Thyroid effects of endocrine disrupting chemicals

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties.     

Thyroid,parathyroid hormones and calcium homeostasis

The thyroid gland secretes thyroxine (T4) and triiodothyronine (T3) in response to thyroid-stimulating hormone (TSH) released from the anterior pituitary gland. Iodine is essential for the synthesis of thyroid hormones. T4 and T3 increase basal metabolic rate, heat production and help to maintain normal growth and development. The parathyroid glands are essential for maintaining normal levels of serum calcium, which is necessary to maintain normal cellular function via calcium acting as a secondary messenger. Calcium is also involved in the coagulation of blood, transmission of nerve impulses and muscular contraction. Calcium is provided by various dietary sources and plasma levels are altered by varying absorption in the gut, mobilization from bone and excretion by the kidney.     

Validation of plasma thyroxine and triiodothyronine methods on the ADVIA Centaur® XP

Standardization programs for thyroid hormones have revealed bias between immunochemical methods and the reference method ED-ID-LC/MS. Lack of standardization between methods, suboptimal reference intervals and replacement of serum with plasma may compromise the capability of the immunochemical thyroid methods to diagnose thyroid disease. To accommodate the demand for faster turn-around times for laboratory replies, we replaced serum with plasma on some serum CE marked thyroid methods. This forced us to do on-board analytical correction for the plasma total T4 (TT4) method on ADVIA Centaur^® XP. We, next, validated the capability of the ADVIA Centaur^® XP thyroid methods on plasma by (1) first carrying out a prospective method comparison with the ED-ID-LC/MS reference method using collected plasma samples, (2) we verified the clinical reference intervals by analyzing collected plasma samples from healthy individuals, and (3) retrospectively compared laboratory results from two different time periods using serum TT4 and serum total triiodothyronine (TT3) versus plasma free thyroxine (FT4) and plasma TT3, respectively, to diagnose thyroid disease. The plasma FT4 method displayed a negative concentration-dependent bias against the reference method. This bias was apparently counteracted by a fitted reference interval for the plasma FT4 method. Indeed, overt hyperthyroid disease was found in 1.0% and 1.1% of the cases using serum and plasma and overt hypothyroid condition were in 1.3% and 0.6% of the cases using serum and plasma, respectively. In conclusion, the ADVIA Centaur^® XP FT4 method displayed a negative bias at high plasma FT4 concentrations against the reference method, but the diagnostic performance was not compromised due to a fitted reference interval.     

甲状腺激素水平与新生儿硬肿症关系的研究

目的 了解新生儿甲状腺激素水平低下与硬肿症发生的因果关系及影响因素.方法 采用放射免疫法对具有低体温、低体重、反应差、心脏抑制等表现、但未发生硬肿的16名早产儿甲状腺激素(T4、T3、rT3、TSH)水平进行追踪性监测,并观察病程中发生新生儿硬肿症的情况.结果 观察对象中,100%小儿T3低于同期小儿甲状腺激素正常低限值,T3、T4同时降低者为93.8%;若以临床实验诊断标准低限值衡量,T3降低者为81.7%,T3、T4同时降低者为25%.其中T3降低者中84.6%在病程中发生了新生儿硬肿症,而T3未降低的患儿均未发生硬肿症.结论 甲状腺激素水平降低,特别是T3水平的严重降低可能是新生儿硬肿症的重要发病原因.     

Hormones and health outcomes in aging men

Increasing age is a predictor of ill-health and mortality related to cardiovascular disease and to frailty, a syndrome characterized by deterioration of multiple organ systems leading to loss of physiological reserve, diminished capacity to cope with stressors, and increased risk of disability and death. As men grow older, their levels of testosterone decline while the prevalence of ill-health increases. Observational studies have linked lower testosterone levels with cardiovascular disease and mortality in middle-aged and older men. More recently, lower testosterone has been shown to predict reduced sexual activity and frailty in aging men. Additional studies are needed to determine whether lower testosterone is a biomarker or a potentially treatable risk factor for poorer health outcomes in older men. During aging, the response of the pituitary–thyroid axis alters to manifest higher thyrotropin levels. The presences of subclinical hypo- and hyper-thyroidism predict adverse cardiovascular outcomes. Newer results indicate that in euthyroid older men, differences in free thyroxine levels within the normal range predict specific health outcomes including frailty. Clarification of the roles of endogenous testosterone and thyroxine in the genesis of ill-health during male aging offers the prospect of future intervention to preserve health and well-being in this growing population.