Endocrine Abstracts

In the last few years studies have shown that subtle variations in thyroid function, including subclinical thyroid dysfunction, and even variation in thyroid function within the normal range, are associated with morbidity and mortality. It is estimated that 40–65% of the inter-individual variation in serum TSH and FT4 levels is determined by genetic factors. To identify these factors, various linkage and candidate gene studies have been performed in the past, which have i...

A 60-year-old Caucasian male was referred to our Endocrine unit with symptoms suggestive of adrenal failure (malaise and fatigue).A Synachten test confirmed the diagnosis (baseline cortisol <5 nmol/l, post Synachten 74 nmol/l) and indicated secondary adrenal failure (baseline ACTH undetectable). Further hormonal tests showed secondary hypothyroidism (TSH 0.43 mU/ml, FT4 7.1 pmol/l) and hypogonadism (testosterone <0.7 nmol/l, LH 0.6 U/l). Prolacti...

Context: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide, affecting 2–8% of all pregnancies. We have previously shown that women with high-normal levels of FT4 during early pregnancy have a 2.1-fold increased risk of preeclampsia – but there was no apparent association with low TSH. However, the thyroid is stimulated by human chorionic gonadotropin (hCG) during early pregnancy and therefore we hypothesized that women with h...

Context: High maternal TSH and/or low FT4 during pregnancy is associated with an increased risk of premature delivery. hCG is the main determinant of thyroid function changes during pregnancy but has a versatile pattern with high inter and intra-individual variability. We hypothesised that the correct interpretation of thyroid function tests and its use in the risk assessment of premature delivery during pregnancy depend on hCG levels.Design, ...

Thyroid hormones play a key role in cellular growth, development, and metabolism, and are known regulators of gene expression through genomic and non-genomic processes including DNA methylation. Using eight cohorts from the ThyroidOmics-Consortium and a standardized meta-analysis quality control pipeline, we conducted an epigenome-wide association study between blood-based leucocyte DNA methylation sites and thyroid hormones (TSH, free T3 and free T4) in up to 7,073 participan...

Introduction: Maternal hypo- and hyperthyroidism during pregnancy have been associated with high and low birth weights, which predispose for various diseases later in life, such as cardiovascular diseases and cancer. However, the effects of variation in maternal thyroid hormone levels within the normal range on fetal growth and birth weight are largely unknown.Methods: First trimester serum TSH, FT4 and TPO-antibody (TPOab) levels were determi...

Introduction: Historically, treatment of follicular thyroid carcinoma (FTC) and oncocytic thyroid carcinoma (OTC) is based on thyroidectomy followed by radioiodine (RAI) therapy. Both tumor types have a good prognosis (10-year survival 80-94%), but this changes significantly once RAI-refractory disease occurs (median 3.5 years), which limits further treatment possibilities. The main risk factors for developing RAI-refractory disease in FTC and OTC are unknown. Our aim was to i...

Introduction: In the last decade, it has become clear that not only overt but also subclinical hypo- and hyperthyroidism are associated with several adverse clinical outcomes, including atrial fibrillation, coronary heart disease, stroke and mortality. More recently, various studies have suggested that even small differences in thyroid function within the reference range are associated with clinical consequences. Genetic factors are responsible for up to 58-71% of the variatio...

Background: MCT8 deficiency is caused by loss-of-function (LoF) mutations in thyroid hormone (TH) transporter MCT8. Patients have developmental delay and abnormal thyroid function tests (TFTs). The large phenotypic variability is not understood. Moreover, phenotypes arising from LoF mutations could be employed to enhance understanding of physiology in the general population. Also, computational disease variant classifiers have poor predictive power to ascertain impact of MCT8 ...

Introduction: Adequate thyroid hormone availability during early life is crucial for normal child growth and development. Fetal growth in utero heavily depends on angiogenesis. Placental growth factor (PlGF) is a proangiogenic factor sharing high homology with vascular endothelial growth factor (VEGF) whereas soluble FMS-like tyrosine kinase-1 (sFlt1) is a potent antagonist of VEGF and PlGF signaling. Since the thyroid is a highly vascularized organ, we hypothesized t...