levels in patients with hyperparathyroidism (PHPT) and healthy controls. Eighty patients with PHPT(n = 40) and age and BMI matched controls (n = 40) were examined. Serum levels of total or free 25(OH)D, vitamin D binding protein (DBP), intact parathyroid hormone (iPTH) and calcium were measured. There was no significant difference in age (61.2 ± 11.9 vs 60.2 ± 7.0 years) and BMI (30.0 ± 6.1 vs 30.0 ± 2.2 kg/m2) between PHPT patients and healthy subjects. Levels of total 25(OH)D were about 20 % lower in PHPT patients (26.4 ± 7.7 ng/mL) compared to controls (31.0 ± 7.8 ng/mL, P < 0.05). There were no significant differences in calculated or measured free 25(OH)D levels between PHPT patients (4.9 ± 1.8 or 4.9 ± 1.6 pg/mL, respectively) and control subjects (5.1 ± 1.2 or 5.3 ± 1.6 pg/mL, respectively). Levels of free 25(OH)D were positively associated with levels of total 25(OH)D (r = 0.28, P < 0.05) but negatively correlated with iPTH and calcium levels (r=-0.22 and -0.23 respectively, P < 0.05). Serum total 25(OH)D levels were lower but the calculated or measured free 25(OH)D levels in patients with PHPT did not differ from healthy subjects. We suggest that total 25(OH)D levels may not reflect true vitamin D nutritional status in patients with PHPT.

Objective: To evaluate vitamin D binding protein and free 25-hydroxyvitamin D [25(OH)D] levels in healthy controls compared to primary hyperparathyroidism (PHPT) patients, and to examine PHPT before and after surgery. Methods: Seventy-five PHPT patients and 75 healthy age, gender, and body mass index (BMI) -matched control subjects were examined. In addition, 25 PHPT patients underwent parathyroidectomy and had a 3-month follow up visit. Levels of total and free 25(OH)D, DBP, and intact parathyroid hormone (iPTH) were determined before and 3 months after surgery. Results: There was no significant difference in age and BMI between PHPT patients and controls. Levels of 25(OH)D and DBP were lower in PHPT patients compared to controls (p < 0.01). There was no significant difference in calculated free and bioavailable 25(OH)D levels between PHPT patients and controls. Calcium and iPTH levels decreased to normal but DBP and DBP-bound-25(OH)D increased (P < 0.001) after parathyroidectomy. Levels of DBP were inversely correlated with iPTH (r = -0.406, P < 0.001) and calcium levels (r = -0.423, P < 0.001). Conclusion: Serum DBP levels were lower in patients with PHPT and parathyroidectomy restored DBP levels. We suggest that lower DBP levels is one of contributing mechanisms of low total 25(OH)D in PTHP patients and the total 25(OH)D levels might not reflect true vitamin D status in PHPT patients.

Objective: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated parathyroid hormone (PTH) levels with persistently normal calcium levels. The diagnosis of NPHPT assumes the absence of secondary causes of elevated FTH levels. The objective of the current study was to examine levels of free 25-hydroxyvitamin D (25[OH]D) in NPHPT subjects and healthy controls. Methods: Ten NPHPT subjects and 20 controls who were age, sex, race, and body mass index (BMI) matched were examined. The diagnosis of NPHPT was made if subjects had (1) a serum calcium level of 8.6 to 10.4 mg/dL total 25(OH)D 30 to 40 ng/mL, and intact FTH (iPTH) >= 66 pg/mL; and (2) normal renal and liver function. Serum total 25(OH)D levels were measured by radioimmunoassay, and free 25(OH)D levels were determined using an enzyme-linked immunoassay. Results: Mean age of NPHPT subjects was 59.9 +/- 5.4 years, and mean BMI was 28.4 +/- 2.3 kg/m(2), which was not significantly different from the mean age and BMI of the control subjects. Mean total 25(OH)D level was 31.9 +/- 1.7 ng/mL in NPHPT subjects and did not differ from that of the controls (32.7 +/- 3.3 ng/mL; P = .52). However, mean free 25(OH)D was 5.0 +/- 0.9 pg/mL in NPHPT subjects, which was 20% lower compared to the mean of the controls (6.2 +/- 1.3 pgIng,; P = .013). Serum iPTH levels were inversely correlated with levels of measured free 25(OH)D (r = -0.42; P<.05) but did not correlate with levels of total 25(OH)D (r = -0.14; P>.10). Conclusion: Measured free 25(OH)D levels are lower in NPHPT subjects than in healthy control subjects. We suggest that some NPHPT subjects may actually have secondary hyperparathyroidism based on their free 25(OH) D levels.