Effects of Genetic and Non-genetic Factors on Total and Bioavailable 25(OH)D Responses to Vitamin D Supplementation.
J Clin Endocrinol Metab. 2016 Oct 21;:jc20162930
Authors: Yao P, Sun L, Lu L, Ding H, Chen X, Tang L, Xu X, Liu G, Hu Y, Ma Y, Wang F, Jin Q, Zheng H, Yin H, Zeng R, Chen Y, Hu FB, Li H, Lin X
CONTEXT: Little is known how genetic and non-genetic factors modify responses of vitamin D supplementation in nonwhite populations.
OBJECTIVE: To investigate factors modifying 25-hydroxyvitamin D (25[OH]D) and bioavailable 25(OH)D (25[OH]DBio) responses after vitamin D3 supplementation. Design, Setting, Participants, and Intervention: In this randomized, double-blinded, placebo-controlled trial, 448 Chinese with vitamin D deficiency (25[OH]D<50 nmol/L) received 2000 IU/d vitamin D3 or placebo for 20 weeks.
MAIN OUTCOME MEASURES: Serum 25(OH)D, parathyroid hormone (PTH) and calcium were measured. Six common polymorphisms in vitamin D metabolism genes were genotyped. Vitamin D-binding protein (VDBP) was measured by monoclonal and polyclonal antibody immunoassays and 25(OH)DBio was calculated based on polyclonal VDBP concentration.
RESULTS: Between-arm net changes (SE) were +30.6±1.7 nmol/L for 25(OH)D, +2.7±0.2 nmol/L for 25(OH)DBio, and -5.2±1.2 pg/ml for PTH, corresponding to 70% (95% CI: 62.8%-77.2%) net reversion rate for vitamin D deficiency at week 20 (P<0.001). Only change of 25(OH)DBio was positively associated with change of calcium (r=0.22; P<0.001). Genetic factors (GC-rs4588/GC-rs7041, VDR-rs2228570 and CYP2R1-rs10741657; P≤0.04) showed stronger influences on 25(OH)D or 25(OH)DBio responses than non-genetic factors including baseline value, BMI and gender. An inverse association of PTH with vitamin D was demonstrated only at 25(OH)D<50.8 (43.6-59.0) nmol/L, or 25(OH)DBio<5.8 (5.1-6.7) nmol/L.
CONCLUSIONS: Supplemented 2000 IU/d vitamin D3 raised 25(OH)D and 25(OH)DBio, but unable to correct deficiency in 25% of Chinese participants, which might be partially attributed to effect of genetic modification on the responses. More studies are needed to elucidate appropriate vitamin D recommendation for Asians and potential clinical implications of 25(OH)DBio.
PMID: 27768857 [PubMed - as supplied by publisher]
Elevated serum tetrac in Graves' disease: potential pathogenic role in thyroid-associated ophthalmopathy.
J Clin Endocrinol Metab. 2016 Oct 21;:jc20162762
Authors: Fernando R, Placzek E, Reese EA, Placzek AT, Schwartz S, Trierweiler A, Niziol LM, Atkins S, Scanlan TS, Smith TJ
CONTEXT: The sources and biological impact of 3,3',5,5' tetraiodothyroacetic acid (TA4) are uncertain. CD34(+) fibrocytes express several proteins involved in the production of thyroid hormones. They infiltrate the orbit in Graves' disease (GD), an autoimmune process known as thyroid-associated ophthalmopathy. It appears that the thyrotropin receptor (TSHR) plays an important role in the pathogenesis of TAO.
OBJECTIVE: To quantify levels of TA4 in healthy subjects and those with Graves' disease. To determine whether fibrocytes generate this TH analogue. To determine whether TA4 influences the actions of TSH and thyroid-stimulating immunoglobulins in orbital fibroblasts.
DESIGN/SETTING/PARTICIPANTS: Patients with GD and healthy donors in an academic medical center clinical practice were recruited.
MAIN OUTCOME MEASURES: liquid chromatography-tandem mass spectrometry, autoradiography, real-time PCR, hyaluronan immunoassay Results: Serum levels of TA4 are elevated in GD. TA4 levels are positively correlated with those of thyroxine and negatively correlated with serum levels of triiodothyronine. Several cell types in culture generate TA4 from ambient thyroxine, including fibrocytes, HELA cells, human Muller stem cells, and retinal pigmented epithelial cells. Propylthiouracil inhibited TA4 generation. TA4 enhances the induction by thyrotropin and thyroid-stimulating immunoglobulins of several participants in the pathogenesis of TAO, including IL-6, hyaluronan synthase-1, prostaglandin endoperoxide H synthase-2, and haluronan production.
CONCLUSION: TA4 may be ubiquitously generated in many tissues and enhances the biological impact of thyrotropin and thyroid-stimulating immunoglobulins in orbital connective tissue. These findings may identify a physiologically important determinant of extra-thyroidal TSH action.
PMID: 27768856 [PubMed - as supplied by publisher]
Population Survey of Iodine Deficiency and Environmental Disruptors of Thyroid Function in Young Children in Haiti.
J Clin Endocrinol Metab. 2016 Oct 21;:jc20162630
Authors: von Oettingen JE, Brathwaite TD, Carpenter C, Bonnell R, He X, Braverman LE, Pearce EN, Larco P, Larco NC, Jean-Baptiste E, Brown RS
CONTEXT: Iodine deficiency is the leading cause of preventable neurodevelopmental delay in children worldwide. It is a possible public health concern in Haiti.
OBJECTIVE: To perform a population iodine survey in Haitian young children, and its influence by environmental factors.
DESIGN: Cross-sectional study, March-June 2015.
SETTING: Community churches in 3 geographical regions in Haiti.
PARTICIPANTS: 299 healthy Haitian children aged 9 months to 6 years; 100 enrolled in coastal (C) and mountainous (M) regions, and 99 in an urban region (U).
MAIN OUTCOME MEASURES: Markers of iodine status including urinary iodide, serum TSH, goitre assessment, and urinary perchlorate and thiocyanate.
RESULTS: Mean age was 3.3±1.6 years, with 51% female, median family income USD 30/week, and 16% moderate or severe malnutrition. Median urinary iodide levels were normal in C (145 mcg/L, interquartile range [IQR] 97-241) and U (187 mcg/L, IQR 92-316) regions, but revealed mild iodine deficiency and were significantly lower in M (89 mcg/L, IQR 56-129), p<0.0001. Grade 1 goitres were palpated in 2 children, but TSH values were normal. Urinary thiocyanate and perchlorate concentrations were not elevated. Predictors of higher urinary iodide included higher levels of urinary thiocyanate and perchlorate, breastfeeding, and not living in M.
CONCLUSIONS: Childhood iodine deficiency is not a significant public health threat in Haiti, although areas of mild deficiency persist in mountainous regions. Exposure to two well-understood environmental thyroid function disruptors is limited. Further studies should identify risk factors, sources of iodine intake, and optimal methods for monitoring iodine deficiency in the community.
PMID: 27768855 [PubMed - as supplied by publisher]