calcitriol and Adenoma

In cancer cell lines and rodent models, calcium and vitamin D favorably modulate cell proliferation, differentiation, and apoptosis in colonic epithelia. These effects may be modulated by local expression of the calcium receptor (CaR), the vitamin D receptor (VDR), and the P450 cytochromes, CYP27B1 and CYP24A1; however, they have yet to be investigated in humans. To address this gap, we conducted a randomized, double-blinded, placebo-controlled 2×2 factorial clinical trial. Patients with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d elemental calcium and/or 800 IU/d vitamin D3 versus placebo over 6 months (n=92; 23 per group). CaR, VDR, CYP27B1, and CYP24A1 expression and distribution in biopsies of normal appearing rectal mucosa were detected by standardized, automated immunohistochemistry and quantified by image analysis. In the calcium-supplemented group, CaR expression increased 27% (P=0.03) and CYP24A1 expression decreased 21% (P=0.79). In the vitamin D3-supplemented group, CaR expression increased 39% (P=0.01) and CYP27B1 expression increased 159% (P=0.06). In patients supplemented with both calcium and vitamin D3, VDR expression increased 19% (P=0.13) and CaR expression increased 24% (P=0.05). These results provide mechanistic support for further investigation of calcium and vitamin D3 as chemopreventive agents against colorectal neoplasms, and CaR, VDR, CYP27B1, and CYP24A1 as modifiable, preneoplastic risk biomarkers for colorectal neoplasms.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Adenoma; Biomarkers, Tumor; Calcium; Cholecalciferol; Colorectal Neoplasms; Double-Blind Method; Female; Humans; Immunohistochemistry; Intestinal Mucosa; Male; Middle Aged; Pilot Projects; Precancerous Conditions; Receptors, Calcitriol; Receptors, Calcium-Sensing; Steroid Hydroxylases; Vitamin D; Vitamin D3 24-Hydroxylase

Primary hyperparathyroidism (PHPT) is associated with reduced plasma 25-hydroxyvitamin D (P-25OHD) and usually increased plasma 1alpha,25-dihydroxyvitamin D (P-1,25(OH)2D). Parathyroid tissue expresses the vitamin D receptor and it is thought that circulating 1,25(OH)2D participate in the regulation of parathyroid cell proliferation, differentiation and secretion.. To investigate the relations between circulating levels of 1,25(OH)2D and 25OHD respectively and parathyroid adenoma weight (AW), plasma-parathyroid hormone (P-PTH) and PTH secretion expressed as P-PTH/AW.. Cross-sectional study.. One hundred and seventy-one consecutive hypercalcaemic caucasian patients aged 19-87 years (median 63, 84% females) with surgically proven parathyroid adenoma.. A weak positive correlation was found between P-25OHD and P-1,25(OH)2D (r=0.24, P<0.005). AW depended on sex and body mass index. Following adjustment, it was correlated positively to P-PTH, calcium (Ca) and alkaline phosphatase (AP) and inversely to plasma phosphate in a multiple regression model. AW was not associated with vitamin D metabolites. Preoperative P-PTH correlated positively to plasma levels of Ca and AP, but inversely to phosphate and 25OHD (P<0.001) levels. P-PTH was not associated with P-1,25(OH)2D (P=0.65). The P-PTH:AW ratio correlated inversely to P-25OHD (P<0.05), but showed no relations to plasma levels of Ca, phosphate or 1,25(OH)2D (P=0.22).. In this material, low levels of 25OHD were related to higher levels of P-PTH and higher PTH:AW ratios in patients with PHPT suggesting that vitamin D deficiency increase PTH secretion activity. Neither PTH secretion nor AW was associated with circulating levels of 1,25(OH)2D.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Organ Size; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Vitamin D; Vitamin D Deficiency

Primary hyperparathyroidism (PHP) during pregnancy is well known to confer an increased risk of complications to both the mother and the fetus. However, the risks and optimal management of patients with mild, asymptomatic disease during pregnancy are much less clear. We observed a patient with mild, asymptomatic PHP who was diagnosed before conception through pregnancy. The patient remained asymptomatic through the first 22 weeks of pregnancy, and her calcium levels remained under 11 mg/dL. This occurred despite a dramatic elevation in the level of 1,25-dihydroxyvitamin D and marked hypercalciuria. Parathyroid surgery was performed at 22 weeks of gestation and a parathyroid adenoma was removed. Postoperatively, the patient's calcium level normalized and the rest of the pregnancy was uncomplicated. The patient delivered a healthy baby at 40 weeks of gestation. The neonatal course was unremarkable. We conclude that mild, asymptomatic PHP during early pregnancy is compatible with normal fetal development and an uncomplicated pregnancy and that the serum calcium level in such patients can remain stable with medical management alone, despite the marked changes in maternal calcium metabolism that characterize normal pregnancy.

Topics: Adenoma; Adult; Calcium; Disease Progression; Embryonic and Fetal Development; Female; Humans; Hypercalcemia; Hyperparathyroidism; Infant, Newborn; Parathyroid Hormone; Parathyroid Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prenatal Diagnosis; Prospective Studies; Ultrasonography, Prenatal; Vitamin D

1,25-dihydroxyvitamin D [1,25(OH)2D] inhibits proliferation and promotes differentiation of human colon cancer cell lines. Epidemiological findings, although not entirely consistent, suggest an inverse relationship between vitamin D intake and colorectal cancer and adenoma, colorectal cancer precursor lesions. We evaluated the relationship of plasma 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] with distal colorectal adenoma among 326 matched case and control pairs (nested in the prospective Nurses' Health Study), who provided blood in 1989-1990 and who underwent endoscopy in 1989-1996. Plasma vitamin D metabolite concentrations were determined blindly by RIA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple conditional logistic regression models. Mean plasma 1,25(OH)2D and 25(OH)D levels did not significantly differ (P = 0.3 and 0.7, respectively) between cases (31.6 +/- 8.4 pg/ml and 26.4 +/- 10.6 ng/ml, respectively) and controls (32.2 +/- 8.6 pg/ml and 26.8 +/-10.2 ng/ml, respectively). However, women whose plasma 1,25(OH)2D concentration was below 26.0 pg/ml (a level typically considered to be below normal) were at increased risk of distal colorectal adenoma (OR, 1.58; 95% CI, 1.03-2.40). Compared with the lowest 1,25(OH)2D quartile, women in the second (OR, 0.64; 95% CI, 0.41-1.02), third (OR, 0.80; 95% CI, 0.50-1.30), or upper (OR, 0.71; 95% CI, 0.43-1.15) quartiles were at a statistically nonsignificant lower risk of adenoma. The relationship was stronger for large/villous adenoma and among those with consistent vitamin D intake over the 10 years prior to blood draw. Compared with women in the lowest quartile, for plasma 25(OH)D, women in the second (OR, 0.64; 95% CI, 0.41-1.00) and third (OR, 0.58; 95% CI, 0.36-0.95) quartiles were at a statistically significantly lower risk of distal colorectal adenoma, but there was no difference in risk in the top quartile (OR, 1.04; 95% CI, 0.66-1.66). We conclude that women who have low levels of circulating 1,25(OH)2D may be at higher risk of distal colorectal adenomas, but additional study is warranted.

Topics: Adenoma; Adenomatous Polyposis Coli; Adult; Colorectal Neoplasms; Epidemiologic Studies; Female; Humans; Middle Aged; Prevalence; Risk Assessment; Vitamin D