The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Sep 2017
Comparative StudyThreshold Effects of Circulating Angiopoietin-Like 3 Levels on Plasma Lipoproteins.
Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function gene mutations results in familial combined hypobetalipoproteinemia type 2 (FHBL2) in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low-density lipoprotein (LDL) phenotype in carriers of ANGPTL3 mutations is unexplained. ⋯ Our results suggest that the hypolipidemic effects of ANGPTL3 mutations in FHBL2 are dependent on a threshold of plasma ANGPTL3 levels, with differential effects on various lipoprotein particles. The increased inactivation of PCSK9 by furin in FHBL1 and FHBL2 is likely to cause increased LDL clearance and suggests novel therapeutic avenues.
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J. Clin. Endocrinol. Metab. · Sep 2017
Randomized Controlled Trial Comparative StudyRandomized Trial Comparing Two Algorithms for Levothyroxine Dose Adjustment in Pregnant Women With Primary Hypothyroidism.
Regulation of maternal thyroid hormones during pregnancy is crucial for optimal maternal and fetal outcomes. There are no specific guidelines addressing maternal levothyroxine (LT4) dose adjustments throughout pregnancy. ⋯ We compared two options for LT4 dose adjustment and showed that an ongoing adjustment approach is as effective as empiric dose increase for maintaining goal TSH in hypothyroid women during pregnancy.
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J. Clin. Endocrinol. Metab. · Aug 2017
Randomized Controlled TrialResponse to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D-Related Genetic Variants.
Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. ⋯ Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity.
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J. Clin. Endocrinol. Metab. · Aug 2017
Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms.
Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1-induced thyroid irAEs. ⋯ Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis and overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T cell, NK cell, and/or monocyte-mediated pathways. Because the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment.
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J. Clin. Endocrinol. Metab. · Jul 2017
Comparative StudyPeak Bone Mass and Bone Microarchitecture in Adults Born With Low Birth Weight Preterm or at Term: A Cohort Study.
Peak bone mass (PBM) is regarded as the most important determinant of osteoporosis. Growing evidence suggests a role of intrauterine programming in skeletal development. We examined PBM and trabecular bone score (TBS) in adults born preterm with very low birth weight (VLBW) or small for gestational age (SGA) at term compared with term-born controls. ⋯ Both low-birth-weight groups displayed lower PBM and higher frequency of osteopenia/osteoporosis, implying increased future fracture risk. The most pronounced bone deficit was seen in VLBW adults.