Endocrine Abstracts

Background: Conservation of genes involved in TH transport, metabolism and action can reveal clues about the origins of TH signaling. A deiodinase homologue (DdDio) was previously identified in the social amoeba Dictyostelium discoideum (Singh, 2014). Dictyostelium cells live as single cell amoebae in soil where they feed on bacteria. However, upon starvation a developmental program is initiated that results in the formation of a multicellular fruiti...

Background: Disrupted thyroid hormone (TH) homeostasis has devastating effects on human neurodevelopment. THs are critical signaling molecules in neurodevelopment, acting on differentiation of neural cells, migration, synaptogenesis and myelination, with deiodinases governing intracellular TH concentrations in a spatiotemporal manner. It is remarkable that fetal neural cells, while being key target cells of TH, exhibit strong activity of the TH inactivating enzyme DIO3. Curren...

Background: Postpartum depression (PPD) is a common mental health disorder with a major impact on maternal health and wellbeing and offspring development. Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for postpartum thyroiditis and via this link, it is hypothesized that TPOAb positivity is a risk factor for PPD. However, the results of currently available single center studies are heterogeneous and affected by major study limitations.<p class="abstext"...

Background and Objective: Disrupted thyroid hormone (TH) signaling has devastating effects on human neurodevelopment. The molecular mechanisms underlying TH regulation and action are largely based on animal models. However, animal models are limited in revealing some of the most fundamental aspects of neurodevelopment that are unique to humans. We employed human induced pluripotent stem cell (iPSC) technology to study the effects of T3 on neurodevelopmental processes in a huma...

Background: Patients with medullary thyroid carcinoma (MTC), a neuroendocrine tumour derived from the parafollicular C-cells, often present with metastasized disease. Survival strongly correlates with stage of disease at diagnosis, illustrating the need for early diagnosis. Calcitonin (CT), a well-established tumour marker for MTC, is limited by a high rate of false positives in the screening phase. Promising new markers for MTC are procalcitonin (PCT) and progastrin releasin...

Background: Resistance to thyroid hormone (TH) alpha (RTHα), caused by heterozygous mutations in THRA, is characterized by abnormal thyroid function tests and features due to tissue-specific hypothyroidism, including disproportional short stature, variable motor and cognitive defects, macrocephaly and macroglossia, constipation and anemia. Mutant receptors display defective T3 binding resulting in impaired transcriptional activity. Dominant negative inhibition of the WT r...

Background: Over the last few decades, in vivo animal experiments have been the gold standard for the assessment of safety of chemicals and pharmaceuticals for human health. However, in vivo animal data has limited relevance for toxicity prediction in humans, especially considering species-specific issues of age, sex and exposure in different life-stages. Within the Virtual Human Platform for Safety Assessment (VHP4Safety) project we aim to develop an animal-...

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...

Background: Previous genetic and animal studies implied a potential association between thyroid hormone and osteoarthritis (OA), but this has not been confirmed in the general population. We aim to investigate whether thyroid function is associated with hand, hip or knee OA.Methods: We included 9,054 participants from Rotterdam Study with baseline measurement of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and radiographs. Joint radiographs we...

Background: Resistance to thyroid hormone (TH) beta (RTHβ), caused by mutations in THRB, is characterized by elevated serum (F)T4 accompanied by non-suppressed TSH concentrations. Disease features arise from variable resistance to TH action in tissues expressing Thyroid Hormone Receptor (TR) β (hypothalamus, pituitary, liver) and from thyrotoxic effects in tissues expressing TRα (heart, bone, brain). In symptomatic patients, treatment mainly involves be...